View source for Medicine:Prostate cancer

{{Short description|Male reproductive organ cancer}}
{{Infobox medical condition (new)
| name            = Prostate cancer
| synonyms        = Carcinoma of the prostate
| image           = Diagram showing the position of the prostate and rectum CRUK 358.svg
| caption         = Position of the prostate
| field           = [[Medicine:Oncology|Oncology]], urology
| symptoms        = None, difficulty [[Biology:Urination|urinating]], blood in the urine, [[Medicine:Pelvic pain|pain in the pelvis]], back, or when urinating<ref name=NCI2014TxPro/><ref name=NCI2013TxPt/>
| complications   = 
| onset           = Age > 50<ref name=WCR2014/>
| duration        = 
| types           = 
| causes          = 
| risks           = Older age, family history, race<ref name=WCR2014/>
| diagnosis       = Tissue biopsy, [[Medicine:Medical imaging|medical imaging]]<ref name=NCI2013TxPt/>
| differential    = [[Medicine:Benign prostatic hyperplasia|Benign prostatic hyperplasia]]<ref name=NCI2014TxPro/>
| prevention      = 
| treatment       = [[Medicine:Active surveillance of prostate cancer|Active surveillance]], surgery, [[Physics:Radiation therapy|radiation therapy]], [[Medicine:Hormonal therapy (oncology)|hormone therapy]], [[Medicine:Chemotherapy|chemotherapy]]<ref name=NCI2013TxPt/>
| medication      = 
| prognosis       = 5-year survival rate 99% (US)<ref name=SEER2014/>
| frequency       = 1.2 million new cases (2018)<ref name=Bray2018/>
| deaths          = 359,000 (2018)<ref name=Bray2018/>
}}
<!-- Definition and symptoms -->
'''Prostate cancer''' is [[Medicine:Cancer|cancer]] of the [[Biology:Prostate|prostate]].<ref>{{Cite web |title=Prostate cancer - Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/prostate-cancer/symptoms-causes/syc-20353087 |access-date=2023-02-11 |website=Mayo Clinic |language=en}}</ref><ref>{{Cite web |title=What Is Prostate Cancer? |url=https://www.cancer.org/cancer/prostate-cancer/about/what-is-prostate-cancer.html |access-date=2023-02-11 |website=www.cancer.org |language=en}}</ref> Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men.<ref>{{cite journal | vauthors = Luining WI, Cysouw MC, Meijer D, Hendrikse NH, Boellaard R, Vis AN, Oprea-Lager DE | title = Targeting PSMA Revolutionizes the Role of Nuclear Medicine in Diagnosis and Treatment of Prostate Cancer | journal = Cancers | volume = 14 | issue = 5 | pages = 1169 | date = February 2022 | pmid = 35267481 | pmc = 8909566 | doi = 10.3390/cancers14051169 | doi-access = free }}</ref> The prostate is a gland in the male reproductive system that surrounds the urethra just below the [[Biology:Bladder|bladder]]. It is located in the hypogastric region of the [[Biology:Abdomen|abdomen]]. To give an idea of where it is located, the bladder is superior to the prostate gland as shown in the image<ref>{{Cite web |title=What Is Prostate Cancer? |url=https://www.cancer.org/cancer/prostate-cancer/about/what-is-prostate-cancer.html |access-date=2022-09-28 |website=www.cancer.org |language=en}}</ref> The [[Biology:Rectum|rectum]] is posterior in perspective to the prostate gland and the [[Biology:Pelvis|ischial]] [[Biology:Tubercle (bone)|tuberosity]] of the pelvic bone is inferior. Most prostate cancers are slow growing. Cancerous cells may [[Medicine:Metastasis|spread]] to other areas of the body, particularly the [[Biology:Bone|bone]]s and [[Biology:Lymph node|lymph node]]s. It may initially cause no symptoms. In later stages, symptoms include pain or difficulty [[Biology:Urination|urinating]], [[Medicine:Hematuria|blood in the urine]], or [[Medicine:Pelvic pain|pain in the pelvis]] or back. [[Medicine:Benign prostatic hyperplasia|Benign prostatic hyperplasia]] may produce similar symptoms. Other late symptoms include fatigue, due to [[Medicine:Anemia|low levels of red blood cells]].

<!-- Risk factors and diagnosis  -->
Factors that increase the risk of prostate cancer include older age, family history and race.<ref name="WCR2014">{{cite book |title=World Cancer Report |date=2014 |publisher=World Health Organization |isbn=978-9283204299 |chapter=Chapter 5.11}}</ref><ref>{{cite journal | vauthors = Kalish LA, McDougal WS, McKinlay JB | title = Family history and the risk of prostate cancer | language = English | journal = Urology | volume = 56 | issue = 5 | pages = 803–806 | date = November 2000 | pmid = 11068306 | doi = 10.1016/S0090-4295(00)00780-9 }}</ref> About 99% of cases occur after age 50.<ref name=WCR2014/> A [[Social:First-degree relative|first-degree relative]] with the disease increases the risk two- to three-fold.<ref name=WCR2014/> Other factors include a diet high in [[Chemistry:Processed meat|processed meat]] and [[Chemistry:Red meat|red meat]],<ref name=WCR2014/> while the risk from a high intake of milk products is inconclusive.<ref>{{cite journal | vauthors = Koh KA, Sesso HD, Paffenbarger RS, Lee IM | title = Dairy products, calcium and prostate cancer risk | journal = British Journal of Cancer | volume = 95 | issue = 11 | pages = 1582–1585 | date = December 2006 | pmid = 17106437 | pmc = 2360740 | doi = 10.1038/sj.bjc.6603475 }}</ref> An association with [[Medicine:Gonorrhea|gonorrhea]] has been found, although no reason for this relationship has been identified.<ref name="CainiGandini2014">{{cite journal | vauthors = Caini S, Gandini S, Dudas M, Bremer V, Severi E, Gherasim A | title = Sexually transmitted infections and prostate cancer risk: a systematic review and meta-analysis | journal = Cancer Epidemiology | volume = 38 | issue = 4 | pages = 329–338 | date = August 2014 | pmid = 24986642 | doi = 10.1016/j.canep.2014.06.002 }}</ref> An increased risk is associated with the [[Medicine:BRCA mutation|''BRCA ''mutations]].<ref>{{cite journal | vauthors = Lee MV, Katabathina VS, Bowerson ML, Mityul MI, Shetty AS, Elsayes KM, Balachandran A, Bhosale PR, McCullough AE, Menias CO | display-authors = 6 | title = BRCA-associated Cancers: Role of Imaging in Screening, Diagnosis, and Management | journal = Radiographics | volume = 37 | issue = 4 | pages = 1005–1023 | date = 2016 | pmid = 28548905 | doi = 10.1148/rg.2017160144 | doi-access = free }}</ref> Diagnosis is by [[Medicine:Biopsy|biopsy]].<ref name="NCI2013TxPt">{{cite web |date=2014-04-08 |title=Prostate Cancer Treatment (PDQ) – Patient Version |url=http://www.cancer.gov/cancertopics/pdq/treatment/prostate/Patient/page1/AllPages |url-status=live |archive-url=https://web.archive.org/web/20140705121244/http://www.cancer.gov/cancertopics/pdq/treatment/prostate/Patient/page1/AllPages |archive-date=5 July 2014 |access-date=1 July 2014 |publisher=National Cancer Institute}}</ref> [[Medicine:Medical imaging|Medical imaging]] may be done to assess whether [[Medicine:Metastasis|metastasis]] is present.<ref name=NCI2013TxPt/>

<!-- Screening and prevention -->
Prostate cancer screening, including [[Biology:Prostate-specific antigen|prostate-specific antigen]] (PSA) testing, increases cancer detection but whether it improves outcomes is controversial.<ref name=WCR2014/><ref name=NCI2018TxPro>{{cite web|title=Prostate Cancer Treatment|url=https://www.cancer.gov/types/prostate/hp/prostate-treatment-pdq#section/all|website=National Cancer Institute|access-date=1 March 2018|language=en|date=6 February 2018|quote=Controversy exists regarding the value of screening... reported no clear evidence that screening for prostate cancer decreases the risk of death from prostate cancer}}</ref><ref name=Catalona2018/><ref name=NHS2015Screen>{{cite web|title=PSA testing|url=https://www.nhs.uk/conditions/prostate-cancer/psa-testing/|website=nhs.uk|access-date=5 March 2018|date=3 January 2015}}</ref> Informed decision making is recommended for those 55 to 69 years old.<ref name=USPSTF2018>{{cite web |title=Final Recommendation Statement: Prostate Cancer: Screening |publisher= US Preventive Services Task Force (USPSTF) |url=https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/prostate-cancer-screening1 |website=www.uspreventiveservicestaskforce.org |access-date=30 August 2018 |language=en}}</ref><ref>{{cite journal | vauthors = Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, Davidson KW, Doubeni CA, Ebell M, Epling JW, Kemper AR, Krist AH, Kubik M, Landefeld CS, Mangione CM, Silverstein M, Simon MA, Siu AL, Tseng CW | display-authors = 6 | title = Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement | journal = JAMA | volume = 319 | issue = 18 | pages = 1901–1913 | date = May 2018 | pmid = 29801017 | doi = 10.1001/jama.2018.3710 | doi-access = free }}</ref> Testing, if carried out, is more appropriate for those with a longer life expectancy.<ref>{{cite journal | vauthors = Cabarkapa S, Perera M, McGrath S, Lawrentschuk N | title = Prostate cancer screening with prostate-specific antigen: A guide to the guidelines | journal = Prostate International | volume = 4 | issue = 4 | pages = 125–129 | date = December 2016 | pmid = 27995110 | pmc = 5153437 | doi = 10.1016/j.prnil.2016.09.002 }}</ref> Although 5α-reductase inhibitors appear to decrease low-grade cancer risk, they do not affect high-grade cancer risk, and are not recommended for prevention.<ref name=WCR2014/> [[Chemistry:Vitamin|Vitamin]] or mineral supplementation does not appear to affect risk.<ref name=WCR2014/><ref name=Strat2011>{{cite journal | vauthors = Stratton J, Godwin M | title = The effect of supplemental vitamins and minerals on the development of prostate cancer: a systematic review and meta-analysis | journal = Family Practice | volume = 28 | issue = 3 | pages = 243–252 | date = June 2011 | pmid = 21273283 | doi = 10.1093/fampra/cmq115 | doi-access = free }}</ref>

<!-- Treatment, prognosis and epidemiology -->
Many cases are managed with [[Medicine:Active surveillance of prostate cancer|active surveillance]] or [[Social:Watchful waiting|watchful waiting]].<ref name=NCI2013TxPt/> Other treatments may include a combination of surgery, [[Physics:Radiation therapy|radiation therapy]], [[Medicine:Hormonal therapy (oncology)|hormone therapy]], or [[Medicine:Chemotherapy|chemotherapy]].<ref name=NCI2013TxPt/> Tumors limited to the prostate may be curable.<ref name=NCI2014TxPro>{{cite web|title=Prostate Cancer Treatment (PDQ) – Health Professional Version|url=http://www.cancer.gov/cancertopics/pdq/treatment/prostate/HealthProfessional/page1/AllPages|publisher=National Cancer Institute|access-date=1 July 2014|date=2014-04-11|url-status=live|archive-url=https://web.archive.org/web/20140705121331/http://www.cancer.gov/cancertopics/pdq/treatment/prostate/HealthProfessional/page1/AllPages|archive-date=5 July 2014}}</ref> Pain medications, [[Chemistry:Bisphosphonate|bisphosphonate]]s, and targeted therapy,<ref name="Luszczak 2020 7">{{cite journal | vauthors = Luszczak S, Kumar C, Sathyadevan VK, Simpson BS, Gately KA, Whitaker HC, Heavey S | title = PIM kinase inhibition: co-targeted therapeutic approaches in prostate cancer | journal = Signal Transduction and Targeted Therapy | volume = 5 | issue = 1 | pages = 7 | date = January 2020 | pmid = 32296034 | pmc = 6992635 | doi = 10.1038/s41392-020-0109-y }}</ref> among others, may be useful.<ref name=NCI2013TxPt/> Outcomes depend on age, health status and how aggressive and extensive the cancer is.<ref name=NCI2013TxPt/> Most men with prostate cancer do not die from it.<ref name=NCI2013TxPt/> The {{wipe|United States}} [[Medicine:Five-year survival rate|five-year survival rate]] is 98%.<ref name=SEER2014>{{cite web|title=SEER Stat Fact Sheets: Prostate Cancer|url=http://seer.cancer.gov/statfacts/html/prost.html|website=NCI|access-date=18 June 2014|url-status=live|archive-url=https://web.archive.org/web/20140706142501/http://seer.cancer.gov/statfacts/html/prost.html|archive-date=6 July 2014}}</ref>

Globally, it is the second-most common cancer. It is the fifth-leading cause of cancer-related death in men.<ref name=WCR2014Epi>{{cite book|title=World Cancer Report |date=2014|publisher=World Health Organization|isbn=978-9283204299|chapter=Chapter 1.1}}</ref> In 2018, it was diagnosed in 1.2 million and caused 359,000 deaths.<ref name=Bray2018>{{cite journal | vauthors = Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A | title = Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries | journal = CA | volume = 68 | issue = 6 | pages = 394–424 | date = November 2018 | pmid = 30207593 | doi = 10.3322/caac.21492 | s2cid = 52188256 | doi-access = free }}</ref> It was the most common cancer in males in 84 countries,<ref name=WCR2014/> occurring more commonly in the developed world.<ref name=Baade2009/> Rates have been increasing in the developing world.<ref name=Baade2009>{{cite journal | vauthors = Baade PD, Youlden DR, Krnjacki LJ | title = International epidemiology of prostate cancer: geographical distribution and secular trends | journal = Molecular Nutrition & Food Research | volume = 53 | issue = 2 | pages = 171–184 | date = February 2009 | pmid = 19101947 | doi = 10.1002/mnfr.200700511 }}</ref> Detection increased significantly in the 1980s and 1990s in many areas due to increased PSA testing.<ref name=WCR2014/> One study reported prostate cancer in 30% to 70% of Russian and Japanese men over age 60 who had died of unrelated causes.<ref name=NCI2014TxPro/>

==Signs and symptoms==
[[File:Diagram showing prostate cancer pressing on the urethra CRUK 182.svg|thumb|right|A diagram of prostate cancer pressing on the urethra, which can cause symptoms]]
[[File:Prostate Cancer.png|thumb|Prostate cancer]]
Early prostate cancer usually has no clear symptoms.<ref>{{Cite web |title=Prostate Cancer Signs and Symptoms |url=https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/signs-symptoms.html |access-date=2023-02-11 |website=www.cancer.org |language=en}}</ref> When they do appear, they are often similar to those of [[Medicine:Benign prostatic hyperplasia|benign prostatic hyperplasia]]. These include frequent urination, nocturia (increased urination at night), difficulty starting and maintaining a steady stream of urine, [[Medicine:Hematuria|hematuria]] (blood in the urine), dysuria (painful urination) as well as fatigue due to anemia, and bone pain.<ref>Leslie SW, Soon-Sutton TL, Sajjad H, Siref LE. Prostate Cancer. 2020 Oct 28. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;  {{PMID|29261872}}.</ref> One study found that about a third of diagnosed patients had one or more such symptoms.<ref name=prostateCApresentation /><ref>{{Cite web |title=Advanced prostate cancer |url=https://prostatecanceruk.org/prostate-information/just-diagnosed/advanced-prostate-cancer/ |access-date=2023-02-11 |website=Prostate Cancer UK |language=en}}</ref>

Prostate cancer is associated with urinary dysfunction as the prostate gland surrounds the prostatic urethra.<ref>{{cite journal | vauthors = Henninger S, Neusser S, Lorenz C, Bitzer EM | title = [Prostate cancer in routine healthcare: health-related quality of life after inpatient treatment] | journal = Der Urologe. Ausg. A | volume = 53 | issue = 12 | pages = 1793–1799 | date = December 2014 | pmid = 25297490 | doi = 10.1007/s00120-014-3615-0 }}</ref><ref>{{cite book | vauthors = Bauer RM |title=Urinary Dysfunction in Prostate Cancer |chapter=Urinary Dysfunction in Prostate Cancer: Male Slings |date=2016 |chapter-url=https://doi.org/10.1007/978-3-319-23817-3_4 |work=Urinary Dysfunction in Prostate Cancer: A Management Guide |pages=53–69 | veditors = Sandhu JS |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/978-3-319-23817-3_4 |isbn=978-3-319-23817-3 |access-date=2022-04-28}}</ref> Changes within the gland directly affect urinary function. Because the vas deferens deposits seminal fluid into the prostatic urethra, and secretions from the prostate are included in semen content, prostate cancer may also cause problems with sexual function and performance, such as difficulty achieving [[Medicine:Erection|erection]] or painful [[Medicine:Ejaculation|ejaculation]].<ref name=prostateCApresentation>{{cite journal | vauthors = Miller DC, Hafez KS, Stewart A, Montie JE, Wei JT | title = Prostate carcinoma presentation, diagnosis, and staging: an update form the National Cancer Data Base | journal = Cancer | volume = 98 | issue = 6 | pages = 1169–1178 | date = September 2003 | pmid = 12973840 | doi = 10.1002/cncr.11635 | s2cid = 22077473 | doi-access = free | hdl = 2027.42/34379 }}</ref>

Metastatic prostate cancer can cause additional symptoms.<ref>{{Cite web |title=Advanced prostate cancer |url=https://prostatecanceruk.org/prostate-information/just-diagnosed/advanced-prostate-cancer/ |access-date=2023-02-11 |website=Prostate Cancer UK |language=en}}</ref> The most common symptom is [[Biology:Bone pain|bone pain]], often in the vertebrae (bones of the spine), [[Biology:Pelvis|pelvis]], or [[Biology:Rib|rib]]s.<ref>{{cite journal | vauthors = Liu Z, Murphy SF, Huang J, Zhao L, Hall CC, Schaeffer AJ, Schaeffer EM, Thumbikat P | display-authors = 6 | title = A novel immunocompetent model of metastatic prostate cancer-induced bone pain | journal = The Prostate | volume = 80 | issue = 10 | pages = 782–794 | date = July 2020 | pmid = 32407603 | pmc = 7375026 | doi = 10.1002/pros.23993 }}</ref> Spread of cancer into other bones such as the [[Biology:Femur|femur]] is usually to the [[Biology:Anatomical terms of location#Proximal and distal|part of the bone nearer to the prostate]]. Prostate cancer in the [[Biology:Vertebral column|spine]] can compress the [[Biology:Spinal cord|spinal cord]], causing tingling, leg weakness, and [[Medicine:Urinary incontinence|urinary]] and fecal incontinence.<ref>{{cite journal | vauthors = van der Cruijsen-Koeter IW, Vis AN, Roobol MJ, Wildhagen MF, de Koning HJ, van der Kwast TH, Schröder FH | title = Comparison of screen detected and clinically diagnosed prostate cancer in the European randomized study of screening for prostate cancer, section rotterdam | journal = The Journal of Urology | volume = 174 | issue = 1 | pages = 121–125 | date = July 2005 | pmid = 15947595 | doi = 10.1097/01.ju.0000162061.40533.0f }}</ref>

==Risk factors==
The primary risk factors are obesity,<ref name="pmid12711737">{{cite journal | vauthors = Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ | title = Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults | journal = The New England Journal of Medicine | volume = 348 | issue = 17 | pages = 1625–1638 | date = April 2003 | pmid = 12711737 | doi = 10.1056/NEJMoa021423 | s2cid = 22714795 }}</ref> age, and family history. Obese men have been found to have a 34% greater death rate from prostate cancer than those with normal weight.<ref name="pmid12711737" /> Prostate cancer is uncommon in men younger than 45, but becomes more common with advancing age.<ref>{{Cite journal | vauthors = Maistro S, Xavier CD, Serio PA, Katayama ML, Roela RA, Koike Folgueira MA |date=2019-05-20 |title=Cancer driver genes in prostate cancer from young men. |url=https://ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.e16586 |journal=Journal of Clinical Oncology |volume=37 |issue=15_suppl |pages=e16586 |doi=10.1200/JCO.2019.37.15_suppl.e16586 |s2cid=190897312 |issn=0732-183X}}</ref><ref>{{cite journal | vauthors = Smith CV, Bauer JJ, Connelly RR, Seay T, Kane C, Foley J, Thrasher JB, Kusuda L, Moul JW | display-authors = 6 | title = Prostate cancer in men age 50 years or younger: a review of the Department of Defense Center for Prostate Disease Research multicenter prostate cancer database | journal = The Journal of Urology | volume = 164 | issue = 6 | pages = 1964–1967 | date = December 2000 | pmid = 11061892 | doi = 10.1016/S0022-5347(05)66929-7 }}</ref> The average age at the time of diagnosis is 70.<ref>{{cite journal | vauthors = Hankey BF, Feuer EJ, Clegg LX, Hayes RB, Legler JM, Prorok PC, Ries LA, Merrill RM, Kaplan RS | display-authors = 6 | title = Cancer surveillance series: interpreting trends in prostate cancer--part I: Evidence of the effects of screening in recent prostate cancer incidence, mortality, and survival rates | journal = Journal of the National Cancer Institute | volume = 91 | issue = 12 | pages = 1017–1024 | date = June 1999 | pmid = 10379964 | doi = 10.1093/jnci/91.12.1017 | doi-access = free }}</ref> Autopsy studies of Chinese, German, Israeli, Jamaican, Swedish, and Ugandan men who died of other causes found prostate cancer in 30% of men in their 50s, and in 80% of men in their 70s.<ref>{{cite journal | vauthors = Breslow N, Chan CW, Dhom G, Drury RA, Franks LM, Gellei B, Lee YS, Lundberg S, Sparke B, Sternby NH, Tulinius H | display-authors = 6 | title = Latent carcinoma of prostate at autopsy in seven areas. The International Agency for Research on Cancer, Lyons, France | journal = International Journal of Cancer | volume = 20 | issue = 5 | pages = 680–688 | date = November 1977 | pmid = 924691 | doi = 10.1002/ijc.2910200506 | s2cid = 42501757 }}</ref><ref name="pmid25821151">{{cite journal | vauthors = Bell KJ, Del Mar C, Wright G, Dickinson J, Glasziou P | title = Prevalence of incidental prostate cancer: A systematic review of autopsy studies | journal = International Journal of Cancer | volume = 137 | issue = 7 | pages = 1749–1757 | date = October 2015 | pmid = 25821151 | pmc = 4682465 | doi = 10.1002/ijc.29538 }}</ref><ref name="pmid25557753">{{cite journal | vauthors = Jahn JL, Giovannucci EL, Stampfer MJ | title = The high prevalence of undiagnosed prostate cancer at autopsy: implications for epidemiology and treatment of prostate cancer in the Prostate-specific Antigen-era | journal = International Journal of Cancer | volume = 137 | issue = 12 | pages = 2795–2802 | date = December 2015 | pmid = 25557753 | pmc = 4485977 | doi = 10.1002/ijc.29408 }}</ref>

Men with high blood pressure are more likely to develop prostate cancer.<ref name="pmid19949849">{{cite journal | vauthors = Martin RM, Vatten L, Gunnell D, Romundstad P | title = Blood pressure and risk of prostate cancer: Cohort Norway (CONOR) | journal = Cancer Causes & Control | volume = 21 | issue = 3 | pages = 463–472 | date = March 2010 | pmid = 19949849 | doi = 10.1007/s10552-009-9477-x | s2cid = 30484327 }}</ref> A small increase in risk is associated with lack of exercise.<ref>{{cite journal | vauthors = Friedenreich CM, Neilson HK, Lynch BM | title = State of the epidemiological evidence on physical activity and cancer prevention | journal = European Journal of Cancer | volume = 46 | issue = 14 | pages = 2593–2604 | date = September 2010 | pmid = 20843488 | doi = 10.1016/j.ejca.2010.07.028 }}</ref> Elevated blood [[Chemistry:Testosterone|testosterone]] levels<ref name="pmid8757191">{{cite journal | vauthors = Gann PH, Hennekens CH, Ma J, Longcope C, Stampfer MJ | title = Prospective study of sex hormone levels and risk of prostate cancer | journal = Journal of the National Cancer Institute | volume = 88 | issue = 16 | pages = 1118–1126 | date = August 1996 | pmid = 8757191 | doi = 10.1093/jnci/88.16.1118 | doi-access = free }}</ref> may increase risk.

