The Japan Association of Endocrine Surgery published the first edition of the "Clinical guidelines on the management of thyroid tumors" in 2010 and the revised edition in 2018. The guideline presented herein is the English translation of the revised third edition, issued in 2024. The aim is to enhance health outcomes for patients suffering from thyroid tumors by facilitating evidence-based shared decision-making between healthcare providers and patients, as well as standardizing the management of thyroid tumors. The focus is on adult patients with thyroid tumors, addressing clinically significant issues categorized into areas such as an overview of the diagnosis and treatment of thyroid nodules, treatment strategies by histological type, radioactive iodine therapy, treatment of advanced differentiated carcinoma, pharmacotherapy, and complications and safety management associated with thyroid surgery. Thirty-two clinical questions were established in these areas. Following a comprehensive search of the literature and systematic review to evaluate the overall evidence, we aimed to present optimal recommendations by considering the balance of benefits and harms from the patient's perspective. We integrated evidence and clinical experience to determine the "Certainty of evidence" and "Strength of recommendations". Based on these, we illustrated overall flows of care as "Clinical algorithms". Necessary background knowledge of diseases and established clinical procedures for understanding the recommendations are presented in "Notes", while information that may be clinically useful but for which evidence remains insufficient is included in "Columns", based on the current state of evidence. Finally, future challenges for the next revision are presented as "Future research questions".

Differentiated thyroid cancer has become a prevalent malignant tumor, particularly papillary thyroid carcinoma (PTC), constituting over 90% of cases. Most PTC lesions are asymptomatic and remain subclinical throughout life, and active surveillance is now being used to monitor the progression of these lesions and intervene when appropriate. This evidence synthesis aims to assess PTC progression in size over time during active surveillance in terms of PTC tumor size progression to or beyond 3 mm during the surveillance period.

A dose-response meta-analysis was conducted using the robust error meta-regression method, using time as the "dose" and cumulative progression (%) was assessed. A comprehensive literature review was done using PubMed/MEDLINE and EMBASE from inception till August 2024.

A total of 21 studies from 7 different countries, including 14 648 participants, were included. Incident progression at 2 years of follow-up was 1%, and this increased linearly to 12% at 20 years of follow-up.

It was concluded that progression over the threshold increases linearly over time at approximately less than 1% per year. Therefore, size progression beyond the threshold occurs in a minority and in less than one eighth of subjects by two decades of follow-up.

Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.

This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.

This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

American Thyroid Association guidelines support active surveillance (AS) for low-risk papillary thyroid cancer (PTC). We developed a calculator to aid patient selection.

From 2004 to 2020, 148,904 PTC patients were selected from the surveillance, epidemiology, and end results (SEER) database. Univariable and multivariable analysis evaluated patient and treatment characteristics. Patients were randomly allocated into training (80%) or validation sets (20%). Coefficients generated a mathematical model to predict 5- and 10-year disease-specific survival (DSS).

The mean DSS was 15.5 years with a 5- and 10-year DSS of 99.3% and 98.6%, respectively. Age, sex, race, median household income (MHI), tumor size, and nodal status were significant on multivariable analysis (p ≤ 0.05) and included variables in our calculator. 2404 patients underwent non-operative management (NOM) and were more likely older, male, higher MHI, larger tumor size, and less nodal positivity. Area under the curve (AUC) for 5- and 10-year DSS were 0.83 and 0.81, respectively, for the training set and 0.81 and 0.79, respectively, for the validation set.

65-year-old White female with a 0.8 cm PTC, cN0 with a MHI ≥ $75,000, had a 10-year predicted DSS was 95.6% with NOM and 99.3% with surgery. Alternatively, changing the patient's race to Hispanic, the 10-year predicted DSS was 94.1% with NOM and 99.0% with surgery.

As awareness of AS for PTC expands, it is important to consider objective data to guide informed decision making. This validated calculator is a useful tool to predict DSS for patients considering AS for PTC.

The active surveillance (AS) program for papillary thyroid carcinoma (≤1 cm) at low risk (mPTC) showed a low percentage of progression.

The aim of this study was to find a molecular signature of cases that showed disease progression during AS, which would allow their early identification.

We performed next-generation sequencing of 95 fine-needle aspiration cytology specimens from cases prospectively enrolled in the AS program to analyze key somatic driver alterations or gene fusions implicated in PTC tumorigenesis. TERT promoter analysis was performed using Sanger sequencing or droplet digital polymerase chain reaction.

BRAF p.V600E was found in 66.3% (63/95) of mPTC and was the most common somatic alteration, followed by RAS oncogene mutations detected in 3.2% of mPTC (3/95: 2 NRAS and 1 KRAS) and gene fusions detected in 3.2% of mPTC (3/95: 1 RET-PTC1, 1 TFG-NTRK1, 1 ALK imbalance). No TERT promoter mutations (C228T and C250T) were found in the analyzed mPTC (84/95). The comparison between the molecular profile and the clinical outcome of the mPTC (stable vs progressive disease) showed no correlation (P = .6) and did not identify a molecular signature able to identify progressive mPTC.

The molecular profile of mPTC is like that of bigger PTC with the exception that none of them showed a TERT promoter mutation. The identification of the most common driver mutations, such as BRAF, RAS, or gene fusions, is not helpful for the early identification of mPTC that will show disease progression during follow-up in the AS program.

Management of clinically unifocal node-negative papillary thyroid carcinoma ≤1 cm (PTMC) is controversial with nonsurgical treatment as a potential alternative to thyroid lobectomy (TL). However, conservative strategies, such as active surveillance or thermal ablation, do not allow the evaluation of biological aggressive features or occult lymph node metastases (LNMs), which play a primary role as prognostic factors.

