Low-risk Papillary Thyroid Microcarcinoma Research Articles

Conformal thyroidectomy is a feasible option in papillary thyroid microcarcinoma: a retrospective cohort study with 10-year follow-up results

BackgroundIn recent years, there has been an increasing prevalence of patients with papillary thyroid microcarcinoma (PTMC) without lymph node involvement in medical centers worldwide. For patients who are unable to undergo active surveillance (AS) and are afraid of postoperative complications, conformal thyroidectomy may be a suitable option to ensure both preservation of function and complete removal of the tumor.MethodsThe patients in the cohort during 2010 to 2015 were retrospectively enrolled strictly following the inclusion and exclusion criteria. The observation and control groups were defined based on the surgical approach, with patients in the observation group undergoing conformal thyroidectomy and patients in the control group undergoing lobectomy. Event-free survival (EFS), the interval from initial surgery to the detection of recurrent or metastatic disease, was defined as the primary observation endpoint.ResultsA total of 319 patients were included in the study, with 124 patients undergoing conformal thyroidectomy and 195 patients undergoing lobectomy. When compared to lobectomy, conformal thyroidectomy demonstrated reduced hospital stays, shorter operative times, and lower rates of vocal cord paralysis and hypoparathyroidism. Furthermore, the mean bleeding volume during the operation and the rate of permanent hypothyroidism were also lower in the conformal thyroidectomy group than in the lobectomy group. However, there was no statistically significant difference observed in the 5- and 10-year EFS between the two groups.ConclusionsConformal thyroidectomy had advantages in perioperative management and short-term complication rates, with an EFS that was not inferior to that of lobectomy. Thus, conformal thyroidectomy is a feasible option for low-risk PTMC patients.

Risk factors for tumor enlargement in low-risk papillary thyroid microcarcinoma patients: a systematic review and meta-analysis.

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.

Expert consensus on thermal ablation of papillary thyroid cancer (2024 edition)

Ultrasound-guided thermal ablation of papillary thyroid cancer (PTC) has been promoted in clinical practice over the past few years. Thermal ablation has the advantages of being minimally invasive, effective, and safe. However, current guidelines and consensus only focus on low-risk papillary thyroid microcarcinoma. With growing clinical application and accumulating scientific research in thermal ablation for PTC, there is considerable evidence to demonstrate that thermal ablation can treat larger PTC tumors and benefit more patients with PTC. To expand the indications and standardize the technical details and perioperative patient management for PTC ablation, experts from the Society of Tumor Ablation Therapy of the Chinese Anti-Cancer Association, the Ablation Expert Committee of the Chinese Society of Clinical Oncology (CSCO), Chinese Medical Doctor Association College of Interventionalists Tumor Ablation Committee, and Chinese Bethune Spirit Research Association Endocrinology and Diabetes Branch Interventional Endocrine Committee discussed and developed a consensus on thermal ablation of PTC based on the latest research results. This consensus aims to promote the rapid development of thermal ablation for PTC in the clinic.

Factors affects the implementation of active surveillance therapy for low-risk papillary thyroid microcarcinoma.

Factors affects the implementation of active surveillance therapy for low-risk papillary thyroid microcarcinoma.

Tumor growth manifested in two-fifths of low-risk papillary thyroid microcarcinoma patients during active surveillance: data from a tertiary center in China.

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 ≤ 5mm), will be a new challenge.

Retrospective Analysis of the Efficacy and Safety of Ultrasound-Guided Radiofrequency Ablation in the Treatment of Papillary Thyroid Microcarcinoma: A Follow-Up Study of Continuous Postoperative Surveillance and Large-Sample Data.

To retrospectively evaluate the efficacy and safety of ultrasound-guided radiofrequency ablation (RFA) in the treatment of papillary thyroid microcarcinoma (PTMC) through a follow-up study of continuous postoperative surveillance and large-sample data. The efficacy of ultrasound-guided RFA was evaluated by measuring the tumor volume reduction rate (VRR), tumor disappearance rate, and disease progression in 358 patients with low-risk unifocal PTMC who underwent ultrasound-guided RFA at Hangzhou Weja Hospital, while the safety was evaluated by measuring their complications. The VRR was -745.69 ± 1012.69 (%), -150.35 ± 395.5 (%), 46.47 ± 138.74 (%), 92.95 ± 27.88 (%), 97.78 ± 10.99 (%), and 99.27 ± 3.82 (%), respectively, at 1, 3, 6, 12, 18, and 24 months after RFA. The corresponding tumor disappearance rate was 1.68%, 9.78%, 43.85%, 82.68%, 92.59%, and 95.63%, respectively. No local recurrence, new tumors, lymph node metastasis, distant metastasis, and deaths caused by recurrent/metastatic PTMC were found at the last follow-up. Except for 3 cases (0.84%) with thickening or hoarseness of voice and 3 cases (0.84%) with coughing during drinking water, no other complications were found. Ultrasound-guided RFA has good efficacy and safety for the treatment of low-risk unifocal PTMC and can be promoted for use in patients who meet the required indications.