===Genetics===
[[Biology:Genetics|Genetics]] may affect risk, as suggested by associations with race, family, and specific [[Biology:Gene|gene]] variants.<ref>{{cite web |title=Prostate cancer |url=https://ghr.nlm.nih.gov/condition/prostate-cancer#inheritance |website=Genetics Home Reference |access-date=1 May 2020 |language=en}}</ref> Men who have a first-degree relative (father or brother) with prostate cancer have twice the risk of developing prostate cancer, and those with two first-degree relatives affected have a five-fold greater risk compared with men with no family history.<ref>{{cite journal | vauthors = Steinberg GD, Carter BS, Beaty TH, Childs B, Walsh PC | title = Family history and the risk of prostate cancer | journal = The Prostate | volume = 17 | issue = 4 | pages = 337–347 | year = 1990 | pmid = 2251225 | doi = 10.1002/pros.2990170409 | s2cid = 44925478 }}</ref><ref>{{cite journal | vauthors = Zeegers MP, Jellema A, Ostrer H | title = Empiric risk of prostate carcinoma for relatives of patients with prostate carcinoma: a meta-analysis | journal = Cancer | volume = 97 | issue = 8 | pages = 1894–1903 | date = April 2003 | pmid = 12673715 | doi = 10.1002/cncr.11262 | s2cid = 12607885 | doi-access = free }}</ref> This risk appears to be greater for men with an affected brother than for those with an affected father. In the United States, prostate cancer more commonly affects black men than white or Hispanic men, and is also more deadly in black men.<ref>{{cite journal | vauthors = Gallagher RP, Fleshner N | title = Prostate cancer: 3. Individual risk factors | journal = CMAJ | volume = 159 | issue = 7 | pages = 807–813 | date = October 1998 | pmid = 9805030 | pmc = 1232741 | url = http://www.cmaj.ca/cgi/reprint/159/7/807.pdf | url-status = live | archive-url = https://web.archive.org/web/20091229022504/http://www.cmaj.ca/cgi/reprint/159/7/807.pdf | archive-date = 2009-12-29 }}</ref><ref>{{cite journal | vauthors = Hoffman RM, Gilliland FD, Eley JW, Harlan LC, Stephenson RA, Stanford JL, Albertson PC, Hamilton AS, Hunt WC, Potosky AL | display-authors = 6 | title = Racial and ethnic differences in advanced-stage prostate cancer: the Prostate Cancer Outcomes Study | journal = Journal of the National Cancer Institute | volume = 93 | issue = 5 | pages = 388–395 | date = March 2001 | pmid = 11238701 | doi = 10.1093/jnci/93.5.388 | doi-access = free }}</ref> In contrast, the incidence and mortality rates for Hispanic men are one-third lower than for non-Hispanic whites. [[Biology:Twin study|Twin studies]] in [[Place:Scandinavia|Scandinavia]] suggest that 58% of prostate cancer risk can be explained by [[Philosophy:Heritability|inherited factors]].<ref name="pmid10891514">{{cite journal | vauthors = Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K | display-authors = 6 | title = Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland | journal = The New England Journal of Medicine | volume = 343 | issue = 2 | pages = 78–85 | date = July 2000 | pmid = 10891514 | doi = 10.1056/NEJM200007133430201 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hjelmborg JB, Scheike T, Holst K, Skytthe A, Penney KL, Graff RE, Pukkala E, Christensen K, Adami HO, Holm NV, Nuttall E, Hansen S, Hartman M, Czene K, Harris JR, Kaprio J, Mucci LA | display-authors = 6 | title = The heritability of prostate cancer in the Nordic Twin Study of Cancer | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 23 | issue = 11 | pages = 2303–2310 | date = November 2014 | pmid = 24812039 | pmc = 4221420 | doi = 10.1158/1055-9965.EPI-13-0568 | s2cid = 29554506 }}</ref>

Many [[Biology:Gene|genes]] are involved in inherited risk for prostate cancer. The first gene linked to inherited prostate cancer in families was hereditary prostate cancer gene 1 (''HPC1'').<ref>{{cite journal | vauthors = Smith JR, Freije D, Carpten JD, Grönberg H, Xu J, Isaacs SD, Brownstein MJ, Bova GS, Guo H, Bujnovszky P, Nusskern DR, Damber JE, Bergh A, Emanuelsson M, Kallioniemi OP, Walker-Daniels J, Bailey-Wilson JE, Beaty TH, Meyers DA, Walsh PC, Collins FS, Trent JM, Isaacs WB | display-authors = 6 | title = Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search | journal = Science | volume = 274 | issue = 5291 | pages = 1371–1374 | date = November 1996 | pmid = 8910276 | doi = 10.1126/science.274.5291.1371 | s2cid = 42684655 | bibcode = 1996Sci...274.1371S | url = https://zenodo.org/record/1231086 }}</ref><ref>{{cite journal | vauthors = Carpten J, Nupponen N, Isaacs S, Sood R, Robbins C, Xu J, Faruque M, Moses T, Ewing C, Gillanders E, Hu P, Bujnovszky P, Makalowska I, Baffoe-Bonnie A, Faith D, Smith J, Stephan D, Wiley K, Brownstein M, Gildea D, Kelly B, Jenkins R, Hostetter G, Matikainen M, Schleutker J, Klinger K, Connors T, Xiang Y, Wang Z, De Marzo A, Papadopoulos N, Kallioniemi OP, Burk R, Meyers D, Grönberg H, Meltzer P, Silverman R, Bailey-Wilson J, Walsh P, Isaacs W, Trent J | display-authors = 6 | title = Germline mutations in the ribonuclease L gene in families showing linkage with HPC1 | journal = Nature Genetics | volume = 30 | issue = 2 | pages = 181–184 | date = February 2002 | pmid = 11799394 | doi = 10.1038/ng823 | s2cid = 2922306 | url = https://zenodo.org/record/1233415 }}</ref> Mutations within the [[Biology:HOXB13|HOXB13]] gene can also carry strong risk for prostate cancer.<ref>{{cite journal | vauthors = Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, Wiley KE, Isaacs SD, Johng D, Wang Y, Bizon C, Yan G, Gielzak M, Partin AW, Shanmugam V, Izatt T, Sinari S, Craig DW, Zheng SL, Walsh PC, Montie JE, Xu J, Carpten JD, Isaacs WB, Cooney KA | display-authors = 6 | title = Germline mutations in HOXB13 and prostate-cancer risk | journal = The New England Journal of Medicine | volume = 366 | issue = 2 | pages = 141–149 | date = January 2012 | pmid = 22236224 | pmc = 3779870 | doi = 10.1056/NEJMoa1110000 }}</ref><ref>{{cite journal | vauthors = Dupont WD, Breyer JP, Johnson SH, Plummer WD, Smith JR | title = Prostate cancer risk variants of the HOXB genetic locus | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 11385 | date = May 2021 | pmid = 34059701 | pmc = 8167119 | doi = 10.1038/s41598-021-89399-7 | s2cid = 235269663 | bibcode = 2021NatSR..1111385D }}</ref> Inherited genetic variation of the chromosome 8q24 locus, one that is prominently observed through [[Philosophy:Genome-wide association study|genome-wide association study]] (GWAS) of both familial and sporadic prostate cancer, can carry near-Mendelian (up to 20-fold) risk for prostate cancer.<ref>{{cite journal | vauthors = Dupont WD, Breyer JP, Plummer WD, Chang SS, Cookson MS, Smith JA, Blue EE, Bamshad MJ, Smith JR | display-authors = 6 | title = 8q24 genetic variation and comprehensive haplotypes altering familial risk of prostate cancer | journal = Nature Communications | volume = 11 | issue = 1 | pages = 1523 | date = March 2020 | pmid = 32251286 | pmc = 7089954 | doi = 10.1038/s41467-020-15122-1 | s2cid = 214606533 | bibcode = 2020NatCo..11.1523D }}</ref> This region encompasses regulatory elements, non-coding genes, and the stem cell related POU5F1B gene. Roughly 4% of families in which multiple men are affected by prostate cancer carry mutations in HOXB13, and another 4% carry mutations at 8q24. Mutations in ''[[Biology:BRCA1|BRCA1]]'' and ''[[Biology:BRCA2|BRCA2]]'' (important risk factors for [[Medicine:Ovarian cancer|ovarian cancer]] and [[Medicine:Breast cancer|breast cancer]] in women) have also been implicated.<ref>{{cite journal | vauthors = Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA | display-authors = 6 | title = The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews | journal = The New England Journal of Medicine | volume = 336 | issue = 20 | pages = 1401–1408 | date = May 1997 | pmid = 9145676 | doi = 10.1056/NEJM199705153362001 | doi-access = free }}</ref>

Two large GWAS discovered common low-risk [[Biology:Single-nucleotide polymorphism|single-nucleotide polymorphism]]s (SNPs) that are associated with prostate cancer in 2008.<ref>{{cite journal | vauthors = Eeles RA, Kote-Jarai Z, Giles GG, Olama AA, Guy M, Jugurnauth SK, Mulholland S, Leongamornlert DA, Edwards SM, Morrison J, Field HI, Southey MC, Severi G, Donovan JL, Hamdy FC, Dearnaley DP, Muir KR, Smith C, Bagnato M, Ardern-Jones AT, Hall AL, O'Brien LT, Gehr-Swain BN, Wilkinson RA, Cox A, Lewis S, Brown PM, Jhavar SG, Tymrakiewicz M, Lophatananon A, Bryant SL, Horwich A, Huddart RA, Khoo VS, Parker CC, Woodhouse CJ, Thompson A, Christmas T, Ogden C, Fisher C, Jamieson C, Cooper CS, English DR, Hopper JL, Neal DE, Easton DF | display-authors = 6 | title = Multiple newly identified loci associated with prostate cancer susceptibility | journal = Nature Genetics | volume = 40 | issue = 3 | pages = 316–321 | date = March 2008 | pmid = 18264097 | doi = 10.1038/ng.90 | s2cid = 30968525 }}</ref><ref>{{cite journal | vauthors = Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholder S, Orr N, Yu K, Chatterjee N, Welch R, Hutchinson A, Crenshaw A, Cancel-Tassin G, Staats BJ, Wang Z, Gonzalez-Bosquet J, Fang J, Deng X, Berndt SI, Calle EE, Feigelson HS, Thun MJ, Rodriguez C, Albanes D, Virtamo J, Weinstein S, Schumacher FR, Giovannucci E, Willett WC, Cussenot O, Valeri A, Andriole GL, Crawford ED, Tucker M, Gerhard DS, Fraumeni JF, Hoover R, Hayes RB, Hunter DJ, Chanock SJ | display-authors = 6 | title = Multiple loci identified in a genome-wide association study of prostate cancer | journal = Nature Genetics | volume = 40 | issue = 3 | pages = 310–315 | date = March 2008 | pmid = 18264096 | doi = 10.1038/ng.91 | s2cid = 22978381 | doi-access = free }}</ref> These studies identified several relevant SNPs. For example, individuals with TT allele pair at SNP rs10993994 were reported to be at 1.6 times higher risk than those with the CC allele pair. This SNP explains part of the increased risk faced by African-Americans. The C allele is much more prevalent in the latter; this SNP is located in the promoter region of the ''MSMB'' gene, thus affects the amount of MSMB protein synthesized and secreted by epithelial cells of the prostate.<ref>{{cite journal | vauthors = Whitaker HC, Kote-Jarai Z, Ross-Adams H, Warren AY, Burge J, George A, Bancroft E, Jhavar S, Leongamornlert D, Tymrakiewicz M, Saunders E, Page E, Mitra A, Mitchell G, Lindeman GJ, Evans DG, Blanco I, Mercer C, Rubinstein WS, Clowes V, Douglas F, Hodgson S, Walker L, Donaldson A, Izatt L, Dorkins H, Male A, Tucker K, Stapleton A, Lam J, Kirk J, Lilja H, Easton D, Cooper C, Eeles R, Neal DE | display-authors = 6 | title = The rs10993994 risk allele for prostate cancer results in clinically relevant changes in microseminoprotein-beta expression in tissue and urine | journal = PLOS ONE | volume = 5 | issue = 10 | pages = e13363 | date = October 2010 | pmid = 20967219 | pmc = 2954177 | doi = 10.1371/journal.pone.0013363 | veditors = Vickers A | doi-access = free | bibcode = 2010PLoSO...513363W }}</ref>

While fewer studies have been conducted assessing the risk of being diagnosed with aggressive prostate cancer, a GWAS of 12,518 prostate cancer cases identified two loci associated with high [[Medicine:Gleason grading system|Gleason sum score]], [[Biology:Single-nucleotide polymorphism|SNP]] rs78943174 nearest to the gene ''[[Biology:NAALADL2|NAALADL2]]'' and SNP rs35148638 nearest to ''[[Biology:RAS p21 protein activator 1|RASA1]]''.<ref>{{cite journal | vauthors = Berndt SI, Wang Z, Yeager M, Alavanja MC, Albanes D, Amundadottir L, Andriole G, Beane Freeman L, Campa D, Cancel-Tassin G, Canzian F, Cornu JN, Cussenot O, Diver WR, Gapstur SM, Grönberg H, Haiman CA, Henderson B, Hutchinson A, Hunter DJ, Key TJ, Kolb S, Koutros S, Kraft P, Le Marchand L, Lindström S, Machiela MJ, Ostrander EA, Riboli E, Schumacher F, Siddiq A, Stanford JL, Stevens VL, Travis RC, Tsilidis KK, Virtamo J, Weinstein S, Wilkund F, Xu J, Lilly Zheng S, Yu K, Wheeler W, Zhang H, Sampson J, Black A, Jacobs K, Hoover RN, Tucker M, Chanock SJ | display-authors = 6 | title = Two susceptibility loci identified for prostate cancer aggressiveness | journal = Nature Communications | volume = 6 | pages = 6889 | date = May 2015 | pmid = 25939597 | pmc = 4422072 | doi = 10.1038/ncomms7889 | bibcode = 2015NatCo...6.6889. }}</ref>

A number of somatic mutations (acquired rather than inherited) have also been defined in prostate tumors that drive their growth.  TMPRSS2-[[Biology:ETS transcription factor family|ETS gene family]] [[Biology:Fusion gene|fusion]], specifically TMPRSS2-[[Biology:ERG (gene)|ERG]] or TMPRSS2-[[Biology:ETV1|ETV1]]/4 promotes cancer cell growth.<ref>{{cite journal | vauthors = Beuzeboc P, Soulié M, Richaud P, Salomon L, Staerman F, Peyromaure M, Mongiat-Artus P, Cornud F, Paparel P, Davin JL, Molinié V | display-authors = 6 | title = [Fusion genes and prostate cancer. From discovery to prognosis and therapeutic perspectives] | language = fr | journal = Progres en Urologie | volume = 19 | issue = 11 | pages = 819–824 | date = December 2009 | pmid = 19945666 | doi = 10.1016/j.purol.2009.06.002 }}</ref> These fusions can arise via complex rearrangement chains called [[Biology:Chromoplexy|chromoplexy]].<ref>{{cite journal | vauthors = Baca SC, Prandi D, Lawrence MS, Mosquera JM, Romanel A, Drier Y, Park K, Kitabayashi N, MacDonald TY, Ghandi M, Van Allen E, Kryukov GV, Sboner A, Theurillat JP, Soong TD, Nickerson E, Auclair D, Tewari A, Beltran H, Onofrio RC, Boysen G, Guiducci C, Barbieri CE, Cibulskis K, Sivachenko A, Carter SL, Saksena G, Voet D, Ramos AH, Winckler W, Cipicchio M, Ardlie K, Kantoff PW, Berger MF, Gabriel SB, Golub TR, Meyerson M, Lander ES, Elemento O, Getz G, Demichelis F, Rubin MA, Garraway LA | display-authors = 6 | title = Punctuated evolution of prostate cancer genomes | journal = Cell | volume = 153 | issue = 3 | pages = 666–677 | date = April 2013 | pmid = 23622249 | pmc = 3690918 | doi = 10.1016/j.cell.2013.03.021 }}</ref>

===Dietary===
[[Biology:Plant-based diet|Plant-based diet]]s are associated with a lower risk for prostate cancer. Switching to a plant-based diet shows favorable results for cancer outcomes in men with prostate cancer. Especially vegan diets consistently show favorable associations with prostate cancer risk and outcomes.<ref>{{cite journal | vauthors = Gupta N, Patel HD, Taylor J, Borin JF, Jacobsohn K, Kenfield SA, Eggener SE, Price C, Davuluri M, Byrne N, Bivalacqua TJ, Loeb S | display-authors = 6 | title = Systematic review of the impact of a plant-based diet on prostate cancer incidence and outcomes | journal = Prostate Cancer and Prostatic Diseases | volume = 25 | issue = 3 | pages = 444–452 | date = September 2022 | pmid = 35790788 | doi = 10.1097/JU.0000000000002518.04 | s2cid = 248030075 }}</ref>

Consuming fruits and vegetables has been found to be of little preventive benefit.<ref>{{cite journal | vauthors = Venkateswaran V, Klotz LH | title = Diet and prostate cancer: mechanisms of action and implications for chemoprevention | journal = Nature Reviews. Urology | volume = 7 | issue = 8 | pages = 442–453 | date = August 2010 | pmid = 20647991 | doi = 10.1038/nrurol.2010.102 | s2cid = 10602814 }}</ref> Some studies report that higher meat consumption was associated with higher risk.<ref>{{cite web|title=Chemicals in Meat Cooked at High Temperatures and Cancer Risk|url=http://www.cancer.gov/cancertopics/factsheet/Risk/cooked-meats|work=National Cancer Institute|url-status=live|archive-url=https://web.archive.org/web/20111106080003/http://www.cancer.gov/cancertopics/factsheet/Risk/cooked-meats|archive-date=2011-11-06|date=2018-04-02}}</ref>

The consumption of milk may be related to prostate cancer.<ref>{{Cite web|title=Milk and Health|url=http://www.acc.org/latest-in-cardiology/ten-points-to-remember/2020/02/13/14/56/milk-and-health|access-date=2021-02-21|website=American College of Cardiology}}</ref><ref>{{cite journal | vauthors = Willett WC, Ludwig DS | title = Milk and Health | journal = The New England Journal of Medicine | volume = 382 | issue = 7 | pages = 644–654 | date = February 2020 | pmid = 32053300 | doi = 10.1056/NEJMra1903547 | s2cid = 211099544 }}</ref> A 2020 systematic review found the results on milk consumption and prostate cancer inconclusive but stated that individuals with higher risk may reduce or eliminate milk.<ref>{{cite journal | vauthors = Sargsyan A, Dubasi HB | title = Milk Consumption and Prostate Cancer: A Systematic Review | journal = The World Journal of Men's Health | volume = 39 | issue = 3 | pages = 419–428 | date = July 2021 | pmid = 32777868 | pmc = 8255404 | doi = 10.5534/wjmh.200051 | doi-access = free }}</ref> A 2019 overview stated that the evidence that linked milk to higher rates of prostate cancer was inconsistent and inconclusive.<ref>{{cite journal | vauthors = López-Plaza B, Bermejo LM, Santurino C, Cavero-Redondo I, Álvarez-Bueno C, Gómez-Candela C | title = Milk and Dairy Product Consumption and Prostate Cancer Risk and Mortality: An Overview of Systematic Reviews and Meta-analyses | journal = Advances in Nutrition | volume = 10 | issue = suppl_2 | pages = S212–S223 | date = May 2019 | pmid = 31089741 | pmc = 6518142 | doi = 10.1093/advances/nmz014 }}</ref> A 2021 study from Japan looking at 26,464 men found that milk consumption increased the risk of prostate cancer by 37%.<ref>{{cite journal | vauthors = Mikami K, Ozasa K, Miki T, Watanabe Y, Mori M, Kubo T, Suzuki K, Wakai K, Nakao M, Tamakoshi A | display-authors = 6 | title = Dairy products and the risk of developing prostate cancer: A large-scale cohort study (JACC Study) in Japan | journal = Cancer Medicine | volume = 10 | issue = 20 | pages = 7298–7307 | date = October 2021 | pmid = 34606688 | pmc = 8525158 | doi = 10.1002/cam4.4233 | s2cid = 238358096 | author11 = JACC Study Group }}</ref>

Lower blood levels of [[Chemistry:Vitamin D|vitamin D]] may increase risks.<ref>{{cite journal | vauthors = Wigle DT, Turner MC, Gomes J, Parent ME | title = Role of hormonal and other factors in human prostate cancer | journal = Journal of Toxicology and Environmental Health Part B: Critical Reviews | volume = 11 | issue = 3–4 | pages = 242–259 | date = March 2008 | pmid = 18368555 | doi = 10.1080/10937400701873548 | s2cid = 24489849 | url = https://zenodo.org/record/1002261 }}</ref> One study found no effect of folic acid supplements on risk.<ref>{{cite journal | vauthors = Qin X, Cui Y, Shen L, Sun N, Zhang Y, Li J, Xu X, Wang B, Xu X, Huo Y, Wang X | display-authors = 6 | title = Folic acid supplementation and cancer risk: a meta-analysis of randomized controlled trials | journal = International Journal of Cancer | volume = 133 | issue = 5 | pages = 1033–1041 | date = September 2013 | pmid = 23338728 | doi = 10.1002/ijc.28038 | s2cid = 19830376 }}</ref>

===Medication exposure===
Some links have been established between prostate cancer and medications, medical procedures, and medical conditions.<ref name="pmid15998950">{{cite journal | vauthors = Jacobs EJ, Rodriguez C, Mondul AM, Connell CJ, Henley SJ, Calle EE, Thun MJ | title = A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence | journal = Journal of the National Cancer Institute | volume = 97 | issue = 13 | pages = 975–980 | date = July 2005 | pmid = 15998950 | doi = 10.1093/jnci/dji173 | doi-access = free }}</ref> [[Biology:Statin|Statin]]s may also decrease risk.<ref name="pmid16014776">{{cite journal | vauthors = Shannon J, Tewoderos S, Garzotto M, Beer TM, Derenick R, Palma A, Farris PE | title = Statins and prostate cancer risk: a case-control study | journal = American Journal of Epidemiology | volume = 162 | issue = 4 | pages = 318–325 | date = August 2005 | pmid = 16014776 | doi = 10.1093/aje/kwi203 | doi-access = free }}</ref>

===Infection===
[[Medicine:Prostatitis|Prostatitis]] ([[Medicine:Infection|infection]] or [[Medicine:Inflammation|inflammation]]) may increase risk. In particular, infection with the [[Medicine:Sexually transmitted infection|sexually transmitted infection]]s [[Medicine:Chlamydia infection|''Chlamydia'']], [[Medicine:Gonorrhea|gonorrhea]], or [[Medicine:Syphilis|syphilis]] seems to increase risk.<ref name="CainiGandini2014"/><ref name="pmid12100928">{{cite journal | vauthors = Dennis LK, Lynch CF, Torner JC | title = Epidemiologic association between prostatitis and prostate cancer | journal = Urology | volume = 60 | issue = 1 | pages = 78–83 | date = July 2002 | pmid = 12100928 | doi = 10.1016/S0090-4295(02)01637-0 }}</ref>

Papilloma virus has been proposed to have a potential role, but as of 2015, the evidence was inconclusive;<ref name=Heidegger2015>{{cite journal | vauthors = Heidegger I, Borena W, Pichler R | title = The role of human papilloma virus in urological malignancies | journal = Anticancer Research | volume = 35 | issue = 5 | pages = 2513–2519 | date = May 2015 | pmid = 25964524 }}</ref> as of 2018, the increased risk was debated.<ref name=Cai2018>{{cite journal | vauthors = Cai T, Di Vico T, Durante J, Tognarelli A, Bartoletti R | title = Human papilloma virus and genitourinary cancers: a narrative review | journal = Minerva Urologica e Nefrologica | volume = 70 | issue = 6 | pages = 579–587 | date = December 2018 | pmid = 30160386 | doi = 10.23736/S0393-2249.18.03141-7 | s2cid = 52118310 }}</ref>

===Environment===
<!-- Research released in May 2007 found that -->US war veterans who had been exposed to [[Biology:Agent Orange|Agent Orange]] had a 48% increased risk of prostate cancer recurrence following surgery.<ref>{{Cite web |title=Prostate Cancer {{!}} Johns Hopkins Brady Urological Institute |url=https://www.hopkinsmedicine.org/brady-urology-institute/conditions_and_treatments/prostate_cancer/index.html |access-date=2022-04-28 |website=www.hopkinsmedicine.org |language=en}}</ref>

=== Sex ===
Although some evidence from [[Prospective cohort study|prospective cohort studies]] indicates that frequent [[Medicine:Ejaculation|ejaculation]] may reduce prostate cancer risk,<ref>{{cite journal | vauthors = Rider JR, Wilson KM, Sinnott JA, Kelly RS, Mucci LA, Giovannucci EL | title = Ejaculation Frequency and Risk of Prostate Cancer: Updated Results with an Additional Decade of Follow-up | journal = European Urology | volume = 70 | issue = 6 | pages = 974–982 | date = December 2016 | pmid = 27033442 | pmc = 5040619 | doi = 10.1016/j.eururo.2016.03.027 }}</ref> no [[Randomized controlled trial|randomized controlled trial]]s reported this benefit.<ref>{{cite journal | vauthors = Aboul-Enein BH, Bernstein J, Ross MW | title = Evidence for Masturbation and Prostate Cancer Risk: Do We Have a Verdict? | journal = Sexual Medicine Reviews | volume = 4 | issue = 3 | pages = 229–234 | date = July 2016 | pmid = 27871956 | doi = 10.1016/j.sxmr.2016.02.006 }}</ref> An association between vasectomy and prostate cancer was found, but causality has not been established.<ref name="bccancer.bc.ca">{{cite web|title=A comprehensive cancer control program for BC|url=http://www.bccancer.bc.ca/health-info/types-of-cancer/pelvic-area/prostate|access-date=2 November 2021}}</ref>

==Pathophysiology==
[[File:Prostatelead.jpg|right|thumb]]

The [[Biology:Prostate|prostate]] is part of the male [[Biology:Reproductive system|reproductive system]] that helps make and store seminal fluid. In adult men, a typical prostate is about 3&nbsp;cm long and weighs about 20 g.<ref>{{Cite book| vauthors = Aumüller G | title=Prostate Gland and Seminal Vesicles| publisher=Springer-Verlag| location=Berlin-Heidelberg| year=1979}}</ref> It is located in the [[Biology:Pelvis|pelvis]], under the [[Biology:Urinary bladder|urinary bladder]] and in front of the [[Biology:Rectum|rectum]]. The prostate surrounds part of the urethra, the tube that carries [[Biology:Urine|urine]] from the bladder during [[Biology:Urination|urination]] and semen during [[Medicine:Ejaculation|ejaculation]].<ref>{{cite book | vauthors = Moore KL, Chubb D | title=Clinically Oriented Anatomy| url = https://archive.org/details/clinicallyorient00moor | url-access = registration | publisher=Lippincott Williams & Wilkins| location=Baltimore, Maryland| year=1999| isbn=978-0-683-06132-1}}</ref> The prostate contains many small glands, which make about 20% of the fluid constituting [[Biology:Semen|semen]].<ref>{{Cite book|title=''Handbuch der mikroskopischen Anatomie des Menschen.'' Vol. VII Part 2|vauthors=Steive H|publisher=Springer|year=1930|location=Berlin|pages=1–399|chapter=Männliche Genitalorgane}}</ref>

Superiorly, the prostate base is contiguous with the bladder outlet. Inferiorly, the prostate's apex heads in the direction of the urogenital diaphragm, which is pointed anterio-inferiorly.<ref>{{Cite journal | vauthors = Collins MA, Terris MK | veditors = Talavera F, Noble MJ | journal = Medscape |date=2021-10-25 |title=Transurethral Resection of the Prostate: Overview, Treatment & Management, Post-Procedure |url=https://emedicine.medscape.com/article/449781-overview}}</ref> The prostate can be divided into four anatomic spaces: peripheral, central, transitional, and anterior fibromuscular [[Biology:Stroma (tissue)|stroma]].<ref>{{cite journal | vauthors = McNeal JE | title = Anatomy of the prostate and morphogenesis of BPH | journal = Progress in Clinical and Biological Research | volume = 145 | pages = 27–53 | date = 1984 | pmid = 6201879 }}</ref> The peripheral space contains the posterior and lateral portions of the prostate, as well as the inferior portions of the prostate.<ref>{{Cite journal | vauthors = Muruve MA | veditors = Gest TR |date=2020-06-11 |title=Prostate Anatomy: Overview, Gross Anatomy, Microscopic Anatomy | journal = Medscape |url=https://emedicine.medscape.com/article/1923122-overview}}</ref> The central space contains the superior portion of the prostate including the most proximal aspects of the urethra and bladder neck.<ref>{{cite book | vauthors = Singh O, Bolla SR | chapter = Anatomy, Abdomen and Pelvis, Prostate |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK540987/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31082031 |access-date=2022-04-28}}</ref> The transitional space is located just anterior to the central space and includes urethra distal to the central gland urethra.<ref>{{Cite journal | vauthors = Schenkman NS, Manger JP | veditors = Gest TR | journal = Medscape |date=2020-06-11 |title=Male Urethra Anatomy: Overview, Gross Anatomy, Microscopic Anatomy |url=https://emedicine.medscape.com/article/1972482-overview}}</ref> The neurovascular bundles course along the posterolateral prostate surface and penetrate the prostatic capsule there as well.<ref>{{cite journal | vauthors = Pisipati S, Ali A, Mandalapu RS, Haines Iii GK, Singhal P, Reddy BN, Leung R, Tewari AK | display-authors = 6 | title = Newer concepts in neural anatomy and neurovascular preservation in robotic radical prostatectomy | journal = Indian Journal of Urology | volume = 30 | issue = 4 | pages = 399–409 | date = October 2014 | pmid = 25378822 | pmc = 4220380 | doi = 10.4103/0970-1591.142064 }}</ref>

Most of the glandular tissue is found in the peripheral and central zones (peripheral zone: 70-80% of glandular tissue; central zone: 20% of glandular tissue).<ref>{{Cite journal| vauthors = Oh WK, Hurwitz M, D'Amico AV, Richie JP, Kantoff PW |date=2003|title=Biology of Prostate Cancer|url=https://www.ncbi.nlm.nih.gov/books/NBK13217/|journal=Holland-Frei Cancer Medicine|edition=6th |language=en}}</ref> Some is found in the transitional space (5% of glandular tissue). Thus, most cancers that develop from glandular tissue are found in the peripheral and central spaces,<ref>{{cite journal | vauthors = Reissigl A, Pointner J, Strasser H, Ennemoser O, Klocker H, Bartsch G | title = Frequency and clinical significance of transition zone cancer in prostate cancer screening | journal = The Prostate | volume = 30 | issue = 2 | pages = 130–135 | date = February 1997 | pmid = 9051151 | doi = 10.1002/(SICI)1097-0045(19970201)30:2<130::AID-PROS8>3.0.CO;2-S | s2cid = 24142928 }}</ref> while about 5% is found in the transitional space. None is found in the anterior fibromuscular stroma since no glands are in that anatomic space.

