Active surveillance for adult low-risk papillary thyroid microcarcinoma—a review focused on the 30-year experience of Kuma Hospital—

Background:Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) was initiated at Kuma Hospital in 1993 and has gradually spread worldwide. We previously demonstrated that AS is associated with a much lower incidence of unfavorable events than immediate surgery (IS). However, conversion surgery (CS) raises concerns about increased surgical complications due to advanced disease. In this study, we conducted a comparative analysis of unfavorable events after IS and CS.Methods:Between 2005 and 2019, 4635 patients clinically diagnosed with low-risk PTMC at Kuma Hospital were enrolled. Of these, 2896 underwent AS (AS group), and the remaining 1739 underwent IS (IS group). To date, 242 patients (8.4%) in the AS group have undergone CS for various reasons (CS group).Results:The incidence of unfavorable events, such as levothyroxine administration after surgery, postoperative hematoma, transient/persistent hypoparathyroidism, and transient/persistent vocal cord paralysis, did not differ between the CS and IS groups. None of the patients in the CS group had permanent vocal cord paralysis; however, this occurred in 15 patients (0.9%) in the IS group and was caused by accidental injury in 4 patients and carcinoma invasion in 11 patients. The incidence of surgery, levothyroxine administration, postoperative hematoma, transient/permanent hypoparathyroidism, and vocal cord paralysis was significantly higher (p < 0.001) in the IS group than in the AS group. There were no differences in the incidence of lymph node recurrence and overall mortality between the AS and IS groups. None of the patients in the AS and IS groups showed distant metastasis or died from thyroid carcinoma.Conclusions:There were no differences in the incidence of unfavorable events between the CS group and the IS group. Although none of the CS and AS groups had permanent vocal cord paralysis, accidental injury of the recurrent laryngeal nerve occurred in four patients (0.2%) in the IS group. The IS group had a significantly higher incidence of unfavorable events than the AS group. The prognoses of patients in both the AS and IS groups were excellent. Therefore, we recommend AS as the first-line management for low-risk PTMC.Correction added on February 20, 2023 after first online publication of November 9, 2022: In the Methods section of the abstract, 242 patients (0.8%) has been corrected to 242 patients (8.4%).

Although the outcomes of active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC) are generally excellent, some patients undergo conversion surgery for various reasons, including disease progression. We studied the outcomes of PTMC patients who underwent AS, who underwent conversion surgery after AS, and who underwent immediate surgery. Between 2005 and 2019, 4,635 patients were diagnosed with low-risk cT1aN0M0 PTMC at Kuma Hospital: 2,896 opted for AS (AS group) and 1,739 underwent immediate surgery (Surgery group). In the AS group, 242 patients underwent conversion surgery (Conversion group): 72 owing to disease progression (Conversion-prog group) and 170 for other reasons (Conversion-non-prog group). Of the 1,739 patients in the Surgery group, 1,625 had no high-risk features (Surgery-low-risk group). Locoregional recurrence (LRR) occurred in 9, 1, 1, and 0 patient in the Surgery-low-risk group, the Conversion-prog group, the AS group, and the Conversion-non-prog group, respectively. The LRR rate of the AS group was significantly lower than that of the Surgery-low-risk group (0.1% vs. 0.7% at 10 years, p = 0.006). Additionally, the LRR rate of the Conversion group (0.6% at 10 years, p = 0.741) and that of the Conversion-prog group (3.3% at 10 years, p = 0.103) did not significantly differ from the LRR of the Surgery-low-risk group. As the postoperative prognosis of patients with progressive PTMC who underwent conversion surgery did not significantly differ from that of patients who underwent immediate surgery, we think that AS may have resulted in efficient identification of the small proportion of patients with progressive PTMC that require surgical treatment.

