Thermal Ablation for Papillary Thyroid Carcinoma

Key Points

Question

What is the long-term outcome of thermal ablation in treating T1N0M0 papillary thyroid microcarcinoma (PTC)?

Findings

In this retrospective, multicenter cohort study of 179 patients with 181 T1N0M0 PTC who underwent thermal ablation, during a mean (SD) follow-up period of 120.8 (10.8) months, the incidence of disease progression was 6.1%, with 97.2% of tumors disappearing radiographically with a low incidence of complications (0.6%) and delayed surgery (0.6%).

Meaning

These findings suggest that thermal ablation is an effective and safe alternative for patients with T1N0M0 PTC who do not undergo surgery or receive active surveillance.

Abstract

Importance

Image-guided thermal ablation has been administered for patients with T1N0M0 papillary thyroid carcinoma (PTC) who elect to not undergo surgery or receive active surveillance. Considering the indolent nature of PTC, long-term outcomes of ablation are needed.

Objective

To investigate l0-year outcomes of thermal ablation in treating T1N0M0 PTC.

Design, Setting, and Participants

This multicenter study was conducted at 4 university-affiliated hospitals in China and included 179 consecutive patients with T1N0M0 PTC (median [IQR] volume, 88.0 [163.2] mm³) who underwent thermal ablation between June 2010 and March 2014. Patients who were ineligible to undergo surgery or elected not to were included, and patients had PTC tumors that were smaller than 20 mm as confirmed by biopsy; no clinical or imaging evidence of extrathyroidal extension, lymph node metastasis (LNM), or distant metastasis; and no history of neck irradiation.

Main Outcomes and Measures

The primary outcomes were disease progression (LNM, newly developed tumors, persistent tumors, and distant metastasis) and disease-free survival (DFS). Secondary outcomes were technical success, volume reduction rate, tumor disappearance, complications, and delayed surgery. DFS was calculated using a Kaplan-Meier analysis.

Results

Among the 179 patients, the mean (SD) age was 45.8 (12.7) years, and 118 (65.9%) were female. During a mean (SD) follow-up period of 120.8 (10.8) months, disease progression was found in 11 of 179 patients (6.1%), including LNM in 4 patients (2.2%), newly developed tumors in 6 patients (3.3%), and persistent tumor in 1 patient (0.6%). The 10-year DFS was 93.9%. The technical success, median volume reduction rate, and tumor disappearance rate was 100%, 100%, and 97.2%, respectively. The magnitude of the disease progression (6.1% vs 7.1%; difference, 1.0%; 95% CI, −6.5% to 25.6%) and DFS (93.9% vs 92.9%; difference, 1.0%, 95% CI, −6.5% to 25.6%) between patients with T1a and T1b tumors was small. The difference in the rate of tumor disappearance between T1a and T1b tumors was large (99.4% vs 71.4%; difference, 28.0%; 95% CI, 10.9%-54.0%). One patient experienced transient voice hoarseness (0.6%). Because of anxiety, 1 patient underwent delayed surgery (0.6%).

Conclusions and Relevance

The results of this 10-year multicenter cohort study suggest that thermal ablation is an effective and safe alternative for patients with T1N0M0 PTC who do not undergo surgery or receive active surveillance. For safe and effective treatment, accurate radiologic evaluation, an understanding of ablation techniques, and experienced physicians are recommended.

This cohort study examines 10-year outcomes of thermal ablation in treating T1N0M0 papillary thyroid carcinoma.

Introduction

Thyroid cancer is the most common endocrine cancer, and papillary thyroid carcinoma (PTC) accounts for more than 85% of all thyroid cancers.¹ Because of the indolent nature and excellent prognosis, multiple international guidelines have endorsed more conservative strategies for managing PTC.^1,2,3 Surgery is the standard treatment for PTC, and lobectomy has been recommended as the first-line surgical option for low-risk PTC (T1 tumor without clinical or imaging evidence of extrathyroidal extension or local or distant metastasis).¹ However, complications, cosmetic problems, and lifelong thyroid hormone replacement still substantially affect patient quality of life.^4,5 Active surveillance (AS) has been recommended as a new nonsurgical option to biopsy and immediate surgery in patients with PTC^1,2 following emerging evidence of the safety and effectiveness of this approach.^6,7,8,9 However, recent research used data from 18 Surveillance, Epidemiology, and End Results US registries and found that AS was only used for less than 1% of PTC annually, suggesting that it has not become a very common management strategy for low-risk PTC.¹⁰ The barriers to implementing AS in clinical practice, especially in low-income countries, included patient preference, anxiety about living with cancer, quality of disease surveillance programs evaluation, lack of a professional team, less economical options for younger patients, and medical insurance and health system policies.^11,12,13,14 Thus, for patients who are not willing to undergoing surgery or AS, local treatment modalities, such as image-guided thermal ablation, may play an increasingly important role.^15,16,17,18

