It Is Time to Understand the Additional Benefits of Active Surveillance for Low-Risk Papillary Thyroid Carcinoma
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Thyroid cancer is the most common endocrine malignancy with a rapidly increasing incidence in recent years, resulting in a large number of living survivors [1,2]. Over the past few decades, the overdiagnosis and overtreatment of thyroid cancer, particularly low-risk papillary thyroid cancer (PTC), have become widespread concerns [3,4]. With this context, active surveillance (AS) was initiated at Kuma Hospital in Japan in 1993 and was incorporated into the 2015 American Thyroid Association guidelines after two decades [5]. During this time, despite compelling evidence from two prospective studies in Japan [6,7], regional limitations and a lack of studies were identified as constraints. In light of these challenges, several countries, including Korea, have been actively conducting clinical studies on AS for low-risk papillary thyroid microcarcinoma (PTMC). Notable among these are Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) [8] and Korean Multicenter Prospective cohort study of Active Surveillance or Surgery (KoMPASS) [9], which are major prospective AS studies in Korea. These studies have recently published their interim results [10,11]. The overall progression rate was 9.6% (68/706) with a mean follow-up of 41.4 months, and the 2- and 5-year progression rates were 5.3% and 14.2%, respectively. Although these progression rates were slightly higher than those previously reported in other populations, the rates of lymph node metastasis and extrathyroidal extension were only 1.3% and 0.4%, respectively, with no distant metastasis reported. These findings suggest that the observed high susceptibility to progression is not limited to specific populations or countries.
In Korea, despite the growing body of evidence on clinical outcomes, AS does not seem to be widely adopted in real-world practice for patients with low-risk PTC. This is due to several obstacles, including clinician inertia, patient misperceptions, and the absence of consensus guidelines.
In this issue, Yoon et al. [12] report on the safety and feasibility of AS as a management option for patients with low-risk PTC. They conducted a systematic review that included recently reported long-term follow-up data. The authors reviewed a total of 20 papers published up to March 2023, organizing them into four categories: disease progression analysis, surgical outcomes analysis, quality of life (QoL) analysis, and cost-effectiveness analysis. They found disease progression rates ranging from 2.2% to 10.8%, with no PTC-specific mortality. Additionally, surgical complications were not significantly different between the delayed surgery and immediate surgery groups, supporting AS as a viable management option for patients with low-risk PTMC to avoid unnecessary surgery. This study is particularly valuable because it not only evaluated disease progression, but also comprehensively assessed QoL and cost-effectiveness. The authors analyzed five studies, two of which were conducted in Korea. Despite the variation in QoL scoring systems, AS was associated with better overall and psychological health compared to the immediate surgery group. In terms of cost-effectiveness, results varied due to differences in healthcare systems and insurance coverage. Data from Korea suggested that immediate surgery was more cost-effective over the long-term, while other studies generally indicated that AS was more cost-effective when considering quality-adjusted life years.
Nonetheless, it is essential for physicians to be aware of the risk factors that differentiate progressive PTMCs from their more indolent counterparts when considering AS. Prior research has identified several significant predictors of tumor growth, including younger age, larger tumor size, male sex, and elevated baseline thyroid-stimulating hormone levels [10,13]. Given the typically slow progression of PTMC, the collection of long-term data is necessary, and it is important to stay up to date with the latest research findings. Adequate shared decision-making between patients and physicians, including endocrinologists, surgeons, and radiologists, is of the utmost importance. Regular and close monitoring for disease progression is mandatory for all patients undergoing AS [14].
Management of thyroid cancer has emerged as one of the most debated topics in the field of thyroid diseases. The areas of disagreement range from the extent of surgery (i.e., whether to perform a total thyroidectomy or a hemithyroidectomy) to the indications for radioactive iodine (RAI) therapy and the appropriate RAI dose (low vs. high). The debate extends to AS of PTMC versus immediate surgery. A trend toward less aggressive and more minimalistic approaches is clearly shaping the management of PTC. In this context, Yoon et al. [12] have provided a comprehensive review that endorses AS as a viable management strategy for patients with low-risk PTMC. This endorsement is based on the low rate of disease progression, the improved QoL, and the QoL-based cost-effectiveness associated with AS. Particularly for low-risk PTMCs, AS is poised to become a standard option alongside surgery. Therefore, it is necessary to understand the importance of careful patient selection, proper follow-up during AS, and the analysis of long-term data from ongoing prospective studies being conducted in Korea.
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CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.