Meta Analysis of the Outcomes in Doing Active Surveillance and Surgical Approach for Micropapillary Thyroid Carcinoma

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.

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.

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.

BackgroundThis study aims to compare the outcomes of active surveillance (AS) in low-risk papillary thyroid carcinoma (PTC) patients with different tumor sizes and lymph node metastasis status, in order to establish appropriate management strategies. By analyzing these results, this study provides valuable insights for the effective management of such patients, addressing the issues and challenges associated with AS in practical clinical practice.MethodsThe study utilized the SEER database supported by the National Cancer Institute of the United States, extracting data of PTC diagnosed between 2000 and 2015. Statistical analyses were conducted using inverse probability weighting (IPTW) and propensity score matching (PSM), including Kaplan-Meier survival curves and Cox regression models, to evaluate the impact of different tumor sizes and lymph node metastasis status on thyroid cancer-specific survival (TCSS).ResultsA total of 57,000 PTC patients were included, with most covariates having standardized mean differences below 10% after IPTW and PSM adjustments. The TCSS of PTC with a diameter smaller than 13mm is significantly better than that of tumors with a diameter larger than 13mm, regardless of the presence of lymph node metastasis. Among PTC cases with a diameter smaller than 13mm, the TCSS of patients is similar, regardless of the presence of lymph node metastasis. However, in PTC cases with a diameter larger than 13mm, the presence of lateral neck lymph node metastasis (N1b stage) significantly impacts the TCSS, although the absolute impact on TCSS rate is minimal.ConclusionThe treatment strategy of AS is safe for patients with T1a stage papillary thyroid microcarcinoma (PTMC). However, for patients with T1b stage, if the tumor diameter exceeds 13mm or there is lymph node metastasis in the lateral neck region, the TCSS will be significantly affected. Nevertheless, the absolute impact on survival is relatively small.

Objective To study the relationship between clinicopathological features and central lymph nodes metastasis in patients with papillary thyroid microcarcinoma(PTMC). Methods From Jan. 2013 to Jun. 2013, 400 cases with PTMC in cN0 stage undergoing thyroidectomy and central neck dissection were collected. Results Univariate analysis showed that the rate of central lymph node metastasis in PTMC was 28.0%, nevertheless, the rate of central lymph node metastasis was 32.5%, 42.6%, 44.1%, 33.3%, and 37.4% respectively in patients aging below 45 years old, in male patients, in patients with extrathyroidal extension, in patients with tumor diameter larger than 5 mm and in patients with multifocality. Gender, age, extrathyroidal extension, tumor diameter, multifocality of patients had correlation with central lymph node metastasis. Multivariate binary logistic regression analysis revealed that the rate of lymph node metastasis significantly increased in cases of male, ageing below 45 years old, with extrathyroidal extension and multifocality(P<0.05). Conclusions The treatment for central lymph node metastasis of PTMC should be different considering elements including gender, age, multifocality of the tumor, and extrathyroidal extension. Prophylactic central lymphadenectomy should be performed when the primary lesion was resected. Key words: Papillary thyroid microcarcinoma; Central lymph node metastasis; Predictive factors

BackgroundIt has been proven that the active surveillance (AS) is safe and feasible for low-risk papillary thyroid microcarcinomas (PTMC). There has been no bibliometric assessment of the scientific advancements in this field. We conducted this study to determine the characteristics and trends of published research on AS for PTMC.MethodsIn this study, articles on AS for PTMC published between 2014 and 2024 were identified using the Web of Science Core Collection database. Bibliometric analysis and visualization were conducted using VOSviewer and CiteSpace.Results277 publications from 39 countries were identified, demonstrating a growth trend between 2014 and 2024. The United States of America dominated with the highest number of published papers, followed closely by South Korea and Japan. The most significant journal was *Thyroid*, and the leading author was Akira Miyauchi. Kuma Hospital and Memorial Sloan Kettering Cancer Center emerged as leading institutions. Keyword analysis revealed that, alongside the title-related terms of this study, “management,” “quality of life,” “lymph node metastasis,” “progression,” and “association guidelines” formed the core keywords in this field.ConclusionActive surveillance for low-risk PTMC has been endorsed and recommended by researchers in numerous countries. This study identified the current most active frontiers in this field and focused on candidate population profiling, tumor progression evaluation, cost-effectiveness of the active surveillance (AS) approach, and quality of life assessment for patients. This paper summarizes the controversial issues and provides a reference direction for researchers seeking to explore novel approaches in this field.