Among 4216 thyroidectomies for malignancy (between September 2014 and September 2023), TL plus ipsilateral central neck dissection was performed in 203 (4.8%) unifocal N0 PTMCs. Completion thyroidectomy was accomplished in case of positive frozen section examination of removed nodes or within 6 months from index operation in presence of biological aggressive features.

Seventy-six out of 203 (37.4%) patients were staged pN1a and extranodal extension was detected in 5 (6.6%) patients. At final histology, biological aggressive features, including multifocality, lymphovascular invasion (LVI), extracapsular invasion, tumor aggressive subtypes, and BRAF-V600E mutation, were detected in 69 (34%), 93 (45.8%), 3 (1.5%), 30 (14.8%), and 7 (3.5%) patients, respectively. A comparative analysis between pN0 and pN1a patients showed younger age (p < 0.001), LVI (p = 0.037), and multifocality (p < 0.001) as risk factors for occult central LNMs. After logistic regression analysis, age (p < 0.001) and multifocality (p < 0.001) were confirmed as independent risk factors for nodal involvement.

Although most PTMC has been widely defined as indolent disease, a non-negligible rate of patients may present one or more biologically aggressive features including nodal involvement. Nonsurgical management should be considered with caution to avoid undertreatment especially in the younger population.

Background/Objectives: There remain several challenges to the acceptance and standardization of active surveillance (AS) in patients with early thyroid cancer. The purpose of this study was to update the evidence of tumor progression outcomes in AS to support resolution of clinical concerns and to examine the effect of follow-up duration, period context such as diagnostic techniques, and tumor size at baseline on outcomes. Methods: PubMed, Web of Science, and Embase were used to search for original articles in English until January 2024. The main outcomes were the pooled proportion of patients who showed tumor growth ≥ 3 mm, metastasis to cervical lymph nodes, and conversion to delayed thyroid surgery. A single-arm meta-analysis was performed using a random-effects model. Results: Fourteen studies with 7291 patients were included in the analysis. Pooled results showed that 5.6% (95% CI: 4.2-7.4) of patients increased tumor diameter by more than 3 mm, 1.1% (95% CI: 0.9-1.4) developed cervical lymph node metastases by clinical diagnosis and 3.6% (95% CI: 3.1-4.2) by pathology, 12.7% (95% CI: 9.9-16.1) of patients converted to delayed surgery, with 31.6% (95% CI: 25.3-38.7) of those conversions being due to tumor progression. Subgroup analysis showed a small difference in the proportion of outcomes by baseline tumor size but no increase in the proportion of tumor progression or conversion to surgery due to other factors. Conclusions: This meta-analysis suggests long-term stability in the proportion of tumor progression in AS and less susceptibility to external influences.

Active surveillance (AS) has been widely adopted as an alternative to immediate surgery owing to the indolent nature and favorable outcomes of papillary thyroid microcarcinoma (PTMC). AS is generally recommended for tumors measuring ≤1 cm without aggressive cytological subtypes, risk of gross extrathyroidal extension (ETE), lymph node metastasis (LNM), or distant metastasis. AS requires careful patient selection based on various patient and tumor characteristics, and ultrasound (US) findings. Moreover, during AS, regular US is performed to monitor any signs of tumor progression, including tumor growth, new US features of potential gross ETE, and LNM. Therefore, appropriate imaging-based assessment plays a crucial role in determining whether AS or surgery should be pursued. However, detailed recommendations concerning US evaluation are currently insufficient, necessitating the formulation of this guideline. The Korean Society of Thyroid Radiology has developed a consensus statement for low-risk PTMC, covering US assessment methods when considering AS as a management option and conducting follow-up imaging tests during AS. This guideline aims to provide optimal scientific evidence and expert opinion consensus regarding a standardized US-based assessment protocol for low-risk PTMC.

Due to overdiagnosis, the incidence of thyroid cancer (TC) has increased in high-income countries, including Italy. Efforts have been made to address this issue since the mid-2010s, but more information is needed about how TC incidence has changed. We aim to examine the trend in TC incidence in the Lazio Region (central Italy) and assess the impact of the 2014 Italian Consensus for the Classification and Reporting of Thyroid Cytology (ICCRTC) to identify potential changes in TC diagnosis.

To identify TC cases, we conducted a population-based study (period 2007-2019) using the data from the Lazio Region Cancer Registry (5.8 million residents). We calculated the annual age-standardized incidence rates of TC for both sexes and analyzed the impact of ICCRTC on monthly incidence rates using segmented linear regression applied to interrupted time-series (ITS).

Throughout the 13 years, there was a significant decline in TC annual incidence rates, more pronounced in females. Our results are consistent with reports from outside Europe (United States and South Korea). Following ICCRTC implementation in 2014, a step-change reduction in both sexes was revealed.

Our study indicates a significant decrease in the incidence of TC, particularly among females. The ITS analysis highlights the possible role of ICCRTC in reducing overdiagnosis. As the Lazio Region reflects the Italian population in terms of various demographic, health, and lifestyle indicators, our findings can be applicable at the national level.

