Thermal ablation for the treatment of malignant thyroid nodules: present and future

Abstract

As the utilization of high-resolution imaging modalities, such as ultrasound, becomes increasingly prevalent, there has been a swift rise in the detection rates of malignant thyroid nodules (MTC). Surgery remains the cornerstone of standard treatment for these nodules. However, the advent and evolution of thermal ablation (TA) techniques, encompassing radiofrequency ablation, laser ablation, and microwave ablation, have emerged as a novel therapeutic avenue for patients with MTC, particularly for those deemed unsuitable for surgery due to high risks or for those who refuse surgery. Presently, TA has been validated as an efficacious and safe intervention for both benign thyroid nodules and a subset of MTC. An expanding body of research has been dedicated to broadening the applicability of TA, initially from recurrent thyroid cancer and lymph nodes to now encompass isolated papillary thyroid microcarcinomas (PTMC) alongside a comprehensive exploration into the expanded parameters such as size, number, and location of PTMC, and its applicability in other types of thyroid cancer. This review provides a detailed synthesis of the clinical evidence about the use of TA in the management of MTC, as endorsed by current guidelines. It further delves into the ongoing research efforts aimed at extending its indications and discusses the prospective implications and challenges of integrating TA into the clinical management paradigms for MTC.

Keywords:

• Thermal ablation
• malignant thyroid nodules
• thyroid cancer
• papillary thyroid cancer
• ultrasound

Introduction

Thyroid nodules are usually detected by ultrasound in 50–65% of the population, and only 5% of these nodules are malignant [1]. Among malignant thyroid nodules (MTC), papillary thyroid cancer (PTC) is the most common type, followed by follicular thyroid cancer (FTC), medullary thyroid cancer, anaplastic thyroid cancer and others [2]. Surgery is usually the standard treatment for thyroid cancer without distant metastasis. However, since thyroidectomy or hemithyroidectomy remove the thyroid gland, hypothyroidism may occur after surgery. Consequently, patients may require medications, potentially for the rest of their lives. Thus, surgical intervention for MTC may significantly affect the quality of life [3,4].

In recent years, with the advancement in interventional thyroidology, thermal ablation (TA) techniques, such as radiofrequency ablation (RFA), laser ablation (LA), and microwave ablation (MWA), have been progressively used for the treatment of thyroid nodules [5]. Currently, TA in MTC is mainly applied to recurrent thyroid cancer and isolated papillary thyroid microcarcinoma (PTMC) [6–10]. A growing body of research supports the efficacy and safety of TA, leading to increased interest in the exploration of TA for MTC, such as PTC with size >10 mm, multifocal, close to thyroid capsule, and other types of thyroid cancer. These favorable results of TA demonstrate its potential as a valuable treatment option in a wider range of thyroid nodules.

In this review, we have summarized the current applications of TA in MTC treatment and provided a broader summary of potential expanded indications, aiming to guide clinical management and practice.

The current guidelines for the use of TA in MTC have been primarily issued by organizations such as Korean Society of Thyroid Radiology (KSThR), Thyroid Tumor Ablation Experts Group of Chinese Medical Doctor Association (CMDA), ETA&CIRSE (European Thyroid Association and the Cardiovascular and Interventional Radiological Society of Europe), European Thyroid Association (ETA) and international joint teams. Indications mainly include recurrent thyroid cancer, primary thyroid cancer, follicular thyroid tumors, and unresectable type (due to distant metastasis or other risks). A detailed description of the indications is summarized in Table 1.

Table 1. Current guidelines for thermal ablation in malignant thyroid nodules.