Background:It has been 30 years since the initiation of active surveillance (AS) for adult patients with low-risk papillary thyroid microcarcinoma (PTMC). This study compared the long-term oncological outcomes of patients who underwent AS or immediate surgery (IS).Methods:This is a retrospective review of extended follow-up data from patients enrolled in a single-center, prospective observational study in Japan. In total, 5646 patients diagnosed with low-risk PTMC at Kuma Hospital between 1993 and 2019 were enrolled in this study. Of these, 3222 patients underwent AS (AS group), whereas 2424 underwent IS (IS group). The patients were followed up regularly, at least once per year. Descriptive outcome data were presented according to the treatment group.Results:In the AS group, 124 patients (3.8%) had tumor enlargement of ≥3 mm, and the 10- and 20-year enlargement rates were 4.7% and 6.6%, respectively. Novel lymph node metastases occurred in 27 patients (0.8%), and the 10- and 20-year nodal metastasis occurrence rates were 1.0% and 1.6%, respectively. In the IS group, 13 patients (0.5%) experienced lymph node recurrence postoperatively, and the 10- and 20-year nodal recurrence rates were 0.4% and 0.7%, respectively. Eighteen (1.4%) of the 1327 patients who underwent hemithyroidectomy experienced recurrence in the residual thyroid. The rate of lymph node metastasis was significantly higher in the AS group than in the IS group (1.1% vs. 0.4% and 1.7% vs. 0.7% at 10 and 20 years, respectively; p = 0.009), but the differences were small. However, the proportion of patients who underwent one or more and two or more surgeries was significantly higher in the IS group than in the AS group (100% vs. 12.3% and 1.07% vs. 0.09%, p < 0.01). Distant metastatic recurrence was observed in one patient after AS and conversion surgery and another after IS; however, they were alive (18.4 and 18.8 years after diagnosis, respectively). None of the patients in this study died of thyroid carcinoma.Conclusions:Long-term oncological outcomes of patients with PTMC generally did not differ clinically significantly between those undergoing AS and IS. AS is a viable initial management option for patients with low-risk PTMC.

Objective: To investigate the rationality of management of active surveillance for papillary thyroid microcarcinoma (PTMC) and the main indications for active surveillance for PTMC. Methods: In this study, two criteria were used to evaluate patients with PTMC: low-risk PTMC conditions defined by Kuma hospital and Chinese Association of Thyroid Oncology (CATO) consensus on PTMC management of active surveillance. The patients had received surgical treatment. Clinicopathological characteristics and prognosis of the patients in different groups were compared. Results: A total of 778 patients were enrolled in the study, 565 (72.6%) of them met Kuma screening criteria and only 112 (14.4%) met CATO screening criteria. Kuma low-risk subgroup had lower incidence of cervical lymph node metastasis than Kuma high-risk PTMC subgroup(30.6% vs 47.9%, P<0.05). There were significant differences in multifocal lesions(6.3% vs 16.4%), extrathyroidal extension (1.8% vs 7.5%) and cervical lymph node metastasis(19.6% vs 38.0%) between low-risk and high-risk CATO PTMC subgroups. Patients in the CATO low-risk PTMC subgroup had lower recurrence and longer disease-free survival (DFS) than those in the CATO high-risk PTMC subgroup. But there was no significant difference in recurrence or DFS between Kuma low-risk and high-risk Kuma PTMC subgroups.The Chi-square test of Fisher's exact probabilities test was used to compare clinicopathological characteristics of patients between different groups.Rates of disease-free survival were calculated using the Kaplan-Meier method. Conclusion: CATO screening criteria is relatively strict and may be more suitable for Chinese patients with active surveillance for PTMC.

Effects of levothyroxine treatment on serum thyroid hormone levels in euthyroid patients with papillary thyroid microcarcinoma

In 1993, active surveillance of low-risk papillary thyroid microcarcinomas (PTMCs) started in Kuma Hospital, Kobe, Japan. It has spread globally after the publishing of American Thyroid Association (ATA) guidelines. During our hospital's active surveillance program, few patients (8.0%) showed tumor size enlargement ≥3 mm or the new appearance of node metastasis (3.8%) at 10-year follow-up. Conversion surgery was recommended for patients with disease progression. To date, no patients showed significant recurrence or metastasis or died with thyroid carcinoma when patients underwent active surveillance or after surgery due to PTMC progression. Unlike clinical papillary thyroid carcinoma (PTC), elderly patients' PTMCs were less progressive compared to those of young and middle-aged patients, indicating that elderly patients are strong candidates for the active surveillance of their PTMC. Although young patients' PTMCs are the most progressive, >50% and >75% of patients in their 20s and 30s would avoid conversion surgical treatment in their lifetime, respectively (according to estimated lifetime probability), indicating that such young patients are still candidates for active surveillance. It can thus be concluded that active surveillance is appropriate to be first management for PTMCs, based on the accumulation of favorable outcomes of PTMC patients who have undergone active surveillance, as well as the lower incidences of unfavorable events and lower medical cost than immediate surgery.