Active surveillance (AS) has been widely adopted as an alternative to immediate surgery owing to the indolent nature and favorable outcomes of papillary thyroid microcarcinoma (PTMC). AS is generally recommended for tumors measuring ≤1 cm without aggressive cytological subtypes, risk of gross extrathyroidal extension (ETE), lymph node metastasis (LNM), or distant metastasis. AS requires careful patient selection based on various patient and tumor characteristics, and ultrasound (US) findings. Moreover, during AS, regular US is performed to monitor any signs of tumor progression, including tumor growth, new US features of potential gross ETE, and LNM. Therefore, appropriate imaging-based assessment plays a crucial role in determining whether AS or surgery should be pursued. However, detailed recommendations concerning US evaluation are currently insufficient, necessitating the formulation of this guideline. The Korean Society of Thyroid Radiology has developed a consensus statement for low-risk PTMC, covering US assessment methods when considering AS as a management option and conducting follow-up imaging tests during AS. This guideline aims to provide optimal scientific evidence and expert opinion consensus regarding a standardized US-based assessment protocol for low-risk PTMC.

This study aimed to develop and validate a prognostic model for elderly patients with differentiated thyroid carcinoma (DTC) based on various demographic and clinical parameters in order to accurately predict patient outcomes. Patients who were diagnosed with DTC and were over 55 years old between 2010 and 2019 were identified from the Surveillance, Epidemiology, and End Results database. The patients were then randomly divided into a training set and a validation set in a 7:3 ratio, and patients from our center were included as an external validation group. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify independent prognostic factors, which were then utilized to develop nomograms for predicting the prognosis. The discriminative ability of the nomograms was evaluated using the concordance index, and the calibration was assessed using calibration plots. The clinical usefulness and benefits of the predictive models were determined through decision curve analysis. The findings of the stepwise Cox regression analysis revealed that several variables, including age, marital status, sex, multifocality, T stage, N stage, and M stage, were significantly associated with overall survival in elderly patients with DTC. Additionally, age, tumor size, multifocality, T stage, N stage, and M stage were identified as the primary determinants of cancer specific survival in elderly patients with DTC. Using these predictors, nomograms were constructed to estimate the probability of overall survival and cancer specific survival. The nomograms demonstrated a high level of predictive accuracy, as evidenced by the concordance index, and the calibration plots indicated that the predicted outcomes were consistent with the actual outcomes. Furthermore, the decision curve analysis demonstrated that the nomograms provided substantial clinical net benefit, indicating their utility in clinical practice.

Objective:To compare the prognosis of papillary thyroid microcarcinoma of the isthmus（PTMCI） after different surgical methods, and to investigate the most appropriate surgical plan for it, so as to provide reference for the selection of clinical surgical plan. Methods:The clinical data of 106 PTMCI patients diagnosed with postoperative pathology after surgical treatment in Department of Otolaryngology Head and Neck Surgery, Ningbo Medical Center Lihuili Hospital from January 2016 to June 2023 were retrospectively analyzed. The patients were divided into 3 groups according to whether there were nodules in the lateral lobe of the thyroid gland, namely, isolated PTMCI group, PTMCI group with unilateral lobe nodules, and PTMCI group with bilateral lobe nodules. Combined with follow-up information, the differences of recurrence rate, survival rate and postoperative complications after different surgical methods were compared among all groups. The surgical procedures included isthmic thyroidectomy, isthmic + unilateral lobectomy, and total thyroidectomy. All patients underwent central lymph node dissection at the same time. Results:There were no significant difference in recurrence rate, survival rate and postoperative complications among all groups and between groups. Postoperative recurrence occurred in 2 patients, among which 1 patient was PTMCI with multiple focal tumors in unilateral lobe undergoing isthmus + unilateral lobectomy + ipsilateral central lymph node dissection. The recurrence was manifested as contralateral cervical lymph node metastasis. Another case of PTMCI with bilateral benign nodules underwent isthmus + unilateral lobe（larger nodule） resection + ipsilateral central lymph node dissection, and the recurrence was manifested as residual glandular recurrence. One patient developed permanent hoarseness after surgery. The postoperative pathology of 31 patients（29.2%） indicated multiple focal thyroid carcinoma. Postoperative pathology of 41 patients（38.7%） suggested lymph node metastasis in the central region of neck. The disease-specific survival rate was 100%. Conclusion:Isthmic thyroidectomy is recommended for isolated PTMCI. Isthmus of thyroid+ unilateral lobectomy is feasible for PTMCI with unilateral lobectomy. If multiple suspicious malignant nodules（≥3） occur in unilateral lobectomy, total thyroidectomy is recommended. Total thyroidectomy is feasible for PTMCI with bilateral nodules. All PTMCI patients should undergo prophylactic central cervical lymph node dissection at the same time.

Differentiated thyroid carcinoma (DTC), mainly papillary (PTC), at low risk of recurrence is currently managed with active surveillance strategies or less aggressive surgeries. However, total thyroidectomy with 131I treatment is still performed both if these tumors are diagnosed before or occasionally after surgery. This real-life study aimed to evaluate the rate of biochemical, structural, and functional events in a large series of consecutive DTCs at low risk of recurrence treated by total thyroidectomy, but not with 131I, in a medium-long-term follow-up.

We evaluated clinical-pathologic data of 383 consecutive patients (2006-2012) with unifocal DTC [T1a/b(s)] at low risk of recurrence, treated with total thyroidectomy but without lymph node dissection and 131I treatment after surgery. We evaluated if structural, biochemical, and functional events were detected during the follow-up.

Females accounted for 75.7% of our study group, and the median age was 50 years. The median tumor dimension was 0.4 cm (range 0.1-1.2). Most of the patients had a unifocal T1a tumor (98.9%), and 73.6% had a classic variant of PTC. We divided the patients according to the absence (group A-n = 276) or presence (group B-n = 107) of interfering TgAb at first control after surgery. After a median follow-up of 10 years, no structural events were detected. Sixteen out of three hundred and eighty-three (4.2%) patients developed biochemical events: 12/276 (4.3%) in group A and 4/107 (3.7%) in group B. The median time elapsed from surgery to detecting a biochemical event was 14.5 and 77.5 months in groups A and B, respectively. No patients performed additional treatments and were followed up with an active surveillance strategy.