Image-guided thermal ablation modalities, including radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA), are the local application of extreme temperatures to induce tumor apoptosis and coagulative necrosis under image guidance.¹⁹ These minimally invasive modalities have been recommended as alternatives to surgery for benign nodules and recurrent thyroid cancers^15,16,17,20 and have favorable results.^{21,22,23,24,25} For the last few decades, several studies have demonstrated encouraging outcomes of ablation for patients with PTC who elected not to undergo surgery or AS.^{26,27,28,29,30,31,32,33,34} However, to our knowledge, long-term outcomes of ablation for PTC are absent because of its relatively short history of clinical application. Considering the indolent course of PTC, long-term follow-up data are required to verify the clinical outcomes of thermal ablation. We hypothesized that thermal ablation is a promising treatment option for patients with T1N0M0 PTC, and the purpose of this multicenter study was to evaluate 10-year long-term clinical outcomes of thermal ablation in treating T1N0M0 PTC.

Methods

Patients

This multicenter retrospective study included patients with T1N0M0 PTC who underwent treatment at 4 university-affiliated hospitals in China from June 2010 to March 2014. This study was approved by the institutional review board of all participating hospitals, and the requirement for obtaining informed consent from patients was waived because of the retrospective nature of the study. During this study period, AS was not recommended.¹ Therefore, in clinical practice, surgery was initially recommended for patients with PTMC. Thermal ablation was only applied for patients who were unsuitable for surgery or who elected not to undergo surgical treatment. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

The inclusion criteria were (1) PTC as confirmed by fine-needle aspiration (FNA) or core-needle biopsy (CNB); (2) a maximum tumor diameter of 20 mm or smaller; (3) no clinical or imaging evidence of extrathyroidal extension (no signs of capsular abutment by the tumor, subtle capsular distortion or disruption, or bulging of the normal thyroid contour but without replacement of the strap muscle or obtuse margins between the tumor and the surrounding structures on ultrasonography)^35,36; (4) no evidence of cervical lymph node metastasis (LNM) on ultrasonography or neck computed tomography (CT) results; (5) no distant metastasis on chest CT; and (6) no history of neck irradiation. The exclusion criteria were (1) evidence of an aggressive subtype of PTC by biopsy and (2) incomplete data or loss to follow-up.

The electronic medical records of consecutive patients with T1N0M0 PTC who underwent ablation from June 2010 to March 2014 were reviewed. After exclusion, 179 patients who elected not to undergo surgery or had medical contraindications for surgery were included in this study (Figure 1).

Figure 1. Study Flow Diagram.

PTC indicates papillary thyroid carcinoma.

Pretreatment Evaluation

All patients underwent a thorough examination before treatment, including laboratory tests, thyroid function tests, ultrasonography, and neck and chest CT. Thyroid background status was defined as normal or Hashimoto thyroiditis (thyroid peroxidase antibody levels >60 IU/mL) with or without antithyroglobulin antibodies (>60 IU/mL). Ultrasonography was used by physicians with 5 years of experience in thyroid ultrasonography to evaluate tumor size, ultrasonography characteristics, thyroid capsules, and cervical lymph nodes to exclude extrathyroidal extension or LNM. Tumor volume was calculated using the following equation: volume = (π × the 3 diameters in the transverse, longitudinal and anteroposterior planes) / 6. The evaluation of tumor characteristics was mainly based on the American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS).³⁷ Neck and chest CT were performed to detect cervical LNM and distant metastasis.