The prostate glands require male [[Biology:Hormone|hormone]]s, known as [[Biology:Androgen|androgen]]s, to work properly. Androgens include [[Chemistry:Testosterone|testosterone]], which is made in the testes;<ref>{{Cite web |title=Androgens: Function, Measurement and Related Disorders |url=https://my.clevelandclinic.org/health/articles/22002-androgens |access-date=2022-04-28 |website=Cleveland Clinic}}</ref>[[Chemistry:Dehydroepiandrosterone|dehydroepiandrosterone]], made in the adrenal glands; and [[Chemistry:Dihydrotestosterone|dihydrotestosterone]], which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass.{{citation needed|date=December 2022}}

Because of the prostate's location, prostate diseases often affect urination, ejaculation, and rarely [[Biology:Defecation|defecation]]. In prostate cancer, the cells of these glands [[Biology:Mutation|mutate]] into cancer cells.<ref name="my.clevelandclinic.org">{{Cite web |title=Prostate Cancer: Symptoms, Diagnosis & Treatment |url=https://my.clevelandclinic.org/health/diseases/8634-prostate-cancer |access-date=2022-04-28 |website=Cleveland Clinic}}</ref>

[[File:Diagram showing prostate cancer that has spread to the lymph nodes CRUK 184.svg|thumb|left|Prostate cancer that has metastasized to the lymph nodes]]
[[File:Diagram showing prostate cancer that has spread to the bones CRUK 183.svg|thumb|left|Prostate cancer that has metastasized to the bone]]

Most prostate cancers are classified as adenocarcinomas, or glandular cancers, that begin when semen-secreting gland cells mutate into cancer cells.<ref>{{Cite web |title=Prostate Tumor - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/prostate-tumor |access-date=2022-04-28 |website=www.sciencedirect.com}}</ref> The region of the prostate gland where the adenocarcinoma is most common is the peripheral zone. Initially, small clumps of cancer cells remain within otherwise normal prostate glands, a condition known as [[Medicine:Carcinoma in situ|carcinoma ''in situ'']] or prostatic intraepithelial neoplasia (PIN).<ref>{{cite journal | vauthors = Zhou M | title = High-grade prostatic intraepithelial neoplasia, PIN-like carcinoma, ductal carcinoma, and intraductal carcinoma of the prostate | journal = Modern Pathology | volume = 31 | issue = S1 | pages = S71–S79 | date = January 2018 | pmid = 29297491 | doi = 10.1038/modpathol.2017.138 | s2cid = 13649812 | doi-access = free }}</ref> Although no proof establishes that PIN is a cancer precursor, it is closely associated with cancer.<ref>{{Cite web | vauthors = Brosman SA, Goluboff ET, Talavera F, Theodorescu D | veditors = Kim ED |date=2021-10-04 |title=Precancerous Lesions of the Prostate: Overview, PIN and ASAP Rates, Diagnostic Significance |url= https://emedicine.medscape.com/article/447780-overview }}</ref> Over time, these cells multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor.

Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum, or tumor cells may develop the ability to travel in the bloodstream and [[Biology:Lymphatic system|lymphatic system]].<ref>{{Cite web |title=Advanced Prostate Cancer: Symptoms, Diagnosis & Treatment - Urology Care Foundation |url=https://www.urologyhealth.org/urology-a-z/a_/advanced-prostate-cancer |access-date=2022-04-28 |website=www.urologyhealth.org}}</ref>

Prostate cancer is considered a malignant tumor because it can invade other areas of the body. This invasion is called [[Medicine:Metastasis|metastasis]].<ref>{{Cite book | vauthors = Martin TA, Ye L, Sanders AJ, Lane J, Jiang WG |url=https://www.ncbi.nlm.nih.gov/books/NBK164700/ |title=Cancer Invasion and Metastasis: Molecular and Cellular Perspective  |date=2013 |publisher=Landes Bioscience |language=en}}</ref> Prostate cancer most commonly metastasizes to the [[Biology:Bone|bone]]s and [[Biology:Lymph node|lymph node]]s, and may invade the rectum, [[Biology:Bladder|bladder]], and lower ureters after local progression.<ref>{{cite book | vauthors = Leslie SW, Soon-Sutton TL, Sajjad H, Siref LE | chapter = Prostate Cancer |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK470550/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=29261872 |access-date=2022-04-28 }}</ref> The route of metastasis to bone is thought to be [[Medicine:Vein|venous]], as the prostatic venous plexus draining the prostate connects with the vertebral veins.<ref name="metastasis-route">{{cite web|url=http://www.med-ed.virginia.edu/courses/path/gu/prostate3.cfm |title=Male Genitals – Prostate Neoplasms |access-date=2011-04-28 |work=Pathology study images |publisher=University of Virginia School of Medicine |archive-url=https://web.archive.org/web/20110720193027/http://www.med-ed.virginia.edu/courses/path/gu/prostate3.cfm |archive-date=2011-07-20 |quote=There are many connections between the prostatic venous plexus and the vertebral veins. The veins forming the prostatic plexus do not contain valves and it is thought that straining to urinate causes prostatic venous blood to flow in a reverse direction and enter the vertebral veins carrying malignant cells to the vertebral column. |url-status=dead }}</ref>

The prostate is a [[Chemistry:Zinc|zinc]]-accumulating, [[Chemistry:Citrate|citrate]]-producing organ. [[Biology:Transport protein|Transport protein]] ZIP1 is responsible for the transport of zinc into prostate cells.<ref name="The clinical relevance of the metab">{{cite journal | vauthors = Costello LC, Franklin RB | title = The clinical relevance of the metabolism of prostate cancer; zinc and tumor suppression: connecting the dots | journal = Molecular Cancer | volume = 5 | pages = 17 | date = May 2006 | pmid = 16700911 | pmc = 1481516 | doi = 10.1186/1476-4598-5-17 }}</ref> One of zinc's important roles is to change the cell's metabolism to produce citrate, an important semen component.<ref>{{cite journal | vauthors = Vickram S, Rohini K, Srinivasan S, Nancy Veenakumari D, Archana K, Anbarasu K, Jeyanthi P, Thanigaivel S, Gulothungan G, Rajendiran N, Srikumar PS | display-authors = 6 | title = Role of Zinc (Zn) in Human Reproduction: A Journey from Initial Spermatogenesis to Childbirth | journal = International Journal of Molecular Sciences | volume = 22 | issue = 4 | pages = 2188 | date = February 2021 | pmid = 33671837 | pmc = 7926410 | doi = 10.3390/ijms22042188 | doi-access = free }}</ref> The process of zinc accumulation, alteration of metabolism, and citrate production is energy inefficient, and prostate cells require enormous amounts of energy ([[Chemistry:Adenosine triphosphate|ATP]]) to accomplish this task. Prostate cancer cells are generally devoid of zinc. Prostate cancer cells save energy by not making citrate, and use the conserved energy to grow, reproduce and spread.<ref>{{cite journal | vauthors = Costello LC, Franklin RB | title = Novel role of zinc in the regulation of prostate citrate metabolism and its implications in prostate cancer | journal = The Prostate | volume = 35 | issue = 4 | pages = 285–296 | date = June 1998 | pmid = 9609552 | doi = 10.1002/(sici)1097-0045(19980601)35:4<285::aid-pros8>3.0.co;2-f | s2cid = 21084346 }}</ref>

The absence of zinc is thought to occur via silencing the gene that produces ZIP1. It is called a tumor suppressor gene product for the gene ''[[Biology:SLC39A1|SLC39A1]]''. The cause of the epigenetic silencing is unknown.<ref>{{cite journal | vauthors = Franklin RB, Feng P, Milon B, Desouki MM, Singh KK, Kajdacsy-Balla A, Bagasra O, Costello LC | display-authors = 6 | title = hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer | journal = Molecular Cancer | volume = 4 | pages = 32 | date = September 2005 | pmid = 16153295 | pmc = 1243239 | doi = 10.1186/1476-4598-4-32 }}</ref> Strategies that transport zinc into transformed prostate cells effectively eliminate these cells in animals. Zinc inhibits [[Biology:NF-κB|NF-κB]] pathways, is antiproliferative, and induces [[Biology:Apoptosis|apoptosis]] in abnormal cells.<ref>{{cite journal | vauthors = Uzzo RG, Leavis P, Hatch W, Gabai VL, Dulin N, Zvartau N, Kolenko VM | title = Zinc inhibits nuclear factor-kappa B activation and sensitizes prostate cancer cells to cytotoxic agents | journal = Clinical Cancer Research | volume = 8 | issue = 11 | pages = 3579–3583 | date = November 2002 | pmid = 12429649 | url = https://pubmed.ncbi.nlm.nih.gov/12429649/ }}</ref> Unfortunately, oral ingestion of zinc is ineffective since high concentrations of zinc into prostate cells is not possible without ZIP1.<ref name="The clinical relevance of the metab"/>

Loss of cancer suppressor genes, early in prostatic carcinogenesis, have been localized to chromosomes'' 8p'', ''10q'', ''13q'', and ''16q''. [[Biology:P53|P53]] mutations in the primary prostate cancer are relatively low and are more frequently seen in metastatic settings, hence, p53 mutations are a late event in the pathology. Other tumor suppressor genes that are thought to play a role include [[Biology:PTEN (gene)|''PTEN'']] and ''KAI1''. "Up to 70 percent of men with prostate cancer have lost one copy of the ''PTEN'' gene at the time of diagnosis".<ref>{{cite web |url=http://www.mskcc.org/mskcc/html/59384.cfm |title=Scientists Discover Anti-Cancer Mechanism that Arrests Early Prostate Cancer |date=August 4, 2005 |url-status=dead |archive-url=https://web.archive.org/web/20080519155217/http://www.mskcc.org/mskcc/html/59384.cfm |archive-date=May 19, 2008 }}</ref> Relative frequency of loss of E-cadherin and [[Biology:CD44|CD44]] has also been observed. Loss of the [[Biology:Retinoblastoma protein|retinoblastoma (RB) protein]] induces androgen receptor deregulation in castration-resistant prostate cancer by deregulating '[[Biology:E2F1|E2F1]] expression''.<ref>{{cite journal | vauthors = Sharma A, Yeow WS, Ertel A, Coleman I, Clegg N, Thangavel C, Morrissey C, Zhang X, Comstock CE, Witkiewicz AK, Gomella L, Knudsen ES, Nelson PS, Knudsen KE | display-authors = 6 | title = The retinoblastoma tumor suppressor controls androgen signaling and human prostate cancer progression | journal = The Journal of Clinical Investigation | volume = 120 | issue = 12 | pages = 4478–4492 | date = December 2010 | pmid = 21099110 | pmc = 2993601 | doi = 10.1172/JCI44239 | doi-access = free }}</ref>''

The factors that drive disease progression and clinical prognosis remain only partly understood but a variety of molecular determinants has been identified that appear to be involved. The most important of these might be the tyrosine phosphatase [[Biology:ACP1|ACP1]] of which the expression might outperform the [[Medicine:Gleason grading system|Gleason grading system]] for predicting disease course.<ref name=Hoekstra_2016>{{cite journal | vauthors = Ruela-de-Sousa RR, Hoekstra E, Hoogland AM, Souza Queiroz KC, Peppelenbosch MP, Stubbs AP, Pelizzaro-Rocha K, van Leenders GJ, Jenster G, Aoyama H, Ferreira CV, Fuhler GM | display-authors = 6 | title = Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential | journal = European Urology | volume = 69 | issue = 4 | pages = 710–719 | date = April 2016 | pmid = 26159288 | doi = 10.1016/j.eururo.2015.06.040 }}</ref> Other molecules identified include the transcription factor [[Biology:RUNX2|RUNX2]] which may prevent cancer cells from undergoing apoptosis,<ref name="pmid19948822">{{cite journal | vauthors = Leav I, Plescia J, Goel HL, Li J, Jiang Z, Cohen RJ, Languino LR, Altieri DC | display-authors = 6 | title = Cytoprotective mitochondrial chaperone TRAP-1 as a novel molecular target in localized and metastatic prostate cancer | journal = The American Journal of Pathology | volume = 176 | issue = 1 | pages = 393–401 | date = January 2010 | pmid = 19948822 | pmc = 2797899 | doi = 10.2353/ajpath.2010.090521 }}</ref> the PI3k/Akt signaling cascade in conjunction with the transforming growth factor beta/[[Biology:SMAD (protein)|SMAD]] signaling cascade that also protect against apoptosis.<ref name="pmid19947572">{{cite journal | vauthors = Zha J, Huang YF | title = [TGF-beta/Smad in prostate cancer: an update] | language = zh | journal = Zhonghua Nan Ke Xue = National Journal of Andrology | volume = 15 | issue = 9 | pages = 840–843 | date = September 2009 | pmid = 19947572 }}</ref> [[Biology:PIM1|Pim-1]] is upregulated in prostate cancer.<ref name="Luszczak 2020 7" /> X-linked inhibitor of apoptosis ([[Biology:XIAP|XIAP]]) is hypothesized to promote cancer cell survival and growth,<ref name="pmid19946707">{{cite journal | vauthors = Watanabe S, Miyata Y, Kanda S, Iwata T, Hayashi T, Kanetake H, Sakai H | title = Expression of X-linked inhibitor of apoptosis protein in human prostate cancer specimens with and without neo-adjuvant hormonal therapy | journal = Journal of Cancer Research and Clinical Oncology | volume = 136 | issue = 5 | pages = 787–793 | date = May 2010 | pmid = 19946707 | doi = 10.1007/s00432-009-0718-x | s2cid = 34855148 }}</ref> the [[Biology:GDF15|Macrophage inhibitory cytokine-1]] (MIC-1) that stimulates the focal adhesion kinase (FAK) signaling pathway.<ref name="pmid19946339">{{cite journal | vauthors = Senapati S, Rachagani S, Chaudhary K, Johansson SL, Singh RK, Batra SK | title = Overexpression of macrophage inhibitory cytokine-1 induces metastasis of human prostate cancer cells through the FAK-RhoA signaling pathway | journal = Oncogene | volume = 29 | issue = 9 | pages = 1293–1302 | date = March 2010 | pmid = 19946339 | pmc = 2896817 | doi = 10.1038/onc.2009.420 }}</ref> Nevertheless, it is fair to say that the molecular factors that determine why some patients have quiescent disease while otherdisplay prognosis remain largely obscure.

The [[Biology:Androgen receptor|androgen receptor]] helps cancer cells to survive.<ref name="pmid19946220">{{cite journal | vauthors = Narizhneva NV, Tararova ND, Ryabokon P, Shyshynova I, Prokvolit A, Komarov PG, Purmal AA, Gudkov AV, Gurova KV | display-authors = 6 | title = Small molecule screening reveals a transcription-independent pro-survival function of androgen receptor in castration-resistant prostate cancer | journal = Cell Cycle | volume = 8 | issue = 24 | pages = 4155–4167 | date = December 2009 | pmid = 19946220 | pmc = 2896895 | doi = 10.4161/cc.8.24.10316 }}</ref> [[Biology:Glutamate carboxypeptidase II|Prostate-specific membrane antigen]] (PSMA) stimulates cancer development by increasing folate levels, helping the cancer cells to survive and grow; it increases available folates for use by hydrolyzing glutamated folates.<ref name="pmid19830782">{{cite journal | vauthors = Yao V, Berkman CE, Choi JK, O'Keefe DS, Bacich DJ | title = Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid | journal = The Prostate | volume = 70 | issue = 3 | pages = 305–316 | date = February 2010 | pmid = 19830782 | doi = 10.1002/pros.21065 | s2cid = 21518526 }}</ref>

==Diagnosis==
[[File:CT of prostate cancer.jpg|thumb|upright=1.3|If already having grown large, a prostate cancer may first be detected on [[CT scan|CT scan]].]]

The American Cancer Society's position regarding early detection by PSA testing is:
{{blockquote|Research has not yet proven that the potential benefits of testing outweigh the harms of testing and treatment. The American Cancer Society believes that men should not be tested without learning about what we know and don't know about the risks and possible benefits of testing and treatment. Starting at age 50, (45 if African American or brother or father suffered from condition before age 65) talk to your doctor about the pros and cons of testing so you can decide if testing is the right choice for you."<ref>{{cite web |url=http://www.cancer.org/Healthy/FindCancerEarly/CancerScreeningGuidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer |title=Cancer Screening Guidelines &#124; Detecting Cancer Early |access-date=2011-06-16 |url-status=live |archive-url=https://web.archive.org/web/20110613085624/http://www.cancer.org/Healthy/FindCancerEarly/CancerScreeningGuidelines/american-cancer-society-guidelines-for-the-early-detection-of-cancer |archive-date=2011-06-13 }} American Cancer Society American Cancer Society Guidelines for the early detection of cancer Cited: September 2011</ref>}}

Several other tests can be used to gather information about the prostate and the urinary tract. Digital rectal examination may allow a doctor to detect prostate abnormalities.<ref>{{Cite web |title=Prostate Cancer and the Digital Rectal Exam |url=https://www.webmd.com/prostate-cancer/guide/prostate-cancer-digital-rectal-exam |access-date=2022-04-28 |website=WebMD |language=en}}</ref> Cystoscopy shows the urinary tract from inside the bladder, using a thin, flexible camera tube inserted in the urethra.<ref>{{Cite web |date=2015-10-19 |title=Cystoscopy: Purpose, Procedure, and Preparation |url=https://www.healthline.com/health/cystoscopy |access-date=2022-04-28 |website=Healthline |language=en}}</ref> [[Medicine:Transrectal ultrasonography|Transrectal ultrasonography]] creates a picture of the prostate using sound waves from a probe in the rectum, but the only test that can fully confirm the diagnosis of prostate cancer is a [[Medicine:Biopsy|biopsy]], the removal of small pieces of the prostate for microscopic examination.<ref>{{Cite journal | vauthors = Shetty S, Faraj K, Shetty Z, Sutcliffe P, Dave CN | veditors = Talavera F | journal = Medscape |date=2021-06-26 |title=Transrectal Ultrasonography of the Prostate: Background, Indications, Contraindications |url=https://emedicine.medscape.com/article/457757-overview}}</ref>

===Imaging===
[[Medicine:Medical ultrasound|Ultrasound]] and [[Physics:Magnetic resonance imaging|magnetic resonance imaging]] (MRI) are the two main imaging methods used for prostate cancer detection.

==== MRI ====

===== Appearance of prostate on MRI =====
On MRI, the central and transitional zones both have lower T2 signal than the peripheral zone. Since the central and transitional zones cannot be distinguished from each other, they can be best described as the central gland on MRI.<ref>{{Cite journal | vauthors = Elian MM, Abdel Gawad EA, Fathelbab TK |date=2015-12-01 |title=Value of functional MRI in evaluation of patients with suspected prostate cancer |journal=The Egyptian Journal of Radiology and Nuclear Medicine |language=en |volume=46 |issue=4 |pages=1183–1191 |doi=10.1016/j.ejrnm.2015.07.007 |issn=0378-603X|doi-access=free }}</ref> Thus, the peripheral gland has a higher signal on T2WI than the central gland. In the peripheral gland, prostate cancer appears as a low-intensity [[Medicine:Lesion|lesion]].<ref>{{cite journal | vauthors = Aydın H, Kızılgöz V, Tekin BO | title = Overview of current multiparametric magnetic resonance imaging approach in the diagnosis and staging of prostate cancer | journal = The Kaohsiung Journal of Medical Sciences | volume = 31 | issue = 4 | pages = 167–178 | date = April 2015 | pmid = 25835272 | doi = 10.1016/j.kjms.2015.01.002 | s2cid = 27489471 | doi-access = free }}</ref> However, in the central gland, low-intensity lesions cannot be distinguished from the low-intensity central gland. Diffusion restriction is instrumental in identifying and characterizing central gland lesions.<ref>{{cite journal | vauthors = Oto A, Kayhan A, Jiang Y, Tretiakova M, Yang C, Antic T, Dahi F, Shalhav AL, Karczmar G, Stadler WM | display-authors = 6 | title = Prostate cancer: differentiation of central gland cancer from benign prostatic hyperplasia by using diffusion-weighted and dynamic contrast-enhanced MR imaging | journal = Radiology | volume = 257 | issue = 3 | pages = 715–723 | date = December 2010 | pmid = 20843992 | pmc = 6939960 | doi = 10.1148/radiol.10100021 }}</ref> Combined diffusion-weighted (DW) imaging and dynamic contrast-enhanced MRI for distinguish malignant from benign prostate lesions can be used. The merged  images,  of  DW  and  MRI  with  dynamic  contrast  enhancement, can  visualise areas with low signal intensity and fast wash-out effect - characteristic of carcinomas.<ref>Georgiev, A. (2016). Case of prostate cancer with anterior localization - Multiparametric MRI study. Rentgenologiya i Radiologiya, 55(4), 285–87.</ref> [[Medicine:Lymphadenopathy|Lymphadenopathy]] can be seen best on postcontrast, fat-suppressed T1WI. Other regions can be described on MRI. The anterior fibromuscular stroma and the prostate capsule along the posterior and lateral prostate have a low T2WI signal, in contrast with the bright signal of the peripheral zone.<ref>{{cite journal | vauthors = Bhavsar A, Verma S | title = Anatomic imaging of the prostate | journal = BioMed Research International | volume = 2014 | pages = 728539 | date = 2014 | pmid = 25243174 | pmc = 4160650 | doi = 10.1155/2014/728539 | doi-access = free }}</ref> Extraprostatic extension can be seen with disruption of capsule integrity.

===== MRI for the detection of prostate cancer =====
As of 2011, MRI was used to identify targets for prostate biopsy using fusion MRI with ultrasound (US) or MRI-guidance alone. An MRI alone will correctly identify 91% of men with clinically significant prostate cancer but will misclassify 63% of men at risk for prostate cancer as having clinically significant prostate cancer.<ref name=":5">{{cite journal | vauthors = Drost FH, Osses DF, Nieboer D, Steyerberg EW, Bangma CH, Roobol MJ, Schoots IG | title = Prostate MRI, with or without MRI-targeted biopsy, and systematic biopsy for detecting prostate cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | pages = CD012663 | date = April 2019 | issue = 4 | pmid = 31022301 | pmc = 6483565 | doi = 10.1002/14651858.CD012663.pub2 | collaboration = Cochrane Urology Group }}</ref> An MRI-targeted biopsy will correctly identify 80% of men with prostate cancer. However, it will classify 6% of men at risk for prostate cancer as having clinically significant prostate cancer.<ref name=":5" /> Detection of clinically insignificant cancer has been shown to be decreased when MRI-targeted biopsy is combined with standard biopsy for men with positive results on MRI, as compared with a standard biopsy method.<ref>{{cite journal | vauthors = Eklund M, Jäderling F, Discacciati A, Bergman M, Annerstedt M, Aly M, Glaessgen A, Carlsson S, Grönberg H, Nordström T | display-authors = 6 | title = MRI-Targeted or Standard Biopsy in Prostate Cancer Screening | journal = The New England Journal of Medicine | volume = 385 | issue = 10 | pages = 908–920 | date = September 2021 | pmid = 34237810 | doi = 10.1056/NEJMoa2100852 }}</ref>

Following an MRI, regions of interest within the scan which may be cancer are often graded on a likelihood scale between 1 and 5.<ref>{{cite journal | vauthors = Kang HC, Jo N, Bamashmos AS, Ahmed M, Sun J, Ward JF, Choi H | title = Accuracy of Prostate Magnetic Resonance Imaging: Reader Experience Matters | journal = European Urology Open Science | volume = 27 | pages = 53–60 | date = May 2021 | pmid = 33899028 | pmc = 8061889 | doi = 10.1016/j.euros.2021.03.004 }}</ref> One such scale is the [[Physics:PI-RADS|prostate imaging-reporting and data system]] (PI-RADS) scale which defines standards of clinical service for multiparametric MRI (mpMRI), including image creation and reporting.<ref>{{cite journal | vauthors = Padhani AR, Weinreb J, Rosenkrantz AB, Villeirs G, Turkbey B, Barentsz J | title = Prostate Imaging-Reporting and Data System Steering Committee: PI-RADS v2 Status Update and Future Directions | journal = European Urology | volume = 75 | issue = 3 | pages = 385–396 | date = March 2019 | pmid = 29908876 | pmc = 6292742 | doi = 10.1016/j.eururo.2018.05.035 }}</ref> PI-RADS version 2 scoring has shown a specificity and sensitivity of 73% and 95%, respectively, for detection of prostate cancer.<ref>{{cite journal | vauthors = Wang X, Bao J, Ping X, Hu C, Hou J, Dong F, Guo L | title = The diagnostic value of PI-RADS V1 and V2 using multiparametric MRI in transition zone prostate clinical cancer | journal = Oncology Letters | volume = 16 | issue = 3 | pages = 3201–3206 | date = September 2018 | pmid = 30127915 | pmc = 6096261 | doi = 10.3892/ol.2018.9038 }}</ref>

When an MRI is used to decide whether to do a biopsy in men who have had a prior biopsy, it is 5% more likely to make a correct diagnosis than a standard biopsy and is 12% more likely to be correct for men who may or may not have had a prior biopsy.<ref name=":5" /> In men who have had a negative biopsy, this combination is 44% more likely to lead to a correct diagnosis.<ref name=":5" />

===== Other uses for MRI =====
Prostate MRI is also used for surgical planning for robotic [[Medicine:Prostatectomy|prostatectomy]].<ref name="pmid21993567"/> It helps surgeons decide whether to resect or spare the neurovascular bundle, determine return to urinary continence, and help assess surgical difficulty.<ref name="pmid21993567">{{cite journal | vauthors = Tan N, Margolis DJ, McClure TD, Thomas A, Finley DS, Reiter RE, Huang J, Raman SS | display-authors = 6 | title = Radical prostatectomy: value of prostate MRI in surgical planning | journal = Abdominal Imaging | volume = 37 | issue = 4 | pages = 664–674 | date = August 2012 | pmid = 21993567 | doi = 10.1007/s00261-011-9805-y | s2cid = 20471235 }}</ref> MRI is used in other types of treatment planning, for both focal therapy<ref>{{cite journal | vauthors = Scheltema MJ, Tay KJ, Postema AW, de Bruin DM, Feller J, Futterer JJ, George AK, Gupta RT, Kahmann F, Kastner C, Laguna MP, Natarajan S, Rais-Bahrami S, Rastinehad AR, de Reijke TM, Salomon G, Stone N, van Velthoven R, Villani R, Villers A, Walz J, Polascik TJ, de la Rosette JJ | display-authors = 6 | title = Utilization of multiparametric prostate magnetic resonance imaging in clinical practice and focal therapy: report from a Delphi consensus project | journal = World Journal of Urology | volume = 35 | issue = 5 | pages = 695–701 | date = May 2017 | pmid = 27637908 | pmc = 5397427 | doi = 10.1007/s00345-016-1932-1 | doi-access = free | oclc = 1188365278 }}</ref> and radiotherapy.<ref>{{cite journal | vauthors = Wang T, Zhou J, Tian S, Wang Y, Patel P, Jani AB, Langen KM, Curran WJ, Liu T, Yang X | display-authors = 6 | title = A planning study of focal dose escalations to multiparametric MRI-defined dominant intraprostatic lesions in prostate proton radiation therapy | journal = The British Journal of Radiology | volume = 93 | issue = 1107 | pages = 20190845 | date = March 2020 | pmid = 31904261 | pmc = 7066949 | doi = 10.1259/bjr.20190845 }}</ref> MRI can also be used to target areas for research sampling in biobanking.<ref>{{cite journal | vauthors = Heavey S, Haider A, Sridhar A, Pye H, Shaw G, Freeman A, Whitaker H | title = Use of Magnetic Resonance Imaging and Biopsy Data to Guide Sampling Procedures for Prostate Cancer Biobanking | journal = Journal of Visualized Experiments | issue = 152 | date = October 2019 | pmid = 31657791 | doi = 10.3791/60216 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Heavey S, Costa H, Pye H, Burt EC, Jenkinson S, Lewis GR, Bosshard-Carter L, Watson F, Jameson C, Ratynska M, Ben-Salha I, Haider A, Johnston EW, Feber A, Shaw G, Sridhar A, Nathan S, Rajan P, Briggs TP, Sooriakumaran P, Kelly JD, Freeman A, Whitaker HC | display-authors = 6 | title = PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens | journal = The Prostate | volume = 79 | issue = 7 | pages = 768–777 | date = May 2019 | pmid = 30807665 | pmc = 6618051 | doi = 10.1002/pros.23782 }}</ref>

