View source for Medicine:Active surveillance of low-risk papillary thyroid microcarcinoma

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'''Active surveillance''' is an [[Observation|observation]]al [[Social:Management|management]] being increasingly accepted as an alternative over immediate [[Medicine:Surgery|surgery]] due to low-risk papillary thyroid microcarcinoma with no evidence of extension or [[Medicine:Metastasis|metastatic]] spread. Patients on active surveillance are observed with periodical [[Physics:Ultrasound|ultrasound]] examinations and [[Chemistry:Thyroid function tests|thyroid function tests]]. If disease progression is detected, patients are treated with [[Medicine:Surgery|surgery]]. The chances of [[Medicine:Thyroid cancer|thyroid cancer]] increased during the past 3 decades in many countries, mostly due to increased detection of small papillary thyroid carcinoma, without associated increase in mortality from thyroid cancer.

Therefore, researchers declared a warning of increased [[Medicine:Overdiagnosis|overdiagnosis]] and overtreatment for thyroid cancer. [https://aot.amegroups.org/article/view/3736 Akira Miyauchi] proposed active surveillance management in 1993,<ref name="40: 516-522, 2016">[https://pubmed.ncbi.nlm.nih.gov/26744340/ Miyauchi A: Clinical Trials of Active Surveillance of Papillary Microcarcinoma of the Thyroid. World J Surg 40: 516-522, 2016]</ref> when he was an associate professor of Department of Surgery, Kagawa Medical University (now Kagawa University Faculty of Medicine) and a registered doctor at Kuma Hospital (Kobe, Hyogo Prefecture, {{wipe|Japan}}).

== History ==
The incidence of thyroid cancer has rapidly increased since the 1980s. However, most of them are microcarcinoma, which are small papillary [[Medicine:Carcinoma|carcinoma]]s that has a diameter of 1&nbsp;[[Centimetre|centimeter]] or smaller.<ref>{{Cite journal |last=Dideban |first=Shiva |last2=Abdollahi |first2=Alireza |last3=Meysamie |first3=Alipasha |last4=Sedghi |first4=Shokouh |last5=Shahriari |first5=Mona |date=2016 |title=Thyroid Papillary Microcarcinoma: Etiology, Clinical Manifestations,Diagnosis, Follow-up, Histopathology and Prognosis |url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749190/ |journal=Iranian Journal of Pathology |volume=11 |issue=1 |pages=1–19 |issn=1735-5303 |pmc=4749190 |pmid=26870138}}</ref> Although thyroid cancer increased, mortality from thyroid cancer remained stable. Therefore, some researchers started warning of overdiagnosis and overtreatment of small papillary thyroid carcinoma.<ref name="295:2164-7, 2006">[https://pubmed.ncbi.nlm.nih.gov/16684987/ Davies L, Welch HG: Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA. 295:2164-7, 2006]</ref> The cause of this phenomenon is the widespread adoption of [[Medicine:Medical imaging|imaging]] modalities, such as ultrasonography, [[CT scan]], [[Physics:Magnetic resonance imaging|MRI]], and fine-needle aspiration cytology (FNAC). With these technologies, detection and diagnosis of small cancers became possible, which were previously not possible.

Many [[Medicine:Autopsy|autopsy]] reports on subjects who had died of non-thyroid [[Disease|disease]]s reported high incidences of small thyroid cancers, tagged as “latent thyroid cancers.” The incidence of latent thyroid cancers 3&nbsp;mm or larger is reported to be 3% to 6%. Most are of papillary carcinoma type. Papillary thyroid carcinoma 3&nbsp;mm or lager can be detected, and easily diagnosed using ultrasound-guided FNAC. A screening study for thyroid cancer on Japanese adult women using ultrasonography and [[Physics:Ultrasound|ultrasound]] guided FNAC reported 3.5% of the subjects having small thyroid cancer.<ref>Takebe K, Date M, Yamamoto Y, Ogino T, Takeuchi Y: Mass screening for thyroid cancer with ultrasonography. Karkinos 7:309-317, 1994 (In Japanese)</ref> This incidence was almost consistent with that of latent cancer at autopsies and was more than 1000 times the prevalence of clinical thyroid cancer in Japanese women being reported at the time.