This study confirmed that patients with DTC at low risk of recurrence showed an excellent outcome in a medium long-term follow-up since no structural events were diagnosed. Significant variations in Tg/TgAb were detected in a few cases, all managed with an active surveillance strategy without the need for other treatments. Therefore, a relaxed follow-up with neck ultrasound and Tg/TgAb measurement is enough to early identify those very unusual cases of recurrence.

Active surveillance (AS) is increasingly recognized as an appropriate strategy for selected patients with papillary thyroid microcarcinomas (PTMC). However, some factors, including physician-related ones, hinder its widespread adoption.

To explore the prevailing barriers and the impact of information on attitudes towards AS implementation, we developed a questionnaire that was completed before and after reading a simple information leaflet by 317 doctors working in different work environments. This leaflet provides information about the overdiagnosis of PTMC, the concept of AS, results of early studies, and main advantages and disadvantages of AS.

We observed a greater resistance to AS among male physicians who were more likely to maintain the initial recommendation for surgery or referral to a head and neck surgeon than female physicians (77 % vs. 46 %, p = 0.01), regardless of their medical specialty. Fear of disease progression and of the patient losing follow-up were the main concerns. Reading the educational material significantly increased the number of physicians who endorsed AS as an initial approach to PTMC without risk factors from 14 % to 34 % (p < 0,001). This change in attitude was even more significant when doctors were confronted with a case of PTMC in an elderly patient. Gender, medical specialty, age range and academic environment were the factors that were determinants on the influence of the informative leaflet on the decision-making. The leaflet also increased the number of doctors who considered themselves capable of dealing with this patient profile; however, 17 % declared that the place where they worked would not be able to meet the need for periodic assessments and necessary examinations. This was particularly true for the 20 % of the professionals working in rural areas.

A simple educational leaflet with basic information presented via social media increased the number of Brazilian physicians who endorsed AS for PTMC management and proved to be a facilitating tool for understanding and accepting it. Our results suggest that this method can be easily extended to larger population.

Differentiated thyroid cancer (DTC) has been increasingly common in women of reproductive age. However, the evidence remains mixed regarding the association of DTC with adverse pregnancy outcomes in pregnant women previously diagnosed with DTC.

We conducted a retrospective cohort study in the Peking University Third Hospital in Beijing, China between January 2012 and December 2022. We included singleton-pregnancy women with a pre-pregnancy DTC managed by surgical treatment (after-surgery DTC) or active surveillance (under-surveillance DTC). To reduce the confounding effects, we adopted a propensity score to match the after-surgery and under-surveillance DTC groups with the non-DTC group, respectively, on age, parity, gravidity, pre-pregnancy weight, height, and Hashimoto's thyroiditis. We used conditional logistics regressions, separately for the after-surgery and under-surveillance DTC groups, to estimate the adjusted associations of DTC with both the composite of adverse pregnancy outcomes and the specific mother-, neonate-, and placenta-related pregnancy outcomes.

After the propensity-score matching, the DTC and non-DTC groups were comparable in the measured confounders. In the after-surgery DTC group (n = 204), the risk of the composite or specific adverse pregnancy outcomes was not significantly different from that of the matched, non-DTC groups (n = 816; P > 0.05), and the results showed no evidence of difference across different maternal thyroid dysfunctions, gestational thyrotropin levels, and other pre-specified subgroup variables. We observed broadly similar results in the under-surveillance DTC group (n = 37), except that the risk of preterm birth, preeclampsia, and delivering the low-birth-weight births was higher than that of the matched, non-DTC group [n = 148; OR (95% CI): 4.79 (1.31, 17.59); 4.00 (1.16, 13.82); 6.67 (1.59, 27.90)].

DTC was not associated with adverse pregnancy outcomes in pregnant women previously treated for DTC. However, more evidence is urgently needed for pregnant women with under-surveillance DTC, which finding will be clinically significant in individualizing prenatal care.

The current management guidelines for low-risk papillary thyroid microcarcinoma (PTMC) do not specify how to screen for growing tumors. We sought to explore the possible risk factors for tumor enlargement in patients with low-risk PTMC under active surveillance (AS).

We searched the PubMed and Embase databases for high quality studies up to January 10th, 2024. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of the included studies, and Review Manager 5.4 was used to analyze possible risk factors and calculate pooled risk ratios (RRs) via the inverse-variance calculation method.

Eleven studies were included in our meta-analysis. Among the 8880 participants, 464 experienced tumor growth, and the incidence of tumor growth varied from 3.4% to 19.4%. The results of the meta-analysis showed that tumor enlargement was associated with younger age (pooled RR = 2.32, 95% CI = 1.85-2.90, p < 0.00001; 8 studies), and higher serum thyroid-stimulating hormone (TSH) levels (pooled RR = 2.28, 95% CI = 1.19-4.37, p = 0.01; 6 studies), and could be related to pregnancy (pooled RR = 2.54, 95% CI = 1.17-5.52, p = 0.02; 2 studies). However, these following factors showed no significant association with tumor growth: sex (pooled RR = 1.07, 95% CI = 0.63-1.84, p = 0.79; 7 studies), tumor size at diagnosis (pooled RR = 1.08, 95% CI = 0.63-1.85, p = 0.77; 5 studies), and Hashimoto's thyroiditis (HT) (pooled RR = 1.56, 95% CI = 0.93-2.60, p = 0.09; 2 studies).