Organization	Year of publication	Indications
		Recurrent thyroid cancer	Primary thyroid cancer	Thyroid follicular neoplasms	Unresectable thyroid cancer
KSThR	2018	Recurrent thyroid cancers at thyroidectomy bed and cervical lymph nodes for patients at high surgical risk or who refuse surgery	Indications have not yet been clearly established. patients with primary thyroid cancer who refuse surgery or who cannot undergo an operation	Not recommend	Advanced thyroid cancers
CMDA	2020	Metastatic cervical lymph nodes after undergoing surgical dissections: (1) Cervical lymph nodes have recurred and metastasized after radical treatment; (2) imaging examination suggests metastasis and the metastatic lymph node is diagnosed by FNA; (3) evaluation shows that patients cannot tolerate surgery or they refuse surgical treatments; (4) the iodine 131 treatment is ineffective for metastatic lymph nodes or patients refuse to take iodine 131 treatment; (5) metastatic lymph nodes can be separated from large blood vessels, allowing important nerves to have a safe operating space.	PTMC: (1) Nonpathological high-risk subtype; (2) tumor diameter = <5 mm (diameter = <1 cm for tumors surrounding tissues that are not close to the capsule), and the distance between nodules and posterior medial capsule should be >2 mm; (3) the thyroid capsule should and surrounding tissues should not be invaded; (4) the lesion is not located in the isthmus; (5) no multifocal thyroid cancer; (6) no family history of thyroid cancer; (7) no history of cervical radiation exposure in adolescent period or childhood; (8) no evidence of lymph node or distant metastasis; (9) refuse to undergo surgery and follow-up visits after being fully informed.	Not mentioned	Not mentioned
ETA&CIRSE	2021	Neck lymph-node recurrences of DTC.	PTMC: A cytology suspicion of aggressive subtypes of thyroid carcinoma, imaging detection of extrathyroidal growth or multiple neoplastic foci, presence of lymph node or distant metastases, and/or a worrisome molecular pattern (e.g., the detection of TERT promoter and TP53 mutations) contraindicate the use of MIT.	Patients with follicular lesions who are at surgical risk and present favorable US features and negative molecular testing.	Unresectable thyroid cancer; Progressive radioactive iodine refractory cervical recurrences; Distant metastases
AHNS, APTS, AME, BAETS, ETA, UEC, KSThR, LATS, TNT Association	2022	US-guided ablation procedures may be considered in patients with suitable recurrent papillary thyroid carcinoma who are unfit for surgery or decline surgery or active surveillance: the number of lesions must be limited (≤3 per patient), confined to the neck, and with maximum tumor diameter below 1.5–2 cm.	PTMC: (1) unifocal microcarcinoma confined to the thyroid gland, without evidence of extrathyroidal extension or capsular contact, (2) cytologic confirmation of papillary thyroid cancer without aggressive subtype, (3) no evidence of metastatic lymphadenopathy, (4) high-risk, ineligible for, or declines surgery	Not mentioned.	Not mentioned.
ETA	2023	Not mentioned.	Bethesda V and VI: MIT may be considered in patients with 5-10 mm nodules, in the absence of suspicious lymph nodes or risk of extra-thyroidal extension.	Not recommend.	Not mentioned.

DTC: Differentiated thyroid carcinoma; MIT: Minimally invasive treatments; KSThR: Korean Society of Thyroid Radiology; CMDA: Thyroid Tumor Ablation Experts Group of Chinese Medical Doctor Association; ETA&CIRSE: European Thyroid Association and the Cardiovascular and Interventional Radiological Society of Europe; AHNS, American Head and Neck Society; APTS, Asia Pacific Society of Thyroid Surgery; AME, Association Medici Endocrinology; BAETS, British Association of Endocrine and Thyroid Surgeons; UEC, Italian Society of Endocrine Surgery Units; LATS, Latin American Thyroid Society; TNT, Thyroid Nodules Therapies Association; ETA, European Thyroid Association.

Recurrent thyroid cancer

Surgery is recommended as the standard treatment for recurrent thyroid cancer. Changes resulting from initial surgery, such as fibrosis and anatomical distortion, can significantly pose the challenges and risks to repeated surgeries for patients. Therefore, for patients with recurrent thyroid cancer who are not suitable or unwilling to undergo a second surgery or active surveillance, TA is an alternative option.

