Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid carcinoma, accounting for 70–90% of differentiated thyroid cancers (1, 2). Although the local recurrence rate of PTC can reach as high as 30%, the associated mortality rate is extremely low, with a 10-year overall survival rate >90% (2), due to its relatively mild biological behavior. The American Joint Committee on Cancer (AJCC) on the tumor, lymph node, metastasis (TNM) staging system defined T1bN0M0 PTC as that limited to the thyroid with tumor >1 cm but ≦2 cm in the greatest dimension with no evidence of locoregical lymph node involvement or of distant metastasis (3). Currently, the 2015 American Thyroid Association (ATA) guidelines (4) still recommend thyroid lobectomy as the first-line treatment for PTC. However, associated incidence of operative complications such as temporary or permanent recurrent laryngeal nerve paralysis, hypothyroidism, and hypoparathyroidism can range from 16.3 to 72.5%, according to previous studies (5–10).

Presently, overdiagnosis and overtreatment of PTC is one of the most controversial issues in the management of thyroid carcinoma (11, 12). Long-term active surveillance (AS) of patients with T1aN0M0 PTC performed in several institutions has revealed that the follow-up approach may constitute an appropriate, conservative management strategy (13–15). The 2015 ATA Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer also mentioned that AS may be employed as an alternative strategy in selected PTC patients (4). However, long-term follow-up on studies on AS for T1bN0M0 PTC have been rarely reported.

In comparison to active surveillance (AS) and surgical resection (SR), the treatment modality of radiofrequency ablation (RFA) utilizes frictional heating, which may lead to cell injury (16) in a bid to achieve E0 resection. RFA is characterized by its technical ease and non-invasive nature. To date, several leading institutes have reported successful outcomes with the use of RFA in the treatment of T1N0M0 PTC, recurrent thyroid cancers, and lymph node metastatic tumors (17–22). As compared to SR, RFA is associated with comparable long-term outcomes, shorter hospital stay, and fewer temporary and permanent complications (23, 24). Unlike AS, RFA allows safe and effective removal of tumors, thereby minimizing harmful consequences of potential growth of the malignancy. However, while tumor size and patient age are related to the prognosis of differentiated thyroid cancers (25, 26), there is a lack of long-term data on researches on the outcomes of RFA performed for the treatment of T1bN0M0 PTC across different age groups. In the present study, we aimed to compare the efficacy and safety of RFA with that of SR for T1bN0M0 PTC, in patients of different age groups.

This retrospective study was approved by the Institutional Review Board of the First Medical Center of the Chinese PLA General Hospital. We reviewed medical records of patients with T1bN0M0 PTC, who underwent RFA or surgery from April 2014 to December 2019. All patients provided written informed consent prior to a treatment procedure.

While thyroid surgery is still the first-line treatment option recommended for T1N0M0 PTC, according to both the 2015 ATA guideline and other guidelines for the management of thyroid cancer (4, 29, 30), clinical management of affected patients remains controversial due to indolent nature of the malignancy. Thyroidectomy was deemed an aggressive treatment option for low-risk PTC, especially in patients with stage I tumors. Moreover, the risk of complications including recurrent laryngeal nerve paralysis, hypoparathyroidism, and hypothyroidism not only significantly impacted the quality of life in affected patients but also made some patients unwilling to undergo SR.

Therefore, to prevent overtreatment, the ATA guidelines and those of the Japan Association mentioned that AS was safe in selected patients with low-risk PTC. According to the AJCC staging system, T1 PTC can be subdivided into T1a and T1b based on tumor diameter. AS in patients with T1aN0M0 was studied in the 1990s in Japan, and thereafter studies were conducted in other countries with huge populations, over long follow-up periods. However, research on T1bN0M0 stage PTC is still nascent, and reported findings vary greatly (31). Other non-surgical options excepting AS, such as ultrasound-guided RFA and microwave ablation (MWA), have been used for primary management of T1N0M0 PTC with expected outcomes (21, 22, 32, 33). However, a lot of research is still needed to explore the suitable population of RFA.