Objective: To investigate high-risk factors for lymph node metastasis (LNM) and 10-year survival rate in patients with papillary thyroid microcarcinoma (PTMC). Methods: We retrospectively analyzed the clinical data of 3 607 patients with PTMC received surgery in our hospital from January 2005 to December 2015. Univariate and multivariate analyses were performed to identify the factors associated with metastasis and 10-year survival rate of the patients was calculated. Results: The patients accepted an average follow-up of 68 months, with follow-up from 18 to 138 months. Total LNM rate in the 3 607 patients with PTMC was 17.13%. Central lymph node metastasis rate was 16.86%, which was related to gender (males 21.89% vs females 15.26%, P<0.01), age (<45 years old 24.44% vs ≥45 years old 11.96%, P<0.01), tumor diameter (P<0.01) and multifocality (P<0.01). Lateral lymph node metastasis rate was 1.05%, which was related to age (<45 vs ≥45, P<0.01) and tumor diameter (P<0.01). The 10-year-survival rate was 93.0% and 10-year recurrence-free survival rate was 87.5%. Conclusion: PTMC may metastasize to cervical lymph node, especially in males, with age younger than 45, multifocal tumors and maximal tumor diameter larger than 0.7 cm. There was no significant correlation between these clinical features associated with LNM and the 10-year survival rate.

With the rapid rise in the incidence of micropapillary carcinoma, there is increasing concern about its overdiagnosis and overtreatment. There is considerable interest in managing patients with micropapillary carcinoma with active surveillance or deferred intervention. Various institutions around the world are practicing active surveillance. The major question remains as to who the ideal candidates are and how best to monitor these patients. This clinical review will discuss the ideal, appropriate, and inappropriate patients for active surveillance. It will also discuss the follow-up strategy for these patients and some of the adverse clinical features that will be used to decide against active surveillance. There are uncertainties as to who should be offered active surveillance. Various studies have shown approximately 10% of the patients switching to surgery primarily related to fear factor rather than increase in the tumor size or lymph node metastasis. The results of immediate surgery do raise issues related to complications of thyroid surgery and quality of life. The most ideal candidate would be patients with a tumor below 1 cm, intrathyroidal. For the patient who is a minimalist, the follow up strategy includes, ultrasound every 6 months for the first 1 or 2 years, and then every year after that. If there is a substantial change in the tumor volume or nodal metastasis, surgery should be considered, which happens in less than 10 percent of patients according to many studies. Based on existing literature and clinical experience, it appears that active surveillance is an appropriate strategy for monitoring micropapillary carcinoma.

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

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.

Papillary thyroid microcarcinoma (PTMC) typically has an indolent course and excellent prognosis. Nonetheless, a subset of PTMC carries a risk of lymph node metastasis (LNM) and local recurrence. PTC from the Middle Eastern population is unique with respect to demographic and clinico-pathological characteristics as compared to other ethnicities of the world. The risk factors of LNM in PTMC patients of Middle Eastern ethnicity have not been fully explored. The present study aims to investigate the influencing factors of LNM in Middle Eastern PTMC patients and its predictive impact on patient’s outcome. A total of 226 confirmed PTMC cases were selected in this retrospective study. The correlation between clinico-pathological, as well as molecular, characteristics and LNM was evaluated. Multivariate analysis was performed by logistic regression and Cox proportional hazards models. Among the 226 patients, the rate of LNM was 43.8% (99/226). Bilaterality, multifocality, gross extrathyroidal extension (ETE), and intermediate-to-high American Thyroid Association (ATA) risk tumors were significantly associated with LNM in PTMC. Multivariate logistic regression analysis showed that bilaterality and gross ETE were independent predictive factors for LNM in PTMC. The recurrence-free survival (RFS) was shorter in PTMC with LNM compared to those without LNM (p = 0.0051) and was significant on multivariate analysis. In conclusion, our study showed that bilaterality and gross ETE were independent influencing factors of LNM in Saudi patients with PTMC. LNM was also associated with shorter RFS. The identification of risk factors for LNM in patients of Middle Eastern ethnicity could help the individualization of clinical management for PTMC patients.