===== Biological basis for prostate cancer visibility on MRI =====
The biological properties which determine whether or not a tumour is visible on MRI is poorly understood. One theory is that tumour cells undergo several genetic changes during [[Biology:Carcinogenesis|transformation]] which alter the cellular rate of growth and formation of new blood vessels, leading to tumours with more aggressive [[Biology:Pathology|histological]] patterns, [[Chemistry:Tumor hypoxia|hypoxic]] regions and increased cell density among other features.<ref name=":4">{{cite journal | vauthors = Norris JM, Simpson BS, Freeman A, Kirkham A, Whitaker HC, Emberton M | title = Conspicuity of prostate cancer on multiparametric magnetic resonance imaging: A cross-disciplinary translational hypothesis | journal = FASEB Journal | volume = 34 | issue = 11 | pages = 14150–14159 | date = November 2020 | pmid = 32920937 | pmc = 8436756 | doi = 10.1096/fj.202001466R | s2cid = 221675029 | doi-access = free }}</ref> Having larger, more dense tumours with changes in blood vessel distributions may feasibly alter signal on MRI through restriction of water and/or fluid movement.<ref name=":4" />

Some studies have linked the presence of rare [[Biology:Histology|histological]] patterns within the tumour such as cribriform pattern.<ref>{{cite journal | vauthors = Truong M, Hollenberg G, Weinberg E, Messing EM, Miyamoto H, Frye TP | title = Impact of Gleason Subtype on Prostate Cancer Detection Using Multiparametric Magnetic Resonance Imaging: Correlation with Final Histopathology | journal = The Journal of Urology | volume = 198 | issue = 2 | pages = 316–321 | date = August 2017 | pmid = 28163032 | doi = 10.1016/j.juro.2017.01.077 | s2cid = 45430609 }}</ref> Although recent research suggests there is a number of histopathological features which may influence tumour detection by MRI.<ref>{{cite journal | vauthors = Norris JM, Carmona Echeverria LM, Simpson BS, Allen C, Ball R, Freeman A, Kelly D, Kirkham A, Kasivisvanathan V, Whitaker HC, Emberton M | display-authors = 6 | title = Prostate cancer visibility on multiparametric magnetic resonance imaging: high Gleason grade and increased tumour volume are not the only important histopathological features | journal = BJU International | volume = 126 | issue = 2 | pages = 237–239 | date = August 2020 | pmid = 32319152 | doi = 10.1111/bju.15085 | doi-access = free }}</ref> At a [[Biology:Genetics|genetic]] level, prostate cancer visibility on MRI seems to be linked with genetic features of aggressive disease including processes such as [[Biology:Cell proliferation|cell proliferation]], tumour [[Chemistry:Tumor hypoxia|hypoxia]] and [[Biology:DNA repair|DNA damage]].<ref name=":3">{{cite journal | vauthors = Norris JM, Simpson BS, Parry MA, Allen C, Ball R, Freeman A, Kelly D, Kim HL, Kirkham A, You S, Kasivisvanathan V, Whitaker HC, Emberton M | display-authors = 6 | title = Genetic Landscape of Prostate Cancer Conspicuity on Multiparametric Magnetic Resonance Imaging: A Systematic Review and Bioinformatic Analysis | journal = European Urology Open Science | volume = 20 | pages = 37–47 | date = July 2020 | pmid = 33000006 | pmc = 7497895 | doi = 10.1016/j.euros.2020.06.006 | doi-access = free }}</ref>  The gene changes consistently observed in MRI-visible tumours include loss of tumour suppressor [[Biology:PTEN (gene)|PTEN]], increased expression of proliferation associated genes CENPF, [[Biology:AGR2|AGR2]] and growth factor [[Biology:GDF15|GDF15]] as well as a number of other genes.<ref name=":3" /> Changes in these pathways and genes may facilitate increased tumour growth, changes in vasculature and density which ultimately change the signal on MRI.<ref name=":4" />

==== Ultrasound ====
Ultrasound imaging can be obtained transrectally and is used during prostate biopsies.<ref>{{Cite web |title=Transrectal Ultrasonography - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/transrectal-ultrasonography |access-date=2022-04-28 |website=www.sciencedirect.com}}</ref> Prostate cancer can be seen as a hypoechoic lesion in 60% of cases. The other 40% of cancerous lesions are either hyperechoic or isoechoic. On Color Doppler, the lesions appear hypervascular.<ref>{{Cite journal | vauthors = Ebeid AI, Elshamy AS |date=2018-09-01 |title=Hypoechoic versus hypervascular lesion in the diagnosis of prostatic carcinoma |journal=African Journal of Urology |language=en |volume=24 |issue=3 |pages=169–174 |doi=10.1016/j.afju.2018.01.004 |s2cid=81718491 |issn=1110-5704|doi-access=free }}</ref>

==== PET ====
A [[Chemistry:PSMA scan|PSMA scan]] is a [[Physics:Positron emission tomography|positron emission tomography]] (PET) imaging technique which targets the overexpression of PSMA in prostate cancer tissue. A range of [[Medicine:Radiopharmaceutical|radiopharmaceutical]]s have been developed, with more under active research.
[[Physics:Gallium-68|Gallium-68]] (<sup>68</sup>Ga) PSMA-11 and [[Physics:Fluorine-18|fluorine-18]] (<sup>18</sup>F) PSMA-DCFPyL received FDA approval for PET-CT imaging in prostate cancer in 2021.<ref>{{Cite web |title=FDA approves novel PSMA-PET imaging product for prostate cancer |url=https://www.urologytimes.com/view/fda-approves-novel-psma-pet-imaging-product-for-prostate-cancer |access-date=2023-01-04 |website=Urology Times |language=en}}</ref><ref>{{cite web |title=PSMA Radiopharmaceutical Effective against Prostate Cancer |url=https://www.cancer.gov/news-events/cancer-currents-blog/2021/prostate-cancer-psma-radiopharmaceutical-vision |website=[[Organization:National Cancer Institute|National Cancer Institute]] |publisher=[[Organization:National Institutes of Health|National Institutes of Health]] |language=en |date=29 June 2021}}</ref> It has a role in evaluation of prostate cancer patients, especially patients who may go on to receive [[Physics:Lutetium-177|lutetium-177]] (<sup>177</sup>Lu) PSMA radioligand therapy.<ref>{{Cite journal |last1=Fallahi |first1=Babak |last2=Khademi |first2=Niloufar |last3=Karamzade-Ziarati |first3=Najme |last4=Fard-Esfahani |first4=Armaghan |last5=Emami-Ardekani |first5=Alireza |last6=Farzanefar |first6=Saeed |last7=Eftekhari |first7=Mohammad |last8=Beiki |first8=Davood |date=February 2021 |title=99mTc-PSMA SPECT/CT Versus 68Ga-PSMA PET/CT in the Evaluation of Metastatic Prostate Cancer |url=https://journals.lww.com/10.1097/RLU.0000000000003410 |journal=Clinical Nuclear Medicine |language=en |volume=46 |issue=2 |pages=e68–e74 |doi=10.1097/RLU.0000000000003410 |pmid=33234922 |s2cid=227168658 |issn=1536-0229}}</ref><ref>{{Cite journal |last1=Harsini |first1=Sara |last2=Fallahi |first2=Babak |last3=Karamzade Ziarati |first3=Najme |last4=Razi |first4=Ali |last5=Amini |first5=Erfan |last6=Emami-Ardekani |first6=Alireza |last7=Fard-Esfahani |first7=Armaghan |last8=Kardoust Parizi |first8=Mehdi |last9=Farzanehfar |first9=Saeed |last10=Beiki |first10=Davood |date=2021 |title=A Prospective Study on [68Ga]-PSMA PET/CT Imaging in Newly Diagnosed Intermediate- and High-Risk Prostate Cancer |journal=Asia Oceania Journal of Nuclear Medicine & Biology |volume=9 |issue=2 |pages=101–110 |doi=10.22038/AOJNMB.2020.52375.1358 |issn=2322-5718 |pmc=8255520 |pmid=34250139}}</ref>

===Biopsy===
{{See|Prostate biopsy}}
[[File:Prostate Needle Biopsy.png|thumb|Prostate needle biopsy]]
If cancer is suspected, a biopsy is offered expediently. During a biopsy, a urologist or [[Medicine:Radiology|radiologist]] obtains tissue samples from the prostate via either the rectum or the perineum. A biopsy gun inserts and removes special hollow-core needles (usually three to six on each side of the prostate) in less than a second.<ref>{{Cite journal | vauthors = El Shafei AR, Jones JS | veditors = Kim ED | journal = Medscape |date=2021-10-04 |title=Prostate Biopsy: Practice Essentials, Background, Indications and Contraindications |url=https://emedicine.medscape.com/article/1949728-overview}}</ref> Prostate biopsies are routinely done on an outpatient basis and rarely require hospitalization. Systematic biopsies correctly identify 63% of men as having clinically significant prostate cancer but will miss the rest.<ref name=":5" /><ref name=":7">{{cite journal | vauthors = Drost FH, Osses D, Nieboer D, Bangma CH, Steyerberg EW, Roobol MJ, Schoots IG | title = Prostate Magnetic Resonance Imaging, with or Without Magnetic Resonance Imaging-targeted Biopsy, and Systematic Biopsy for Detecting Prostate Cancer: A Cochrane Systematic Review and Meta-analysis | journal = European Urology | volume = 77 | issue = 1 | pages = 78–94 | date = January 2020 | pmid = 31326219 | doi = 10.1016/j.eururo.2019.06.023 | s2cid = 198131275 | url = https://pure.eur.nl/en/publications/1b7f16a1-839a-447f-be10-5fae2a62dce7 }}</ref> For men at risk for prostate cancer, biopsy will not misclassify any of the men as having clinically significant prostate cancer.<ref name=":5" /><ref name=":7" />

[[Chemistry:Antibiotic|Antibiotic]]s should be used to prevent complications such as [[Medicine:Fever|fever]], [[Medicine:Urinary tract infection|urinary tract infection]]s, and [[Medicine:Sepsis|sepsis]]<ref>{{cite journal | vauthors = Yaghi MD, Kehinde EO | title = Oral antibiotics in trans-rectal prostate biopsy and its efficacy to reduce infectious complications: Systematic review | journal = Urology Annals | volume = 7 | issue = 4 | pages = 417–427 | year = 2015 | pmid = 26538868 | pmc = 4660689 | doi = 10.4103/0974-7796.164860 }}</ref> even if the most appropriate course or dose is undefined.<ref>{{cite journal | vauthors = Zani EL, Clark OA, Rodrigues Netto N | title = Antibiotic prophylaxis for transrectal prostate biopsy | journal = The Cochrane Database of Systematic Reviews | issue = 5 | pages = CD006576 | date = May 2011 | pmid = 21563156 | doi = 10.1002/14651858.CD006576.pub2 }}</ref> About 55% of men report discomfort during prostate biopsy.<ref name="pmid9637143">{{cite journal | vauthors = Essink-Bot ML, de Koning HJ, Nijs HG, Kirkels WJ, van der Maas PJ, Schröder FH | title = Short-term effects of population-based screening for prostate cancer on health-related quality of life | journal = Journal of the National Cancer Institute | volume = 90 | issue = 12 | pages = 925–931 | date = June 1998 | pmid = 9637143 | doi = 10.1093/jnci/90.12.925 | doi-access = free }}</ref>

====Histopathologic diagnosis====
{{Main|Medicine:Histopathologic diagnosis of prostate cancer}}
[[File:Prostate cancer types.svg|thumb|300px|Pie chart of [[Medicine:Histopathologic diagnosis of prostate cancer|histopathologic subdiagnoses of prostate cancer]].<ref>References for pie chart are located in table in the article Histopathologic diagnosis of prostate cancer: Incidences{{verify spelling|date=September 2022|reason=''incidence'' is normally used only in the singular form, perhaps ''incidence'', ''incidents'',  or ''instances'' was intended}} generally include cases where the pattern is found admixed with usual acinar adenocarcinoma.</ref>]]
[[File:Prostatic adenocarcinoma with perineural invasion.JPG|thumb|right|[[Micrograph|Micrograph]] showing a prostate cancer (conventional adenocarcinoma) with perineural invasion. H&E stain.]]
A [[Medicine:Histopathology|histopathologic]] diagnosis mainly includes assessment of whether a cancer exists, as well as any subdiagnosis, if possible.<ref>{{cite journal | vauthors = Sharma S | title = Tumor markers in clinical practice: General principles and guidelines | journal = Indian Journal of Medical and Paediatric Oncology | volume = 30 | issue = 1 | pages = 1–8 | date = January 2009 | pmid = 20668599 | pmc = 2902207 | doi = 10.4103/0971-5851.56328 }}</ref> Histopathologic subdiagnosis has implications for the possibility and methodology of Gleason scoring.<ref name=Wang2016>{{cite journal | vauthors = Li J, Wang Z | title = The pathology of unusual subtypes of prostate cancer | journal = Chinese Journal of Cancer Research = Chung-Kuo Yen Cheng Yen Chiu | volume = 28 | issue = 1 | pages = 130–143 | date = February 2016 | pmid = 27041935 | pmc = 4779761 | doi = 10.3978/j.issn.1000-9604.2016.01.06 }}</ref> The most common histopathological subdiagnosis is acinar adenocarcinoma, constituting 93% of diagnoses.<ref name="BaigHamid2015">{{cite journal | vauthors = Baig FA, Hamid A, Mirza T, Syed S | title = Ductal and Acinar Adenocarcinoma of Prostate: Morphological and Immunohistochemical Characterization | journal = Oman Medical Journal | volume = 30 | issue = 3 | pages = 162–166 | date = May 2015 | pmid = 26171121 | pmc = 4459157 | doi = 10.5001/omj.2015.36 }}</ref> The most common form of acinar adenocarcinoma, in turn, is "adenocarcinoma, not otherwise specified", also termed conventional, or usual acinar adenocarcinoma.<ref>{{cite web|url=http://surgpathcriteria.stanford.edu/prostate/adenocarcinoma/classification-lists.html|title=Prostatic Adenocarcinoma|website=Stanford University School of Medicine|access-date=2019-10-30}}</ref>

====Biochemical diagnosis====
[[Biology:Alkaline phosphatase|Alkaline phosphatase]] is more elevated in [[Medicine:Metastasis|metastatic]] than non-metastatic cells.<ref name="pmid28006818">{{cite journal | vauthors = Rao SR, Snaith AE, Marino D, Cheng X, Lwin ST, Orriss IR, Hamdy FC, Edwards CM | display-authors = 6 | title = Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer | journal = British Journal of Cancer | volume = 116 | issue = 2 | pages = 227–236 | date = January 2017 | pmid = 28006818 | pmc = 5243990 | doi = 10.1038/bjc.2016.402 }}</ref> High levels of alkaline phosphatase is associated with a significant decrease in survival.<ref name="pmid28006818" />

====Gleason score====
The Gleason grading system is used to help evaluate the [[Medicine:Prognosis|prognosis]] and helps guide therapy. A Gleason score is based upon the tumor's appearance.<ref name="urlMale Genital Pathology">{{cite web |url=http://library.med.utah.edu/WebPath/MALEHTML/MALE075.html |title=Male Genital Pathology |access-date=2009-05-13}}</ref> Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 through 10, with a higher number indicating greater risks and higher mortality.<ref>{{Cite web |title=Gleason Score - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/gleason-score |access-date=2022-04-28 |website=www.sciencedirect.com}}</ref>

==== ISUP score ====
In 2014, the International Society of Urological Pathology (ISUP) provided a new prostate cancer grading system called the ISUP scores.<ref>{{cite journal | vauthors = Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA | title = The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System | journal = The American Journal of Surgical Pathology | volume = 40 | issue = 2 | pages = 244–252 | date = February 2016 | pmid = 26492179 | doi = 10.1097/PAS.0000000000000530 }}</ref>
{| class="wikitable"
|+ISUP grading equivalence<ref>{{Cite web|title=The Gleason Score & ISUP Grading|url=https://tackleprostate.org/the-gleason-score.php|access-date=2021-09-07|website=tackle prostate cancer|language=en|archive-date=2021-09-07|archive-url=https://web.archive.org/web/20210907140700/https://tackleprostate.org/the-gleason-score.php|url-status=dead}}</ref> 
!Risk group
!ISUP Grade Group
!Gleason Score
|-
|Low
|Grade Group 1
|Gleason < 6
|-
|Intermediate Favourable
|Grade Group 2
|Gleason 7 (3+4)
|-
|Intermediate Unfavourable
|Grade Group 3
|Gleason 7 (4+3)
|-
| rowspan="2" |High 
|Grade Group 4
|Gleason 8
|-
|Grade Group 5
|Gleason 9-10
|}

===Tumor markers===
Tissue samples can be stained for the presence of [[Biology:Prostate-specific antigen|PSA]] and other tumor markers to determine the origin of malignant cells that have metastasized.<ref name="pmid17667550">{{cite journal | vauthors = Chuang AY, DeMarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI | title = Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma | journal = The American Journal of Surgical Pathology | volume = 31 | issue = 8 | pages = 1246–1255 | date = August 2007 | pmid = 17667550 | doi = 10.1097/PAS.0b013e31802f5d33 | s2cid = 11535862 }}</ref>

Small cell carcinoma is a rare (1%<ref name="pmid9227387">{{cite journal | vauthors = Nutting C, Horwich A, Fisher C, Parsons C, Dearnaley DP | title = Small-cell carcinoma of the prostate | journal = Journal of the Royal Society of Medicine | volume = 90 | issue = 6 | pages = 340–341 | date = June 1997 | pmid = 9227387 | pmc = 1296316 | doi = 10.1177/014107689709000615 }}</ref>) type that cannot be diagnosed using PSA.<ref name="pmid9227387"/><ref name="pmid19947569">{{cite journal | vauthors = Wei ZF, Xu H, Wang H, Wei W, Cheng W, Zhou WQ, Ge JP, Zhang ZY, Gao JP, Yin HL | display-authors = 6 | title = [Clinicopathological characterization of prostatic small cell carcinoma: a case report and review of the literature] | language = zh | journal = Zhonghua Nan Ke Xue = National Journal of Andrology | volume = 15 | issue = 9 | pages = 829–832 | date = September 2009 | pmid = 19947569 }}</ref> {{As of|2009}} researchers were investigating ways to screen for this type, because it is quick to metastasize.<ref name="pmid19947569"/>

The [[Biology:Oncogene|oncoprotein]] BCL-2 is associated with the development of androgen-independent prostate cancer, due to its high levels of expression in androgen-independent tumours in advanced stages.<ref>{{cite journal | vauthors = Catz SD, Johnson JL | title = BCL-2 in prostate cancer: a minireview | journal = Apoptosis | volume = 8 | issue = 1 | pages = 29–37 | date = January 2003 | pmid = 12510149 | doi = 10.1023/a:1021692801278 | s2cid = 21948907 }}</ref> The upregulation of BCL-2 after androgen ablation in prostate carcinoma cell lines and in a castrated-male rat model further established a connection between BCL-2 expression and prostate cancer progression.<ref name="pmid12510149">{{cite journal | vauthors = Catz SD, Johnson JL | title = BCL-2 in prostate cancer: a minireview | journal = Apoptosis | volume = 8 | issue = 1 | pages = 29–37 | date = January 2003 | pmid = 12510149 | doi = 10.1023/A:1021692801278 | s2cid = 21948907 }}</ref>

===Staging===
[[File:Diagram showing T1-3 stages of prostate cancer CRUK 278.svg|thumb|Diagram showing T1-3 stages of prostate cancer.]]
An important part of evaluating prostate cancer is determining the [[Medicine:Cancer staging|stage]], or degree of spread. Knowing the stage helps define [[Medicine:Prognosis|prognosis]] and is useful when selecting therapies.<ref name="emedicine.medscape.com">{{Cite journal | vauthors = Cheuck L, Ghiraldi EM | veditors = Kim ED | journal = Medscape |date=2021-10-04 |title=Prostate Cancer Diagnosis and Staging: Practice Essentials, Overview, Relevant Anatomy |url=https://emedicine.medscape.com/article/458011-overview}}</ref> The most common system is the four-stage TNM system (abbreviated from tumor/nodes/metastases). Its components include the size of the tumor, the number of involved [[Biology:Lymph node|lymph node]]s, and the presence of any other [[Medicine:Metastasis|metastases]].<ref>{{cite news |url=https://www.theguardian.com/lifeandstyle/besttreatments/prostate-cancer-how-far-has-your-cancer-spread-the-tnm-system |title=Prostate cancer: How far has your cancer spread? The TNM system |author=BMJ Group |date=8 December 2009 |website=Guardian.co.uk |access-date=9 August 2010 |location=London |archive-date=4 April 2009 |archive-url=https://web.archive.org/web/20090404040930/http://www.guardian.co.uk/lifeandstyle/besttreatments/prostate-cancer-how-far-has-your-cancer-spread-the-tnm-system |url-status=dead }}</ref> In the United Kingdom the Cambridge Prognostic Group (CPG) is used for categorising prostate cancer into 5 risk groups (CPG1 to CPG5).<ref name=":2">{{Cite web |title=Prostate cancer: diagnosis and management. NICE guideline [NG131] |url=https://www.nice.org.uk/guidance/ng131/chapter/Recommendations#assessment-and-diagnosis |access-date=2022-10-03 |website=National Institute for Health and Care Excellence (NICE)}}</ref>

The most important distinction made by any staging system is whether the cancer is confined to the prostate. In the TNM system, clinical T1 and T2 cancers are found only in the prostate, while T3 and T4 cancers have metastasized.<ref name="emedicine.medscape.com"/> Several tests can be used to look for evidence of spread. Medical specialty professional organizations recommend against the use of [[Physics:Positron emission tomography|PET scans]], [[Astronomy:X-ray computed tomography|CT scans]], or [[Engineering:Bone scintigraphy|bone scans]] when a physician stages early prostate cancer with low risk for metastasis.<ref name="ASCOfive">{{cite journal | author = American Society of Clinical Oncology | title = Five things physicians and patients should question | journal = The Journal of the Oklahoma State Medical Association | volume = 106 | issue = 4 | pages = 150–151 | date = April 2013 | pmid = 23795527 | url = http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Clin_Onc.pdf | url-status = dead |  archive-url = https://web.archive.org/web/20120731073425/http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Clin_Onc.pdf | archive-date = 2012-07-31 }}
* {{cite journal | vauthors = Makarov DV, Desai RA, Yu JB, Sharma R, Abraham N, Albertsen PC, Penson DF, Gross CP | display-authors = 6 | title = The population level prevalence and correlates of appropriate and inappropriate imaging to stage incident prostate cancer in the medicare population | journal = The Journal of Urology | volume = 187 | issue = 1 | pages = 97–102 | date = January 2012 | pmid = 22088337 | doi = 10.1016/j.juro.2011.09.042 }}
* {{cite web |url=http://www.nccn.org/professionals/physician_gls/f_guidelines.asp |title=NCCN Clinical Practice Guidelines in Oncology |author=National Comprehensive Cancer Network – Prostate |work=nccn.org |year=2012 |access-date=15 November 2012 |url-status=live |archive-url=https://web.archive.org/web/20121109143827/http://www.nccn.org/professionals/physician_gls/f_guidelines.asp |archive-date=9 November 2012 }}
* {{cite journal | vauthors = Thompson I, Thrasher JB, Aus G, Burnett AL, Canby-Hagino ED, Cookson MS, D'Amico AV, Dmochowski RR, Eton DT, Forman JD, Goldenberg SL, Hernandez J, Higano CS, Kraus SR, Moul JW, Tangen CM | display-authors = 6 | title = Guideline for the management of clinically localized prostate cancer: 2007 update | journal = The Journal of Urology | volume = 177 | issue = 6 | pages = 2106–2131 | date = June 2007 | pmid = 17509297 | doi = 10.1016/j.juro.2007.03.003 }}</ref> Those tests would be appropriate in cases such as when a CT scan evaluates spread within the pelvis, a bone scan looks for spread to the bones, and [[Physics:Endorectal coil magnetic resonance imaging|endorectal coil magnetic resonance imaging]] evaluates the prostatic capsule and the seminal vesicles. Bone scans should reveal [[Biology:Osteoblast|osteoblast]]ic appearance due to ''increased'' bone density in the areas of [[Medicine:Bone metastasis|bone metastasis]]—the reverse of what is found in many other metastatic cancers.<ref>{{cite journal | vauthors = Macedo F, Ladeira K, Pinho F, Saraiva N, Bonito N, Pinto L, Goncalves F | title = Bone Metastases: An Overview | journal = Oncology Reviews | volume = 11 | issue = 1 | pages = 321 | date = March 2017 | pmid = 28584570 | pmc = 5444408 | doi = 10.4081/oncol.2017.321 }}</ref> Approved [[Medicine:Radiopharmaceutical|radiopharmaceutical]] diagnostic agents used in PET: [[Biology:Fluciclovine (18F)|fluciclovine]] (2016), Ga 68 PSMA-11 (2020), piflufolastat (2021).

After a biopsy, a [[Biology:Pathology|pathologist]] examines the samples under a microscope. If cancer is present, the pathologist reports the [[Medicine:Grading (tumors)|grade]] of the tumor. The grade tells how much the tumor tissue differs from normal prostate tissue and suggests how fast the tumor is likely to grow. The pathologist assigns a Gleason number from 1 to 5 for the most common pattern observed under the microscope, then does the same for the second-most common pattern. The sum of these two numbers is the Gleason score. The Whitmore-Jewett stage is another method.