Background: Active surveillance (AS) of papillary thyroid microcarcinomas (PTMC) is emerging as an alternative to immediate surgery. While thermal ablation has also shown promise for low-risk PTMC, it has not been prospectively studied in patients appropriate for AS. This study aimed to evaluate the efficacy and safety of ultrasound (US)-guided radiofrequency ablation (RFA) for tumor control and quality of life (QoL) management in patients with PTMC who favored AS over immediate surgery. Methods: This prospective clinical trial was conducted at a single tertiary referral hospital from 2018 to 2021. Of 227 adult patients aged ≤60 years with low-risk unifocal PTMC favoring AS over immediate surgery, 100 patients underwent RFA for their management. The primary endpoint was the disease progression rate, and secondary endpoints were technical success, volume reduction rate (VRR), complication rates, and QoL. Results: The median age of the study population was 42 years (range, 27-59 years), and 83% (83/100, [CI: 66.1-100]) were female. The median follow-up was 30 months (range, 12-56 months). All 100 patients underwent RFA with technical success. Most of the ablation zones showed continuous volume reduction, and 95.9% (94/98, [CI: 77.5-100.0]) showed complete disappearance at the last follow-up. The median VRR was 100.0% at 1-year follow-up and persisted throughout the last follow-up. The cumulative disease progression rate among 98 patients who underwent at least 1-year follow-up was 3.1% (3/98, [CI: 0.6-9.0]); one patient had lymph node metastasis (treated with surgery), and two patients had new PTMC (1 treated with RFA, 1 ongoing AS). Major complications were not observed. Psychological (baseline vs. last follow-up, 7.3 vs. 8.0, p = 0.002) and social (8.0 vs. 8.7, p = 0.005) QoL scores significantly improved during follow-up without compromising physical QoL (8.6 vs. 8.5, p = 0.99). Conclusions: RFA can be a reasonable strategy for effectively and safely controlling tumors and improving QoL in non-elderly patients with low-risk PTMC appropriate for AS. Clinical Trial registration: This trial is registered with ClinicalTrials.gov: NCT03432299.

Background: Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PMC) was adopted as a management modality in both the Japanese guidelines in 2011 and the American Thyroid Association guidelines in 2015. AS was initiated at Kuma Hospital in 1993 but was not immediately accepted by all physicians. This study investigated the history of acceptance of AS at Kuma Hospital over time. The results should assist in the implementation of AS at other hospitals in Japan and other countries.Methods: This study included 4023 patients who were cytologically diagnosed with low-risk PMC at Kuma Hospital during the 24-year period between October 1993 and June 2016. The trend in the frequency of AS use over time was analyzed, dividing the 24-year study period into five parts based on the change in frequency of AS use: 1993–1997, 1998–2002, 2003–2006, 2007–2013, and 2014–2016.Results: The frequency of AS use in the present cohort was 65%. The frequency gradually increased from 30% in 1993–1997 to 88% in 2014–2016, with a slight decrease from 51% in 1998–2002 to 42% in 2003–2006. Until 2007, patients were mostly seen by surgeons, and the frequency of AS use varied remarkably among individual surgeons. Since 2007, the number of patients whose therapeutic strategies are determined by endocrinologists has increased, and the frequency of AS use for low-risk PMC by endocrinologists has been higher than that by surgeons.Conclusions: At Kuma Hospital, acceptance of AS for low-risk PMC gradually increased over the 24-year study period, but AS was not equally accepted by all physicians. Such variations in the acceptance of AS among individual physicians are also expected to exist in other hospitals. However, due to increasing evidence of the safety and superiority of AS over immediate surgery for this indolent disease, it is expected that AS will gain faster acceptance in other hospitals in Japan and around the world.