Several early retrospective and prospective studies involving patients with recurrent thyroid cancer treated with RFA have demonstrated symptoms alleviation over short-term follow-ups (ranging from 6 to 40 months), confirming the viability of RFA in recurrent thyroid cancer cases where surgical risks are prohibitive [11–13]. Further studies have investigated the feasibility of RFA, MWA, and LA in small cohorts of recurrent thyroid cancer. These studies, with follow-up periods averaging less than 26 months, revealed volume reduction rates (VRR) between 91% and 98%. At the final follow-up, the complete disappearance rate varied from 30% to 82%, with no regrowth of treated nodules or distant metastases and the absence of severe or permanent complications [14–16]. A long-term study tracking 29 patients over periods of up to 80 months reported an average VRR of 99.5% and a complete disappearance rate of 91.3%. There were no delayed RFA-related complications during the follow-up period [17].

On the basis of confirming the short- and long-term efficacy and safety of RFA for recurrent thyroid cancer, studies have investigated the expanded parameters. In terms of recurrent nodule size, one study extended the size limit to 1.5 cm and found results comparable to radioactive iodine therapy [18]. Another study expanded the size limit to 2 cm, showing that the 1-year and 3-year recurrence-free survival rates and complication rates in TA group were similar to those in the surgery group [19].

In terms of the position of recurrent nodules, one study focusing on recurrent nodules invading the trachea discovered a negative correlation between the angle of the nodule relative to the trachea and efficacy, suggesting that anatomical position impacts the effectiveness of the procedure. A comprehensive study involving 119 cases (172 recurrent nodules), the average VRR was 81%, and the complete disappearance rate was 72% over approximately 48 months. The study concluded that TA is feasible even for recurrent tumors invading the airway [20].

Although a large number of studies have confirmed the efficacy and safety of TA in recurrent thyroid nodules, several studies have reported varying rates of complications. As far as complications are concerned, different studies have reported different results. A study involving 129 RTC cases reported a complication rate of 5%, notably higher than that for benign nodules (0.9%) [21]. Other research documented complication rates up to 21%. However, a substantial study encompassing 321 patients with 498 recurrent lymph nodes from various international regions found a low complication rate of just 4% [22].

Primary thyroid cancer

For primary thyroid cancer, the standard treatment is surgery. However, TA has emerged as a recommended alternative for patients who are either not suitable for surgery due to associated risks or who refuse to undergo surgery. When considering the treatment or active surveillance of MTC, factors such as larger diameter (>10mm), multifocality, located in the isthmus, and adjacent to the thyroid capsule are traditionally regarded as potential risk factors. As a result, nearly all current guidelines recommend TA for low risk PTMC specifically within the indication of primary thyroid cancer. Before the procedure, it is crucial to assess and exclude common risk factors to ensure the safety.

Unifocal PTMC

RFA

RFA is currently the most widely reported application in unifocal PTMC, and has been adopted in many large-sample studies. RFA is indicated for MTC surrounded by more uninvolved tissue since it generates a wider single ablation area. A study encompassing 95 patients with unifocal PTMC, revealed that tumor volume did not commence shrinking until the third month post-RFA, and at the sixth month that reduction started with the VRR reaching 99% by the 18 month [23]. Another study with 198 cases, 91% of the VRR was researched after 6 months of RFA [24]. Although the pace of recovery may vary among different patient populations, studies with larger cohort have indicated that over 39–60 months of follow-up, the complete disappearance rate of tumors lies within the range of 88%–100% [25–27]. This substantiates RFA is an effective treatment for low-risk PTMC after a long-term follow-up period for a large cohort.

Recurrent PTMC, lymph node metastasis (LNM), and distant metastasis are pivotal indicators for long-term prognosis. A study including 414 cases that reported the local recurrence rate of 2.42% and LNM rate of 0.97% [27]. Another study comprising 142 cases reported a considerably higher LNM rate of 13.4%, and in some patients, tumors were not fully inactivated post-RFA, and metastases were observed in the central compartment lymph nodes [28].