In men with high-risk localised prostate cancer, staging with PSMA PET/CT may be appropriate to detect nodal or distant metastatic spread. In 2020, a randomised phase 3 trial compared Gallium-68 PSMA PET/CT to standard imaging (CT and bone scan). It reported superior accuracy of [[Chemistry:Gallium scan|Gallium-68 PSMA-11]] PET/CT (92% vs 65%), higher significant change in management (28% vs 15%), less equivocal/uncertain imaging findings (7% vs 23%) and lower radiation exposure (10 msV vs 19 mSv). The study concluded that PSMA PET/CT is a suitable replacement for conventional imaging.<ref name="pmid32209449">{{cite journal | vauthors = Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, Rutherford N, Martin JM, Frydenberg M, Shakher R, Wong LM, Taubman K, Ting Lee S, Hsiao E, Roach P, Nottage M, Kirkwood I, Hayne D, Link E, Marusic P, Matera A, Herschtal A, Iravani A, Hicks RJ, Williams S, Murphy DG | display-authors = 6 | title = Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study | journal = Lancet | volume = 395 | issue = 10231 | pages = 1208–1216 | date = April 2020 | pmid = 32209449 | doi = 10.1016/S0140-6736(20)30314-7 | s2cid = 214609500 }}</ref>

<gallery>
File:ScleroticmetastaticdiseasespineLCT.png|Sclerosis of the bones of the thoracic spine due to prostate cancer metastases (CT image)
File:Scleroticmetastaticdiseasespine.png|Sclerosis of the bones of the thoracic spine due to prostate cancer metastases (CT image)
File:ScleroticmetastaticdiseasePelvis.png|Sclerosis of the bones of the pelvis due to prostate cancer metastases
</gallery>

==Prevention==

===Diet and lifestyle===
The data on the relationship between diet and prostate cancer are poor.<ref name=Masko2012/> However, the rate of prostate cancer is linked to the consumption of the Western diet.<ref name="Masko2012">{{cite journal | vauthors = Masko EM, Allott EH, Freedland SJ | title = The relationship between nutrition and prostate cancer: is more always better? | journal = European Urology | volume = 63 | issue = 5 | pages = 810–820 | date = May 2013 | pmid = 23219353 | pmc = 3597758 | doi = 10.1016/j.eururo.2012.11.012 }}</ref> Little if any evidence associates [[Chemistry:Trans fat|trans fat]], [[Chemistry:Saturated fat|saturated fat]], and [[Chemistry:Carbohydrate|carbohydrate]] intake and prostate cancer.<ref name=Masko2012/><ref>{{cite journal | vauthors = Thompson AK, Shaw DI, Minihane AM, Williams CM | title = Trans-fatty acids and cancer: the evidence reviewed | journal = Nutrition Research Reviews | volume = 21 | issue = 2 | pages = 174–188 | date = December 2008 | pmid = 19087370 | doi = 10.1017/S0954422408110964 | doi-access = free }}</ref> Evidence does not support  a role for [[Chemistry:Omega-3 fatty acid|omega-3 fatty acid]]s in preventing prostate cancer.<ref name=Masko2012/><ref>{{cite journal | vauthors = Heinze VM, Actis AB | title = Dietary conjugated linoleic acid and long-chain n-3 fatty acids in mammary and prostate cancer protection: a review | journal = International Journal of Food Sciences and Nutrition | volume = 63 | issue = 1 | pages = 66–78 | date = February 2012 | pmid = 21762028 | doi = 10.3109/09637486.2011.598849 | s2cid = 21614046 }}</ref> Vitamin supplements appear to have no effect and some may increase the risk.<ref name=Strat2011/><ref name=Masko2012/> High supplemental calcium intake has been linked to advanced prostate cancer.<ref>{{cite journal | vauthors = Datta M, Schwartz GG | title = Calcium and vitamin D supplementation during androgen deprivation therapy for prostate cancer: a critical review | journal = The Oncologist | volume = 17 | issue = 9 | pages = 1171–1179 | year = 2012 | pmid = 22836449 | pmc = 3448410 | doi = 10.1634/theoncologist.2012-0051 }}</ref>

Fish may lower prostate-cancer deaths, but does not appear to affect occurrence.<ref>{{cite journal | vauthors = Szymanski KM, Wheeler DC, Mucci LA | title = Fish consumption and prostate cancer risk: a review and meta-analysis | journal = The American Journal of Clinical Nutrition | volume = 92 | issue = 5 | pages = 1223–1233 | date = November 2010 | pmid = 20844069 | doi = 10.3945/ajcn.2010.29530 | doi-access = free }}</ref> Some evidence supports lower rates of prostate cancer with a vegetarian diet,<ref>{{cite journal | title = Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets | journal = Journal of the American Dietetic Association | volume = 103 | issue = 6 | pages = 748–765 | date = June 2003 | pmid = 12778049 | doi = 10.1053/jada.2003.50142 | doi-access = free | author1 = American Dietetic Association }}</ref> [[Chemistry:Lycopene|lycopene]], [[Chemistry:Selenium|selenium]]<ref name=WCR2007>{{cite book| author1 = World Cancer Research Fund | author2 = American Institute for Cancer |title=Food, nutrition, physical activity, and the prevention of cancer a global perspective|year=2007|publisher=American Institute for Cancer Research|location=Washington, D.C.|isbn=978-0-9722522-2-5|pages=76|url=http://eprints.ucl.ac.uk/4841/1/4841.pdf|url-status=dead|archive-url=https://web.archive.org/web/20130523121425/http://eprints.ucl.ac.uk/4841/1/4841.pdf|archive-date=2013-05-23}}</ref><ref>{{cite journal | vauthors = Rowles JL, Ranard KM, Applegate CC, Jeon S, An R, Erdman JW | title = Processed and raw tomato consumption and risk of prostate cancer: a systematic review and dose-response meta-analysis | language = En | journal = Prostate Cancer and Prostatic Diseases | volume = 21 | issue = 3 | pages = 319–336 | date = September 2018 | pmid = 29317772 | doi = 10.1038/s41391-017-0005-x | s2cid = 3306182 }}</ref> cruciferous vegetables, soy, beans and/or other [[Biology:Legume|legume]]s.<ref name=Cancer.org/>

Regular exercise may slightly lower risk, especially vigorous activity.<ref name=Cancer.org>{{cite web |url=http://www.cancer.org/acs/groups/cid/documents/webcontent/002577-pdf.pdf |title=American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention |website=American Cancer Society |url-status=live |archive-url=https://web.archive.org/web/20120625074325/http://www.cancer.org/acs/groups/cid/documents/webcontent/002577-pdf.pdf |archive-date=2012-06-25 }}</ref><ref>{{cite journal | vauthors = Torti DC, Matheson GO | title = Exercise and prostate cancer | journal = Sports Medicine | volume = 34 | issue = 6 | pages = 363–369 | date = 2004-05-01 | pmid = 15157121 | doi = 10.2165/00007256-200434060-00003 | s2cid = 43085964 }}</ref>

===Medications===
In those who are regularly screened, 5-alpha-reductase inhibitors ([[Chemistry:Finasteride|finasteride]] and [[Biology:Dutasteride|dutasteride]]) reduce the overall risk of prostate cancer.<ref>{{Cite web |title=5-Alpha-Reductase Inhibitor - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/5-alpha-reductase-inhibitor |access-date=2022-04-28 |website=www.sciencedirect.com}}</ref> Data are insufficient to determine if they affect fatality risk and they may increase the chance of more serious cases.<ref name="pmid18425978">{{cite journal | vauthors = Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Kramer BS | title = Five-alpha-reductase Inhibitors for prostate cancer prevention | journal = The Cochrane Database of Systematic Reviews | issue = 2 | pages = CD007091 | date = April 2008 | pmid = 18425978 | doi = 10.1002/14651858.CD007091 | veditors = Wilt TJ }}</ref>

==Screening==
Prostate cancer [[Medicine:Screening|screening]] searches for cancers in those without symptoms. Options include the digital rectal exam and the PSA blood test.<ref name=Alb2015>{{cite journal | vauthors = Alberts AR, Schoots IG, Roobol MJ | title = Prostate-specific antigen-based prostate cancer screening: Past and future | journal = International Journal of Urology | volume = 22 | issue = 6 | pages = 524–532 | date = June 2015 | pmid = 25847604 | doi = 10.1111/iju.12750 | s2cid = 7525080 | doi-access = free }}</ref> Such screening is controversial,<ref name=Rendon2017/> and for many, may lead to unnecessary disruption and possibly harmful consequences.<ref name=USPSTF-2018>{{cite web|title=Home Page – USPSTF Draft Prostate Screening Recommendations|url=https://screeningforprostatecancer.org/|website=USPSTF Draft Prostate Screening Recommendations|access-date=2 March 2018|archive-url=https://web.archive.org/web/20180302225801/https://screeningforprostatecancer.org/|archive-date=2 March 2018|url-status=dead}}</ref> Harms of population-based screening, primarily due to overdiagnosis (the detection of [[Medicine:Incubation period|latent]] cancers that would have otherwise not been discovered) may outweigh the benefits.<ref name=Alb2015/> Others recommend shared decision-making, an approach where screening may occur after a physician consultation.<ref>{{cite journal | vauthors = Mulhem E, Fulbright N, Duncan N | title = Prostate Cancer Screening | journal = American Family Physician | volume = 92 | issue = 8 | pages = 683–688 | date = October 2015 | pmid = 26554408 }}</ref>

The United States Preventive Services Task Force (USPSTF) suggests the decision whether to have PSA screening be based on [[Medicine:Shared decision-making in medicine|consultation with a physician]] for men 55 to 69 years of age.<ref name=Catalona2018>{{cite journal | vauthors = Catalona WJ | title = Prostate Cancer Screening | journal = The Medical Clinics of North America | volume = 102 | issue = 2 | pages = 199–214 | date = March 2018 | pmid = 29406053 | pmc = 5935113 | doi = 10.1016/j.mcna.2017.11.001 }}</ref> USPSTF recommends against PSA screening after age 70.<ref name=USPSTF2018/> The Centers for Disease Control and Prevention endorsed USPSTF's conclusion.<ref name="CDC">[https://www.cdc.gov/cancer/Prostate/basic_info/screening.htm Prostate Cancer Screening] {{webarchive|url=https://web.archive.org/web/20170907151112/https://www.cdc.gov/cancer/prostate/basic_info/screening.htm |date=2017-09-07 }} CDC, updated April 6, 2010</ref> The American Society of Clinical Oncology and the American College of Physicians discourage screening for those who are expected to live less than 10–15 years, while those with a greater life expectancy a decision should individually balance the potential risks and benefits.<ref name=Qa2013>{{cite journal | vauthors = Qaseem A, Barry MJ, Denberg TD, Owens DK, Shekelle P | title = Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians | journal = Annals of Internal Medicine | volume = 158 | issue = 10 | pages = 761–769 | date = May 2013 | pmid = 23567643 | doi = 10.7326/0003-4819-158-10-201305210-00633 | doi-access = free }}</ref> In general, they concluded, "it is uncertain whether the benefits associated with PSA testing for prostate cancer screening are worth the harms associated with screening and subsequent unnecessary treatment."<ref>{{cite journal | vauthors = Basch E, Oliver TK, Vickers A, Thompson I, Kantoff P, Parnes H, Loblaw DA, Roth B, Williams J, Nam RK | display-authors = 6 | title = Screening for prostate cancer with prostate-specific antigen testing: American Society of Clinical Oncology Provisional Clinical Opinion | journal = Journal of Clinical Oncology | volume = 30 | issue = 24 | pages = 3020–3025 | date = August 2012 | pmid = 22802323 | pmc = 3776923 | doi = 10.1200/JCO.2012.43.3441 }}</ref>

American Urological Association (AUA 2013) guidelines call for weighing the uncertain benefits of screening against the known harms associated with diagnostic tests and treatment.<ref>{{cite journal | vauthors = Carter HB | title = American Urological Association (AUA) guideline on prostate cancer detection: process and rationale | journal = BJU International | volume = 112 | issue = 5 | pages = 543–547 | date = September 2013 | pmid = 23924423 | doi = 10.1111/bju.12318 | s2cid = 19703425 }}</ref> The AUA recommends that shared decision-making should control screening for those 55 to 69, and that screening should occur no more often than every two years.<ref>{{cite web|title=Early Detection of Prostate Cancer: AUA Guidelines|url=http://www.auanet.org/education/guidelines/prostate-cancer-detection.cfm|work=American Urological Association|access-date=10 May 2013|year=2013|url-status=dead|archive-url=https://web.archive.org/web/20130507095505/http://www.auanet.org/education/guidelines/prostate-cancer-detection.cfm|archive-date=7 May 2013}}</ref> In the {{wipe|United Kingdom}} as of 2018, no program existed to screen for prostate cancer.<ref name=NHS2015Screen/>

==Management==
{{Main|Medicine:Management of prostate cancer}}
The first decision is whether treatment is needed. Low-grade forms found in elderly men often grow so slowly that treatment is not required.<ref name=Filson2015>{{cite journal | vauthors = Filson CP, Marks LS, Litwin MS | title = Expectant management for men with early stage prostate cancer | journal = CA | volume = 65 | issue = 4 | pages = 265–282 | date = 8 May 2015 | pmid = 25958817 | doi = 10.3322/caac.21278 | s2cid = 36057004 | doi-access = free }}</ref> Treatment may be inappropriate if a person has other serious health problems or is not expected to live long enough for symptoms to appear. Approaches in which treatment is postponed are termed "expectant management".<ref name=Filson2015/> Expectant management is divided into two approaches: [[Social:Watchful waiting|Watchful waiting]], which has palliative intent (aims to treat symptoms only), and [[Medicine:Active surveillance of prostate cancer|active surveillance]], which has curative intent (aims to prevent the cancer from advancing).<ref name=Filson2015/>

Which option is best depends on disease stage, the Gleason score, and the PSA level. Other important factors are age, general health and a person's views about potential treatments and their possible side effects. Because most treatments can have significant side effects, such as [[Medicine:Erectile dysfunction|erectile dysfunction]] and [[Medicine:Urinary incontinence|urinary incontinence]], treatment discussions often focus on balancing the goals of therapy with the risks of lifestyle alterations. A 2017 review found that more research focused on person-centered outcomes is needed to guide patients.<ref>{{cite journal | vauthors = Jayadevappa R, Chhatre S, Wong YN, Wittink MN, Cook R, Morales KH, Vapiwala N, Newman DK, Guzzo T, Wein AJ, Malkowicz SB, Lee DI, Schwartz JS, Gallo JJ | display-authors = 6 | title = Comparative effectiveness of prostate cancer treatments for patient-centered outcomes: A systematic review and meta-analysis (PRISMA Compliant) | journal = Medicine | volume = 96 | issue = 18 | pages = e6790 | date = May 2017 | pmid = 28471976 | pmc = 5419922 | doi = 10.1097/MD.0000000000006790 }}</ref> A combination of treatment options is often recommended.<ref>{{cite journal | vauthors = Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS, Barry MJ, Zietman A, O'Leary M, Walker-Corkery E, Yao SL | display-authors = 6 | title = Outcomes of localized prostate cancer following conservative management | journal = JAMA | volume = 302 | issue = 11 | pages = 1202–1209 | date = September 2009 | pmid = 19755699 | pmc = 2822438 | doi = 10.1001/jama.2009.1348 }}</ref><ref name="pmid19945664">{{cite journal | vauthors = Mongiat-Artus P, Peyromaure M, Richaud P, Droz JP, Rainfray M, Jeandel C, Rebillard X, Moreau JL, Davin JL, Salomon L, Soulié M | display-authors = 6 | title = [Recommendations for the treatment of prostate cancer in the elderly man: A study by the oncology committee of the French association of urology] | language = fr | journal = Progres en Urologie | volume = 19 | issue = 11 | pages = 810–817 | date = December 2009 | pmid = 19945664 | doi = 10.1016/j.purol.2009.02.008 }}</ref><ref name="pmid19945310">{{cite journal | vauthors = Picard JC, Golshayan AR, Marshall DT, Opfermann KJ, Keane TE | title = The multi-disciplinary management of high-risk prostate cancer | journal = Urologic Oncology | volume = 30 | issue = 1 | pages = 3–15 | date = November 2009 | pmid = 19945310 | doi = 10.1016/j.urolonc.2009.09.002 }}</ref>

Guidelines for specific clinical situations require estimation of life expectancy.<ref name="pmid21842788">{{cite journal | vauthors = Mohan R, Schellhammer PF | title = Treatment options for localized prostate cancer | journal = American Family Physician | volume = 84 | issue = 4 | pages = 413–420 | date = August 2011 | pmid = 21842788 }}</ref> As average life expectancy increases due to advances in the treatment of other diseases, more patients will live long enough for their prostate cancer to express symptoms.<ref>{{cite journal | vauthors = Rawla P | title = Epidemiology of Prostate Cancer | journal = World Journal of Oncology | volume = 10 | issue = 2 | pages = 63–89 | date = April 2019 | pmid = 31068988 | pmc = 6497009 | doi = 10.14740/wjon1191 }}</ref> An 18-item questionnaire was proposed to learn whether patients have adequate knowledge and understanding of their treatment options. In one 2015 study, most of those who were newly diagnosed correctly answered fewer than half of the questions.<ref name="pmid21842788" />

The widespread use of PSA screening in the US has resulted in diagnosis at earlier age and cancer stage, but almost all cases are still diagnosed after age 65, while about 25% are diagnosed after age 75.<ref>{{cite journal | vauthors = Fitzpatrick JM | title = Management of localized prostate cancer in senior adults: the crucial role of comorbidity | journal = BJU International | volume = 101 Suppl 2 | issue = Suppl 2 | pages = 16–22 | date = March 2008 | pmid = 18307688 | doi = 10.1111/j.1464-410X.2007.07487.x | s2cid = 205538470 | doi-access = free }}</ref> Though US National Comprehensive Cancer Network guidelines recommend using life expectancy to help make treatment decisions, in practice, many elderly patients are not offered curative treatment options such as [[Medicine:Prostatectomy|radical prostatectomy]] or [[Physics:Radiation therapy|radiation therapy]] and are instead treated with [[Medicine:Hormonal therapy (oncology)|hormonal therapy]] or watchful waiting.<ref>{{cite web|url=http://www.nccn.org/index.asp|title=Evidence-Based Cancer Guidelines, Oncology Drug Compendium, Oncology Continuing Medical Education|publisher=NCCN|access-date=2011-08-29}}</ref>

===Surveillance===
Many men diagnosed with low-risk prostate cancer are eligible for active surveillance. The tumor is carefully observed over time, with the intention of initiating treatment if signs of progression appear.<ref>{{Cite book | vauthors = Cooper GM |date=2000 | chapter = The Development and Causes of Cancer | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK9963/ | title = The Cell: A Molecular Approach. | edition = 2nd |language=en}}</ref> Active surveillance is ''not'' synonymous with [[Social:Watchful waiting|watchful waiting]], a term which implies no treatment or specific program of monitoring, with the assumption that only palliative treatment would be used if advanced, symptomatic disease develops.<ref name=Filson2015/>

Active surveillance involves monitoring the tumor for growth or symptoms, which trigger treatment. The monitoring process may involve PSA tests, digital rectal examination, or repeated biopsies every few months.<ref>{{Cite web|url=https://www.cancercareontario.ca/en/guidelines-advice/types-of-cancer/2286|title=Active Surveillance for the Management of Localized Prostate Cancer|website=Cancer Care Ontario|url-status=dead|archive-url=https://web.archive.org/web/20200410154624/https://www.cancercareontario.ca/en/guidelines-advice/types-of-cancer/2286|archive-date=2020-04-10}}</ref> The goal of active surveillance is to postpone treatment, and avoid overtreatment and its side effects, given a slow-growing or self-limited tumor that in most people is unlikely to cause problems.<ref>{{cite journal | vauthors = Ellis SD, Hwang S, Morrow E, Kimminau KS, Goonan K, Petty L, Ellerbeck E, Thrasher JB | display-authors = 6 | title = Perceived barriers to the adoption of active surveillance in low-risk prostate cancer: a qualitative analysis of community and academic urologists | journal = BMC Cancer | volume = 21 | issue = 1 | pages = 649 | date = May 2021 | pmid = 34058998 | pmc = 8165996 | doi = 10.1186/s12885-021-08386-3 }}</ref> This approach is not used for aggressive cancers, and may cause [[Medicine:Anxiety|anxiety]] for people who wrongly believe that all cancers are deadly or that their condition is life-threatening.<ref>{{Cite web |title=Cancer |url=https://www.who.int/news-room/fact-sheets/detail/cancer |access-date=2022-04-28 |website=www.who.int |language=en}}</ref> Between 50 and 75% of patients die from other causes without experiencing prostate symptoms.<ref>{{cite web|url=http://www.cancer.gov/ncicancerbulletin/041911/page2 |title=Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer |publisher=Cancer.gov |date=2011-04-19 |access-date=2011-08-29 |url-status=dead |archive-url=https://web.archive.org/web/20110503081607/http://www.cancer.gov/ncicancerbulletin/041911/page2 |archive-date=2011-05-03 }}</ref>  In localized disease, based on long-term follow-up, [[Medicine:Prostatectomy|radical prostatectomy]] results in significantly improved oncological outcomes when compared with watchful waiting.<ref name=Vernooij2020>{{cite journal | vauthors = Vernooij RW, Lancee M, Cleves A, Dahm P, Bangma CH, Aben KK | title = Radical prostatectomy versus deferred treatment for localised prostate cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 6 | pages = CD006590 | date = June 2020 | pmid = 32495338 | pmc = 7270852 | doi = 10.1002/14651858.CD006590.pub3 }}</ref>  Prostatectomy is associated with increased rates of urinary incontinence and erectile dysfunction, but these findings are based primarily on men diagnosed before widespread PSA screening and cannot be highly generalized.<ref name=Vernooij2020/> When compared to [[Medicine:Active surveillance of prostate cancer|active monitoring/surveillance]], on follow-up at ten years, radical prostatectomy probably has similar outcomes for disease-specific survival and probably reduces risk of disease progression and spreading.<ref name=Vernooij2020/>  Urinary and sexual function are probably decreased in patients treated with radical prostatectomy.<ref name=Vernooij2020/>

===Active treatment===
Both surgical and nonsurgical treatments are available, but treatment can be difficult, and combinations can be used.<ref name="SartorLongo2018">{{cite journal | vauthors = Sartor O, de Bono JS | title = Metastatic Prostate Cancer | journal = The New England Journal of Medicine | volume = 378 | issue = 7 | pages = 645–657 | date = February 2018 | pmid = 29412780 | doi = 10.1056/NEJMra1701695 }}</ref> Treatment by [[Medicine:External beam radiotherapy|external beam radiation therapy]], [[Medicine:Prostate brachytherapy|brachytherapy]], [[Biology:Cryosurgery|cryosurgery]], HIFU -->, and prostatectomy are, in general, offered to men whose cancer remains within the prostate.<ref>{{Cite web |title=Prostate cancer - Diagnosis and treatment - Mayo Clinic |url=https://www.mayoclinic.org/diseases-conditions/prostate-cancer/diagnosis-treatment/drc-20353093 |access-date=2022-04-28 |website=www.mayoclinic.org |language=en}}</ref> Hormonal therapy and chemotherapy are often reserved for metastatic disease. Exceptions include local or metastasis-directed therapy with radiation may be used for advanced tumors with limited metastasis.<ref>{{cite journal | vauthors = Dhondt B, De Bleser E, Claeys T, Buelens S, Lumen N, Vandesompele J, Beckers A, Fonteyne V, Van der Eecken K, De Bruycker A, Paul J, Gramme P, Ost P | display-authors = 6 | title = Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time | journal = World Journal of Urology | volume = 37 | issue = 12 | pages = 2557–2564 | date = December 2019 | pmid = 30578441 | doi = 10.1007/s00345-018-2609-8 | s2cid = 58594673 }}</ref> Hormonal therapy is used for some early-stage tumors. [[Unsolved:Cryotherapy|Cryotherapy]] (the process of freezing the tumor), hormonal therapy, and chemotherapy may be offered if initial treatment fails and the cancer progresses.<ref>{{Cite web |title=Hormone Therapy for Breast Cancer {{!}} Breast Cancer Treatment |url=https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html |access-date=2022-04-28 |website=www.cancer.org |language=en}}</ref> [[Chemistry:Sipuleucel-T|Sipuleucel-T]], a [[Medicine:Cancer vaccine|cancer vaccine]], was reported to offer a four-month increase in survival in metastatic prostate cancer,<ref>{{cite journal | vauthors = Hammerstrom AE, Cauley DH, Atkinson BJ, Sharma P | title = Cancer immunotherapy: sipuleucel-T and beyond | journal = Pharmacotherapy | volume = 31 | issue = 8 | pages = 813–828 | date = August 2011 | pmid = 21923608 | pmc = 4159742 | doi = 10.1592/phco.31.8.813 }}</ref> but the marketing authorisation for it was withdrawn on 19 May 2015.