BRAF V600E status may facilitate decision-making on active surveillance of low-risk papillary thyroid microcarcinoma

Background: Two Japanese prospective trials of active surveillance (AS) for adult patients with low-risk papillary thyroid carcinoma (PTC) ≤1 cm (cT1aN0M0 PTMC) have verified the safety of AS in oncological control and its superiority over immediate surgery with respect to unfavorable outcomes. Thus, AS has been accepted as an alternative to immediate surgery for asymptomatic papillary thyroid microcarcinomas (PTMCs). However, the real-world clinical approach for PTMC is unknown. Thus, this study aimed to investigate the current state of management of asymptomatic PTMCs in Japan.Methods: We conducted a questionnaire survey on the actual treatment patterns for adult patients with low-risk PTMCs. The subjects were member institutions of the Japan Association of Endocrine Surgery (JAES) or Japanese Society of Thyroid Surgery (JSTS), including the departments of surgery and head and neck surgery (HNS).Results: Responses were obtained from 134 institutes, where 72.4% of Japanese thyroid cancer cases operated by surgeons were treated. For suspicious tumors on ultrasound, 18 responders (13.4%) conducted cytological examination routinely, while 69 (51.5%) and 40 (27.8%) conducted it only for tumors >5 and >10 mm, respectively. After the diagnosis, 42 responders (31.3%) recommend AS, 35 (26.1%) recommend immediate surgery as the management, and 52 (38.8%) allowed patients to decide the treatment course. The present responders tended to recommend surgery for PTMCs that were located adjacent to the dorsal surface of the thyroid, were multiple, or measured almost 10 mm in size. At these institutions, 1176 patients with PTMC underwent surgery in 2017, accounting for 18.1% of surgeries for PTC. During the succeeding three months, 310 of 576 (53.8%) PTMC patients underwent AS. The treatment strategies did not differ between the departments (Surgery or HNS). The institutions that have six or more surgeons, that were located in metropolitan areas, or that were certified by JAES or JSTS performed AS more actively.Conclusion: More than 50% of low-risk PTMCs are on AS in Japan. However, the indication and recommendation for AS vary significantly between institutions. To improve the implementation of this management modality, physicians and patients should be further educated, and the sociomedical environment should be improved.

Papillary thyroid microcarcinoma (PTMC) management has evolved, with active surveillance (AS) gaining prominence as a management option. However, a key concern for both clinicians and patients is the potential for patient loss to follow-up during AS. This study aimed to determine adherence and loss-to-follow-up rates in low-risk PTMC patients undergoing AS versus surgical intervention, in order to gain insights into clinical pathways and safety profiles. This cohort study analyzed the 2016 data from a single registered institution of Japan's public National Cancer Registry. We identified and retrospectively analyzed the cases of 327 patients diagnosed with low-risk PTMC; 227 patients chose to undergo AS while the other 100 underwent PTMC surgery. Main outcomes were the adherence rate and loss-to-follow-up rate of each group, factors influencing discontinuation, and safety considerations. The rate of AS adoption was substantial in the complete series of 327 low-risk PTMC patients (69.4%). There was a significantly higher loss-to-follow-up rate at 5 years in the AS group (28.6%) compared to the Surgery group (17.8%) (HR 1.62, 95% CI: 1.01-2.61; p = 0.046). Both univariate and multivariate analyses confirmed the significantly higher loss-to-follow-up rate in the AS group as well as in older patients. No deaths due to PTMC progression were observed in the cases lost to follow-up. Despite concerns about loss to follow-up, active surveillance remains a safe option for low-risk PTMCs. Consistent follow-up strategies are crucial, and further research is needed to enhance patient counseling and care for the management of patients with PTMC.

Background: The Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) started in June 2016. As a follow-up study of comparing the quality of life (QoL) of the active surveillance (AS) and immediate surgery (OP) groups at 8 months (9.3±4.8 and 7.1±4.2 months, respectively), here we aimed to compare the QoL between the AS and OP groups after 18 months (22.8±4.0 and 22.3±4.3 months, respectively) of follow-up.Methods: QoL of 108 participants who chose AS, 101 who underwent OP, twelve who changed from AS to OP was evaluated using a thyroid‐specific QoL questionnaire at diagnosis and during follow‐up (median 23 months).Results: The mean ages of the participants in the AS and OP groups were 47.7±11.0 and 45.1±10.0 years (p=0.075), respectively. At baseline, better physical (8.2±1.4 vs. 7.6±1.8, p=0.032), psychological (7.4±1.2 vs. 6.7±1.6, p=0.010), and total health (7.4±1.0 vs. 6.7±1.3, p=0.005) were observed in the AS group than in the OP group. After a mean follow up of 22.7±4.2 months, better physical (8.1±1.5 vs. 7.4±1.7, p=0.008), psychological (7.7±1.3 vs. 7.0±1.5, p=0.002), and total health (7.5±1.2 vs. 6.8±1.3, p=0.001) were observed in the AS group than in the OP group, whereas spiritual health was comparable between the two groups: compared with the AS group, the OP group experienced more alterations in appetite, sleep, menstrual cycle, voice, motor skill, weight, appearance, cold or heat tolerance, and body swelling. Furthermore, better QOL scores were observed in the AS group in self-concept, personal relationships, sexual life, work motivation, productivity and quality of work, feeling of isolation, driving, doing household chores, preparing meals and doing leisure activities after long term follow up.Conclusion: Patients who underwent AS had better QOL even after long term follow up. Low risk papillary thyroid microcarcinomas do not influence survival, however surgery related deterioration of QOL lasted long and did not improve even in late post-operative stages when patients were fully recovered from surgery.Keywords: Quality of life; papillary thyroid microcarcinoma; active surveillance; immediate surgery