Age is a unique factor that negatively affects prognosis of patients with PTC. Many studies have considered 45 years of age as the cut-off point for staging dichotomization (34) for two reasons. First, the median age of patients at diagnosis in most studies is 45 years old (35). Second, some research results like Miyauchi et al. (36) reported that PTC patients aged ≥45 years experienced a tumor progression rate of <20% during AS, as compared to the >20% rate observed in their younger counterparts. In this study, we compared the efficacy and safety of RFA and SR in patients with T1bN0M0 PTC between different age subgroups (<45 years vs ≥45 years).

No significant differences in treatment outcomes were observed between the two age subgroups. The difference in VRR between that calculated at the 3- and 6-month follow-ups after RFA in patients ≥45 years of age was lower than estimated in younger patients. However, there was no difference in the rate of tumor shrinkage between the two subgroups either in the early period within 1 month or in the long-term (≥1 year). RFA is a traumatic procedure that causes coagulative necrosis in the central zone and leads to aseptic inflammation in the early postprocedural stage (16). Therefore, the reduction in the ablation zone is not initially obvious. Later, fragments of the necrotic tissue are gradually engulfed by infiltrating macrophages and other inflammatory cells until the ablated tissue completely disappears. Our results showed that this absorption process in young patients was faster than that in elderly patients, but both age subgroups experienced comparable level of therapeutic benefit by 1 year after the procedure, which means that the final effect of RFA in patients of different age subgroups was consistent. Cao et al. (21) reported two patients <45 years and one patients >45 years who underwent ablation therapy developed tumor progression, but without comparing whether there were differences between age subgroups. In our study, two patients in each age subgroup recurred tumor progression with no significant difference.

In the SR group, the difference was mainly reflected in the hospital cost. Results showed that older patients who underwent SR incurred higher hospital costs than faced by their younger counterparts. This was mainly because older patients require more postoperative care than younger patients. This conclusion was also confirmed by Sahli Z.T. et al. (37); they found advanced age was related to higher rates of extended length of hospital stay and surgery-related readmissions. In terms of the efficiency and safety, Joseph et al. (38) also reported an increased complication recurrence rate and reduced disease-free survival in a meta-analysis performed to investigate survival prognosis and complications in elderly patients with PTC, who underwent thyroidectomy. However, the rates for complications and tumor prognosis did not differ significantly between the age subgroups in the present study.

Adam et al. (34) showed that patient age was a prognostic factor for cancer-related death; no patient experienced PTC-related deaths in our study. RFA exhibited a number of obvious advantages as compared to SR in both age groups. First, tumor progression did not differ significantly between the RFA and SR groups, which indicated that patients suffered with T1bN0M0 PTC who underwent RFA could achieve almost the same therapeutic effect as SR regardless of whether they were older or younger than 45 years old. Second, irrespective of age group, complication rate, procedure duration, and hospital costs associated with RFA treatment were lower than those observed with SR. What’s more, less invasive and shorter hospital stay allows patients to receive treatment more easily (39).

This study has certain limitations. Firstly, given its retrospective nature, selection bias could not be excluded. The decision to perform either RFA or SR was taken according to clinical considerations and based on a patient’s willingness to undergo either procedure, but not through a randomized treatment allocation process. Secondly, all information was collated from a single center, and multicenter data are needed to verify our observations. Thirdly, considering the indolent nature of PTC, the follow-up duration of this study was insufficient.

In conclusion, ultrasound-guided RFA appears to be a feasible and safe treatment alternative for the management of T1bN0M0 PTC in both young and older patients. This minimally invasive technique allows patients to avoid the trauma associated with SR. However, larger studies conducted over longer periods are needed to verify our finding.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

This study was approved by the Ethics Committee of the Chinese People’s Liberation Army General Hospital.

HH contributed to design, acquisition, analysis of data, and presented this study. QS, RW, and JZ contributed to data collection and analysis. YZ took full responsibility for the study data and revising it critically. The final version of the manuscript for submission was approved by the YL. All authors contributed to the article and approved the submitted version. The scientific guarantor of this publication is YL.

This study was supported by the National Natural Science Foundation of China (grant no. 81771834 and no. 81901746) and the Medical Big Data and AI R&D Project of Chinese PLA General Hospital (2019MBD-040).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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