Adverse events after RFA are usually another important concern along with our focus on efficacy. The majority of these events entail short-term discomforts such as pain, temporary voice changes, little bleeding, and thyroid function alterations, with an incidence of less than 3%. Most of these symptoms spontaneously recovery within hours to a month, necessitating no additional therapeutic intervention. Furthermore, the incidence of thermal damage to structures located near vital blood vessels, nerves and airway structures can also be reduced by water separation techniques.

LA

LA is especially effective for small-diameter MTC due to its precise energy delivery, minimizing harm to nearby tissues. In a study involving 90 patients with a follow-up period extending up to 112 months, all the lesions vanished or transformed into scars within 10 months, with complete disappearance by the 12th month [29]. Another study, averaging 65 months of follow-up, reported an 82% complete disappearance rate, a 96% VRR at 36 months, and a 100% VRR at 4 years [30]. Both studies indicated that 18–67% of cases displayed scar-like changes in ablated area.

Regarding the recurrence rate and lymph node metastasis rate after LA, research has shown that they are relatively low, within 5.5% and 2.7%, respectively. Some opinions suggest that there may have been occult cervical lymph node metastasis before treatment, leading to the discovery of cervical LNM after LA, which is not a true recurrence [29–31].

Post-LA, pain is the most common adverse event, experienced by 81.9%–100% of patients, the majority of which were transient. In approximately 25% of patients, pain and neck discomfort could persist post-procedure; however, all cases spontaneously resolved within 1–2 weeks [30–32]. Temporary post-ablation thyroid function abnormalities might occur due to excessive ablation or a large ablation area. Nonetheless, these typically resolved without the need for medication within 6 months post-LA [31].

MWA

MWA generates more energy in a single treatment session compared to RFA and LA, resulting in a larger and more homogeneous ablation zone. A study encompassing 63 unifocal PTMC patients and a follow-up period of 24 months identified a VRR of up to 100% at the follow-up endpoint, with no recurrences or metastases [33]. Another large-sample single-center retrospective study involving 404 cases revealed that the VRR did not decrease in the initial 3 months. Nevertheless, at the final follow-up, the VRR reached 99%, confirming the efficacy of MWA for unifocal PTMC [34]. Furthermore, long-term efficacy and outcomes of MWA were investigated in a study with a follow-up period of 60 months, all nodules were completely ablated, the VRR was 99%, with no permanent complications observed over 5 years. Only a very small proportion of patients experienced temporary hoarseness, which resolved within a few months [35]. There were no recurrences, metastatic cervical lymph nodes, or distant metastases, aligning with the results of above short-term follow-up studies.

The primary discomfort with MWA is mild to moderate pain due to high temperatures during the procedure. Additionally, approximately 1.9–5.4% of patients may experience temporary recurrent laryngeal nerve injury due to compression from swollen tissues or heat transfer. However, all cases spontaneously resolve within 2–3 months post-MWA. In contrast to patients undergoing thyroid lobectomy for PTMC, patients treated with MWA do not face the risk of postoperative thyroid dysfunction. In the surgical group, 29.9% of patients require lifelong thyroid hormone replacement therapy [33–37]. In a retrospective study that included 92 PTMC patients in a 1:1 ratio and had a 42-month follow-up, the MWA group exhibited a lower average length of stay, cost, mean blood loss, surgical incision, operating room time, and fewer complications in comparison to the surgery group [37].

In conclusion, RFA, LA, and MWA have been extensively researched and confirmed as safe and effective methods for treating unifocal PTMC. Although these three TA techniques demonstrate relatively low rates of adverse events in the treatment of unifocal PTMC, which are generally consistent and primarily include varying degrees of pain, bleeding, transient hoarseness, and other symptoms, there have been scarce reports of irreversible hoarseness. For cases with larger ablation areas, there may be a degree of thyroid function impairment, this is generally uncommon due to the size of the lesions. TA has a lesser impact on thyroid function, whereas surgery may necessitate lifelong medication for patients. In terms of treatment cost, the TA procedures are shorter in duration, can typically be performed on an outpatient basis in most regions, involve less bleeding, and do not result in significant incisions, leading to shorter recovery times. Therefore, TA incurs lower medical expenses than surgery in the short term. While both surgery and TA require long-term follow-up to monitor the complete disappearance of lesions, lymph node metastasis, and other factors. Thus, considering both efficacy and safety comparable to surgery, TA may hold advantages in terms of time, medical cost, and patient quality of life.