A nomogram for predicting adverse pathologic features in low-risk papillary thyroid microcarcinoma

BackgroundIdentifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients.MethodsA total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors.ResultsMost PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p < 0.05). Other factors (age, gender, family history of thyroid cancer, history of autoimmune thyroiditis, and BRAFV600E mutation) had no significant correlation with adverse pathologic features (p > 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAFV600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580–0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit.ConclusionTumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.

Re: "Active Surveillance Outcomes of Patients with Low-Risk Papillary Thyroid Microcarcinoma According to Levothyroxine Treatment Status" by Yamamoto et al.

Not Applicable.

Response to Xiang and Zhang re: "Active Surveillance Outcomes of Patients with Low-Risk Papillary Thyroid Microcarcinoma According to Levothyroxine Treatment Status".

Not available.

Radiofrequency ablation for papillary thyroid microcarcinoma with a trachea-adjacent versus trachea-distant location

Objective To evaluate the outcomes of radiofrequency ablation (RFA) for papillary thyroid microcarcinoma (PTMC) adjacent to the trachea and compare them with those of PTMC distant from the trachea. Methods Patients who received RFA for solitary low-risk PTMC between June 2014 and July 2020 were reviewed and classified into adjacent and distant groups. To balance between-group confounders, the propensity score matching approach was employed. Volume, volume reduction ratio (VRR), tumor disappearance, complications, and disease progression were assessed and compared between the groups. Furthermore, factors affecting disease progression were evaluated. Results A total of 122 and 470 patients were included in the adjacent and distant groups, respectively. Overall VRR was 99.5% ± 3.1 and cumulative tumor disappearance rate was 99.4% after a mean follow-up time of 40.1 months ± 16.2. Overall disease progression and complications incidence were 3.7% and 1.0%, respectively. No substantial differences were observed between the two groups in the latest volume (0.8 mm3 ± 4.1 vs. 0.9 mm3 ± 4.2, p = .77), VRR (99.7% ± 1.6 vs. 99.5% ± 2.7, p = .75), cumulative tumor disappearance rate (92.6% vs. 94.2%, p = .58), and incidence of disease progression (4.1% vs. 4.5%, p = .70) and complication (1.7% vs. 0.8%, p = .86) after 1:2 matching. Additionally, tracheal adjacency exhibited no association with disease progression in multivariate Cox regression analysis (p = .73). Conclusion For eligible patients with PTMC located adjacent to or distant from the trachea, RFA may offer a safe and effective alternative treatment method.

Radiofrequency ablation for capsular-located versus noncapsular-located papillary thyroid microcarcinoma: a propensity score matching study of 1095 patients.

To assess the safety and efficacy of radiofrequency ablation (RFA) for capsular-located papillary thyroid microcarcinoma (PTMC) in a large cohort and to compare its outcomes with those of noncapsular-located PTMC. We retrospectively reviewed patients who underwent RFA for solitary capsular-located and noncapsular-located low-risk PTMC (n = 1095) from June 2014 to October 2020. To balance confounding variables between capsular and noncapsular groups, we employed the 1:1 propensity score matching approach. We evaluated and compared tumor changes, disease progression, and complications in both groups. Furthermore, we analyzed the association between capsular location and disease progression using multivariable Cox regression. During a mean follow-up time of 29.86 ± 16.14months and 29.73 ± 15.69months, no substantial difference was observed between capsular and noncapsular groups in the latest volume (0.83 ± 3.66 mm3 vs. 0.85 ± 3.67 mm3, p = 0.44) and volume reduction ratio (99.29 ± 4.04% vs. 99.43 ± 3.03%, p = 0.43), and cumulative disappearance rate (87.87% vs. 86.07%, p = 0.31). In addition, no significant differences were observed in complication incidence (1.35% vs. 1.12%, p = 0.76) and progression-free survival (p = 0.53). Based on adjusted multivariate Cox proportional hazard analysis, the association between capsular location and disease progression was nonsignificant (all p > 0.05). This study demonstrates that the short-term outcomes of RFA for capsular-located PTMCs are comparable to those of noncapsular-located PTMCs. These findings indicate that RFA may be a viable and effective alternative for eligible patients with solitary capsular-located PTMC. Radiofrequency ablation may serve as a safe and effective alternative treatment method for eligible patients with capsular-located and noncapsular-located papillary thyroid microcarcinoma. • The safety and efficacy of radiofrequency ablation for capsular-located and noncapsular-located papillary thyroid microcarcinomas were comparable. • Disease progression did not differ significantly between capsular-located and noncapsular-located papillary thyroid microcarcinomas. • The incidence of complications for capsular-located papillary thyroid microcarcinoma was low.