Considering all these facts, Akira Miyauchi&nbsp;proposed the following hypothesis: “Most papillary microcarcinomas stay small and harmless. It will not be too late to perform surgery only for those that show marginal progression during observational management. Performing surgery for all microcarcinoma may result in more harm than good.”<ref name="40: 516-522, 2016"/> With due consideration, he proposed an observational management [[Engineering:Clinical trial|clinical trial]] at the Medical Meeting of Kuma Hospital. His proposal was approved and the study for low-risk papillary microcarcinoma began in the same year. The management was termed active surveillance. In 1995, a similar trial was begun at Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR) in Tokyo, Japan.

Active surveillance was conducted for 1,235 patients at Kuma Hospital for an average period of 5 years and 409 patients at Cancer Institute Hospital of JFCR for an average period of 6.8 years. The results of the trials in these institutes were [[Medicine:Cancer|cancer]] growth by 3 mm or more in 10 years in 7% to 8% of the patients and [[Medicine:Metastasis|metastasis]] to cervical lymph node in 1% to 4% of the patients.<ref name="31:183-192, 2021.">[https://pubmed.ncbi.nlm.nih.gov/33023426/ Sugitani I, Ito Y, Takeuchi D, Nakayama H, Masaki C, Shindo H, Teshima M, Horiguchi K, Yoshida Y, Kanai T, Hirokawa M, Hames KY, Tabei I, Miyauchi A: Indications and strategy for active surveillance of adult low-risk papillary thyroid microcarcinoma: consensus statements from the Japan Association of Endocrine Surgery task force on management for papillary thyroid microcarcinoma. Thyroid 31:183-192, 2021.]</ref> There were no patients who developed distant metastasis, or died of thyroid cancer. None of those who underwent conversion surgery had recurrence of the disease. Active surveillance was performed in the {{wipe|United States}}, {{wipe|South Korea}}, Italy and Colombia. Through these surveillance managements, a small number of patients had disease progression, while the majority of the patients had stable disease, as observed in Japan.<ref name="31:183-192, 2021."/>

Even after [[Medicine:Surgery|surgery]] on patients with low-risk papillary thyroid microcarcinoma by well-experienced thyroid surgeons, complications such as temporary vocal cord paralysis, permanent vocal cord paralysis, temporary [[Medicine:Hypoparathyroidism|hypoparathyroidism]], permanent hypoparathyroidism&nbsp;developed with the incidence of 4.1%, 0.2%, 16.7% and 1.6%, respectively.<ref name="40: 516-522, 2016"/> The incidences of such unfavorable events was significantly higher in the group of immediate surgery than in the group of active surveillance. Also, the proportions of patients requiring [[Biology:Thyroid hormones|thyroid hormone]] medications and those having scars due to thyroid surgery was significantly higher in the group of immediate surgery than the group of active surveillance. In addition, the 10-year medical care costs for the patients undergoing immediate surgery was 4.1 times the costs for those who chose active surveillance.<ref name="40: 516-522, 2016"/>

One may have an opinion that watching the progress without surgery may cause psychological concerns such as [[Medicine:Anxiety|anxiety]] in the patients. Davie L. et al. conducted a questionnaire survey on patients under active surveillance at Kuma Hospital,<ref>Davies L, Roman BR, Fukushima M, Ito Y, Miyauchi A.: Patient Experience of Thyroid Cancer Active Surveillance in Japan. JAMA Otolaryngol Head Neck Surg 145: 363-370, 2019 {{doi|10.1001/jamaoto.2018.4131}}</ref> and reported that 37% of the patients sometimes had cancer concerns, but 60% of them said such anxiety diminished over time. Very importantly, 83% of the patients responded that choosing active surveillance was their best choice. The comparison between the immediate surgery group and the active surveillance group showed that the immediate surgery group had a higher rate of physical problems such as discomfort in their voice or the [[Medicine:Neck|cervical region]]. Regarding psychological aspects such as anxiety about cancer, either there was no difference between both groups, or marginally higher in the immediate surgery group.<ref>Yoshida Y, Horiuchi&nbsp; K, Okamoto T&nbsp; Patients' View on the Management of Papillary Thyroid Microcarcinoma: Active Surveillance or Surgery Thyroid 30: 681-687, 2020. {{PMID|31910100}}</ref><ref>Kong SH, et al. Longitudinal Assessment of Quality of Life According to Treatment Options in Low-Risk Papillary Thyroid Microcarcinoma Patients: Active Surveillance or Immediate Surgery (Interim Analysis of MAeSTro). Thyroid 29: 1089-1096, 2019. {{doi|10.1089/thy.2018.0624}}</ref><ref>Nakamura T, Miyauchi A, Ito Y, Ito M, Kudo T, Tanaka M, Kohsaka K, Kasahara T, Nishihara E, Fukata S, Nishikawa M: Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery. Endocrine Prctice 16:1451-1457, 2020. {{PMID|33471737}}</ref>
These results may be due to factors that worried patients opted for surgery.