PTC with size >10 mm

Considering its favorable efficacy and safety profile in unifocal PTMC, some research has delved further into the exploration of size-related parameters for the application of TA. Initially, for T1bN0M0 PTC, a multicenter study involving 172 T1bN0M0 PTC patients underwent MWA or RFA. After an average follow-up of 25 months, 61.6% of the tumors had completely disappeared. Only one case showed lymph node metastasis, and two new tumors emerged. The overall complication rate was 5.2%, all of which resolved within 4 months post-ablation [38]. In another single-center study involving 66 patients with T1bN0M0 PTC patients who underwent RFA and were followed for 21 months, the final VRR reached 99%, with a complete disappearance rate of 57.6%. In two cases (3.0%), malignant cells appear within the ablation zone, and one case (1.5%) exhibited lymph node metastasis [39]. Further study compared the short-term and long-term efficacy of RFA for T1a N0M0 and T1b N0M0 PTC. Using propensity score matching, they followed 262 patients (131 with T1b N0M0) for 25 months after RFA and found no significant differences in local tumor progression rates or outcomes between the two groups [40]. By including 358 T1N0M0 PTC patients (including 55 with T1bN0M0 PTC) who received RFA and were followed for 76 months, they discovered no significant differences in disease progression, LNM, recurrent tumors, or 5-year recurrence-free survival rates between the T1aN0M0 and T1bN0M0 groups, confirming that long-term efficacy did not significantly differ between the two groups [41]. Investigation was expanded to larger tumor sizes, examining 12 T2 N0M0 PTC patients treated with RFA and followed for 24 months. It was found that the VRR is 94%, and no local or distant recurrence of the tumor was observed nor were there life-threatening or delayed complications. This preliminary result extends the size of PTC treated by RFA to 2 cm [42]. In the future, more studies with larger sample sizes and longer follow-up periods are needed to confirm this conclusion.

Additionally, a cost comparison was conducted between RFA and surgery based on the efficacy in T1bN0M0 PTC. Among 283 unifocal T1bN0M0 PTC cases (91 in the RFA group) with an average follow-up of 50 months, no significant differences were found in terms of local tumor progression, lymph node metastasis, recurrent tumors, persistent tumors, and recurrence-free survival rates between the RFA and surgery groups. Moreover, neither group observed distant metastases. Notably, the RFA group exhibited a lower complication rate. Regarding costs, patients in the RFA group had shorter hospital stays, shorter operating times, lower blood loss and lower costs [43].

Multifocal PTC

Multifocality is generally considered a risk factor that can impact the prognosis of thyroid cancer. Therefore, early studies of TA for PTC have primarily focused on unifocal PTMC. In a long-term follow-up study involving 47 cases of bilateral PTMC treated with RFA, after a 48-month follow-up, it was found that the average VRR was nearly 100%, with a complete disappearance rate of 92%. During the follow-up period, one patient (2.13%) experienced lymph node metastasis, and two patients (4.26%) had recurrent PTMC. All recurrent lesions completely disappeared after additional RFA, providing preliminary evidence of the effectiveness of RFA in multifocal PTMC [44]. Furthermore, this team conducted a comparative analysis between unifocal and multifocal cases using propensity score matching in a larger cohort of 487 patients (including 55 with multifocal lesions). After a 50-month follow-up, both groups achieved almost 100% VRR, with no significant differences in complete disappearance rate, local tumor progression rate, LNM, recurrent PTMC, or disease-free survival rates [45]. The efficacy of LA and MWA in multifocal PTC has also been confirmed in small sample studies [46–48]. Lesions treated with these methods nearly completely disappeared or left only scar remnants. Adverse events occurred in the range of 0% to 6.8% during the follow-up period.