Choice of management strategy for papillary thyroid microcarcinoma: active surveillance or immediate surgery?

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.

The frequency of risk pathological characteristics in clinically low-risk papillary thyroid microcarcinoma suitable for active surveillance.

Active surveillance has emerged as an initial management strategy for patients with low-risk papillary thyroid microcarcinoma (PTMC). The main objective of this research was to investigate the frequency of risk pathological characteristics among patients with clinically low-risk PTMC who are suitable for Active Surveillance. A retrospective review was conducted on patients who underwent lobectomy for PTMC between January 2013 and December 2018. Patients with bilateral tumors, macroscopic multifocal tumors, macroscopic extrathyroidal extension (ETE), clinical lymph node metastases, macroscopic extranodal extension (ENE), distant metastases, a history of neck radiation or familial thyroid cancer were excluded. Pathological characteristics were collected from the postoperative pathological results. Aggressive variants, multifocality, ETE, lymphovascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LNs) ≥ 5, and ENE were defined as risk characteristics. The study included 4923 patients, of whom 1229 (25.0%) were male. The mean age was 43years. A total of 2250 patients (45.7%) exhibited risk characteristics. Among them, 15 patients presented with aggressive variants, and 1813 patients (36.8%) had ETE. Multifocality, LVI, and PNI were observed in 551 (11.2%), 21 (0.4%), and 40 (0.8%) patients, respectively. A total of 139 patients (2.8%) had five or more metastatic LNs, and ENE was identified in 140 patients. Notably, 172 patients (3.5%) fulfilled the criteria for completion thyroidectomy, as they had aggressive variants, LVI, or five or more metastatic LNs. Nearly half of the patients diagnosed with clinically low-risk PTMC exhibited risk pathological characteristics, and a small proportion of patients met the criteria for completion thyroidectomy.

A prediction model for identifying high-risk lymph node metastasis in clinical low-risk papillary thyroid microcarcinoma

BackgroundThe presence of high-volume lymph node metastasis (LNM) and extranodal extension (ENE) greatly increases the risk of recurrence in patients with low-risk papillary thyroid microcarcinoma (PTMC). The goal of this research was to analyze the factors that contribute to high-risk lymph node metastasis in patients with low-risk PTMC.MethodsWe analyzed the records of 7344 patients who were diagnosed with low-risk PTMC and treated at our center from January 2013 to June 2018.LNM with a high volume or ENE was classified as high-risk lymph node metastasis (hr-LNM). A logistic regression analysis was conducted to identify the risk factors associated with hr-LNM. A nomogram was created and verified using risk factors obtained from LASSO regression analysis, to predict the likelihood of hr-LNM.ResultsThe rate of hr-LNM was 6.5%. LASSO regression revealed six variables that independently contribute to hr-LNM: sex, age, tumor size, tumor location, Hashimoto’s thyroiditis (HT), and microscopic capsular invasion. A predictive nomogram was developed by integrating these risk factors, demonstrating its excellent performance. Upon analyzing the receiver operating characteristic (ROC) curve for predicting hr-LNM, it was observed that the area under the curve (AUC) had a value of 0.745 and 0.730 in the training and testing groups showed strong agreement, affirming great reliability.ConclusionSex, age, tumor size, tumor location, HT, and microscopic capsular invasion were determined to be key factors associated with hr-LNM in low-risk PTMC. Utilizing these factors, a nomogram was developed to evaluate the risk of hr-LNM in patients with low-risk PTMC.

Clinical factors for choosing active surveillance: an analysis of papillary thyroid microcarcinoma patients with recurrence.