Our analysis identified that younger age and higher serum TSH levels were higher risk factors for tumor enlargement in low-risk PTMC patients. Pregnancy is a suspected risk factor.

Current management options for PTMC include lobo-isthmectomy and active surveillance (AS). Recently, ultrasound-guided minimally invasive procedures (MITs) are offered as a nonsurgical therapy for PTMC because they do not require hospitalization and general anaesthesia, and do not result in loss of thyroid function or cosmetic damage. MITs are reported to consistently provide, mostly in large retrospective series of patients, a rapid, safe, and cost-effective way to eradicate low-risk thyroid malignancies. However, conclusive data from well-conducted prospective studies on the histologically-proven completeness of tumor ablation and the long-term clinical advantages versus AS are still lacking.

This study aimed to evaluate the efficacy and safety of ultrasound-guided minimally invasive treatments (MITs) for PTMC in comparison to traditional surgical methods and active surveillance, and to assess their role in current clinical practice.

A structured literature review was conducted using keywords related to PTMC, MIT, and comparative techniques. Studies were evaluated based on treatment modality, patient selection, follow-up duration, complication rates, and clinical outcomes.

MITs have shown promising results in the management of PTMC. These treatments offer several advantages over surgery, such as reduced use of surgical resources, lower costs, minimal work disruption, and fewer major complications. However, there are still limitations, including the need for long-term surveillance and the potential risk of incomplete tumor ablation.

MITs represent a promising non-surgical option for managing low-risk PTMC, especially for patients ineligible for or refusing surgery. Despite favorable outcomes, more robust prospective data are needed to confirm their long-term benefits and completeness of tumor ablation. Interdisciplinary discussions and thorough patient education on the advantages and limitations of MITs are crucial for informed decision-making.

The recent surge in the incidence of small papillary thyroid cancers (PTCs) has been linked to the widespread use of ultrasonography, thereby prompting concerns regarding overdiagnosis. Active surveillance (AS) has emerged as a less invasive alternative management strategy for low-risk PTCs, especially for PTCs measuring ≤1 cm in maximal diameter. Recent studies report low disease progression rates of low-risk PTCs ≤1 cm under AS. Ongoing research is currently exploring the feasibility of AS for larger PTCs (<20 mm). AS protocols include meticulous ultrasound assessment, emphasis on standardized techniques, and a multidisciplinary approach; they involve monitoring the nodules for size, growth, potential extrathyroidal extension, proximity to the trachea and recurrent laryngeal nerve, and potential cervical nodal metastases. The criteria for progression, often defined as an increase in the maximum diameter of the PTC, warrant a review of precision and ongoing examinations. Challenges exist regarding the reliability of volume measurements for defining PTC disease progression. Although ultrasonography plays a pivotal role, challenges in assessing progression and minor extrathyroidal extension underscore the importance of a multidisciplinary approach in disease management. This comprehensive overview highlights the evolving landscape of AS for PTCs, emphasizing the need for standardized protocols, meticulous assessments, and ongoing research to inform decision-making.

To compare the long-term medical costs of active surveillance (AS), partial thyroidectomy (PT), and total thyroidectomy (TT) in patients with low-risk papillary thyroid microcarcinoma (PTMC) receiving care covered by the Brazilian Public Health System.

After reviewing AS cohorts and our own data, we created a model of AS, PT, and TT flow care for low-risk PTMC over 10, 20, and 30 years. The medical costs included those associated with diagnosis, surgery, and follow-up. We considered that 13.3% of the patients on AS would require surgery after a mean of 21.3 months, 4% undergoing TT would develop permanent hypoparathyroidism, and 43% undergoing PT would develop hypothyroidism.

The most economical alternative was AS. The costs of TT per patient were higher than those of AS by 182.8% over 10 years (866.89 versus 306.49 US dollars [USD], respectively), by 152.9% over 20 years (1,023.66 versus 404.73 USD, respectively), and by 134.7% over 30 years (1,180.42 versus 502.96 USD, respectively). The costs of PT per patient were higher than those of AS by 16.0% over 10 years (355.66 versus 306.49 USD, respectively), by 16.9% over 20 years (473.41 versus 404.73 USD, respectively), and by 17.5% over 30 years (591.17 versus 502.96 USD, respectively).

The AS approach was less costly than immediate surgery throughout 30 years of follow-up. Hence, the implementation of AS in Brazil should not be hindered by cost considerations.

Active surveillance for papillary thyroid cancer (PTC) meeting criteria for surgical resection is uncommon. Which patients may prove reasonable candidates for this approach is not well defined.

This work aimed to examine the feasibility and safety of active surveillance for patients with known or suspected intrathyroidal PTC up to 4 cm in diameter.

A retrospective review was conducted of all consecutive patients who underwent nonoperative active surveillance of suspicious or malignant thyroid nodules over a 20-year period from 2001 to 2021. We included patients with an initial ultrasound-fine-needle aspiration confirming either (a) Bethesda 5 or 6 cytology or (b) a "suspicious" Afirma molecular test. The primary outcomes and measures included the rate of adverse oncologic outcomes (mortality and recurrence), as well as the cumulative incidence of size/volume growth.

