Endocrinology and Metabolism

Review Article

Thyroid
Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines: Min Joo Kim, Jae Hoon Moon, Eun Kyung Lee, Young Shin Song, Kyong Yeun Jung, Ji Ye Lee, Ji-hoon Kim, Kyungsik Kim, Sue K. Park, Young Joo Park; Endocrinol Metab. 2024;39(1):47-60. Published online February 15, 2024; DOI: https://doi.org/10.3803/EnM.2024.1937

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The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Citations

Citations to this article as recorded by

2023 Update of the Korean Thyroid Association Guidelines for the Management of Thyroid Nodules
Eun Kyung Lee, Young Joo Park
Clinical Thyroidology®.2024; 36(4): 153. CrossRef
Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study
Jiyun Park, Jin-Hyung Jung, Hyunju Park, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyungdo Han, Kyung-Soo Kim
BMC Medicine.2024;[Epub] CrossRef
Prediction of Recurrent Laryngeal Nerve Invasion in Thyroid Cancer by Ultrasound
Jin Hyang Jung, Eunji Kim, Byung Ju Kang
Journal of Surgical Ultrasound.2024; 11(1): 18. CrossRef
Advances in clinical research on ultrasound-guided radiofrequency ablation for papillary thyroid microcarcinoma
Hua Xu, Jin-yan Yang, Xing Zhao, Zhe Ma
Frontiers in Oncology.2024;[Epub] CrossRef
Systemic therapy for differentiated thyroid cancer with distant metastasis
Eun Kyung Lee
Journal of the Korean Medical Association.2024; 67(7): 484. CrossRef

Original Articles

Thyroid
Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review: Jee Hee Yoon, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2024;39(1):152-163. Published online January 22, 2024; DOI: https://doi.org/10.3803/EnM.2023.1794

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Background
Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).
Methods
Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.
Results
In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%–10.8% and 16.0%–25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%–1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.
Conclusion
AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

Citations

Citations to this article as recorded by

It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Kyeong Jin Kim
Endocrinology and Metabolism.2024; 39(1): 95. CrossRef
Thyroid Nodules: Past, Present, and Future
Alan A. Parsa, Hossein Gharib
Endocrine Practice.2024;[Epub] CrossRef

Clinical Study
Protocol for a Korean Multicenter Prospective Cohort Study of Active Surveillance or Surgery (KoMPASS) in Papillary Thyroid Microcarcinoma: Min Ji Jeon, Yea Eun Kang, Jae Hoon Moon, Dong Jun Lim, Chang Yoon Lee, Yong Sang Lee, Sun Wook Kim, Min-Hee Kim, Bo Hyun Kim, Ho-Cheol Kang, Minho Shong, Sun Wook Cho, Won Bae Kim; Endocrinol Metab. 2021;36(2):359-364. Published online March 23, 2021; DOI: https://doi.org/10.3803/EnM.2020.890; Correction in: Endocrinol Metab 2022;37(1):181

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Background
A Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) for papillary thyroid microcarcinomas (PTMCs) has been initiated. The aim is to compare clinical outcomes between active surveillance (AS) and an immediate lobectomy for low-risk PTMCs. We here outline the detailed protocol for this study.
Methods
Adult patients with a cytopathologically confirmed PTMC sized 6.0 to 10.0 mm by ultrasound (US) will be included. Patients will be excluded if they have a suspicious extra-thyroidal extension or metastasis of a PTMC or multiple thyroid nodules or other thyroid diseases which require a total thyroidectomy. Printed material describing the prognosis of PTMCs, and the pros and cons of each management option, will be provided to eligible patients to select their preferred intervention. For the AS group, thyroid US, thyroid function, and quality of life (QoL) parameters will be monitored every 6 months during the first year, and then annually thereafter. Disease progression will be defined as a ≥3 mm increase in maximal diameter of a PTMC, or the development of new thyroid cancers or metastases. If progression is detected, patients should undergo appropriate surgery. For the lobectomy group, a lobectomy with prophylactic central neck dissection will be done within 6 months. After initial surgery, thyroid US, thyroid function, serum thyroglobulin (Tg), anti-Tg antibody, and QoL parameters will be monitored every 6 months during the first year and annually thereafter. Disease progression will be defined in these cases as the development of new thyroid cancers or metastases.
Conclusion
KoMPASS findings will help to confirm the role of AS, and develop individualized management strategies, for low-risk PTMCs.

