Active Surveillance or Surgery in Papillary Thyroid Microcarcinoma: An Ongoing Controversy

BackgroundOvertreatment of papillary thyroid microcarcinoma (PTMC) has become a common concern. This study aimed to compare clinicopathological features between PTMC and papillary thyroid carcinoma (PTC) and to explore whether surgery can confer significant survival benefits in all patients with PTC or PTMC.MethodsData of 145,951 patients with PTC registered in Surveillance, Epidemiology, and End Results (SEER) database and 8,751 patients with PTC in our institution were retrospectively collected. Patients with tumors less than 10 mm in diameter were classified as PTMC cohort and the rest as PTC cohort. Clinicopathological features between PTMC and PTC were compared on the basis of SEER cohort and validated with institutional data. Survival analysis was conducted to explore the effect of surgery on the prognosis of patients. To minimize potential confounders and selection bias, we performed propensity score matching (PSM) analysis to match more comparable cohorts.ResultsCompared with PTC, PTMC exhibited the following characteristics: more common in women and whites, older age at diagnosis, lower proportion of follicular variants, intraglandular dissemination, extraglandular and capsular invasion, higher proportion of multifocality, fewer lymph node and distant metastases, and higher cancer-specific survival (CSS) and overall survival (OS) (all p-value < 0.05). Regarding treatment, patients with PTMC received a lower proportion of radiotherapy, chemotherapy, and total thyroidectomy but a higher proportion of lobectomy and/or isthmectomy. There was no significant difference in CSS for patients with PTMC at stage T1N0M0 with or without surgery (P = 0.36).ConclusionGenerally, PTMC showed higher biological indolence than PTC, which meant a higher survival rate for patients in both OS and CSS. For patients with PTMC at staged T1N0M0, active surveillance (AS) may be a potentially feasible management strategy. However, the maintenance of good medical compliance and the management of psychological burden cannot be ignored for patients included in AS.

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.

The clinical significance of papillary thyroid microcarcinoma (PTMC) tumors < or =1 cm is widely debated. The objective of this study was to compare conventional papillary thyroid carcinoma (PTC) (tumors >1 cm) to PTMC and assess for differences in tumor characteristics and patient outcome. A retrospective chart review of patients with PTC or PTMC who were followed for a minimum of 3 years postoperatively and managed at a single academic institute was performed. Of 202 patients in the study, 66 (32.7%) had PTMC and 136 (67.3%) had conventional PTC. Patient and tumor characteristics including tumor multifocality, extrathyroidal extension, angiolymphatic invasion, and lymph node metastasis were similar between both groups. Twenty-one percent of the PTMC tumors were discovered incidentally. Patients with conventional PTC were significantly more likely to undergo treatment with radioactive iodine therapy compared to PTMC patients (86.4% vs. 66.7%, respectively, p < 0.003). Disease recurrence was observed in 40 patients and was not statistically different between the two groups; 11 (16.7%) in PTMC and 29 (21.3%) in conventional PTC, p = 0.57. Within the PTMC group, tumors of patients that recurred were significantly larger than those who remained disease free (8.1 mm vs. 6.4 mm, p < 0.05). None of the patients with incidental PTMC had disease recurrence. Angiolymphatic invasion was the only significant prognostic indicator of recurrence on multivariate analysis (p < 0.02). Nonincidental PTMC can have aggressive tumor features and disease recurrence similar to conventional PTC. These tumors should be managed like any other papillary thyroid malignancy.

In this study, we compared the cost-effectiveness comparison of the active surveillance (AS) and early surgery (ES) approaches for papillary thyroid microcarcinoma (PTMC) from the perspective of the Chinese healthcare system. We performed a cost-effectiveness analysis using a Markov model of PTMC we developed to evaluate the incremental cost-effectiveness ratio of AS and ES. Our reference case was of a 40-year-old woman diagnosed with unifocal (<10mm) PTMC. Relevant data were extracted after an extensive literature review, and the cost incurred in each state was determined using China Medicare data on payments for ES and AS. The willingness-to-pay threshold was set at ¥242,928/quality-adjusted life-year (QALY) gained. Sensitivity analyses were performed to account for any uncertainty in the model's variables. Additional subgroup analyses were performed to determine whether AS was cost-effective when different initial monitoring ages were used. ES exhibited an effectiveness of 5.2 QALYs, whereas AS showed an effectiveness of 25.8 QALYs. Furthermore, the incremental cost-effectiveness ratio for ES versus AS was ¥1,009/QALY. The findings of all sensitivity analyses were robust. Compared with ES, AS was found to be the cost-effective strategy at initial monitoring ages of 20 and 60 years, with an incremental cost-effectiveness ratio of ¥3,431/QALY and -¥1,316/QALY at 20 and 60 years, respectively. AS was a more cost-effective strategy in patients with PTMC aged more than 60. With respect to the norms of the Chinese healthcare system, AS was more cost-effective for PTMC over lifetime surveillance than ES. Furthermore, it was cost-effective even when the initial monitoring ages were different. In addition, if AS is incorporated into the management plan for PTMC in China at the earliest possible stage, a predicted savings of ¥10 × 108/year could be enabled for every 50,000 cases of PTMC, which indicates a good economic return for future management programs. The identification of such nuances can help physicians and patients determine the best and most individualized long-term management strategy for low-risk PTMC.