If radiation therapy fails, radical prostatectomy may be an option,<ref>{{cite web | title = Prostate Cancer: Radical Prostatectomy
 | publisher = WebMD | url = https://www.webmd.com/prostate-cancer/guide/prostate-cancer-radical-prostatectomy#1 | access-date = 10 May 2020}}</ref> though it is a technically challenging surgery.<ref>{{Cite web |title=Radical Prostatectomy for Prostate Cancer {{!}} Memorial Sloan Kettering Cancer Center |url=https://www.mskcc.org/cancer-care/types/prostate/treatment/radical-prostatectomy |access-date=2022-05-25 |website=www.mskcc.org |language=en}}</ref> However, radiation therapy ''after'' surgical failure may have many complications.<ref name="pmid16314889">{{cite journal | vauthors = Mouraviev V, Evans B, Polascik TJ | title = Salvage prostate cryoablation after primary interstitial brachytherapy failure: a feasible approach | journal = Prostate Cancer and Prostatic Diseases | volume = 9 | issue = 1 | pages = 99–101 | year = 2006 | pmid = 16314889 | doi = 10.1038/sj.pcan.4500853 | doi-access = free }}</ref> It is associated with a small increase in bladder and colon cancer.<ref>{{cite journal | vauthors = Wallis CJ, Mahar AL, Choo R, Herschorn S, Kodama RT, Shah PS, Danjoux C, Narod SA, Nam RK | display-authors = 6 | title = Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis | journal = BMJ | volume = 352 | pages = i851 | date = March 2016 | pmid = 26936410 | pmc = 4775870 | doi = 10.1136/bmj.i851 }}</ref> Radiotherapy and surgery appear to result in similar outcomes with respect to bowel, erectile and urinary function after five years.<ref>{{cite journal | vauthors = Wallis CJ, Glaser A, Hu JC, Huland H, Lawrentschuk N, Moon D, Murphy DG, Nguyen PL, Resnick MJ, Nam RK | display-authors = 6 | title = Survival and Complications Following Surgery and Radiation for Localized Prostate Cancer: An International Collaborative Review | journal = European Urology | volume = 73 | issue = 1 | pages = 11–20 | date = January 2018 | pmid = 28610779 | doi = 10.1016/j.eururo.2017.05.055 | url = http://eprints.whiterose.ac.uk/118323/1/EU%20Collab%20Review%20v9%20clean.pdf }}</ref>

==== Nonsurgical treatment ====
Non-surgical treatment may involve radiation therapy, chemotherapy, hormonal therapy, external beam radiation therapy, and [[Physics:Particle therapy|particle therapy]], high-intensity focused ultrasound, or some combination.<ref name="pmid19946787">{{cite journal | vauthors = Hong H, Zhang Y, Sun J, Cai W | title = Positron emission tomography imaging of prostate cancer | journal = Amino Acids | volume = 39 | issue = 1 | pages = 11–27 | date = June 2010 | pmid = 19946787 | pmc = 2883014 | doi = 10.1007/s00726-009-0394-9 }}</ref><ref name="pmid19945663">{{cite journal | vauthors = Peyromaure M, Valéri A, Rebillard X, Beuzeboc P, Richaud P, Soulié M, Salomon L | title = [Characteristics of prostate cancer in men less than 50-year-old] | language = fr | journal = Progres en Urologie | volume = 19 | issue = 11 | pages = 803–809 | date = December 2009 | pmid = 19945663 | doi = 10.1016/j.purol.2009.04.010 }}</ref>

Prostate cancer that persists when testosterone levels are lowered by hormonal therapy is called castrate-resistant prostate cancer (CRPC).<ref name="nci">{{cite web|url=https://www.cancer.gov/publications/dictionaries/cancer-terms/def/castrate-resistant-prostate-cancer|title=Castrate-resistant prostate cancer: In NCI Dictionary of Cancer Terms|date=2019|publisher=National Cancer Institute, US National Institutes of Health|access-date=17 September 2019}}</ref><ref name="ccs">{{cite web|url=https://www.cancer.ca/en/cancer-information/cancer-type/prostate/treatment/castrate-resistant-prostate-cancer/?region=on|title=Treatments for castrate-resistant prostate cancer|date=2019|publisher=Canadian Cancer Society|access-date=17 September 2019}}</ref> Many early-stage cancers need normal levels of testosterone to grow, but CRPC does not. Previously considered "hormone-refractory prostate cancer" or "androgen-independent prostate cancer", the term CRPC emerged because these cancers show reliance upon hormones, particularly testosterone, for [[Biology:Androgen receptor|androgen receptor]] activation.<ref>Tran K, McGill S. Treatment Sequences of Androgen Receptor–Targeted Agents for Prostate Cancer [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2021 March  Available from: https://www.ncbi.nlm.nih.gov/books/NBK571920/</ref><ref name="pmid20859283">{{cite journal | vauthors = Seruga B, Ocana A, Tannock IF | title = Drug resistance in metastatic castration-resistant prostate cancer | journal = Nature Reviews. Clinical Oncology | volume = 8 | issue = 1 | pages = 12–23 | date = January 2011 | pmid = 20859283 | doi = 10.1038/nrclinonc.2010.136 | s2cid = 24512148 }}</ref>

The cancer chemotherapeutic [[Chemistry:Docetaxel|docetaxel]] has been used as treatment for CRPC with a median survival benefit of 2 to 3 months.<ref>{{cite web|url=http://www.nice.org.uk/nicemedia/live/11577/33321/33321.pdf|title=Docetaxel for the Treatment of Hormone Refractory Prostate Cancer|year= 2005|url-status=dead|archive-url=https://web.archive.org/web/20120712170651/http://www.nice.org.uk/nicemedia/live/11577/33321/33321.pdf|archive-date=2012-07-12|vauthors=Clarke NW}}</ref><ref name="urlProstate cancer (hormone-refractory) - docetaxel">{{cite web|url=http://www.nice.org.uk/TA101|title=Prostate cancer (hormone-refractory) - docetaxel|date=2010-12-10|publisher=National Institute for Health and Clinical Excellence|url-status=dead|archive-url=https://web.archive.org/web/20120202194343/http://www.nice.org.uk/TA101|archive-date=2012-02-02|access-date=2011-07-04}}</ref> A second-line chemotherapy treatment is [[Chemistry:Cabazitaxel|cabazitaxel]].<ref name="pmid20888992">{{cite journal | vauthors = de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO | display-authors = 6 | title = Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial | journal = Lancet | volume = 376 | issue = 9747 | pages = 1147–1154 | date = October 2010 | pmid = 20888992 | doi = 10.1016/S0140-6736(10)61389-X | s2cid = 4791847 }}</ref> A combination of [[Chemistry:Bevacizumab|bevacizumab]], [[Chemistry:Docetaxel|docetaxel]], [[Chemistry:Thalidomide|thalidomide]] and [[Chemistry:Prednisone|prednisone]] appears effective in the treatment of CRPC.<ref>{{cite web|url=http://professional.cancerconsultants.com/oncology_main_news.aspx?id=44815|title=Avastin, Thalomid, Taxotere, and Prednisone Effective for Men with Hormone Refractory Prostate Cancer|date=March 2010|url-status=dead|archive-url=https://web.archive.org/web/20100615041037/http://professional.cancerconsultants.com/oncology_main_news.aspx?id=44815|archive-date=15 June 2010|access-date=10 May 2010}}</ref>

[[Medicine:Immunotherapy|Immunotherapy]] treatment with [[Chemistry:Sipuleucel-T|sipuleucel-T]] in CRPC appeared to increase survival by four months.<ref name="pmid20818862">{{cite journal | vauthors = Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF | display-authors = 6 | title = Sipuleucel-T immunotherapy for castration-resistant prostate cancer | journal = The New England Journal of Medicine | volume = 363 | issue = 5 | pages = 411–422 | date = July 2010 | pmid = 20818862 | doi = 10.1056/NEJMoa1001294 | s2cid = 12168204 }}</ref> However, marketing authorisation for sipuleucel-T was withdrawn on 19 May 2015. The second line hormonal therapy [[Chemistry:Abiraterone|abiraterone]] increases survival by about 4.6 months.<ref>{{cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm253055.htm|title=FDA approves Zytiga for late-stage prostate cancer|date=2011-04-28|publisher=U.S. Food and Drug Administration|url-status=live|archive-url=https://web.archive.org/web/20130922143109/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm253055.htm|archive-date=2013-09-22}}</ref> [[Chemistry:Enzalutamide|Enzalutamide]] is another second line hormonal agent with a five-month survival advantage. Both abiraterone and enzalutamide are currently in clinical trials in those with CRPC who have not previously received chemotherapy.<ref name="Xtandi-1">{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm317838.htm|title=FDA approves new treatment for a type of late stage prostate cancer|publisher=Food and Drug Administration|date=2012-08-31|url-status=dead|archive-url=https://web.archive.org/web/20131002031203/https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm317838.htm|archive-date=2013-10-02}}</ref><ref name="Xtandi-2">{{cite web|url=http://www.cancernetwork.com/prostate-cancer/content/article/10165/2099887|title=FDA Approves Enzalutamide (Xtandi) for Late-Stage Prostate Cancer| vauthors = Azvolinsky A |date=September 4, 2012|publisher=CancerNetwork|url-status=live|archive-url=https://web.archive.org/web/20120913055443/http://www.cancernetwork.com/prostate-cancer/content/article/10165/2099887|archive-date=September 13, 2012}}</ref>

Not all patients respond to androgen signaling-blocking drugs. Certain cells with characteristics resembling stem cells remain unaffected.<ref>{{cite journal | vauthors = Qin J, Liu X, Laffin B, Chen X, Choy G, Jeter CR, Calhoun-Davis T, Li H, Palapattu GS, Pang S, Lin K, Huang J, Ivanov I, Li W, Suraneni MV, Tang DG | display-authors = 6 | title = The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration | journal = Cell Stem Cell | volume = 10 | issue = 5 | pages = 556–569 | date = May 2012 | pmid = 22560078 | pmc = 3348510 | doi = 10.1016/j.stem.2012.03.009 }}</ref><ref>{{cite journal | vauthors = Maitland NJ, Collins AT | title = Prostate cancer stem cells: a new target for therapy | journal = Journal of Clinical Oncology | volume = 26 | issue = 17 | pages = 2862–2870 | date = June 2008 | pmid = 18539965 | doi = 10.1200/JCO.2007.15.1472 }}</ref> Therefore, the desire to improve CRPC outcomes resulted in increasing doses or combination therapy with synergistic androgen-signaling blocking agents.<ref>{{cite journal | vauthors = Attard G, Richards J, de Bono JS | title = New strategies in metastatic prostate cancer: targeting the androgen receptor signaling pathway | journal = Clinical Cancer Research | volume = 17 | issue = 7 | pages = 1649–1657 | date = April 2011 | pmid = 21372223 | pmc = 3513706 | doi = 10.1158/1078-0432.CCR-10-0567 }}</ref> But even these combination will not affect stem-like cells that do not exhibit androgen signaling.<ref name="Rane2012">{{cite journal | vauthors = Rane JK, Pellacani D, Maitland NJ | title = Advanced prostate cancer--a case for adjuvant differentiation therapy | journal = Nature Reviews. Urology | volume = 9 | issue = 10 | pages = 595–602 | date = October 2012 | pmid = 22890299 | doi = 10.1038/nrurol.2012.157 | s2cid = 43634798 }}</ref>

For patients with metastatic prostate cancer that has spread to their bones, doctors use a variety of bone-modifying agents to prevent skeletal complications and support the formation of new bone mass.<ref name=Jakob2020>{{cite journal | vauthors = Jakob T, Tesfamariam YM, Macherey S, Kuhr K, Adams A, Monsef I, Heidenreich A, Skoetz N | display-authors = 6 | title = Bisphosphonates or RANK-ligand-inhibitors for men with prostate cancer and bone metastases: a network meta-analysis | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 12 | pages = CD013020 | date = December 2020 | pmid = 33270906 | pmc = 8095056 | doi = 10.1002/14651858.CD013020.pub2 | collaboration = Cochrane Urology Group }}</ref> Zoledronic acid (a [[Chemistry:Bisphosphonate|bisphosphonate]]) and denosumab (a [[Biology:RANKL|RANK-ligand-inhibitor]]) appear to be effective agents, but are associated with more frequent and serious adverse events.<ref name= Jakob2020/>

==== Surgery ====
[[Medicine:Prostatectomy|Radical prostatectomy]] is considered the mainstay of surgical treatment of prostate cancer, where the surgeon removes the prostate, seminal vesicles, and surrounding [[Biology:Lymph node|lymph node]]s.<ref>{{Cite web |title=Radical prostatectomy: MedlinePlus Medical Encyclopedia |url=https://medlineplus.gov/ency/article/007300.htm |access-date=2022-04-28 |website=medlineplus.gov |language=en}}</ref> It can be done by an open technique (a skin incision at the lower abdomen), or [[Medicine:Laparoscopy|laparoscopically]]. Radical retropubic prostatectomy is the most commonly used open surgical technique.<ref>{{Cite journal | vauthors = Khera M, Miles BJ, Cornell RJ, Colen JS | veditors = Schwartz BF | journal = Medscape |date=2021-10-16 |title=Simple Prostatectomy: Overview, Preparation, Technique |url=https://emedicine.medscape.com/article/445996-overview}}</ref> [[Engineering:Robot-assisted surgery|Robotic-assisted]] prostatectomy has become common.<ref name=Cancer.org2>{{Cite web|url=https://www.cancer.org/cancer/prostate-cancer/treating/surgery.html|title=Surgery for Prostate Cancer|website=www.cancer.org|access-date=2020-03-30}}</ref> Men with localized prostate cancer, having [[Medicine:Laparoscopic radical prostatectomy|laparoscopic radical prostatectomy]] or robotic-assisted radical prostatectomy, might have shorter stays in the hospital and get fewer blood transfusions than men undergoing open radical prostatectomy.<ref name=Ilic2017>{{cite journal | vauthors = Ilic D, Evans SM, Allan CA, Jung JH, Murphy D, Frydenberg M | title = Laparoscopic and robotic-assisted versus open radical prostatectomy for the treatment of localised prostate cancer | journal = The Cochrane Database of Systematic Reviews | volume = 2017 | issue = 9 | pages = CD009625 | date = September 2017 | pmid = 28895658 | pmc = 6486168 | doi = 10.1002/14651858.cd009625.pub2 }}</ref> How these treatments compare with regard to overall survival or recurrence-free survival is unknown.<ref name=Ilic2017/>

Transurethral resection of the prostate <!-- (TURP) --> is the standard surgical treatment for [[Medicine:Benign prostatic hyperplasia|benign enlargement of the prostate]].<ref name=Cancer.org2/> In prostate cancer, this procedure can be used to relieve symptoms of [[Medicine:Urinary retention|urinary retention]] caused by a large prostate tumor, but it is not used to treat the cancer itself. The procedure is done under spinal anesthesia, a resectoscope is inserted inside the penis and the extra prostatic tissue is cut to clear the way for the urine to pass.<ref name="my.clevelandclinic.org"/>

==== Complications ====
The two main complications encountered after prostatectomy and prostate radiotherapy are [[Medicine:Erectile dysfunction|erectile dysfunction]] and [[Medicine:Urinary incontinence|urinary incontinence]], mainly stress-type. Most men regain continence within 6 to 12 months after the operation, so doctors usually wait at least one year before resorting to invasive treatments.<ref>{{Cite web|url=https://www.continence.org.au/pages/continence-management-following-prostate-surgery.html|title=Continence management following prostate surgery|website=Continence Foundation of Australia|url-status=dead|archive-url=https://web.archive.org/web/20200410155813/https://www.continence.org.au/pages/continence-management-following-prostate-surgery.html|archive-date=2020-04-10}}</ref>

Stress urinary incontinence usually happens after prostate surgery or radiation therapy due to factors that include damage to the urethral sphincter or surrounding tissue and nerves.<ref>{{Cite web |title=Prostate Cancer and Urinary Incontinence |url=https://www.webmd.com/urinary-incontinence-oab/mens-guide/urinary-incontinence |access-date=2022-04-28 |website=WebMD |language=en}}</ref> The prostate surrounds the urethra, a muscular tube that closes the urinary bladder.<ref>{{Cite web |title=Incontinence After Prostate Cancer Surgery |url=https://my.clevelandclinic.org/health/treatments/8096-prostate-cancer-urinary-incontinence-after-surgery |access-date=2022-04-28 |website=Cleveland Clinic}}</ref> Any of the mentioned reasons can lead to incompetent closure of the urethra and hence incontinence.<ref>{{cite journal | vauthors = Singla N, Singla AK | title = Post-prostatectomy incontinence: Etiology, evaluation, and management | journal = Turkish Journal of Urology | volume = 40 | issue = 1 | pages = 1–8 | date = March 2014 | pmid = 26328137 | pmc = 4548645 | doi = 10.5152/tud.2014.222014 }}</ref> Initial therapy includes bladder training, lifestyle changes, kegel exercises, and the use of incontinence pads. More invasive surgical treatment can include the insertion of a [[Medicine:Urethral sling|urethral sling]] or an [[Medicine:Artificial urinary sphincter|artificial urinary sphincter]], which is a mechanical device that mimics the function of the urethral sphincter, and is activated manually by the patient through a switch implanted in the scrotum.<ref>{{Cite journal | vauthors = Sajadi KP, Terris MK | veditors = Talavera F | journal = Medscape |date=2021-11-29 |title=Artificial Urinary Sphincter Placement: Practice Essentials, History of the Procedure, Problem |url=https://emedicine.medscape.com/article/443737-overview}}</ref> The latter is considered the gold standard in patients with moderate or severe stress urinary incontinence.<ref>{{Cite journal|date=2018|title=EAU Guidelines on Urinary Incontinence in Adults|url=https://uroweb.org/wp-content/uploads/EAU-Guidelines-on-Urinary-Incontinence-2018-large-text.pdf|journal=European Association of Urology|access-date=2020-04-01|archive-date=2020-02-08|archive-url=https://web.archive.org/web/20200208090241/https://uroweb.org/wp-content/uploads/EAU-Guidelines-on-Urinary-Incontinence-2018-large-text.pdf|url-status=dead}}</ref>

Erectile dysfunction happens in different degrees in nearly all men who undergo prostate cancer treatment, including radiotherapy or surgery; however, within one year, most of them will notice improvement. If nerves were damaged, this progress may not take place. Pharmacological treatment includes PDE-5 inhibitors such as [[Chemistry:Sildenafil|viagra]] or [[Chemistry:Tadalafil|cialis]], or injectable intracavernous drugs injected directly into the penis ([[Chemistry:Prostaglandin E1|prostaglandin E1]] and vasoactive drug mixtures). Other nonpharmacological therapy includes vacuum constriction devices and [[Medicine:Penile implant|penile implant]]s.<ref>{{Cite news|url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/prostate-cancer/erectile-dysfunction-after-prostate-cancer|title=Erectile Dysfunction After Prostate Cancer|website=www.hopkinsmedicine.org|date=19 November 2019 |language=en|access-date=2020-04-01}}</ref>

=== Psychological ===
Psychological interventions such as [[Medicine:Psychoeducation|psychoeducation]], cognitive behavioural therapy (CBT) and [[Philosophy:Mindfulness|mindfulness]] are recommended for the management of mental and emotional complications of disease symptoms and those associated with active treatment.<ref>{{cite journal | vauthors = Parahoo K, McDonough S, McCaughan E, Noyes J, Semple C, Halstead EJ, Neuberger MM, Dahm P | display-authors = 6 | title = Psychosocial interventions for men with prostate cancer | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD008529 | date = December 2013 | pmid = 24368598 | doi = 10.1002/14651858.CD008529.pub3 |  veditors = Parahoo K }}</ref><ref>{{cite journal | vauthors = Vartolomei L, Shariat SF, Vartolomei MD | title = Psychotherapeutic Interventions Targeting Prostate Cancer Patients: A Systematic Review of the Literature | journal = European Urology Oncology | volume = 1 | issue = 4 | pages = 283–291 | date = September 2018 | pmid = 31100249 | doi = 10.1016/j.euo.2018.04.011 | s2cid = 81502256 }}</ref> Due to limited research and inadequate methodological rigor of published literature, solid recommendations cannot be made on the effectiveness of mindfulness in men with prostate cancer.<ref name=Nnate2021>{{cite journal | vauthors = Nnate DA, Anyachukwu CC, Igwe SE, Abaraogu UO | title = Mindfulness-based interventions for psychological wellbeing and quality of life in men with prostate cancer: A systematic review and meta-analysis | journal = Psycho-Oncology | volume = 30 | issue = 10 | pages = 1680–1690 | date = October 2021 | pmid = 34139035 | doi = 10.1002/pon.5749 | s2cid = 235470939 | doi-access = free }}</ref>

==Prognosis==
Many prostate cancers are not destined to be lethal, and most men will ultimately not die as a result of the disease. Mortality varies widely across geography and other elements. In the United States, five-year survival rates range from 29% (distant metastases) to 100% (local or regional tumors).<ref name="SEER2017">{{cite web|title=Cancer of the Prostate - Cancer Stat Facts|url=https://seer.cancer.gov/statfacts/html/prost.html|website=seer.cancer.gov|access-date=11 April 2017|language=en|url-status=dead|archive-url=https://web.archive.org/web/20170318055053/https://seer.cancer.gov/statfacts/html/prost.html|archive-date=18 March 2017}}</ref> In Japan, the fatality rate rose to 8.6/100,000 in 2000.<ref name="pmid15714967">{{cite journal | vauthors = Wakai K | title = [Descriptive epidemiology of prostate cancer in Japan and Western countries] | language = ja | journal = Nihon Rinsho. Japanese Journal of Clinical Medicine | volume = 63 | issue = 2 | pages = 207–212 | date = February 2005 | pmid = 15714967 }}</ref> In {{wipe|India}} in the 1990s, half of those diagnosed with local cancer died within 19 years.<ref name="pmid1259345">{{cite journal | vauthors = Jaubert de Beaujeu M, Chavrier Y | title = [Deformations of the anterior thoracic wall (author's transl)] | language = fr | journal = Annales de Chirurgie Thoracique et Cardio-Vasculaire | volume = 15 | issue = 1 | pages = 1–6 | date = January 1976 | pmid = 1259345 }}</ref> One study reported that African-Americans have 50–60 times more deaths than found in Shanghai, China.<ref name="pmid10585584">{{cite journal | vauthors = Hsing AW, Tsao L, Devesa SS | title = International trends and patterns of prostate cancer incidence and mortality | journal = International Journal of Cancer | volume = 85 | issue = 1 | pages = 60–67 | date = January 2000 | pmid = 10585584 | doi = 10.1002/(SICI)1097-0215(20000101)85:1<60::AID-IJC11>3.0.CO;2-B | s2cid = 21911559 }}</ref> In Nigeria, 2% of men develop prostate cancer, and 64% of them are dead after 2 years.<ref name="pmid9120935">{{cite journal | vauthors = Osegbe DN | title = Prostate cancer in Nigerians: facts and nonfacts | journal = The Journal of Urology | volume = 157 | issue = 4 | pages = 1340–1343 | date = April 1997 | pmid = 9120935 | doi = 10.1016/S0022-5347(01)64966-8 }}</ref> Most Nigerian men present with metastatic disease with a typical survival of 40 months.<ref name="PMID28558685">{{cite journal | vauthors = Bello JO | title = Predictors of survival outcomes in native sub Saharan black men newly diagnosed with metastatic prostate cancer | journal = BMC Urology | volume = 17 | issue = 1 | pages = 39 | date = May 2017 | pmid = 28558685 | pmc = 5450414 | doi = 10.1186/s12894-017-0228-0 }}</ref>

In patients who undergo treatment, the most important clinical prognostic indicators of disease outcome are the stage, pretherapy PSA level, and Gleason score.<ref>{{cite book | vauthors = Nelson WG, Antonarakis ES, Carter HB, De Marzo AM, DeWeese TL | chapter = 81 - Prostate Cancer |date=2020-01-01  | title = Abeloff's Clinical Oncology | edition = Sixth |pages=1401–1432.e7 | veditors = Niederhuber JE, Armitage JO, Kastan MB, Doroshow JH |place=Philadelphia |publisher=Elsevier |language=en |isbn=978-0-323-47674-4 }}</ref> The higher the grade and the stage, the poorer the prognosis. [[Nomogram]]s can be used to calculate the estimated risk of the individual patient. The predictions are based on the experience of large groups of patients.<ref name="pmid14571407">{{cite journal | vauthors = Di Blasio CJ, Rhee AC, Cho D, Scardino PT, Kattan MW | title = Predicting clinical end points: treatment nomograms in prostate cancer | journal = Seminars in Oncology | volume = 30 | issue = 5 | pages = 567–586 | date = October 2003 | pmid = 14571407 | doi = 10.1016/S0093-7754(03)00351-8 }}</ref> A complicating factor is that the majority of patients have multiple independent tumor foci upon diagnosis, and these foci have independent genetic changes and molecular features.<ref name="pmid30181068">{{cite journal | vauthors = Løvf M, Zhao S, Axcrona U, Johannessen B, Bakken AC, Carm KT, Hoff AM, Myklebost O, Meza-Zepeda LA, Lie AK, Axcrona K, Lothe RA, Skotheim RI | display-authors = 6 | title = Multifocal Primary Prostate Cancer Exhibits High Degree of Genomic Heterogeneity | journal = European Urology | volume = 75 | issue = 3 | pages = 498–505 | date = March 2019 | pmid = 30181068 | doi = 10.1016/j.eururo.2018.08.009 | s2cid = 52156954 }}</ref> Because of this extensive inter-focal heterogeneity, it is a risk that the prognostication is set based on the wrong tumor focus.

An important aspect of decision making on the value of treatment is how to balance prognosis from prostate cancer with other causes of mortality and the morbidity of treatment. The PREDICT Prostate algorithm (https://prostate.predict.nhs.uk) is a multivariable prognostic model that provides individualised cancer-specific and overall long-term survival estimates in early stage non-metastatic PCa patients.<ref>{{cite journal | vauthors = Devos G, Joniau S | title = PREDICT Prostate, a useful tool in men with low- and intermediate-risk prostate cancer who are hesitant between conservative management and active treatment | journal = BMC Medicine | volume = 18 | issue = 1 | pages = 213 | date = July 2020 | pmid = 32669105 | pmc = 7364577 | doi = 10.1186/s12916-020-01681-z | s2cid = 220544109 }}</ref> In addition to the use of routinely available preoperative clinical-pathological variables such as PSA, biopsy Gleason score (ISUP grade group), and clinical T-stage, the PREDICT Prostate tool also includes the impact of patient characteristics (age and comorbidity status) and radical treatment (radical prostatectomy or radiotherapy) on survival. The tool provides patients with estimated survival rates after treatment in the context of absolute mortality rate, which allows patients to make an informed decision as to the value of treatment and its potential side effects. Thurtle et al.<ref>{{cite journal | vauthors = Thurtle D, Bratt O, Stattin P, Pharoah P, Gnanapragasam V | title = Comparative performance and external validation of the multivariable PREDICT Prostate tool for non-metastatic prostate cancer: a study in 69,206 men from Prostate Cancer data Base Sweden (PCBaSe) | journal = BMC Medicine | volume = 18 | issue = 1 | pages = 139 | date = June 2020 | pmid = 32539712 | pmc = 7296776 | doi = 10.1186/s12916-020-01606-w | s2cid = 219691220 }}</ref> performed an external validation of their previously published PREDICT Prostate model.<ref>{{cite journal | vauthors = Thurtle DR, Greenberg DC, Lee LS, Huang HH, Pharoah PD, Gnanapragasam VJ | title = Individual prognosis at diagnosis in nonmetastatic prostate cancer: Development and external validation of the PREDICT Prostate multivariable model | journal = PLOS Medicine | volume = 16 | issue = 3 | pages = e1002758 | date = March 2019 | pmid = 30860997 | pmc = 6413892 | doi = 10.1371/journal.pmed.1002758 }}</ref> The tool outperformed other widely used models and was proven to have high c-indices for all-cause and PCa-specific mortality, and the model calibration was good and remained accurate within the treatment subgroups. Recent work has also shown that it significantly alters clinician treatment recommendations and improves patients confidence in decision making and in their understanding of mortality risks from a new prostate cancer diagnosis <ref>{{cite journal | vauthors = Thurtle DR, Jenkins V, Pharoah PD, Gnanapragasam VJ | title = Understanding of prognosis in non-metastatic prostate cancer: a randomised comparative study of clinician estimates measured against the PREDICT prostate prognostic model | journal = British Journal of Cancer | volume = 121 | issue = 8 | pages = 715–718 | date = October 2019 | pmid = 31523057 | pmc = 6889281 | doi = 10.1038/s41416-019-0569-4 | s2cid = 202573988 }}</ref><ref>{{cite journal | vauthors = Thurtle D, Jenkins V, Freeman A, Pearson M, Recchia G, Tamer P, Leonard K, Pharoah P, Aning J, Madaan S, Goh C, Hilman S, McCracken S, Ilie PC, Lazarowicz H, Gnanapragasam V | display-authors = 6 | title = Clinical Impact of the Predict Prostate Risk Communication Tool in Men Newly Diagnosed with Nonmetastatic Prostate Cancer: A Multicentre Randomised Controlled Trial | journal = European Urology | volume = 80 | issue = 5 | pages = 661–669 | date = November 2021 | pmid = 34493413 | doi = 10.1016/j.eururo.2021.08.001 | s2cid = 237440530 | url = http://sro.sussex.ac.uk/id/eprint/101050/1/EurUrol_PredictRCT%20Accepted.pdf }}</ref> Predict Prostate is endorsed for use as a decision aid for prostate cancer by the UK National Institute for Health and Care Excellence <ref>{{cite web | url=https://www.nice.org.uk/guidance/ng131/resources/endorsed-resource-predict-prostate-6898604077 | title=Endorsed resource – Predict Prostate &#124; Prostate cancer: Diagnosis and management &#124; Guidance &#124; NICE }}</ref>

Androgen ablation therapy causes remission in 80–90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months. After remission, an androgen-independent phenotype typically emerges, wherein the median overall survival is 23–37 months from the time of initiation of androgen ablation therapy.<ref>{{cite journal | vauthors = Hellerstedt BA, Pienta KJ | title = The current state of hormonal therapy for prostate cancer | journal = CA | volume = 52 | issue = 3 | pages = 154–179 | year = 2002 | pmid = 12018929 | doi = 10.3322/canjclin.52.3.154 | s2cid = 25311034 | doi-access = free }}</ref> How androgen-independence is established and how it re-establishes progression is unclear.<ref>{{cite journal | vauthors = Feldman BJ, Feldman D | title = The development of androgen-independent prostate cancer | journal = Nature Reviews. Cancer | volume = 1 | issue = 1 | pages = 34–45 | date = October 2001 | pmid = 11900250 | doi = 10.1038/35094009 | s2cid = 205020623 }}</ref>

===Classification systems===
[[File:Prostate cancer with Gleason pattern 4 low mag.jpg|thumb|[[Micrograph|Micrograph]] of prostate adenocarcinoma, acinar type, the most common type of prostate cancer. Needle biopsy, H&E stain]]
Several tools are available to help predict outcomes, such as pathologic stage and recurrence after surgery or radiation therapy. Most combine stage, grade, and PSA level, and some include the number or percentage of biopsy cores positive, age, and/or other information.