No agreement has been made about the optimal extent of thyroidectomy or lymph node dissection in papillary thyroid microcarcinoma (PTMC). Our aim was to find out the factors associated with the presence of lymph node metastases in the patients with PTMC and to discuss the extent of thyroidectomy and lymphadenectomy. A total of 254 patients with PTMC (212 women, 42 men; age 14 to 85 years, median 47 years) were treated at our institute between 1975 and 2007. Lymph node metastases were confirmed in 59 patients (23%) by histopathology. The median observation time was 56 (range, 1-397) months, and the recurrence was diagnosed in seven patients. Modified radical neck dissection and central neck dissection were performed in 55 and 30 patients, respectively. The data on the clinicopathological characteristics of patients and treatment were collected. An incidental PTMC was diagnosed in 107 patients postoperatively. In none of them was a lymph node metastasis or tumor recurrence detected. Preoperatively, an overt PTMC was diagnosed in 147 patients. Clinically manifest metastases were diagnosed in 59 (40%) of them: in 51 preoperatively, and in 8 during the surgical procedure. In 147 patients who had preoperative diagnosis of PTMC, the factors that correlated (P < 0.05) with the presence of lymph node metastases were sex, age, and tumor type. The patients with high-risk PTMC with preoperatively confirmed lymph node metastases had a higher recurrence rate than those with low-risk PTMC without preoperatively detectable lymph node metastases; therefore, careful therapeutic node dissection is necessary in high-risk patients.

Active surveillance is emerging as a viable clinical alternative to immediate surgery in the management of low-risk papillary thyroid microcarcinoma (PMC). While indolent PMC may be present in up to 10% of the United States population, only a small proportion of this subclinical disease evolves into clinically significant disease (1-3). Instead, the vast majority of lesions are asymptomatic and detected incidentally by imaging studies (neck US, CT, MRI) done for unrelated reasons (4). Active surveillance has arisen as an attractive alternative management strategy because the natural history of PMC is one of slow growing or stable tumors with low rates of lymph node metastasis, and extremely low risk of distant metastasis and disease-related mortality. Even more importantly, a delayed surgical approach has proven to be a very effective salvage therapy for the few patients who demonstrate structural disease progression (5). Several recent reports continue to demonstrate that active surveillance is associated with excellent clinical outcomes (5-8).

The increasing detection of papillary thyroid microcarcinoma (PTMC) has raised concerns regarding overtreatment. For low-risk PTMC, either immediate surgery or active surveillance (AS) can be considered. To facilitate the implementation of AS, the Korean Thyroid Association convened a multidisciplinary panel and developed the first Korean guideline. AS is recommended for adults with pathologically confirmed Bethesda V-VI PTMC who have no clinical evidence of lymph node or distant metastasis, gross extrathyroidal extension, invasion of the trachea or recurrent laryngeal nerve, or aggressive histology. A baseline assessment requires high-resolution neck ultrasound performed by experienced operators to exclude extrathyroidal extension, tracheal or recurrent laryngeal nerve invasion, and lymph node metastasis; contrast-enhanced neck computed tomography is optional. Patient characteristics, including age, comorbidities, and the capacity for long-term follow-up, should be thoroughly assessed. Shared decision-making should carefully weigh the benefits and risks of surgery versus AS, considering expected oncologic outcomes, potential complications, quality of life, anxiety, medical costs, and patient preference. Follow-up involves neck ultrasound and thyroid function tests every 6 months for 2 years and annually thereafter. Disease progression, defined as significant tumor growth or newly detected nodal or distant metastasis, warrants surgery. Despite remaining uncertainties, this guideline provides a structured framework to ensure oncologic safety and supports patient-centered AS.

Objective: To study the clinical and pathologic factors of papillary thyroid microcarcinoma (PTMC) and its significance as a histopathologic subtype of papillary thyroid carcinoma (PTC). Methods: A retrospective study of 719 patients with non-high-risk PTMC who underwent surgery for the first time in the Peking University People's Hospital from January 2007 to June 2019 was conducted, the relationship between clinicopathologic factors and lymph node metastasis, and the expression of four tumor markers CK19, HMBE1, Galectin-3 and CD56 by immunohistochemistry were evaluated. Some comparisons were made with PTC. Results: The peak patients' age was 40-49 years for both non-high-risk PTMC and PTC; the lymph node metastasis rate was higher in the 30-39 years age group than the 50-59 years age group (P<0.05); the lymph nodes metastasis rate was significantly higher for multiple lesions than for single lesion (P<0.05). Lymph node metastasis rate of PTMC with capsular invasion was significantly higher than those without (P<0.05). There was no significant correlation between lymph node metastasis of PTMC and patients' gender, tumor location, tumor size, and lymphocytic thyroiditis. The expression rates of CK19, HMBE1 and Galectin-3 both in PTMC and PTC were 100%, and the expression rates of CD56 were 25.6% (85/332) and 20.0% (70/350) respectively. Conclusion: As the main pathologic subtype of PTC, a variety of clinicopathologic factors of PTMC are related to lymph node metastasis, and it is highly recommended to pay close attention to PTMC. The expression of tumor marker CD56 alone cannot be used as a basis to exclude PTMC and PTC.