Citations

Citations to this article as recorded by

Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines
Min Joo Kim, Jae Hoon Moon, Eun Kyung Lee, Young Shin Song, Kyong Yeun Jung, Ji Ye Lee, Ji-hoon Kim, Kyungsik Kim, Sue K. Park, Young Joo Park
Endocrinology and Metabolism.2024; 39(1): 47. CrossRef
It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
Kyeong Jin Kim
Endocrinology and Metabolism.2024; 39(1): 95. CrossRef
Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review
Jee Hee Yoon, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang
Endocrinology and Metabolism.2024; 39(1): 152. CrossRef
Active Surveillance for Low-Risk Papillary Thyroid Carcinoma as an Acceptable Management Option with Additional Benefits: A Comprehensive Systematic Review
Jee Hee Yoon, Wonsuk Choi, Ji Yong Park, A Ram Hong, Hee Kyung Kim, Ho-Cheol Kang
Endocrinology and Metabolism.2024; 39(1): 152. CrossRef
Thyroid‐Stimulating Hormone, Age, and Tumor Size are Risk Factors for Progression During Active Surveillance of Low‐Risk Papillary Thyroid Microcarcinoma in Adults
Yasuhiro Ito, Akira Miyauchi, Makoto Fujishima, Takuya Noda, Tsutomu Sano, Takahiro Sasaki, Taketoshi Kishi, Tomohiko Nakamura
World Journal of Surgery.2023; 47(2): 392. CrossRef
Thyroid FNA cytology: The Eastern versus Western perspectives
Mitsuyoshi Hirokawa, Manon Auger, Chan Kwon Jung, Fabiano Mesquita Callegari
Cancer Cytopathology.2023; 131(7): 415. CrossRef
To Screen or Not to Screen?
Do Joon Park
Endocrinology and Metabolism.2023; 38(1): 69. CrossRef
Lower Thyroid Cancer Mortality in Patients Detected by Screening: A Meta-Analysis
Shinje Moon, Young Shin Song, Kyong Yeun Jung, Eun Kyung Lee, Young Joo Park
Endocrinology and Metabolism.2023; 38(1): 93. CrossRef
Long-Term Outcomes of Active Surveillance and Immediate Surgery for Adult Patients with Low-Risk Papillary Thyroid Microcarcinoma: 30-Year Experience
Akira Miyauchi, Yasuhiro Ito, Makoto Fujishima, Akihiro Miya, Naoyoshi Onoda, Minoru Kihara, Takuya Higashiyama, Hiroo Masuoka, Shiori Kawano, Takahiro Sasaki, Mitsushige Nishikawa, Shuji Fukata, Takashi Akamizu, Mitsuru Ito, Eijun Nishihara, Mako Hisakad
Thyroid®.2023; 33(7): 817. CrossRef
Active Surveillance Outcomes of Patients with Low-Risk Papillary Thyroid Microcarcinoma According to Levothyroxine Treatment Status
Masashi Yamamoto, Akira Miyauchi, Yasuhiro Ito, Makoto Fujishima, Takahiro Sasaki, Takumi Kudo
Thyroid®.2023; 33(10): 1182. CrossRef
Cost-Effectiveness of Active Surveillance Compared to Early Surgery of Small Papillary Thyroid Cancer: A Retrospective Study on a Korean Population
Han-Sang Baek, Jeonghoon Ha, Kwangsoon Kim, Jaseong Bae, Jeong Soo Kim, Sungju Kim, Dong-Jun Lim, Chulmin Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef
Optimal Cutoff Values of the Contact Angle of Tumor on Sonography System for Predicting Extrathyroidal Extension of Papillary Thyroid Carcinoma by Tumor Location
Ik Beom Shin, Do Hoon Koo, Dong Sik Bae
Clinical Medicine Insights: Oncology.2023;[Epub] CrossRef
Thermal Ablation for Papillary Thyroid Microcarcinoma Located in The Isthmus: a Study With 3 Years Of Follow-Up
Lin Zheng, Fang-yi Liu, Jie Yu, Zhi-gang Cheng, Xiao-ling Yu, Xiao-cong Dong, Zhi-yu Han, Ping Liang
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Trends in the Management of Localized Papillary Thyroid Carcinoma in the United States (2000–2018)
Elisa Pasqual, Julie Ann Sosa, Yingxi Chen, Sara J. Schonfeld, Amy Berrington de González, Cari M. Kitahara
Thyroid.2022; 32(4): 397. CrossRef
Management of Low-Risk Thyroid Cancers: Is Active Surveillance a Valid Option? A Systematic Review of the Literature
Renato Patrone, Nunzio Velotti, Stefania Masone, Alessandra Conzo, Luigi Flagiello, Chiara Cacciatore, Marco Filardo, Vincenza Granata, Francesco Izzo, Domenico Testa, Stefano Avenia, Alessandro Sanguinetti, Andrea Polistena, Giovanni Conzo
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Cost-Effectiveness Analysis of Active Surveillance Compared to Early Surgery in Small Papillary Thyroid Cancer: A Systemic Review
Han-sang Baek, Chai-ho Jeong, Jeonghoon Ha, Ja-Seong Bae, Jeong-soo Kim, Dong-Jun Lim, Chul-Min Kim
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Active Surveillance as an Effective Management Option for Low-Risk Papillary Thyroid Microcarcinoma
Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Won Bae Kim
Endocrinology and Metabolism.2021; 36(4): 717. CrossRef