Based on favorable results of the active surveillance conducted by Kuma Hospital and Cancer Institute Hospital of JFCR, active surveillance was acknowledged as one of the management strategies in Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules in 2010<ref name="31:183-192, 2021." /> on the premise that thorough explanation was given to the patient and consent was obtained. In 2015, active surveillance for low-risk papillary thyroid microcarcinoma was also adopted in American Thyroid Association's Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer.<ref name="26(1):1-133, 2016">[https://pubmed.ncbi.nlm.nih.gov/26462967/ Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L.: 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer Thyroid. 26(1):1-133, 2016]</ref>&nbsp;Medical Guidelines for Clinical Practice for the Diagnosis and Management of Thyroid Nodules in 2018 (published by Japan Association of Endocrine Surgeons and the Japanese Society of Thyroid Surgery), actively recommends active surveillance for low-risk papillary thyroid microcarcinoma.<ref name="31:183-192, 2021."/>

Generally, the [[Medicine:Prognosis|prognosis]] of clinical papillary thyroid cancer in patients aged 55 years or older is poorer than in younger patients. However, quite strangely, in papillary microcarcinoma, patients 40 years or younger are more likely to have [[Medicine:Neoplasm|tumor]] growth and [[Biology:Lymph node|lymph node]] metastases than patients aged 41 to 60 years, or 61 or older.<ref>Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A.: Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid. 24:27-34, 2014 {{PMID|24001104}}</ref> However, as already stated above by us; the prognosis of papillary thyroid cancer is good in young patients. Thus, marginal disease progression in young patients will not lead to a serious condition. Curiously, the tumors shrank in 17% of the patient during active surveillance.<ref>Miyauchi A, Kudo T, Ito Y, Oda H, Yamamoto M, Sasai H, Higashiyama T, Masuoka H, Fukushima M, Kihara M, Miya A.: Natural history of papillary thyroid microcarcinoma: Kinetic analyses on tumor volume during active surveillance and before presentation. Surgery 165: 25-30, 2019. {{doi|10.1016/j.surg.2018.07.045}}</ref>

== Indication ==
Active Surveillance is indicated for low-risk thyroid microcarcinoma<ref>{{Cite web |title=Microcarcinomas of the Thyroid Gland |url=https://www.thyroid.org/microcarcinomas-thyroid-gland/ |access-date=2023-12-30 |website=American Thyroid Association |language=en-US}}</ref> 10&nbsp;mm or smaller in maximum diameter. However, surgery is recommended as a high-risk thyroid microcarcinoma in the following cases.<ref name="40: 516-522, 2016"/><ref name="31:183-192, 2021."/>

* Presence of [[Biology:Lymph node|lymph node]] [[Medicine:Metastasis|metastasis]] or distant metastasis (very rare).
* Invasion into the [[Medicine:Recurrent laryngeal nerve|recurrent laryngeal nerve]] or the [[Biology:Trachea|trachea]].
* The tumor is located along the course of the recurrent laryngeal nerve.
* The tumor is widely adherent to the trachea.
* Diagnosis of aggressive subtype of papillary thyroid carcinoma on cytology (very rare).
* The patient is a minor (There is no data on active surveillance in minors).

== Method ==
During the examination, tumor growth, appearance of any new lesions, and lymph node metastases should be checked, and if there are such findings, surgery should be recommended.<ref name="31:183-192, 2021."/>

== References ==
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[[Category:Cancer treatments]]

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