*The D'Amico classification stratifies men by low, intermediate, or high risk based on stage, grade and PSA. It is used widely in clinical practice and research settings.<ref>{{cite journal | vauthors = Hernandez DJ, Nielsen ME, Han M, Partin AW | title = Contemporary evaluation of the D'amico risk classification of prostate cancer | journal = Urology | volume = 70 | issue = 5 | pages = 931–935 | date = November 2007 | pmid = 18068450 | doi = 10.1016/j.urology.2007.08.055 }}</ref> The major downside to the three-level system is that it does not account for multiple adverse parameters (e.g., high Gleason score ''and'' high PSA) in stratifying patients.
*The Partin tables<ref>{{cite journal | vauthors = Eifler JB, Feng Z, Lin BM, Partin MT, Humphreys EB, Han M, Epstein JI, Walsh PC, Trock BJ, Partin AW | display-authors = 6 | title = An updated prostate cancer staging nomogram (Partin tables) based on cases from 2006 to 2011 | journal = BJU International | volume = 111 | issue = 1 | pages = 22–29 | date = January 2013 | pmid = 22834909 | pmc = 3876476 | doi = 10.1111/j.1464-410X.2012.11324.x }}</ref> predict pathologic outcomes (margin status, extraprostatic extension, and seminal vesicle invasion) based on the same three variables and are published as lookup tables.
*The Kattan nomograms predict recurrence after surgery and/or radiation therapy, based on data available at the time of diagnosis or after surgery.<ref>{{Cite web |title=Prostate Cancer Nomograms {{!}} Memorial Sloan Kettering Cancer Center |url=https://www.mskcc.org/nomograms/prostate |access-date=2022-04-28 |website=www.mskcc.org |language=en}}</ref> The Kattan score represents the likelihood of remaining free of disease at a given time interval following treatment.
*The UCSF Cancer of the Prostate Risk Assessment (CAPRA) score predicts both pathologic status and recurrence after surgery. It offers accuracy comparable to the Kattan preoperative nomogram and can be calculated without tables or a calculator. Points are assigned based on PSA, grade, stage, age, and percentage of cores positive; the sum yields a 0–10 score, with every two points representing roughly a doubling of risk of recurrence. The CAPRA score was derived from community-based data in the CaPSURE database.<ref>{{Cite web|date=2006-09-27|title=CaPSURE.net Home Page|url=http://www.capsure.net/index.html|access-date=2020-08-08|archive-url=https://web.archive.org/web/20060927010510/http://www.capsure.net/index.html|archive-date=2006-09-27}}</ref> It has been validated among over 10,000 prostatectomy patients, including patients from CaPSURE;<ref>{{cite journal | vauthors = Cooperberg MR, Pasta DJ, Elkin EP, Litwin MS, Latini DM, Du Chane J, Carroll PR | title = The University of California, San Francisco Cancer of the Prostate Risk Assessment score: a straightforward and reliable preoperative predictor of disease recurrence after radical prostatectomy | journal = The Journal of Urology | volume = 173 | issue = 6 | pages = 1938–1942 | date = June 2005 | pmid = 15879786 | pmc = 2948569 | doi = 10.1097/01.ju.0000158155.33890.e7 }}</ref> the SEARCH registry, representing data from several Veterans Health Administration and military medical centers;<ref>{{cite journal | vauthors = Cooperberg MR, Freedland SJ, Pasta DJ, Elkin EP, Presti JC, Amling CL, Terris MK, Aronson WJ, Kane CJ, Carroll PR | display-authors = 6 | title = Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy | journal = Cancer | volume = 107 | issue = 10 | pages = 2384–2391 | date = November 2006 | pmid = 17039503 | doi = 10.1002/cncr.22262 | s2cid = 17420454 | doi-access = free }}</ref> a multi-institutional cohort in Germany;<ref>{{cite journal | vauthors = May M, Knoll N, Siegsmund M, Fahlenkamp D, Vogler H, Hoschke B, Gralla O | title = Validity of the CAPRA score to predict biochemical recurrence-free survival after radical prostatectomy. Results from a european multicenter survey of 1,296 patients | journal = The Journal of Urology | volume = 178 | issue = 5 | pages = 1957–62; discussion 1962 | date = November 2007 | pmid = 17868719 | doi = 10.1016/j.juro.2007.07.043 }}</ref> and the prostatectomy cohort at Johns Hopkins University.<ref>{{cite journal | vauthors = Zhao KH, Hernandez DJ, Han M, Humphreys EB, Mangold LA, Partin AW | title = External validation of University of California, San Francisco, Cancer of the Prostate Risk Assessment score | journal = Urology | volume = 72 | issue = 2 | pages = 396–400 | date = August 2008 | pmid = 18372031 | doi = 10.1016/j.urology.2007.11.165 }}</ref> More recently, it has been shown to predict metastasis and mortality following prostatectomy, radiation therapy, watchful waiting, or androgen deprivation therapy.<ref name="pmid19509351">{{cite journal | vauthors = Cooperberg MR, Broering JM, Carroll PR | title = Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis | journal = Journal of the National Cancer Institute | volume = 101 | issue = 12 | pages = 878–887 | date = June 2009 | pmid = 19509351 | pmc = 2697208 | doi = 10.1093/jnci/djp122 }}</ref>
* The UK National Institute for Health and Care Excellence guidelines recommends use of the Cambridge Prognostic Groups (CPG) 5-tier model when determining treatment options. The rationale for the change related to recent evidence, which suggests that 5-tier risk stratification model was better at predicting prostate cancer specific mortality than older 3-tier models <ref>{{cite journal | vauthors =  | title = New guidance regarding the diagnosis and risk stratification of patients with prostate cancer | journal = BJU International | volume = 129 | issue = 3 | pages = 304–305 | date = March 2022 | pmid = 35297163 | doi = 10.1111/bju.15703 | s2cid = 247475696 }}</ref> The CPG model has been tested and validated in studies including >80,000 men <ref>{{cite journal | vauthors = Gnanapragasam VJ, Lophatananon A, Wright KA, Muir KR, Gavin A, Greenberg DC | title = Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study | journal = PLOS Medicine | volume = 13 | issue = 8 | pages = e1002063 | date = August 2016 | pmid = 27483464 | pmc = 4970710 | doi = 10.1371/journal.pmed.1002063 }}</ref><ref>{{cite journal | vauthors = Gnanapragasam VJ, Bratt O, Muir K, Lee LS, Huang HH, Stattin P, Lophatananon A | title = The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study | journal = BMC Medicine | volume = 16 | issue = 1 | pages = 31 | date = February 2018 | pmid = 29490658 | pmc = 5831573 | doi = 10.1186/s12916-018-1019-5 | s2cid = 3649203 }}</ref><ref>{{cite journal | vauthors = Parry MG, Cowling TE, Sujenthiran A, Nossiter J, Berry B, Cathcart P, Aggarwal A, Payne H, van der Meulen J, Clarke NW, Gnanapragasam VJ | display-authors = 6 | title = Risk stratification for prostate cancer management: value of the Cambridge Prognostic Group classification for assessing treatment allocation | journal = BMC Medicine | volume = 18 | issue = 1 | pages = 114 | date = May 2020 | pmid = 32460859 | pmc = 7254634 | doi = 10.1186/s12916-020-01588-9 }}</ref> The NICE CPG model and treatment recommendations can be viewed at the NICE guideline website.<ref>{{cite web | url=https://www.nice.org.uk/guidance/ng131/chapter/Recommendations#localised-and-locally-advanced-prostate-cancer | title=Recommendations &#124; Prostate cancer: Diagnosis and management &#124; Guidance &#124; NICE }}</ref>

===Life expectancy===
Life expectancy projections are averages for an entire male population, and many medical and lifestyle factors modify these numbers.<ref>{{Cite web |title=Life expectancy increases by 5 years, but inequalities persist |url=https://www.who.int/news/item/19-05-2016-life-expectancy-increased-by-5-years-since-2000-but-health-inequalities-persist |access-date=2022-04-28 |website=www.who.int |language=en}}</ref> For example, studies have shown that a 40-year-old man will lose 3.1 years of life if he is overweight (BMI 25–29) and 5.8 years of life if he is obese (BMI 30 or more), compared to men of normal weight. If he is both overweight and a smoker, he will lose 6.7 years, and if obese and a smoker, he will lose 13.7 years.<ref>{{cite web|url=https://www.cdc.gov/nchs/fastats/prostate.htm|title=CDC FastStats|publisher=Centers for Disease Control|url-status=live|archive-url=https://web.archive.org/web/20170728022146/https://www.cdc.gov/nchs/fastats/prostate.htm|archive-date=2017-07-28}}</ref>

No evidence shows that either surgery or beam radiation has an advantage over the other in this regard. The lower death rates reported with surgery appear to occur because surgery is more likely to be offered to younger men with less severe cancers. Insufficient information is available to determine whether seed radiation extends life more readily than the other treatments, but data so far do not suggest that it does.<ref>{{cite web|url=http://www.cancer.gov/publications/patient-education/understanding-prostate-cancer-treatment|title=Treatment Choices for Men With Early-Stage Prostate Cancer|publisher=National Cancer Institute|url-status=live|archive-url=https://web.archive.org/web/20150404184205/http://www.cancer.gov/publications/patient-education/understanding-prostate-cancer-treatment|archive-date=2015-04-04|date=2014-10-17}}</ref>

Men with low-grade disease (Gleason 2–4) were unlikely to die of prostate cancer within 15 years of diagnosis.<ref>{{cite journal | vauthors = Ahmed HU, Arya M, Freeman A, Emberton M | title = Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy? | journal = The Lancet. Oncology | volume = 13 | issue = 11 | pages = e509–e517 | date = November 2012 | pmid = 23117005 | doi = 10.1016/S1470-2045(12)70388-1 | doi-access = free }}</ref> Older men (age 70–75) with low-grade disease had a roughly 20% overall survival at 15 years due to deaths from competing causes. Men with high-grade disease (Gleason 8–10) experienced high mortality within 15 years of diagnosis, regardless of their age.<ref>{{cite journal | vauthors = Eggener SE, Badani K, Barocas DA, Barrisford GW, Cheng JS, Chin AI, Corcoran A, Epstein JI, George AK, Gupta GN, Hayn MH, Kauffman EC, Lane B, Liss MA, Mirza M, Morgan TM, Moses K, Nepple KG, Preston MA, Rais-Bahrami S, Resnick MJ, Siddiqui MM, Silberstein J, Singer EA, Sonn GA, Sprenkle P, Stratton KL, Taylor J, Tomaszewski J, Tollefson M, Vickers A, White WM, Lowrance WT | display-authors = 6 | title = Gleason 6 Prostate Cancer: Translating Biology into Population Health | journal = The Journal of Urology | volume = 194 | issue = 3 | pages = 626–634 | date = September 2015 | pmid = 25849602 | pmc = 4551510 | doi = 10.1016/j.juro.2015.01.126 }}</ref>

==Epidemiology==
[[File:Prostate cancer world map - Death - WHO2004.svg|thumb|upright=1.3|[[Age adjustment|Age-standardized]] death from prostate cancer per 100,000&nbsp;inhabitants in 2004.<ref>{{cite web |url=https://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |title=WHO Disease and injury country estimates |year=2009 |work=World Health Organization |access-date=Nov 11, 2009 |url-status=live |archive-url=https://web.archive.org/web/20091111101009/http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html |archive-date=2009-11-11 }}</ref>{{refbegin|3}}
{{legend|#b3b3b3|no data}}
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{{legend|#cb0000|>44}}
{{refend}}]]
As of 2012, prostate cancer is the second-most frequently diagnosed cancer (at 15% of all male cancers)<ref>{{cite book |title = World Cancer Report 2014 |publisher = International Agency for Research on Cancer, World Health Organization |isbn = 978-92-832-0432-9}}</ref> and the sixth leading cause of cancer death in males worldwide.<ref>{{cite journal | vauthors = Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D | title = Global cancer statistics | journal = CA | volume = 61 | issue = 2 | pages = 69–90 | year = 2011 | pmid = 21296855 | doi = 10.3322/caac.20107 | s2cid = 30500384 | doi-access = free }}</ref> In 2010, prostate cancer resulted in 256,000 deaths, up from 156,000 deaths in 1990.<ref name=Loz2012>{{cite journal | vauthors = Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA | display-authors = 6 | title = Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 | journal = Lancet | volume = 380 | issue = 9859 | pages = 2095–2128 | date = December 2012 | pmid = 23245604 | doi = 10.1016/S0140-6736(12)61728-0 | hdl-access = free | s2cid = 1541253 | hdl = 10536/DRO/DU:30050819 | url = http://www.cobiss.si/scripts/cobiss?command=DISPLAY&base=cobib&rid=1537267652&fmt=11 }}</ref> Rates of prostate cancer vary widely. Rates vary widely between countries. It is least common in South and East Asia, and more common in Europe, North America, Australia, and New Zealand.<ref name="prostates.com.au">{{cite web|url=http://www.prostates.com.au/statistics/|title=Prostate Cancer Statistics|publisher=Laparoscopic Urology|access-date=19 June 2016|url-status=dead|archive-url=https://web.archive.org/web/20160624145341/http://www.prostates.com.au/statistics/|archive-date=24 June 2016}}</ref> Prostate cancer is least common among Asian men and most common among black men, with white men in between.<ref name="cancer.org">[http://www.cancer.org/docroot/CRI/content/CRI_2_2_2X_What_causes_prostate_cancer_36.asp?sitearea= Overview: Prostate Cancer – What Causes Prostate Cancer?] {{webarchive|url=https://web.archive.org/web/20060404065618/http://www.cancer.org/docroot/CRI/content/CRI_2_2_2X_What_causes_prostate_cancer_36.asp?sitearea= |date=2006-04-04 }} American Cancer Society (2 May 2006). Retrieved on 5 April 2007</ref><ref name="Prostate Cancer FAQs">[http://www.hsc.stonybrook.edu/som/urology/urology_cp_prostatecancer.cfm Prostate Cancer FAQs.] {{webarchive|url=https://web.archive.org/web/20060529193822/http://www.hsc.stonybrook.edu/som/urology/urology_cp_prostatecancer.cfm |date=2006-05-29 }} State University of New York School of Medicine Department of Urology (31 August 2006). Retrieved on 5 April 2007</ref>

The average annual incidence rate of prostate cancer between 1988 and 1992 among Chinese men in the United States was 15 times higher than that of their counterparts living in Shanghai and Tianjin,<ref name="cancer.org" /><ref name="Prostate Cancer FAQs" /><ref>{{cite journal | vauthors = Lee MM, Gomez SL, Chang JS, Wey M, Wang RT, Hsing AW | title = Soy and isoflavone consumption in relation to prostate cancer risk in China | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 12 | issue = 7 | pages = 665–668 | date = July 2003 | pmid = 12869409 }}</ref> but these high rates may be affected by higher rates of detection.<ref>{{cite journal | vauthors = Potosky AL, Miller BA, Albertsen PC, Kramer BS | title = The role of increasing detection in the rising incidence of prostate cancer | journal = JAMA | volume = 273 | issue = 7 | pages = 548–552 | date = February 1995 | pmid = 7530782 | doi = 10.1001/jama.273.7.548 }}</ref> Many suggest that prostate cancer may be under-reported, yet benign prostatic hyperplasia incidence in China and Japan is similar to rates in Western countries.<ref>Hanno P.M., Malcowicz S.B., Wein A.J., "Clinical Manual of Urology" McGraw Hill 2001</ref><ref>{{cite journal | vauthors = Homma Y, Kawabe K, Tsukamoto T, Yamanaka H, Okada K, Okajima E, Yoshida O, Kumazawa J, Gu FL, Lee C, Hsu TC, dela Cruz RC, Tantiwang A, Lim PH, Sheikh MA, Bapat SD, Marshall VR, Tajima K, Aso Y | display-authors = 6 | title = Epidemiologic survey of lower urinary tract symptoms in Asia and Australia using the international prostate symptom score | journal = International Journal of Urology | volume = 4 | issue = 1 | pages = 40–46 | date = January 1997 | pmid = 9179665 | doi = 10.1111/j.1442-2042.1997.tb00138.x | s2cid = 19636484 }}</ref>

More than 80% of men develop prostate cancer by age 80.<ref>{{cite book | vauthors = Bostwick DG, Eble JN |year=2007 |title=Urological Surgical Pathology |url=https://archive.org/details/urologicsurgical00fcap |url-access=limited |location=St. Louis |publisher=Mosby |page=[https://archive.org/details/urologicsurgical00fcap/page/n473 468] |isbn=978-0-323-01970-5}}</ref>

===United States===
 [[File:Longterm LineGraph Site 062 Sex 1.png|thumb|upright=1.3|New cases and deaths from prostate cancer in the United States per 100,000 males between 1975 and 2014]]
Prostate cancer is the third-leading cause of cancer death in men, exceeded by lung cancer and colorectal cancer. It accounts for 19% of all male cancers and 9% of male cancer-related deaths.<ref>{{cite journal | vauthors = Taitt HE | title = Global Trends and Prostate Cancer: A Review of Incidence, Detection, and Mortality as Influenced by Race, Ethnicity, and Geographic Location | journal = American Journal of Men's Health | volume = 12 | issue = 6 | pages = 1807–1823 | date = November 2018 | pmid = 30203706 | pmc = 6199451 | doi = 10.1177/1557988318798279 }}</ref>

Cases ranged from an estimated 230,000 in 2005<ref name="pmid15661684" /> to an estimated 164,690 In 2018.<ref>{{Cite web |title=Extensively drug-resistant Shigella sonnei infections - Europe |url=https://www.who.int/emergencies/disease-outbreak-news/item/extensively-drug-resistant-shigella-sonnei-infections---europe |access-date=2022-04-28 |website=www.who.int |language=en}}</ref>

Deaths held steady around 30,000 in 2005<ref name="pmid15661684">{{cite journal | vauthors = Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ | display-authors = 6 | title = Cancer statistics, 2005 | journal = CA | volume = 55 | issue = 1 | pages = 10–30 | year = 2005 | pmid = 15661684 | doi = 10.3322/canjclin.55.1.10 | s2cid = 22356919 | doi-access = free }}</ref> and 29,430 in 2018.

Age-adjusted incidence rates increased steadily from 1975 through 1992, with particularly dramatic increases associated with the spread of PSA screening in the late 1980s, later followed by a fall in incidence. A decline in early-stage incidence rates from 2011 to 2012 (19%) in men aged 50 years and older persisted through 2013 (6%).

Declines in mortality rates in certain jurisdictions may reflect the interaction of PSA screening and improved treatment.<ref>{{Citation |last=PDQ Screening and Prevention Editorial Board |title=Prostate Cancer Screening (PDQ®): Health Professional Version |date=2002 |url=http://www.ncbi.nlm.nih.gov/books/NBK65945/ |work=PDQ Cancer Information Summaries |place=Bethesda (MD) |publisher=National Cancer Institute (US) |pmid=26389383 |access-date=2022-05-25}}</ref> The estimated lifetime risk is about 14.0%, and the lifetime mortality risk is 2.6%.<ref>{{Cite web |title=Lifetime Risk of Developing or Dying From Cancer |url=https://www.cancer.org/healthy/cancer-causes/general-info/lifetime-probability-of-developing-or-dying-from-cancer.html |access-date=2022-05-25 |website=www.cancer.org |language=en}}</ref>

Between 2005 and 2011, the proportion of disease diagnosed at a locoregional stage was 93% for whites and 92% for African Americans;<ref name="Virnig 2009 160–168">{{cite journal | vauthors = Virnig BA, Baxter NN, Habermann EB, Feldman RD, Bradley CJ | title = A matter of race: early-versus late-stage cancer diagnosis | journal = Health Affairs | volume = 28 | issue = 1 | pages = 160–168 | date = 2009 | pmid = 19124866 | pmc = 2766845 | doi = 10.1377/hlthaff.28.1.160 }}</ref> the proportion of disease diagnosed at a late stage was 4% for European Americans and 5% for African Americans.<ref name="Virnig 2009 160–168"/>

Prostate cancer is more common in the African American population than the European American population.<ref name="WCR2014" /> An autopsy study of White and Asian men also found an increase in occult prostate cancer with age,<ref name="pmid25557753"/> reaching nearly 60% in men older than 80 years. More than 50% of cancers in Asian men and 25% of cancers in White men had a Gleason score of 7 or greater,<ref>{{cite journal | vauthors = Zlotta AR, Egawa S, Pushkar D, Govorov A, Kimura T, Kido M, Takahashi H, Kuk C, Kovylina M, Aldaoud N, Fleshner N, Finelli A, Klotz L, Sykes J, Lockwood G, van der Kwast TH | display-authors = 6 | title = Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian and Asian men | journal = Journal of the National Cancer Institute | volume = 105 | issue = 14 | pages = 1050–1058 | date = July 2013 | pmid = 23847245 | doi = 10.1093/jnci/djt151 }}</ref> suggesting that Gleason score may be an imprecise indicator of clinically insignificant cases.<ref>{{Cite book|chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK65945/|title=PDQ Cancer Information Summaries|last=PDQ Screening and Prevention Editorial Board|date=2002|publisher=National Cancer Institute (US)|location=Bethesda (MD)|pmid=26389383|chapter=Prostate Cancer Screening (PDQ®): Health Professional Version}}{{PD-notice}}</ref>

=== Canada ===
Prostate cancer is the third-leading type of cancer in Canadian men. In 2016, around 4,000 died and 21,600 men were diagnosed with prostate cancer.<ref name=Rendon2017>{{cite journal | vauthors = Rendon RA, Mason RJ, Marzouk K, Finelli A, Saad F, So A, Violette P, Breau RH | display-authors = 6 | title = Recommandations de l'Association des urologues du Canada sur le dépistage et le diagnostic précoce du cancer de la prostate | journal = Canadian Urological Association Journal = Journal de l'Association des Urologues du Canada | volume = 11 | issue = 10 | pages = 298–309 | date = October 2017 | pmid = 29381452 | pmc = 5659858 | doi = 10.5489/cuaj.4888 }}</ref>

===Europe===
In Europe in 2012, it was the third-most diagnosed cancer after breast and colorectal cancers at 417,000 cases.<ref>{{cite journal | vauthors = Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, Forman D, Bray F | display-authors = 6 | title = Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012 | journal = European Journal of Cancer | volume = 49 | issue = 6 | pages = 1374–1403 | date = April 2013 | pmid = 23485231 | doi = 10.1016/j.ejca.2012.12.027 | doi-access = free }}</ref>

In the United Kingdom, it is the second-most common cause of cancer death after lung cancer, where around 35,000 cases are diagnosed every year, of which around 10,000 are fatal.<ref>{{cite web|title=Prostate cancer statistics|url=http://www.cancerresearchuk.org/cancer-info/cancerstats/types/prostate/|website=Cancer Research UK|access-date=3 October 2014|url-status=live|archive-url=https://web.archive.org/web/20141006052815/http://www.cancerresearchuk.org/cancer-info/cancerstats/types/prostate/|archive-date=6 October 2014}}</ref>

==History==
The prostate was first described by Venetian anatomist Niccolò Massa in 1536, and illustrated by Flemish anatomist Andreas Vesalius in 1538.<ref name="Ghabili2016">{{cite journal | vauthors = Ghabili K, Tosoian JJ, Schaeffer EM, Pavlovich CP, Golzari SE, Khajir G, Andreas D, Benzon B, Vuica-Ross M, Ross AE | display-authors = 6 | title = The History of Prostate Cancer From Antiquity: Review of Paleopathological Studies | journal = Urology | volume = 97 | pages = 8–12 | date = November 2016 | pmid = 27591810 | doi = 10.1016/j.urology.2016.08.032 }}</ref> Prostate cancer was identified in 1853.<ref name="Nahon2011">{{cite journal | vauthors = Nahon I, Waddington G, Dorey G, Adams R | title = The history of urologic surgery: from reeds to robotics | journal = Urologic Nursing | volume = 31 | issue = 3 | pages = 173–180 | date = 2011 | pmid = 21805756 | doi = 10.7257/1053-816X.2011.31.3.173 }}</ref><ref>{{cite journal | vauthors = Adams J | title = The case of scirrhous of the prostate gland with corresponding affliction of the lymphatic glands in the lumbar region and in the pelvis | journal = Lancet | volume = 1 | issue = 1547 | pages = 393–94 | year = 1853 | doi = 10.1016/S0140-6736(02)68759-8 }}</ref> It was initially considered a rare disease, probably because of shorter [[Biology:Life expectancy|life expectancies]] and poorer detection methods in the 19th century. The first treatments were surgeries to relieve urinary obstruction.<ref>{{cite journal | vauthors = Lytton B | title = Prostate cancer: a brief history and the discovery of hormonal ablation treatment | journal = The Journal of Urology | volume = 165 | issue = 6 Pt 1 | pages = 1859–1862 | date = June 2001 | pmid = 11371867 | doi = 10.1016/S0022-5347(05)66228-3 }}</ref>

Removal of the gland was first described in 1851,<ref>{{cite book |author1=Samuel David Gross |title=A Practical Treatise On the Diseases and Injuries of the Urinary Bladder, the Prostate Gland, and the Urethra |url=https://archive.org/details/apracticaltreat06grosgoog |date=1851 |publisher=Blanchard and Lea |location=Philadelphia}}</ref> and radical perineal [[Medicine:Prostatectomy|prostatectomy]] was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital.<ref>{{cite journal | vauthors = Young HH | title = Four cases of radical prostatectomy | journal = Johns Hopkins Bull. | volume = 16 | year = 1905 }}</ref><ref name=Nahon2011 />

Surgical removal of the testes ([[Medicine:Orchiectomy|orchiectomy]]) to treat prostate cancer was first performed in the 1890s, with limited success.<ref>{{cite book | vauthors = Okoye E, Saikali SW | chapter = Orchiectomy |date=2022 | chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK562336/ | title = StatPearls |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32966007 |access-date=2022-04-28 }}</ref> Transurethral resection of the prostate (TURP) replaced radical prostatectomy for symptomatic relief of obstruction in the middle of the 20th century because it could better preserve penile erectile function. Radical retropubic prostatectomy was developed in 1983 by Patrick Walsh.<ref>{{cite journal | vauthors = Walsh PC, Lepor H, Eggleston JC | title = Radical prostatectomy with preservation of sexual function: anatomical and pathological considerations | journal = The Prostate | volume = 4 | issue = 5 | pages = 473–485 | year = 1983 | pmid = 6889192 | doi = 10.1002/pros.2990040506 | s2cid = 30740301 }}</ref> This surgical approach allowed for removal of the prostate and lymph nodes with maintenance of penile function.