Active surveillance (AS) has been suggested as a management option for low-risk papillary thyroid microcarcinoma (PTMC). However, the currently proposed selection criteria for AS application do not consider various clinical factors. The purpose of this study was to analyze clinical factors related to recurrence that could be confirmed preoperatively in patients who underwent surgery for PTMC and to identify factors worth considering when deciding whether to apply AS. Data were collected from patients with PTMC who underwent surgical treatment at Chungnam National University Hospital. A retrospective cohort was established according to the presence or absence of recurrence during the follow-up period. In total, 2717 patients were enrolled, of whom 60 experienced recurrence. Various clinical factors that could be identified before surgery were analyzed. The relationship between various clinical factors that could be confirmed preoperatively and recurrence was confirmed through Cox regression analysis and Kaplan-Meier curve analysis. BRAF mutation and the tall cell variant were significantly more common in patients with recurrence. In patients aged 55 years or older, the risk of recurrence was lower than in younger patients, while the recurrence-free survival (RFS) rate was higher. When choosing between surgical treatment or AS in PTMC patients, additional consideration of the patient's clinical factors, such as age and BRAF mutation status, may be required in addition to the existing criteria.

The safety and efficacy of delayed surgery by simulating clinical progression of observable papillary thyroid microcarcinoma: a retrospective analysis of 524 patients from a single medical center.

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

Incidence and risk factors for occult lesions in low-risk papillary thyroid microcarcinoma patients with tumor characteristics appropriate for thermal ablation: A retrospective study.

In recent years, thermal ablation has been increasingly employed for the treatment of low-risk papillary thyroid microcarcinoma (PTMC) across various institutions. Its use as a standard or initial treatment continues to be a subject of debate. Retrospective analyses of the surgical pathology in post-ablation patients have indicated that occult lesions are not uncommon. This retrospective study aimed to examine the incidence and risk factors of occult lesions via postoperative pathology in low-risk PTMC patients who fulfilled the criteria for thermal ablation therapy. We examined the medical records of patients who underwent thyroid surgery and had a Bethesda classification V or VI based on fine needle aspiration cytology between November 22, 2020, and December 31, 2022. A total of 413 patients with preoperative tumor characteristics appropriate for thermal ablation were included in this study. Occult lesions, encompassing ipsilateral or contralateral occult carcinoma or central lymph node metastases may have occurred in 34.7% of patients. Male gender (OR: 2.526, 95% CI: 1.521-4.195, P = .000), tumor location in the lower pole (OR: 1.969, 95% CI: 1.186-3.267, P = .009), multiple microcalcifications (OR: 5.620, 95% CI: 2.837-11.134, P = .000), and Hashimoto's thyroiditis (OR: 2.245, 95% CI: 1.292-3.899, P = .004) were independent risk factors for the presence of occult lesions. In low-risk PTMC patients exhibiting tumor characteristics amenable to thermal ablation, over one-third of the patients may present with occult lesions. Meticulous evaluation of the presence of additional lesions is necessary before performing thermal ablation, particularly in patients exhibiting high-risk factors for occult lesions.

A novel nomogram for identifying high-risk patients among active surveillance candidates with papillary thyroid microcarcinoma.

Active surveillance (AS) has been recommended as the first-line treatment strategy for low-risk (LR) papillary thyroid microcarcinoma (PTMC) according to the guidelines. However, preoperative imaging and fine-needle aspiration could not rule out a small group of patients with aggressive PTMC with large-volume lymph node micro-metastasis, extrathryoidal invasion to surrounding soft tissue, or high-grade malignancy from the AS candidates. Among 2,809 PTMC patients, 2,473 patients were enrolled in this study according to the inclusion criteria. Backward stepwise multivariate logistic regression analysis was used to filter clinical characteristics and ultrasound features to identify independent predictors of high-risk (HR) patients. A nomogram was developed and validated according to selected risk factors for the identification of an HR subgroup among "LR" PTMC patients before operation. For identifying independent risk factors, multivariable logistic regression analysis was performed using the backward stepwise method and revealed that male sex [3.91 (2.58-5.92)], older age [0.94 (0.92-0.96)], largest tumor diameter [26.7 (10.57-69.22)], bilaterality [1.44 (1.01-2.3)], and multifocality [1.14 (1.01-2.26)] were independent predictors of the HR group. Based on these independent risk factors, a nomogram model was developed for predicting the probability of HR. The C index was 0.806 (95% CI, 0.765-0.847), which indicated satisfactory accuracy of the nomogram in predicting the probability of HR. Taken together, we developed and validated a nomogram model to predict HR of PTMC, which could be useful for patient counseling and facilitating treatment-related decision-making.

Response to Letter to the Editor on Surgical Outcomes in Patients With Low-Risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation Following Active Surveillance: A Multicenter Prospective Cohort Study.

Response to Letter to the Editor on Surgical Outcomes in Patients With Low-Risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation Following Active Surveillance: A Multicenter Prospective Cohort Study.

Efficacy and safety of radiofrequency ablation in active surveillance candidate for low-risk papillary thyroid microcarcinoma

Efficacy and safety of radiofrequency ablation in active surveillance candidate for low-risk papillary thyroid microcarcinoma