Additionally, research has explored the expanded parameters related the tumor size and number simultaneously. In a study involving 57 patients with T1N0M0 multifocal (≤3) PTC, MWA was performed. All lesions were successfully ablated, and after an 18-month follow-up, the overall complete disappearance rate was 43.9%, with T1aN0M0 significantly higher than T1bN0M0. The overall disease progression rate was 7%, and the overall complication rate was 5.3%, with no significant differences between the two groups. This preliminary study suggests that MWA is a safe and effective treatment for T1N0M0 multifocal (≤3) PTC [49].

PTC with thyroid extracapsular extension

Thyroid extracapsular extension is commonly associated with a high risk of LNM and poor prognosis in thyroid cancer. When dealing with thyroid cancer that are close to the thyroid capsule, a more cautious approach is typically taken. There is ongoing exploration regarding whether lesions close to the thyroid capsule or those showing capsule invasion in PTC can be adopt TA, and the recommendations in various guidelines are generally against it. Regarding the scope of TA in PTMC, further exploration is underway. In one study involving 69 cases treated with MWA, with an average follow-up of 26 months, 68% of the nodules completely disappeared during the follow-up period, and no local recurrence was detected. The incidence rates of new lesions and LNM were 4.3% each, and all new lesions and LNM were eliminated through repeat MWA. The only complication reported was mild voice changes, with an incidence rate of 2.9%, which resolved within 6 months [50]. In another larger, multicenter prospective study involving 461 subjects (including 83 patients with capsule invasion), after a 20-month follow-up, MWA was successfully performed in nearly all patients, with 1 case and 11 cases of complications in the groups with and without capsule invasion, respectively. There was no significant difference in disease progression or tumor reduction between the two groups [51].

Follicular thyroid neoplasms

Currently, the definitive diagnosis for follicular thyroid neoplasms is mainly made by pathological examination after surgery. Even with fine needle aspiration biopsy, it is often difficult to definitively distinguish between follicular thyroid adenomas (FTA) and FTC. These two are typically categorized as Bethesda IV. Currently, almost all TA guidelines do not recommend the use of TA for follicular thyroid neoplasms.

A study involving 31 patients diagnosed as Bethesda IV who underwent RFA or MWA reported promising results. One patient experienced pain after the procedure, which was relieved within 2 h. During 16 months of follow-up, a 95% VRR was achieved, and there were no cases of recurrence, LNM, or distant metastases. These preliminary results suggest the effectiveness and safety of TA in treating these lesions [52]. Additionally, this study compared TA to surgery in terms of surgical time, incision length, bleeding, length of hospital stay, and treatment costs, finding that the ablation group had better outcomes in all these aspects. Another study involving 130 patients similarly supported these findings. These results suggest that TA may also be suitable for Bethesda IV nodules and could potentially reduce the medical costs for patients [53].

However, it is important to note that the current research on the use of TA for thyroid follicular neoplasms is based on small-sample studies with short follow-up periods. There is a need for further investigation, including large-scale, multi-center prospective studies, to assess the long-term effectiveness of TA in the treatment.

Unresectable thyroid cancer

For tumors with high malignant potential that cannot be surgically resected, have distant metastasis, or for patients who are not suitable for surgery or I¹³¹ treatment due to various risks, some guidelines recommend considering TA for palliative purposes.

Emilia Biamonte et al. reported the application of RFA in patients with non-metastatic medullary thyroid cancer. They described a patient who did not undergo surgery due to high anesthesia risk. Ultrasound showed complete necrosis of the tumor after 6 months. At 15 months, fibrous tissue had replaced the thyroid nodule, and no cervical lymph node metastasis was detected [54]. Another case report described the short-term effects of LA for anaplastic thyroid cancer, suggesting its potential use to reduce tumor tissue volume before external radiation or chemotherapy, particularly for highly malignant tumors not suitable for surgery or radioactive iodine therapy [55]. However, a study has compared the efficacy of RFA in treating PTC and anaplastic thyroid cancer and found that RFA achieved good local tumor control in PTC, but had no significant effect on anaplastic thyroid cancer [56].

