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

The incidence of thyroid carcinoma has been increasing worldwide. This is interpreted as an increase in the incidental detection of papillary thyroid microcarcinomas (PTMCs). However, mortality has not changed, suggesting overdiagnosis and overtreatment. Prospective clinical trials of active surveillance for low-risk PTMC (T1aN0M0) have been conducted in two Japanese institutions since the 1990s. Based on the favorable outcomes of these trials, active surveillance has been gradually adopted worldwide. A task force on the management of PTMC in adults organized by the Japan Thyroid Association therefore conducted a systematic review and has produced the present position paper based on the scientific evidence concerning active surveillance. This paper indicates evidence for the increased incidence of PTMC, favorable surgical outcomes for low-risk PTMC, recommended criteria for diagnosis using fine needle aspiration cytology, and evaluation of lymph node metastasis (LNM), extrathyroidal extension (ETE) and distant metastasis. Active surveillance has also been reported with a low incidence of disease progression and no subsequent recurrence or adverse events on survival if conversion surgery was performed at a slightly advanced stage. Active surveillance is a safe and valid strategy for PTMC, because it might preserve physical quality of life and reduce 10-year medical costs. However, some points should be noted when performing active surveillance. Immediate surgery is needed for PTMC showing high-risk features, such as clinical LNM, ETE or distant metastasis. Active surveillance should be performed under an appropriate medical team and should be continued for life.

Active surveillance (AS) can be considered as an alternative to immediate surgery in low-risk papillary thyroid microcarcinoma (PTMC) without clinically apparent lymph nodes, gross extrathyroidal extension (ETE), and/or distant metastasis according to American Thyroid Association. However, in the past AS has been controversial, as evidence supporting AS in the management of PTMC was scarce. The most prominent of these controversies included, the limited accuracy and utility of ultrasound (US) in the detection of ETE, malignant lymph node involvement or the advent of novel lymph node malignancy during AS, and disease progression. We summarized publications and indicated: (1) US, performer-dependent, could not accurately diagnose gross ETE or malignant lymph node involvement in PTMC. However, the combination of computed tomography and US provided more accurate diagnostic performance, especially in terms of selection sensitivity. (2) Compared to immediate surgery patients, low-risk PTMC patients had a slightly higher rate of lymph node metastases (LNM), although the overall rate for both groups remained low. (3) Recent advances in the sensitivity and specificity of imaging and incorporation of diagnostic biomarkers have significantly improved confidence in the ability to differentiate indolent vs. aggressive PTMCs. Our paper reviewed current imagings and biomarkers with initial promise to help select AS candidates more safely and effectively. These challenges and prospects are important areas for future research to promote AS in PTMC.

Papillary thyroid microcarcinoma(PTMC)of the thyroid is defined as papillary thyroid carcinoma measuring<1 cm. The incidence of differentiated thyroid cancer is increasing greatly. However, roughly half of this increase is attributable to the identification of PTMC. Serum thyroid stimulating hormone, thyroid ultrasound and ultrasound guided thyroid fine needle aspiration cytology(FNAC)are still the cornerstone for its diagnosis. The active surveillance approach in which active treatment is delayed until the cancer shows signs of substantial progression could be considered in selected patients with low-risk PTMC. Active surgery is still the first line treatment for other PTMC patients, although thermal ablation may be an alternative option for low-risk patients with PTMC. (Chin J Endocrinol Metab, 2018, 34: 353-358) Key words: Papillary thyroid microcarcinoma; Active surveillance; Thermal ablation

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: 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.

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.

Thermal ablation presents a therapeutic option other than active surveillance and immediate surgery for patients with low-risk papillary thyroid microcarcinomas (PTMC). Here, we have reviewed the current oncologic outcome of thermal ablation in PTMC cases and compared it with active surveillance and surgery. Thermal ablation in PTMC cases revealed no tumor progression for pooled 5-year follow-up data. This oncologic outcome of thermal ablation was comparable to that of immediate surgery with less morbidity. Additionally, no patient who underwent thermal ablation received delayed surgery during the follow-up period due to anxiety. However, active surveillance has indicated that a substantial proportion (range, 8-32%) of patients underwent surgery mainly due to anxiety. In a subset of PTMC patients who are high-risk surgical candidates or who refuse surgery, especially those who have failed or are reluctant to pursue active surveillance, thermal ablation can be a good option.

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.

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.

Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC), which was initiated at Kuma Hospital (Kobe, Japan) in 1993 and Cancer Institute Hospital (Tokyo) in 1995, is now gradually being adopted worldwide, and several prospective studies have described the favorable outcomes of PTMC patients who underwent AS. The most important factor predicting PTMC growth is young age, and PTMC enlargement in young patients may be affected by high serum levels of thyroid-stimulating hormone. This review notes that one patient showed lung metastasis after conversion surgery (CS) following AS, but there are no reports of patients dying of thyroid carcinoma during or after AS. Some PTMCs enlarge or show newly appeared metastatic nodes requiring CS, and findings on the postoperative prognosis and incidence of significant surgical complications (e.g., permanent vocal cord paralysis, hypoparathyroidism) do not differ significantly between patients who underwent CS after AS and those who underwent immediate surgery (IS). IS has been associated with significantly higher incidences of these complications compared to AS as the initial management. Several studies have examined the quality of life (QoL) of patients who underwent AS versus IS, and reported discrepant findings regarding various psychological conditions (including anxiety). Medical costs for AS and IS vary regionally, and in Japan, the 10-year total cost of IS was 4.1 times greater than that of AS in 2017. Taken together, the existing findings demonstrate that AS can be appropriate for the initial management of patients with PTMC.

ObjectiveWhen active surveillance (AS) is developed in the patients with low-risk papillary thyroid microcarcinoma (PTMC), a medical center needs to ensure the delayed operation that is caused by PTMC clinical progression to have the same prognosis as that of immediate operation. The objective of this study was to investigate the efficacy of delayed surgery by simulating clinical progression (tumor size enlargement and appearance of lymph node metastasis) of PTMCs with AS in a single medical center.MethodsWe retrospectively analyzed the response to therapy in 317 papillary thyroid carcinoma patients treated with total thyroidectomy and post-operative radioactive iodine ablation. They were classified into three groups according to tumor size (group A ≤0.5 cm; group B >0.5 cm and ≤1 cm; group C >1 cm and ≤1.5 cm) or two groups according to the presence (cN1) or absence (cN0) of the clinical lymph node (LN) metastasis. Groups C and cN1 were regarded as simulated clinical progression of observational PTMC and the operation for them was assumed to be “delayed surgery”. However, Groups A, B and cN0 were regarded as no clinical progression and the operation for them was considered as immediate surgery.ResultsThere were no significantly differences in excellent response to therapy and recurrence-free survival not only among the group A, B and C, but also between the group cN0 and cN1. In other words, these insignificant differences were found between immediate and simulated “delayed” surgeries.ConclusionFor the PTMC patients suitable for AS, the oncological outcomes were also excellent even if surgery was delayed until after the presence of clinical progression, according to our clinical simulation. Furthermore, we consider that it was feasible for medical centers to assess the ability to implement AS for PTMC patients by retrospectively analyzing their own previous clinical data using the described simulation.

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

Background: Active surveillance (AS) has been considered one of the management options in patients with low-risk papillary thyroid microcarcinoma (PTMC). It is important to evaluate clinical lymph node (LN) metastasis to select appropriate candidates with low-risk disease. We investigated the predictive accuracy of computed tomography (CT) for cervical LN metastasis in patients who have PTMC with tumor characteristics appropriate for AS. Methods: This was a retrospective study. Medical records from December 2014 to the end of 2016 were reviewed. Patients who underwent thyroidectomy and who had pathologically confirmed PTMC were included. A total of 464 patients who had tumors with ultrasound (US) characteristics appropriate for AS and who underwent preoperative CT were included in the analysis. Results: CT showed higher diagnostic values especially in positive predictive value (PPV) than US. In patient-based analyses, CT showed low sensitivity and negative predictive value (NPV) (16.0% and 58.5%, respectively), but high specificity and PPV (99.6% and 97.1%, respectively) for detecting cervical LN metastasis. Similar trends were observed for the results of the central neck-level by CT (sensitivity, 14.9%; specificity, 97.4%; PPV, 82.9%; and NPV, 57.4%) in level-by-level analyses. When restricted to lateral neck levels, CT showed high diagnostic accuracy of 95.4% for detecting LN metastasis. In all analyses, CT showed better diagnostic values for cervical LN metastasis than US. Combining US and CT did not improve the diagnostic accuracy compared with CT. Conclusions: In patients with PTMC whose tumor has characteristics suitable for AS, CT had additional benefit after cervical LN assessment by US. Further studies are needed to evaluate routine initial CT scanning for patients who are candidates for AS.

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

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