Sixty-nine patients were followed with active surveillance for 1 year or longer (average 55 months), with 26 patients (38%) having nodules 2 cm or larger. No patients were found to develop new-incident occurrence of lymph node or distant metastasis. One patient, however, demonstrated concern for progression to a dedifferentiated cancer on repeat core biopsy 17 years after initial start of nonoperative selection. A total of 21% of patients had an increase in maximum diameter more than 3 mm, while volume increase of 50% or greater was noted in 25% of patients. Thirteen patients ultimately underwent delayed (rescue) surgery, and no disease recurrence was noted after such treatment. Age and initial nodule size were not predictors of nodule growth.

These data expand consideration of active surveillance of PTC in select patients with intrathyroidal suspected malignancy greater than 1 cm in diameter. Rescue surgery, if required at a later time point, appears effective.

The incidence of thyroid cancer is increasing globally, but mortality rates have remained steady. Many patients with thyroid cancer have low-risk, nonmetastatic intrathyroidal tumors smaller than 2 cm. Active surveillance has shown benefits in these patients, but the adoption of this approach remains below standard in Latin America. The purpose of this article is to identify ways to improve the incorporation of active surveillance into clinical practice for patients with low-risk thyroid carcinoma in Latin America, taking into consideration cultural and geographic factors. Current recommendations include three steps involving patient participation. The first step, which consists of the initial clinical examination, has eight factors requiring special attention. Anxiety must be managed while considering individual, disease-related, cognitive, and environmental aspects. Terms like "overdiagnosis", "incidentaloma," and "overtreatment" must be explained to the patient. Implementing precise terminology contributes to adequate disease perception, substantially reducing stress and anxiety. Clarifying the nonprogressive nature of thyroid cancer helps dispel myths surrounding the disease. The second step includes advice about procedures and guidelines for patients who choose active surveillance. Flexible monitoring techniques should be implemented, with regular check-ins scheduled based on patient needs. Reasons for adjusting treatment must be clearly communicated to the patient, and changes in preference regarding active surveillance should be considered in advance. The third step includes assistance during follow-up. Patients must be educated about ultrasound results and receive surgical indications from specialized physicians. The effectiveness of active surveillance can be reinforced by explaining to the patients the dynamics of changes in nodule size using clear and concise visual aids.

Background: It is important to understand cancer survivors' perceptions about their treatment decisions and quality of life. Methods: We performed a prospective observational cohort study of Canadian patients with small (<2 cm) low-risk papillary thyroid cancer (PTC) who were offered the choice of active surveillance (AS) or surgery (Clinicaltrials.gov NCT03271892). Participants completed a questionnaire one year after their treatment decision. The primary intention-to-treat analysis compared the mean decision regret scale total score between patients who chose AS or surgery. A secondary analysis examined one-year decision regret score according to treatment status. Secondary outcomes included quality of life, mood, fear of disease progression, and body image perception. We adjusted for age, sex, and follow-up duration in linear regression analyses. Results: The overall questionnaire response rate was 95.5% (191/200). The initial treatment choices of respondents were AS 79.1% (151/191) and surgery 20.9% (40/191). The mean age was 53 years (standard deviation [SD] 15 years) and 77% (147/191) were females. In the AS group, 7.3% (11/151) of patients crossed over to definitive treatment (two for disease progression) before the time of questionnaire completion. The mean level of decision regret did not differ significantly between patients who chose AS (mean 22.4, SD 13.9) or surgery (mean 20.9, SD 12.2) in crude (p = 0.730) or adjusted (p = 0.29) analyses. However, the adjusted level of decision regret was significantly higher in patients who initially chose AS and crossed over to surgery (beta coefficient 10.1 [confidence interval; CI 1.3-18.9], p = 0.02), compared with those remaining under AS. In secondary adjusted analyses, respondents who chose surgery reported that symptoms related to their cancer or its treatment interfered with life to a greater extent than those who chose AS (p = 0.02), but there were no significant group differences in the levels of depression, anxiety, fear of disease progression, or overall body image perception. Conclusions: In this study of patients with small, low-risk PTC, the mean level of decision regret pertaining to the initial disease management choice was relatively low after one year and it did not differ significantly for respondents who chose AS or surgery.

Surgery plays a key role in the treatment of thyroid cancer (TC) patients. Locally advanced cases, however, can require an extensive surgical approach with technical issues and a high risk of complications. In these cases, a multidisciplinary evaluation should be carried out to evaluate pros and cons. The aim of this study was to share our experience, as a multidisciplinary team, in the management of patients with locally advanced TC with a particularly extensive local disease, whose surgical approach could be challenging and part of a multimodal treatment.

We retrospectively evaluated clinical, surgical, and oncologic features of all patients with locally advanced TC who had undergone multidisciplinary surgery from January 2019 to June 2020.

Six patients (two cases each of poorly differentiated, papillary, and medullary TC) were included. Four out of six were suffering from symptoms related to the advanced disease. At pre-surgical evaluation, a multidisciplinary team proposed extended surgery with radical intent via cervicotomy and sternotomy, considering other therapies not feasible or probably ineffective without it. No one passed away in intra- or perioperative time. At the end of follow-up (median 2.6 years), all patients presented a remission of symptoms due to the advanced disease, four patients were submitted to adjuvant therapies and only one patient died for a cause unrelated to the disease.

This series of very advanced TCs shows the effectiveness of a surgery performed by a multidisciplinary team in controlling symptoms, allowing adjuvant therapies, and improving the survival of patients whose cases would otherwise be very difficult to manage.