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.

BackgroundLow-risk papillary thyroid microcarcinoma (PTMC) without clinically evident lymph nodes, extrathyroidal expansions, and distant metastases may be candidates for active monitoring.ObjectiveThe purpose of this research is to identify risk factors for papillary thyroid microcarcinoma (PTMC) metastasis to central cervical lymph nodes (CLNM) and to discuss the viability of an active surveillance strategy to minimize unnecessary therapy for patients.MethodsThis single-center retrospective study was conducted on the data and medical records of the patients who were diagnosed with PTMC and underwent surgery at the Baotou Cancer Hospital, China, between January 1, 2018, and December 31, 2019. Both lobectomy and complete thyroid resections were performed, and central lymph node dissections (CLND) were used in all patients. Comparisons and analyses were conducted on the preoperative ultrasound (US) characteristics, the post-operation pathological results, and lymph node metastasis.ResultsWe analyzed 172 patients with PTMC with average age 48.32 ± 10.59 years old, with 31 males and 142 females. US testing showed 74 (43.0%) patients had suspicious lymph nodes; 31 (41.9%) had capsular invasion and 52 (30.2%) patients were confirmed to have CLNM. Based on logistic regression analysis, central lymph node metastasis was shown to be more common in individuals with PTMC who were older than 45 years old, male, and had tumors that lacked micro-calcification on US imaging. Postoperative pathology assessments suggested that 58 cases (33.7%) were more suitable candidates for active surveillance cohorts.ConclusionsWhile active surveillance might benefit many PTMC patients, treatments for the patients should also encompass occult lymph node metastasis, especially in patients with over 45 years old, male, tumor without micro-calcification in the US imaging. Furthermore, the prediction of lymph nodes in the central cervical via the preoperative US and the PTMC risk stratification accuracy need to be improved. Our findings showed about 30% of the patients with PTMC had no active surveillance high-risk factors but required surgical treatment. Fear of cancer in the PTMC patients, although informed of the details, is still the main reason for choosing surgical treatment over active surveillance.

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.

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.

Surgery alone for papillary thyroid microcarcinoma is less costly and more effective than long term active surveillance

Papillary thyroid carcinoma is the most common endocrine malignancy. Papillary thyroid microcarcinomas (PTMCs) are tumors with a size of ≤1 cm. The biological behavior of these tumors differs due to the presence of their aggressive features. The prognosis of PTMCs with high-risk features, such as clinical node metastasis, distant metastasis, and significant extrathyroidal extension to the tracheal or recurrent laryngeal nerve invasion, is poor, even if a sufficient immediate surgery is performed at diagnosis. However, PTMCs without these aggressive features are low-risk tumors because of their indolent and slow growth behaviors. The increase in thyroid cancer incidence is mostly a result of overdiagnosis of small low-risk PTMCs with indolent clinical course. Despite the sudden increase in thyroid cancer incidence worldwide, cancer mortality did not increase. Although the traditional treatment strategy for PTMC is immediate surgery at diagnosis, because of the rather low disease-specific mortality rate, low recurrence rate, and potential risk for postoperative complications, active surveillance has been proposed recently as an alternative option for PTMCs without invasion, metastasis, or cytological or molecular characteristics. The recent data support that active surveillance of low-risk PTMC should be the initial treatment modality, because only a small percentage of low-risk PTMCs show signs of progression, and delayed surgery has not caused significant recurrence. However, recent management guidelines are shifting toward more conservative treatments, such as active surveillance. Although there is an increase in the number of studies related to active surveillance, prospective studies have been mostly from academic referral centers in Japan. The world still needs class 1 evidence extended prospective studies originating from different geographic regions. Active surveillance may be a good alternative to immediate surgery for appropriately selected patients with PTMC.

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.

ABSTRACTIntroduction: Active surveillance of low-risk papillary thyroid microcarcinomas (PTMCs) was initiated in Japan in 1993 and has since been adopted in many countries, especially after its approval by the American Thyroid Association in 2015.Areas covered: We performed a literature review in Medline/PubMed to identify studies that used active surveillance for PTMCs. Moreover, we performed a literature review about the increased incidence of thyroid microcarcinomas in relation to the relative stability of deaths due to thyroid carcinomas.Expert opinion: No patients showed life-threatening metastasis/recurrence or died of thyroid carcinoma during active surveillance or after conversion surgery following PTMC progression. Thus, active surveillance should be the first-line management of PTMCs without high-risk features. In the future, molecular testing of actively growing PTMCs using cytology specimens could be useful to guide the treatment plan.