Quality of Life in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Active Surveillance Versus Immediate Surgery

Disclosure: G. Effraimidis: None. E. Sazakli: None. O. Karapanou: None. K. Saltiki: None. M.A. Michalaki: None.Introduction. Current guidelines emphasize active surveillance (AS) over immediate surgery for low-risk papillary thyroid microcarcinomas (PTMCs). Alternative minimally invasive treatments, such as thermal ablation, are being explored. If thyroidectomy is performed, lobectomy is preferred, and radioactive iodine (RAI) remnant ablation is not routinely recommended for low-risk PTMC patients. Previously, surveys from Brazil, Australia and New Zealand and the United States examined the attitudes of physicians and surgeons toward AS and the management of low-risk PTMCs. Aim. This study aimed to assess the approach of Greek endocrinologists toward AS and the management of low-risk PTMCs. Methods. A web-based survey was conducted among members of the Hellenic Endocrine Society (HES). Two clinical scenarios involving a 60-year-old woman with low-risk PTMC were analyzed. Surveyed endocrinologists were asked whether they would recommend AS, thermal ablation, lobectomy, or total thyroidectomy as primary treatment; and if total thyroidectomy was performed, whether they would recommend RAI ablation therapy. Results. A total of 201 endocrinologists (25% of HES members) participated. As primary treatment for low-risk PTMC, 46.8% recommended total thyroidectomy, 31.3% chose AS, and 20.9% opted for lobectomy and 1.0% selected thermal ablation. If total thyroidectomy was performed, 95% considered RAI ablation unlikely, and only 5% would use RAI. Demographic characteristics, including age, sex, experience, and geographic location, did not significantly influence these choices. The primary reason cited by endocrinologists for non-compliance is skepticism about implementing the guidelines, likely stemming from resource limitations and educational gaps. Conclusion. In this highly representative of the HES members with high response rate survey, one-third of the Greek endocrinologists preferred AS for managing low-risk PTMCs and almost all responded that it is very likely or likely not to use RAI remnant ablation in very low-risk PTMC. This is the first known survey conducted in Europe on AS and the management of low-risk PTMCs. Insights from the survey may help to reduce overtreatment in low-risk PTMC management.Presentation: Saturday, July 12, 2025

Active surveillance (AS) of low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0) in adults was initiated in 1993 at Kuma Hospital (Kobe, Japan) and in 1995 at the Cancer Institute Hospital (Tokyo, Japan). Since then, numerous studies from various countries have reported favorable outcomes for patients managed with AS. Notably, no cases of thyroid carcinoma-related death have been reported among patients who have undergone AS. Young age has been identified as a predictor of high tumor growth activity; however, previous studies have shown that young adult patients may still be suitable candidates for AS. Although surgery for PTMC is not technically complex, it carries risks, even when performed by experienced thyroid surgeons, including permanent recurrent laryngeal nerve paralysis and hypoparathyroidism. No significant difference in prognosis has been observed between patients managed with AS and those who undergo immediate surgery (IS). Some patients initially on AS later opt for conversion surgery (CS) for various reasons. Importantly, the postoperative prognosis and incidence of unfavorable events in patients undergoing CS do not differ significantly from those in patients undergoing IS. However, the overall incidence of unfavorable events has been reported to be higher among patients who initially chose IS than among those who began with AS. Patients managed with AS have demonstrated better physical quality of life (QOL) than those who underwent IS. Although findings on mental QOL have been inconsistent, this may depend on the attitudes and approach of the attending clinicians. Presently, AS is considered an excellent initial management strategy for patients with PTMC.