In recent decades, the prevalence of thyroid cancer has risen substantially, with papillary thyroid microcarcinoma (PTMC) constituting over 50% of cases. Although most PTMCs exhibit indolent growth and a favorable prognosis, some present an increased risk of recurrence and an unfavorable prognosis due to high-risk characteristics such as lymph node metastasis, extrathyroidal extension, and distant metastasis. The early identification of clinically progressing PTMC remains elusive. In this review, the authors summarize findings from PTMC progression-related literature, highlighting that factors such as larger tumor size, cervical lymph node metastasis, extrathyroidal extension, younger age, higher preoperative serum thyroid-stimulating hormone levels, family history, and obesity positively correlate with PTMC progression. The role of multifocality in promoting PTMC progression; however, remains contentious. Furthermore, recent studies have shed light on the impact of mutations, such as BRAF and TERT mutations, on PTMC progression. Researchers have identified several mRNAs, noncoding RNAs, and proteins associated with various features of PTMC progression. Some studies propose that peripheral and tumor tissue-infiltrating immune cells could serve as biomarkers for the clinical progression of PTMC. Collectively, these clinical and molecular features offer a rationale for the early detection and the development of precision theranostic strategies of clinically progressive PTMC.

Active surveillance of low-risk papillary thyroid microcarcinomas has gained popularity worldwide as a management strategy. We previously reported that young age was associated with tumor enlargement by ≥3 mm. Here, we used the tumor volume-doubling rate to study the age-related tumor volume dynamics of papillary thyroid microcarcinomas under active surveillance.

Between 2005 and 2019, 2,896 patients diagnosed with low-risk papillary thyroid microcarcinomas underwent active surveillance. We excluded patients who underwent ultrasound examination fewer than 4 times, had coexisting Graves' disease, or were treated with levothyroxine at the time of diagnosis, and we enrolled 2,129 patients for this study. We divided them into 3 subsets based on the age at diagnosis: young (<40 years), middle-aged (40-59 years), and elderly (≥60 years). The tumor volume-doubling rate was calculated based on ultrasound-derived tumor sizes and the respective examination date for each patient.

Overall, 140 patients (6.6%) had moderate or rapid growth (tumor volume-doubling rate ≥0.3/year), and the incidence significantly decreased with advanced age (P < .01): 11.3%, 7.1%, and 5.0% in the young, middle-aged, and elderly groups, respectively. Tumor regression (tumor volume-doubling rate <0/year) was detected in 1,200 patients (56.4%), and the incidence significantly increased with age (P < .01): 44.6%, 55.3%, and 60.0% in the young, middle-aged, and elderly groups, respectively. On multivariate analysis, both the ≥60 years and 40 to 59 years age groups were independent negative predictors of papillary thyroid microcarcinoma enlargement and positive predictors of tumor regression.

Tumor volume-doubling rate analysis demonstrated that the incidence of tumor enlargement decreased and that of tumor regression increased with advancing age in patients with papillary thyroid microcarcinomas.

To assess tumor growth using tumor doubling rate (TDR) during active surveillance (AS) in China.

Between January 2016 and June 2020, a total of 219 patients with low-risk papillary thyroid microcarcinoma (PTMC) (aged 23-75 years) were consecutively enrolled in the AS program.

Four sections of TDR, >0.5, 0.1~0.5, -0.1~0.1 and <-0.1, corresponded with four categories of tumor volume kinetics: rapid growth, slow growth, stable, and decreased size. We found that 10.5% of PTMCs exhibited rapid growth, 33.33% exhibited slow growth, 26.48% were stable, and 29.68% decreased in size. Tumor growth was associated with two factors: age and volume of PTMC at diagnosis. 85.72% of elderly patients (≥ 61 years old) had tumors that remained stable or even shrank and rapidly growing tumors were not found in them. When the volume was small (≤14.13 mm3), the proportion of rapid growth was high (41.67%), whereas when the volume was large (> 179.5 mm3), the proportion of non-growth was 68.75%.

TDR may be a better metric for evaluating tumor growth in observational PTMCs. A certain proportion of PTMCs grow during the period of AS and tumor growth was associated with age and volume of PTMC at initial diagnosis. Therefore, how to block tumor growth during the AS period, especially for young patients and patients with early-stage PTMC (size ≤ 5 mm), will be a new challenge.

Papillary thyroid carcinoma (PTC) is the most frequent malignant tumor in thyroid carcinoma. The aim of this study was to explore the risk factors associated with central lymph node metastasis in papillary thyroid microcarcinoma (PTMC) and establish a nomogram model that can assess the probability of central lymph node metastasis (CLNM).

The clinicopathological data of 377 patients with cN0 PTMC were collected and analyzed from The Second Affiliated Hospital of Fujian Medical University from July 1st, 2019 to December 30th, 2021. All patients were examined by underwent ultrasound (US), found without metastasis to central lymph nodes, and diagnosed with PTMC through pathologic examination. All patients received thyroid lobectomy or total thyroidectomy with therapeutic or prophylactic central lymph node dissection (CLND). R software (Version 4.1.0) was employed to conduct a series of statistical analyses and establish the nomogram.

A total of 119 patients with PTMC had central lymph node metastases (31.56%). After that, age (P < 0.05), gender (P < 0.05), tumor size (P < 0.05), tumor multifocality (P < 0.05), and ultrasound imaging-suggested tumor boundaries (P < 0.05) were identified as the risk factors associated with CLNM. Subsequently, multivariate logistic regression analysis indicated that the area under the receiver operating characteristic (ROC) curve (AUC) of the training cohort was 0.703 and that of the validation cohort was 0.656, demonstrating that the prediction ability of this model is relatively good compared to existing models. The calibration curves indicated a good fit for the nomogram model. Finally, the decision curve analysis (DCA) showed that a probability threshold of 0.15-0.50 could benefit patients clinically. The probability threshold used in DCA captures the relative value the patient places on receiving treatment for the disease, if present, compared to the value of avoiding treatment if the disease is not present.