Background: Active surveillance (AS) is recommended as an alternative to immediate surgery in patients with papillary thyroid microcarcinoma (PTMC), but the impact of AS on quality of life has not been reported. The aim of this study was to compare quality-of-life parameters in patients with PTMC under AS versus those who underwent lobectomy (LB). Methods: In this cross-sectional study, patients with PTMC were prospectively enrolled between June 2016 and October 2017. All patients completed three questionnaires: the 12-item short-form health survey, thyroid cancer-specific quality of life, and fear of progression. The results were compared after adjusting for age, sex, and serum thyrotropin levels. Results: The AS group comprised 43 patients, and the LB group comprised 148 patients. According to the 12-item short-form health survey questionnaire, the score for role limitations due to emotional problems showed a significant negative association between the groups (coefficient [coef]: -7.71 [confidence interval (CI) -15.26 to -0.16], p = 0.045). The thyroid cancer-specific quality of life questionnaire also showed statistically significant differences between the groups with respect to three scores: neuromuscular problems (coef: 4.99 [CI 0.63-10.62], p = 0.020), throat/mouth problems (coef: 5.28 [CI 0.18-10.38], p = 0.043), and scar problems (coef: 9.34 [CI 4.38-14.29], p < 0.001), suggesting a higher level of complaint in the LB group than in the AS group. No significant differences in fear of progression scores were seen between the two groups. Conclusions: Patients with PTMC underwent LB experienced more health-related problems than those managed by AS. These findings support the role of AS as a reasonable management option for patients with PTMC.

The incidence of thyroid cancer is increasing globally due to the increase in detection of subclinical, low volume papillary thyroid microcarcinomas (PTMC) (<1cm). Several international groups have recommended an active surveillance approach for this low-risk disease. In contrast to many other countries, the United Kingdom's (UK's) approach to thyroid nodules is to avoid detection of incidental lesions where appropriate. This study aims to establish the proportion of patients with thyroid cancer in the UK that would benefit from active surveillance. Individuals with PTMC in NHS Lothian from 2009-2020 were reviewed from a local thyroid cancer database. The mode of detection of PTMC and proportion of patients who might benefit from active surveillance were established. From 651 individuals with differentiated thyroid cancer managed over 12-year period, 185 individuals with PTMC were identified (28.4%). The majority of PTMC 151/185 (81.6%) were either diagnosed post-operatively following thyroidectomy for benign disease or with nodal disease. Only 24 individuals with PTMC were identified following palpable thyroid nodule, incidental finding on imaging, and surveillance screening. Therefore, when the indication for surgery was considered, only 24/651 (3.7%) patients were identified pre-operatively and would, therefore, be realistic candidates for active surveillance. Less than 4% of patients with thyroid cancer in the UK would be appropriate for active surveillance. Rather than developing programmes to deal with this minority of patients, focus should be maintained on minimising detection of these low-risk cases.

Introduction: Micropapillary thyroid carcinoma was emerging as an epidemic disease worldwide. Due to its unaggressiveness and slow-growing feature, either doing active surveillance or surgical approach were controversial for its management. This meta analysis aimed to determine the pooled proportion outcomes of doing active surveillance and surgery in micropapillary thyroid carcinoma. Methods: This meta analysis of the results in doing active surveillance and surgical approach for micropapillary thyroid carcinoma, designed followed the PRISMA guidelines. Relevant studies were obtained from Medline (2008-2018) and SCOPUS (2008-2018) in the last 20 years. The scope of data collection is about the author, year of study, and number of subjects. The parameter of this study was pooled proportion. Data were analyzed by MedCalc 13.5 and the significance limit was 0.05. Results: The pooled proportion of cases of surgery conversion, increasing tumor size more than 3 cm, and the presence of lymph node metastases during active surveillance of micropapillary thyroid carcinoma were 14.996; 6.125%; and 4.988%, respectively. The pooled proportion of cases of recurrence and lymph node metastases after surgery of micropapillary thyroid carcinoma were 3.539% and 14.071%, respectively. Discussion: In this study, it was showed that result was favorable in doing active surveillance. The rate of lymph node metastases were comparable in non and interventional group. However, this approach should be considered cases by cases. Many individual factors like age, gender, and comorbidities should be considered. Conclusion: Active surveillance was a safe and considered approach for micropapillary thyroid carcinoma. However, some risk factor should be considered for surveillance exclusion.