Thyroid
Study Protocol of Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro): Jae Hoon Moon, Ji-hoon Kim, Eun Kyung Lee, Kyu Eun Lee, Sung Hye Kong, Yeo Koon Kim, Woo-jin Jung, Chang Yoon Lee, Roh-Eul Yoo, Yul Hwangbo, Young Shin Song, Min Joo Kim, Sun Wook Cho, Su-jin Kim, Eun Jae Jung, June Young Choi, Chang Hwan Ryu, You Jin Lee, Jeong Hun Hah, Yuh-Seog Jung, Junsun Ryu, Yunji Hwang, Sue K. Park, Ho Kyung Sung, Ka Hee Yi, Do Joon Park, Young Joo Park; Endocrinol Metab. 2018;33(2):278-286. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.278

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Background

The ongoing Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) aims to observe the natural course of papillary thyroid microcarcinoma (PTMC), develop a protocol for active surveillance (AS), and compare the long-term prognosis, quality of life, and medical costs between the AS and immediate surgery groups.

Methods

This multicenter prospective cohort study of PTMC started in June 2016. The inclusion criteria were suspicious of malignancy or malignancy based on fine needle aspiration or core needle biopsy, age of ≥18 years, and a maximum diameter of ≤1 cm. If there was no major organ involvement, no lymph node/distant metastasis, and no variants with poor prognosis, the patients were explained of the pros and cons of immediate surgery and AS before selecting AS or immediate surgery. Follow-up visits (physical examination, ultrasonography, thyroid function, and questionnaires) are scheduled every 6 months during the first 2 years, and then every 1 year thereafter. Progression was defined as a maximum diameter increase of ≥3, ≥2 mm in two dimensions, suspected organ involvement, or lymph node/distant metastasis.

Results

Among 439 enrolled patients, 290 patients (66.1%) chose AS and 149 patients (33.9%) chose immediate surgery. The median follow-up was 6.7 months (range, 0.2 to 11.9). The immediate surgery group had a larger maximum tumor diameter, compared to the AS group (7.1±1.9 mm vs. 6.6±2.0 mm, respectively; P=0.014).

Conclusion

The results will be useful for developing an appropriate PTMC treatment policy based on its natural course and risk factors for progression.

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Review Articles

Thyroid
Management of Low-Risk Papillary Thyroid Cancer: Nicole M. Iñiguez-Ariza, Juan P. Brito; Endocrinol Metab. 2018;33(2):185-194. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.185

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The incidence of thyroid cancer has increased, mainly due to the incidental finding of low-risk papillary thyroid cancers (PTC). These malignancies grow slowly, and are unlikely to cause morbidity and mortality. New understanding about the prognosis of tumor features has led to reclassification of many tumors within the low-risk thyroid category, and to the development of a new one “very low-risk tumors.” Alternative less aggressive approaches to therapy are now available including active surveillance and minimally invasive interventions. In this narrative review, we have summarized the available evidence for the management of low-risk PTC.

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Active Surveillance of Papillary Thyroid Microcarcinoma: A Mini-Review from Korea: Tae Yong Kim, Young Kee Shong; Endocrinol Metab. 2017;32(4):399-406. Published online December 14, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.4.399

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Abstract PDF PubReader

In Korea, the incidence of thyroid cancer increased explosively in the early 2000s, and reached a plateau in the early 2010s. Most cases of newly diagnosed thyroid cancer are small indolent microcarcinoma and could be good candidates for active surveillance (AS) instead of immediate surgery. Many considerations must be taken into account for establishing selection criteria for candidates for AS of papillary thyroid microcarcinoma (PTMC), including the characteristics of the tumor, the patient, and the medical team. If possible, AS of PTMC should be a part of a prospective clinical trial to ensure long-term safety and to identify clinical and/or molecular markers of the progression of PTMC. In this review, we discuss lessons regarding surgical interventions for PTMC, and then describe the concept, application, caveats, unanswered questions, and future perspectives of AS of PTMC. For appropriately selected patients with PTMC, AS can be a good alternative to immediate surgery.

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