CLNM is associated with many risk factors, including age, gender, tumor size, tumor multifocality, and ultrasound imaging-suggested tumor boundaries. The nomogram established in our study has moderate predictive ability for CLNM and can be applied to the clinical management of patients with PTMC. Our findings will provide a better preoperative assessment and treatment strategies for patients with PTMC whether to undergo central lymph node dissection.

The current approach for patients with differentiated thyroid carcinoma should be individualized according to the risk of recurrence, and this stratification could be used to identify the risk of persistent/recurrent disease in three scenarios: preoperatively, immediately postoperatively, and during long-term follow-up. The initial risk of recurrence will tailor the management of the patient in the preoperative and immediate postoperative settings, while the dynamic risk, which considers the responses to treatment, could guide the decision-making process for remnant ablation and long-term management.This review provides a summary of the existing information regarding the dynamic risk of recurrence and recommended management for patients with differentiated thyroid cancer. The application of this approach is essential to avoid unnecessary treatments for most patients who will have a favorable prognosis. On the other hand, it allows specific therapeutic interventions for those patients at high risk of recurrence. In the future, analysis of tumor biology and prospective studies will surely improve the accuracy of recurrence risk prediction.

Active surveillance (AS) has been introduced as a management strategy for low-risk papillary thyroid carcinoma (PTC) due to its typically indolent nature. Despite this, the widespread adoption of AS has encountered several challenges. The aim of this systematic review was to evaluate the safety of AS related to disease progression and its benefits compared with immediate surgery (IS).

Studies related to AS in patients with low-risk PTC were searched through the Ovid MEDLINE, Embase, Cochrane Library, and KoreaMed databases. Studies on disease progression, surgical complication, quality of life (QoL), and cost-effectiveness were separately analyzed and narratively synthesized.

In the evaluation of disease progression, the proportions of cases with tumor growth ≥3 mm and a volume increase >50% were 2.2%-10.8% and 16.0%-25.5%, respectively. Newly detected lymph node metastasis was identified in 0.0%-1.4% of patients. No significant difference was found between IS and delayed surgery in surgical complications, including vocal cord paralysis and postoperative hypoparathyroidism. AS was associated with better QoL than IS. Studies on the cost-effectiveness of AS reported inconsistent data, but AS was more cost-effective when quality-adjusted life years were considered.

AS is an acceptable management option for patients with low-risk PTC based on the low rate of disease progression and the absence of an increased mortality risk. AS has additional benefits, including improved QoL and greater QoL-based cost-effectiveness.

The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Bibliometrics has been used to analyze the literature in the field of thyroid disease studies in the early 21st century, indicating the changes in current international study trends.

In this study, a bibliometric analysis of data retrieved from the Web of Science (WoS) database was conducted, and the publication trends and thematic evolution in the field of thyroid disease research from January 1, 2000, to November 16, 2022, were analyzed. A total of 69283 articles related to thyroid diseases were evaluated for their characteristics, including annual publication volume, countries, journals, institutions, authors, keywords, and references. VOSviewer was utilized to perform the analysis of co-authorship, co-citation, co-occurrence and descriptive.

The annual publication volume of thyroid disease research literature showed a fluctuating upward trend from 2000 to 2021, exceeding 5,000 articles for the first time in 2021. The United States (16120 counts, 678255 cities) ranks first in terms of publication volume and citation. Thyroid (n=3201) and Journal of Clinical Endocrinology&Metabolism (n=140399) are the most prolific and cited journals, respectively. The organization with the highest publication volume and citation frequency is Harvard University (1011 counts, 59429 cities), Miyauchi Akira (n=422), Schlumberger, and Martin (n=24839) possess the highest publication volume and citation frequency, respectively. Co-occurrence analysis of 307 keywords with frequencies of more than 20 resulted in 6 clusters (1): Thyroid dysfunction and diseases (2); mechanism of occurrence and development of thyroid cancer (3); autoimmune thyroiditis (4); scope and postoperative management of thyroid surgery (5); fine needle aspiration of thyroid nodules (6); radioactive iodine therapy for thyroid cancer. Active monitoring, thermal ablation, Lenvatinib, and long noncoding RNA refer to the latest keywords. Discussing the six clusters helps scholars to determine the scope and direction of studies.

Over the past two decades, the literature related to thyroid diseases has increased year by year, with closer collaboration between countries, institutions, and authors. In this study, the global trends, research hotspots, emerging subjects, and basic knowledge of literature related to thyroid diseases were respectively elucidated, which will facilitate researchers in this field to seek better development.

Overdiagnosis of papillary thyroid microcarcinoma (PTMC) is prevalent, and effective management of PTMC is an important matter. The high incidence and low mortality rate of papillary thyroid carcinoma (PTC) justify the preference for active surveillance (AS) over immediate surgery (IS), particularly in cases of low-risk PTMC. Japan began AS in the 1990s as an alternative surgical option for PTMC and it has shown promising results. The safety and efficacy of AS management in PTMC have been verified. However, AS may not be suitable for all PTMC cases. How to find the balance between the decision-making of AS and IS requires careful consideration. Therefore, we collected and analyzed the relevant evidence on the clinical strategies for PTC and discussed AS and IS from the perspectives of health, economic, and psychological aspects, to help clinicians in choosing a more appropriate clinical strategy for PTC.

To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)].

AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS.

A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed.

A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression.

These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed.

ClinicalTrials.gov Identifier: NCT02938702.