In 1941, Charles B. Huggins published studies in which he used [[Biology:Estrogen|estrogen]] to oppose testosterone production in men with metastatic prostate cancer. This discovery of "chemical [[Medicine:Castration|castration]]" won Huggins the 1966 Nobel Prize in Physiology or Medicine.<ref>{{cite journal | vauthors = Huggins CB, Hodges CV | title = Studies on prostate cancer: 1. The effects of castration, of estrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate | journal = Cancer Res | volume = 1 | issue = 4 | pages = 293 | year = 1941 | url = http://cancerres.aacrjournals.org/content/1/4/293 | url-status = dead | archive-url = https://web.archive.org/web/20170630121943/http://cancerres.aacrjournals.org/content/1/4/293 | archive-date = 2017-06-30 | access-date = 2015-09-02 }}</ref> The role of the [[Biology:Gonadotropin-releasing hormone|gonadotropin-releasing hormone]] (GnRH) in reproduction was determined by Andrzej W. Schally and [[Biography:Roger Guillemin|Roger Guillemin]], who shared the 1977 Nobel Prize in Physiology or Medicine for this work. GnRH receptor agonists, such as [[Chemistry:Leuprorelin|leuprorelin]] and [[Chemistry:Goserelin|goserelin]], were subsequently developed and used to treat prostate cancer.<ref>{{cite journal | vauthors = Schally AV, Kastin AJ, Arimura A | title = Hypothalamic follicle-stimulating hormone (FSH) and luteinizing hormone (LH)-regulating hormone: structure, physiology, and clinical studies | journal = Fertility and Sterility | volume = 22 | issue = 11 | pages = 703–721 | date = November 1971 | pmid = 4941683 | doi = 10.1016/S0015-0282(16)38580-6 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Tolis G, Ackman D, Stellos A, Mehta A, Labrie F, Fazekas AT, Comaru-Schally AM, Schally AV | display-authors = 6 | title = Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 79 | issue = 5 | pages = 1658–1662 | date = March 1982 | pmid = 6461861 | pmc = 346035 | doi = 10.1073/pnas.79.5.1658 | doi-access = free | bibcode = 1982PNAS...79.1658T }}</ref>

[[Physics:Radiation therapy|Radiation therapy]] for prostate cancer was first developed in the early 20th century and initially consisted of intraprostatic [[Chemistry:Radium|radium]] implants. [[Medicine:External beam radiotherapy|External beam radiotherapy]] became more popular as stronger [X-ray] radiation sources became available in the middle of the 20th century. [[Medicine:Brachytherapy|Brachytherapy]] with implanted seeds (for prostate cancer) was first described in 1983.<ref>{{cite journal | vauthors = Denmeade SR, Isaacs JT | title = A history of prostate cancer treatment | journal = Nature Reviews. Cancer | volume = 2 | issue = 5 | pages = 389–396 | date = May 2002 | pmid = 12044015 | pmc = 4124639 | doi = 10.1038/nrc801 }}</ref>

Systemic [[Medicine:Chemotherapy|chemotherapy]] for prostate cancer was first studied in the 1970s. The initial regimen of [[Chemistry:Cyclophosphamide|cyclophosphamide]] and 5-fluorouracil was quickly joined by regimens using other systemic chemotherapy drugs.<ref>{{cite journal | vauthors = Scott WW, Johnson DE, Schmidt JE, Gibbons RP, Prout GR, Joiner JR, Saroff J, Murphy GP | display-authors = 6 | title = Chemotherapy of advanced prostatic carcinoma with cyclophosphamide or 5-fluorouracil: results of first national randomized study | journal = The Journal of Urology | volume = 114 | issue = 6 | pages = 909–911 | date = December 1975 | pmid = 1104900 | doi = 10.1016/S0022-5347(17)67172-6 }}</ref>

[[Chemistry:Enzalutamide|Enzalutamide]] gained FDA approval in 2012 for the treatment of castration-resistant prostate cancer (CRPC).<ref name="Xtandi-1" /><ref name="Xtandi-2" /> Alpharadin won FDA approval in 2013, under the priority review program.<ref>{{cite press release|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm352363.htm|title=FDA approves new drug for advanced prostate cancer|publisher=Food and Drug Administration|date=15 May 2013|url-status=dead|archive-url=https://web.archive.org/web/20130604012752/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm352363.htm|archive-date=4 June 2013}}</ref>

In 2006, a previously unknown retrovirus, Xenotropic MuLV-related virus (XMRV), was associated with human prostate tumors,<ref name="pmid16609730">{{cite journal | vauthors = Urisman A, Molinaro RJ, Fischer N, Plummer SJ, Casey G, Klein EA, Malathi K, Magi-Galluzzi C, Tubbs RR, Ganem D, Silverman RH, DeRisi JL | display-authors = 6 | title = Identification of a novel Gammaretrovirus in prostate tumors of patients homozygous for R462Q RNASEL variant | journal = PLOS Pathogens | volume = 2 | issue = 3 | pages = e25 | date = March 2006 | pmid = 16609730 | pmc = 1434790 | doi = 10.1371/journal.ppat.0020025 }} {{Retracted|doi=10.1371/annotation/7e2efc01-2e9b-4e9b-aef0-87ab0e4e4732|intentional=yes}}</ref> but ''PLOS Pathogens'' retracted the article in 2012.<ref name="pmid16609730" />

==Society and culture==
Men with prostate cancer generally encounter significant disparities in awareness, funding, media coverage, and research—and therefore, inferior treatment and poorer outcomes—compared to other cancers of equal prevalence.<ref name="Businessweek 2007-06-13">{{cite web | vauthors = Arnst C |url= http://www.businessweek.com/technology/content/jun2007/tc20070612_953676.htm |title=A Gender Gap in Cancer |publisher=Businessweek.com |date=2007-06-13 |access-date=2011-08-29 |url-status=live |archive-url=https://web.archive.org/web/20110806185800/http://www.businessweek.com/technology/content/jun2007/tc20070612_953676.htm |archive-date=2011-08-06 }}</ref> In 2001, ''{{wipe|The Guardian}}'' noted that Britain had 3,000 nurses specializing in [[Medicine:Breast cancer|breast cancer]], compared to a single nurse for prostate cancer.<ref>{{cite journal | vauthors = Bailey K | title = The nurse's role in promoting breast awareness | journal = Nursing Standard | volume = 14 | issue = 30 | pages = 34–36 | date = Apr 12–18, 2000 | pmid = 11973892 | doi = 10.7748/ns2000.04.14.30.34.c2811 }}</ref> Waiting time between referral and diagnosis was two weeks for breast cancer but three months for prostate cancer.<ref>{{cite news | url=https://www.theguardian.com/society/2001/oct/07/cancercare | location=London | work=The Guardian | vauthors = Browne A | title=Cancer bias puts breasts first | date=2001-10-07 | url-status=live | archive-url=https://web.archive.org/web/20161226194151/https://www.theguardian.com/society/2001/oct/07/cancercare | archive-date=2016-12-26 }}</ref>

A 2007 report by the U.S.-based National Prostate Cancer Coalition stated that prostate cancer drugs were outnumbered seven to one by breast cancer drugs.<ref>{{cite journal | vauthors = Fagerlund A, Cormio L, Palangi L, Lewin R, Santanelli di Pompeo F, Elander A, Selvaggi G | title = Gynecomastia in Patients with Prostate Cancer: A Systematic Review | journal = PLOS ONE | volume = 10 | issue = 8 | pages = e0136094 | date = 2015-08-26 | pmid = 26308532 | pmc = 4550398 | doi = 10.1371/journal.pone.0136094 | doi-access = free | bibcode = 2015PLoSO..1036094F }}</ref> ''The Times'' also noted an "anti-male bias in cancer funding" with a four-to-one discrepancy in the United Kingdom by both the government and by cancer charities such as Cancer Research UK.<ref name="Businessweek 2007-06-13" /><ref name="st16Oct2005">{{cite news | vauthors = Templeton SK |date=2005-10-16 |title=Men lose out in battle for cancer cash |url=http://www.timesonline.co.uk/tol/news/uk/article579050.ece |newspaper=Sunday Times |archive-url=https://web.archive.org/web/20110524065813/http://www.timesonline.co.uk/tol/news/uk/article579050.ece |archive-date=2011-05-24}}</ref> Critics cite such figures when claiming that women's health is favored over men's health.<ref>{{cite book|url=https://books.google.com/books?id=mRkqAAAAYAAJ&q=prostate |title = Does feminism discriminate against men? : a debate |year=2008 |access-date=2011-08-29|isbn=978-0-19-531283-6| vauthors = Farrell W, Sterba JP }}</ref>

Disparities extend into detection, with governments failing to fund or mandate prostate cancer screening while fully supporting breast cancer programs. For example, a 2007 report found 49 U.S. states mandate insurance coverage for routine breast cancer screening, compared to 28 for prostate cancer.<ref>{{cite web | work = National Prostate Cancer Coalition. | title = The Prostate Cancer Gap. A Crisis in Men's Health | url = http://www.zerocancer.org/site/DocServer/2007_Prostate_Cancer_Gap2.pdf?docID=681 }}{{Dead link|date=October 2022 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

Prostate cancer experiences significantly less media coverage than other, equally prevalent cancers, outcovered 2.6:1 by breast cancer.<ref name="Businessweek 2007-06-13" />

Prostate Cancer Awareness Month takes place in September in a number of countries. A light blue ribbon is used to promote the cause.<ref>{{cite web|access-date=2019-08-27|title=Men, don't wait until there's a problem to see a doctor|url=https://www.tampabay.com/news/health/men-dont-wait-until-theres-a-problem-to-see-a-doctor/2284568|date=7 July 2016|website=Tampa Bay Times}}</ref><ref>{{cite web| vauthors = Minium H |access-date=2019-08-27|title=Men need to hear the story of ODU coach Jeff Jones' recovery from prostate cancer|url=https://www.pilotonline.com/sports/college/old-dominion/article_49677cfc-0a25-5abf-b4a8-00d44b8cbbe5.html|website=The Virginian-Pilot}}</ref>

==Research==

=== Castration-resistant prostate cancer ===
''Castration-resitant prostate cancer'' is prostate cancer that progresses despite androgen depletion therapy.<ref>Saad F, Hotte SJ. Guidelines for the management of castrate-resistant prostate cancer. Can Urol Assoc J. 2010 Dec;4(6):380-4. doi: 10.5489/cuaj.10167. PMID 21191494; PMCID: PMC2997826.</ref>

[[Chemistry:Enzalutamide|Enzalutamide]] is a [[Biology:Nonsteroidal antiandrogen|nonsteroidal antiandrogen]] (NSAA).<ref name="Xtandi-1" /><ref name="Xtandi-2" /> It has been used with abiraterone in studies involving [[Biology:Whole genome sequencing|Whole genome sequencing]] that have shown how androgen receptors acquire resistance to them, which determines the use of new therapies against this pathology such as degraders of the protein or of the N-terminal domain of this receptor. This has been seen thanks to the sequencing of [[Biology:Circulating tumor DNA|circulating tumor DNA]] in patients.<ref name=Herberts2022>{{Cite journal |last1=Herberts |first1=Cameron |last2=Annala |first2=Matti |last3=Sipola |first3=Joonatan |last4=Ng |first4=Sarah W. S. |last5=Chen |first5=Xinyi E. |last6=Nurminen |first6=Anssi |last7=Korhonen |first7=Olga V. |last8=Munzur |first8=Aslı D. |last9=Beja |first9=Kevin |last10=Schönlau |first10=Elena |last11=Bernales |first11=Cecily Q. |last12=Ritch |first12=Elie |last13=Bacon |first13=Jack V. W. |last14=Lack |first14=Nathan A. |last15=Nykter |first15=Matti |date= August 2022 |title=Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer |url=https://www.nature.com/articles/s41586-022-04975-9 |journal=Nature |language=en |volume=608 |issue=7921 |pages=199–208 |doi=10.1038/s41586-022-04975-9 |pmid=35859180 |s2cid=250730778 |issn=1476-4687}}</ref>

Alpharadin uses bone targeted [[Chemistry:Radium-223|Radium-223]] isotopes to kill cancer cells by alpha radiation.<ref>{{cite press release |url= http://algeta.com/xml_press_underside.asp?xml=http://cws.huginonline.com/A/134655/PR/201106/1521246.xml&m=34572&s=34686&ss=&d=2011-06-06 |title= Positive Outcome of Interim Analysis of pivotal Alpharadin study: Primary endpoint met in Phase III ALSYMPCA study |date= 2011-06-06 |publisher= Algeta ASA |access-date= 2011-07-04 |url-status= usurped |archive-url= https://web.archive.org/web/20110811081805/http://algeta.com/xml_press_underside.asp?xml=http%3A%2F%2Fcws.huginonline.com%2FA%2F134655%2FPR%2F201106%2F1521246.xml&m=34572&s=34686&ss=&d=2011-06-06 |archive-date= 2011-08-11 }}</ref> {{ums|date=November 2017}}

PARP inhibitor [[Chemistry:Olaparib|olaparib]] is an approved breast/ovarian cancer drug that is undergoing clinical trials.<ref name=PCWG3-Geet>{{cite journal | vauthors = Geethakumari PR, Cookson MS, Kelly WK | title = The Evolving Biology of Castration-Resistant Prostate Cancer: Review of Recommendations From the Prostate Cancer Clinical Trials Working Group 3 | journal = Oncology | volume = 30 | issue = 2 | pages = 187–95, 199 | date = February 2016 | pmid = 26888794 | url = http://www.cancernetwork.com/oncology-journal/evolving-biology-castration-resistant-prostate-cancer-review-recommendations-PCWG3 | url-status = live | archive-url = https://web.archive.org/web/20160222235842/http://www.cancernetwork.com/oncology-journal/evolving-biology-castration-resistant-prostate-cancer-review-recommendations-PCWG3 | archive-date = 22 February 2016 }}</ref> Also in trials for CRPC are : [[Biology:Checkpoint inhibitor|checkpoint inhibitor]] [[Chemistry:Ipilimumab|ipilimumab]], CYP17 inhibitor [[Chemistry:Galeterone|galeterone]] (TOK-001), and [[Medicine:Immunotherapy|immunotherapy]] PROSTVAC.<ref name=PCWG3-Geet/>

All medications for CRPC block [[Biology:Androgen receptor|androgen receptor]] (AR) signaling via direct or indirect targeting of the AR [[Biology:Nuclear receptor|ligand binding domain]] (LBD). AR belongs to the steroid [[Biology:Nuclear receptor|nuclear receptor]] family.<ref name="Elshan2019"/> Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important for disease progression.<ref>{{cite journal | vauthors = Suzuki H, Ueda T, Ichikawa T, Ito H | title = Androgen receptor involvement in the progression of prostate cancer | journal = Endocrine-Related Cancer | volume = 10 | issue = 2 | pages = 209–216 | date = June 2003 | pmid = 12790784 | doi = 10.1677/erc.0.0100209 | doi-access = free }}</ref> Molecules that could successfully target alternative domains have emerged.<ref name=Elshan2019>{{cite journal | vauthors = Elshan NG, Rettig MB, Jung ME | title = Molecules targeting the androgen receptor (AR) signaling axis beyond the AR-Ligand binding domain | journal = Medicinal Research Reviews | volume = 39 | issue = 3 | pages = 910–960 | date = May 2019 | pmid = 30565725 | pmc = 6608750 | doi = 10.1002/med.21548 }}</ref> Such therapies could provide an advantage; particularly in treating prostate cancers that are resistant to current therapies.<ref name=Elshan2019 />

==== Evolution ====
Sequencing techniques, in addition to reflecting the mechanisms of resistance to treatment, through the [[Biology:Circulating tumor DNA|circulating tumor DNA]], distinguish between the evolutionary history of this cancer when it metastasizes and the temporal subclonal dynamics, determining how the tumor is found when it is diagnosed.<ref name=Herberts2022 />

===Pre-clinical===
[[Biology:Arachidonate 5-lipoxygenase|Arachidonate 5-lipoxygenase]] has been identified as playing a significant role in the survival of prostate cancer cells.<ref name="Primary source cited in 1st review" /><ref name="MEDRS review 1" /><ref name="MEDRS review 2" /> Medications that target this enzyme are undergoing development.<ref name="Primary source cited in 1st review">{{cite journal | vauthors = Ghosh J, Myers CE | title = Inhibition of arachidonate 5-lipoxygenase triggers massive apoptosis in human prostate cancer cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 22 | pages = 13182–13187 | date = October 1998 | pmid = 9789062 | pmc = 23752 | doi = 10.1073/pnas.95.22.13182 | quote = Inhibition of 5-lipoxygenase by MK886 completely blocks 5-HETE production and induces massive apoptosis in both hormone-responsive (LNCaP) and -nonresponsive (PC3) human prostate cancer cells. This cell death is very rapid | doi-access = free | bibcode = 1998PNAS...9513182G }}</ref><ref name="MEDRS review 1">{{cite journal | vauthors = Greene ER, Huang S, Serhan CN, Panigrahy D | title = Regulation of inflammation in cancer by eicosanoids | journal = Prostaglandins & Other Lipid Mediators | volume = 96 | issue = 1–4 | pages = 27–36 | date = November 2011 | pmid = 21864702 | pmc = 4051344 | doi = 10.1016/j.prostaglandins.2011.08.004 | quote = The 5-lipoxygenase (5-LOX) pathway is implicated in the development and progression of human cancers. 5-LOX, whose crystal structure was recently identified (118), is a key enzyme in metabolizing arachidonic acid to leukotrienes. 5-LOX can be induced by proinflammatory stimuli and is expressed in epithelial cancers including lung, prostate, breast, and colon (113). Hence, 5-LOX inhibitors have been targeted for their chemopreventive effects. Inhibition of 5-LOX activity is shown to block prostate cancer cell proliferation as well as carcinogen-induced lung tumorigenesis (119, 120).&nbsp;... Both 5-HETE and 12-HETE are also products of lipoxygenase and are involved in tumor progression (12). Exogenous 5-HETE can stimulate the proliferation of prostate cancer cells and act as a survival factor (137, 138). These results require relatively high concentrations (at a concentration of 10 μM). Blocking the formation of 5-HETE, by inhibiting 5-lipoxygenase, results in massive apoptosis of human prostate cancer cells (139). }}</ref><ref name="MEDRS review 2">{{cite journal | vauthors = Bishayee K, Khuda-Bukhsh AR | title = 5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy | journal = Acta Biochimica et Biophysica Sinica | volume = 45 | issue = 9 | pages = 709–719 | date = September 2013 | pmid = 23752617 | doi = 10.1093/abbs/gmt064 | quote = Recent studies demonstrated the involvement of growth factors, such as epidermal growth factor (EGF) and neurotensin in the 5-LOX-mediated tumor progression in prostate cancer [22,23]. Recent studies with 5-LOX siRNA [10] and specific blocker of 5-LOX [24] revealed the relation of this gene with the tumor cell proliferation.&nbsp;... Meclofenamate sodium (MS) is known for its anti-inflammatory activity, and apart from this, Boctor et al. [37] reported that it caused reduction in the formation of 5-HETE in human leucocytes when used. MS can thus be considered a dual inhibitor of 5-LOX and COX pathways of arachidonic acid cascade. Further investigation with this substance revealed that it could interfere with the LT receptors in the lung carcinoma [38]. In a recent study, a group of scientists have shown the effect of MS on prostate cancer cells both in vitro and in vivo [39], and their result suggests a profound reduction in the tumor growth and cancer metastasis.&nbsp;... While the commonly used inhibitors produced strong cytotoxicity, notably, zileuton, the only commercialized 5-LOX inhibitor, failed to induce an anti-proliferative or cytotoxic response in all other types of tumor cells where 5-LOX was in inactive state (e.g. HeLa cells).  But where 5-LOX was in active state, zileuton could effectively inhibit progression, as in case of prostate cancer. | doi-access = free }}</ref> In particular, arachidonate 5-lipoxygenase inhibitors produce massive, rapid programmed cell death in prostate cancer cells.<ref name="Primary source cited in 1st review" /><ref name="MEDRS review 1" /><ref name="MEDRS review 2" />

[[Biology:Galectin-3|Galectin-3]] is another potential target.<ref name=Martínez-Bosch2019>{{cite journal | vauthors = Martínez-Bosch N, Rodriguez-Vida A, Juanpere N, Lloreta J, Rovira A, Albanell J, Bellmunt J, Navarro P | display-authors = 6 | title = Galectins in prostate and bladder cancer: tumorigenic roles and clinical opportunities | journal = Nature Reviews. Urology | volume = 16 | issue = 7 | pages = 433–445 | date = July 2019 | pmid = 31015643 | doi = 10.1038/s41585-019-0183-5 | hdl-access = free | s2cid = 128360958 | hdl = 10261/201560 }}</ref> Aberrant glycan profiles have been described in prostate cancer,<ref>{{cite journal | vauthors = Munkley J, Mills IG, Elliott DJ | title = The role of glycans in the development and progression of prostate cancer | journal = Nature Reviews. Urology | volume = 13 | issue = 6 | pages = 324–333 | date = June 2016 | pmid = 27091662 | doi = 10.1038/nrurol.2016.65 | s2cid = 25916024 | url = https://eprint.ncl.ac.uk/fulltext.aspx?url=219656/13FDD2AE-20DB-42AD-A50E-911D4F1FAD05.pdf&pub_id=219656 }}</ref><ref>{{cite book |vauthors=Drake RR, Jones EE, Powers TW, Nyalwidhe JO |chapter=Altered glycosylation in prostate cancer |veditors=Drake RR, Ball LE |title=Glycosylation and Cancer |volume=126 |pages=345–82 |date=2015 |pmid=25727153 |doi=10.1016/bs.acr.2014.12.001 |isbn=9780128013816 |series=Advances in Cancer Research Vol. 126}}</ref> and studies have found specific links between the galectin signature and prostate cancer.<ref>{{cite journal | vauthors = Laderach DJ, Gentilini LD, Giribaldi L, Delgado VC, Nugnes L, Croci DO, Al Nakouzi N, Sacca P, Casas G, Mazza O, Shipp MA, Vazquez E, Chauchereau A, Kutok JL, Rodig SJ, Elola MT, Compagno D, Rabinovich GA | display-authors = 6 | title = A unique galectin signature in human prostate cancer progression suggests galectin-1 as a key target for treatment of advanced disease | journal = Cancer Research | volume = 73 | issue = 1 | pages = 86–96 | date = January 2013 | pmid = 23108139 | doi = 10.1158/0008-5472.CAN-12-1260 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Compagno D, Gentilini LD, Jaworski FM, Pérez IG, Contrufo G, Laderach DJ | title = Glycans and galectins in prostate cancer biology, angiogenesis and metastasis | journal = Glycobiology | volume = 24 | issue = 10 | pages = 899–906 | date = October 2014 | pmid = 24939371 | doi = 10.1093/glycob/cwu055 | doi-access = free }}</ref>

The [[Biology:PIM1|PIM kinase]] family is another potential target for selective inhibition. A number of related drugs are under development. It has been suggested the most promising approach may be to co-target this family with other pathways including PI3K.<ref name="Luszczak 2020 7"/>

===Cancer models===
Scientists have established prostate cancer cell lines to investigate disease progression. [[Biology:LNCaP|LNCaP]], PC-3 ([[Biology:PC3|PC3]]), and DU-145 ([[Biology:DU145|DU145]]) are commonly used prostate cancer cell lines.<ref>{{cite journal | vauthors = Alimirah F, Chen J, Basrawala Z, Xin H, Choubey D | title = DU-145 and PC-3 human prostate cancer cell lines express androgen receptor: implications for the androgen receptor functions and regulation | journal = FEBS Letters | volume = 580 | issue = 9 | pages = 2294–2300 | date = April 2006 | pmid = 16580667 | doi = 10.1016/j.febslet.2006.03.041 | s2cid = 21777101 }}</ref> The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express AR, but PC-3 and DU-145 cells express very little or no AR.{{citation needed|date=December 2022}}

The proliferation of LNCaP cells is [[Biology:Androgen|androgen]]-dependent but the proliferation of PC-3 and DU-145 cells is [[Biology:Androgen|androgen]]-insensitive. Elevation of AR expression is often observed in advanced prostate tumors in patients.<ref>{{cite journal | vauthors = Linja MJ, Savinainen KJ, Saramäki OR, Tammela TL, Vessella RL, Visakorpi T | title = Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer | journal = Cancer Research | volume = 61 | issue = 9 | pages = 3550–3555 | date = May 2001 | pmid = 11325816 | url = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11325816 }}</ref><ref>{{cite journal | vauthors = Ford OH, Gregory CW, Kim D, Smitherman AB, Mohler JL | title = Androgen receptor gene amplification and protein expression in recurrent prostate cancer | journal = The Journal of Urology | volume = 170 | issue = 5 | pages = 1817–1821 | date = November 2003 | pmid = 14532783 | doi = 10.1097/01.ju.0000091873.09677.f4 }}</ref> Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These [[Biology:Androgen|androgen]]-independent LNCaP cells have elevated [[Biology:Androgen receptor|AR]] expression and express prostate specific antigen upon androgen treatment. Paradoxically, androgens inhibit the proliferation of these androgen-independent prostate [[Medicine:Cancer|cancer]] cells.<ref>{{cite journal | vauthors = Kokontis J, Takakura K, Hay N, Liao S | title = Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation | journal = Cancer Research | volume = 54 | issue = 6 | pages = 1566–1573 | date = March 1994 | pmid = 7511045 | url = http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7511045 }}</ref><ref>{{cite journal | vauthors = Umekita Y, Hiipakka RA, Kokontis JM, Liao S | title = Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 21 | pages = 11802–11807 | date = October 1996 | pmid = 8876218 | pmc = 38139 | doi = 10.1073/pnas.93.21.11802 | doi-access = free | bibcode = 1996PNAS...9311802U }}</ref><ref>{{cite journal | vauthors = Kokontis JM, Hsu S, Chuu CP, Dang M, Fukuchi J, Hiipakka RA, Liao S | title = Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity | journal = The Prostate | volume = 65 | issue = 4 | pages = 287–298 | date = December 2005 | pmid = 16015608 | doi = 10.1002/pros.20285 | s2cid = 22349673 }}</ref>

===Diagnosis===
One active research area and non-clinically applied investigations involves non-invasive methods of tumor detection.<ref>{{Cite web |title=Tumor Detection - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/computer-science/tumor-detection |access-date=2022-04-29 |website=www.sciencedirect.com}}</ref> A molecular test that detects the presence of cell-associated [[Biology:PCA3|PCA3]] mRNA in fluid obtained from the prostate and first-void urine sample is under investigation. PCA3 mRNA is expressed almost exclusively by prostate cells and has been shown to be highly over-expressed in prostate cancer cells. The test result is currently reported as a specimen ratio of PCA3 mRNA to PSA mRNA.<ref>{{Cite web |title=PCA3 - an overview {{!}} ScienceDirect Topics |url=https://www.sciencedirect.com/topics/medicine-and-dentistry/pca3 |access-date=2022-04-29 |website=www.sciencedirect.com}}</ref>

The PCA3 test attempts to help decide whether, in men suspected of having prostate cancer (especially if an initial biopsy fails to explain the elevated serum PSA), a biopsy/rebiopsy is needed. The higher the expression of PCA3 in the sample, the greater the likelihood of a positive biopsy.<ref name="pmid21176272">{{cite journal | vauthors = Bourdoumis A, Papatsoris AG, Chrisofos M, Efstathiou E, Skolarikos A, Deliveliotis C | title = The novel prostate cancer antigen 3 (PCA3) biomarker | journal = International Braz J Urol | volume = 36 | issue = 6 | pages = 665–8; discussion 669 | year = 2010 | pmid = 21176272 | doi = 10.1590/S1677-55382010000600003 | doi-access = free }}</ref> The CDC's Evaluation of Genomic Applications in Practice and Prevention Working Group discourages clinical use.<ref>{{Cite web|date=2018-11-19|title=Does PCA3 Testing for the Diagnosis and Management of Prostate Cancer improve patient health outcomes|url=https://www.cdc.gov/egappreviews/recommendations/PCA3.html|access-date=2020-08-09|website=www.cdc.gov|language=en-us}}</ref>

== See also ==
*Prostate Cancer Foundation
*[[Medicine:Testicular cancer|Testicular cancer]]

== References ==
{{Reflist}}

== External links ==
{{Medical resources
|  ICD10          = {{ICD10|C|61||c|60}} 
|  ICD9           = {{ICD9|185}} 
|  ICDO           =
|  OMIM           = 176807
|  DiseasesDB     = 10780
|  MedlinePlus    = 000380
|  eMedicineSubj  = radio
|  eMedicineTopic = 574
|  MeshID         = D011471 
}}
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*[https://web.archive.org/web/20160922192529/http://patients.uroweb.org/i-am-a-urology-patient/prostate-cancer/ Patient-centered information from the European Urological Association]
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{{DEFAULTSORT:Prostate Cancer}}
[[Category:Histopathology]]
[[Category:Wikipedia medicine articles ready to translate]]

{{Sourceattribution|Prostate cancer|1}}