Conclusion and prospect

According to current principles for the treatment of MTC, it is advocated to consider the overall well-being of patients in medical management while avoiding unnecessary or overly invasive treatments. Minimally invasive interventions offer a relatively gentle and proactive clinical management strategy that can bridge the gap between active surveillance and surgery. However, the mainstream indications for TA are currently limited to recurrent thyroid cancer and unifocal PTMC.

In the treatment of recurrent thyroid cancer, TA not only reduces the risks and challenges associated with repeat surgery but also demonstrates efficacy comparable to surgical intervention. Most reports indicate that three different TA techniques can effectively eliminate PTMC while preserving thyroid function, with low rates of recurrence and LNM during follow-up. This suggests that TA has similar efficacy to surgery in treating recurrent thyroid cancer and unifocal PTMC. In terms of complications, some studies suggest that the incidence rates are similar, while others report lower adverse events associated with TA. Notably, TA has lower time and healthcare costs.

These positive results have spurred interest in expanding the indications of TA for MTC, leading to extensive research on various parameters such as nodule size, number, and location. In terms of expanding the size of MTC, from the initial T1aN0M0 to T1b N0M0 and then to T2 N0M0, preliminary results from small sample studies suggest that TA remains feasible for T2N0M0 PTC, even though the rate of VRR may be slower compared to smaller diameter MTC. In terms of the expansion of the number of MTC, some large-sample studies suggest that TA for multifocal PTMC is as safe and effective as TA for unifocal PTMC, with low complication rates in both groups.

MTC located close to the thyroid capsule are typically considered to need cautious management, and TA or active surveillance was generally not recommended in the past. However, some preliminary research results suggest that TA can be used for nodules near the capsule, similar to nodules located farther from the capsule, which is an encouraging finding. In the past, MTC close to the capsule was typically recommended for surgery, even in the absence of lymph node metastasis. These results indicate that TA might be an alternative option for such cases.

The safety and efficacy of TA in MTC have been widely confirmed in previous studies, but it is important to monitor for adverse events and disease progression during follow-up, even though the reported rates are generally low. Common major complications include temporary hoarseness, typically resolving within days to six months after TA, with almost no reports of irreversible hoarseness. Other adverse events such as pain and minor bleeding usually recover in a short period. Intra-procedural measures to protect nerves and blood vessels can reduce the risk of damage and minimize complications. Techniques like liquid isolation are often used to protect the dangerous triangle area. Additionally, monitoring blood flow during needle insertion can help avoid damage to small blood vessels, reducing unnecessary bleeding. After TA, regular ultrasound follow-up is typically needed to observe the VRR in the TA zone and monitor for recurrence, new lesions, LNM, and distant metastasis, enabling timely treatment if disease progression is observed. According to previous research, the rates of recurrence and lymph node metastasis after TA are usually very low, with no reported cases of distant metastasis.

The widespread application of TA will continue to transform the clinical management of MTC. Most current studies primarily focus on assessing the short-term treatment outcomes and cost-effectiveness of TA. In addition, although the above results have further expanded the indications for TA, most of the extended parameters are still in the exploratory stage, especially through retrospective studies, and the sample size is not large enough. In addition, it is worth noting that current research mainly comes from high-capacity centers in Asian and some European countries, highlighting the differences in the application of TA in MTC and regional imbalances.

However, it is crucial to emphasize the importance of longer follow-up, not overlooking the necessity and challenges of evaluating long-term complications and monitoring for recurrences. More large-sample data from various regions around the world and prospective trial designs are required to establish reliable evidence regarding the long-term efficacy of TA in MTC, thus providing a more solid foundation for evidence-based clinical practice.

In conclusion, TA offers a new alternative for the treatment of MTC.

Acknowledgments

We thank our colleagues for their support in this work.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data in this work are available for scientific research with formal authorization. If necessary, please contact the corresponding author.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (82071923).