Treatment

The thermal ablation procedure was performed by 4 ultrasonography physicians with 10 years or more of experience in interventional ultrasonography. The RFA or MWA was selected according to the physician’s experience and modality preference¹⁵ (eTable 1 in Supplement 1); some patients underwent RFA and others underwent MWA in the outpatient clinic. Before ablation, patients were placed in a supine position with the neck extended and administered local anesthesia with lidocaine, 1%. RFA and MWA procedures were performed using the hydrodissection technique, transisthmic approach, moving-shot technique, and enlarged ablation technique according to the guidelines^38,39(eMethods in Supplement 1). The ablation was terminated when the target tumor had changed to transient hyperechoic zones. Contrast-enhanced ultrasonography (CEUS) was performed immediately after ablation to evaluate the ablation area. Complementary ablation was performed if any enhancement was seen on CEUS. The presence of complications occurring during or after thermal ablation and corresponding treatment was carefully evaluated.⁴⁰ All the patients were closely observed for 1 to 2 hours after ablation in the hospital.

Follow-Up

Thermal ablation follow-ups were performed at 1, 3, 6, 12, 18, and 24 months and every 12 months thereafter. Laboratory tests, ultrasonography, and CEUS were performed at each follow-up evaluation, and chest CT was performed annually to monitor for distant metastasis. The volume reduction rate (VRR) was calculated at each follow-up visit as follows: VRR = ([initial volume − final volume] × 100) / initial volume. During the follow-up period, FNA was performed when suspicious nodules (TI-RADS TR4 or TR5)³⁷ and lymph nodes (with at least 1 of the suspicious features, like microcalcifications, partially cystic appearance, increased vascularization, and hypoechogenicity)¹ were observed. If the ablated tumor incompletely disappeared within the first year after ablation or showed blood perfusion (blood flow visible on color Doppler imaging or contrast medium perfusion on CEUS), CNB was performed in the central, peripheral, and surrounding thyroid parenchyma of the ablated tumor to verify the persistence of residual cancer cells. After ablation, patients were advised to take levothyroxine to maintain thyrotropin levels between 0.5 and 2 mIU/L. If the patients had pretreatment serum thyrotropin levels in this target range, levothyroxine was not administered. Gradual discontinuation of levothyroxine was considered when the serum thyrotropin level remained at less than 2 mIU/L.

End Points and Definitions

The primary outcome was disease progression and disease-free survival (DFS). Disease progression was classified as follows: (1) cervical LNM confirmed by FNA or CNB; (2) newly developed tumor, defined as a new tumor found in the thyroid lobe as confirmed by FNA or CNB; (3) persistent tumor, defined as residual cancer cells at the site of the ablated tumor as confirmed by CNB; and (4) distant metastasis. DFS was calculated from treatment initiation to disease progression or the last follow-up date. The treatment management of disease progression was made by the physician and patient in consultation based on the patient’s circumstances and preferences.

Secondary outcomes included (1) technical success, which was defined as complete absence of enhancement at CEUS at the end of ablation procedure^40,41; (2) VRR; (3) tumor disappearance, defined as a complete disappearance of ablated tumor on ultrasonography and CEUS; (4) complications, as recorded by the standard for image-guided thyroid ablation⁴⁰; and (5) delayed surgery, defined as patients who underwent surgery at a later date due to disease progression or anxiety during the follow-up.

Statistical Analysis

Normally distributed continuous covariables were presented as mean (SD) and non-normally distributed continuous covariables were expressed as medians with IQRs. Categorical covariables were expressed as frequency with percentages. The results used effect size measures to report the magnitude of the difference (or strength of association) and 95% CIs to describe the precision of the estimate and whether the results were compatible with clinically meaningful differences. DFS was calculated using the Kaplan-Meier method with the log-rank test. Univariate hazard ratios and associated 95% CI were performed to compare variables associated with disease progression after ablation. Statistical analyses were performed using SPSS, version 25.0, and R, version 3.6.2.

Results

The patient and tumor characteristics at baseline are presented in Table 1. A total of 179 patients (mean [SD] age, 45.8 [12.7] years; 127 [70.9%] who elected not to undergo surgery and 52 [29.1%] or had medical contraindications for surgery) with 181 tumors (median [IQR] volume, 88.0 [163.2] mm³) were included in this study. Among them, 177 patients had unifocal PTC (97.8%) and 2 patients had unilateral multifocal T1aN0M0 PTC (2.2%). Based on the maximum diameter, 165 patients with 167 tumors were classified as having T1a tumors (median [IQR] maximum diameter, 6.0 [3.0] mm³), whereas 14 patients were classified as having T1b tumors (median [IQR] maximum diameter, 12.0 [2.0] mm³). The mean (SD) follow-up period was 120.8 (10.8) months.

Table 1. Patient and Tumor Characteristics at Baseline.

Characteristic	No. (%)
Patients, No.	179
Tumors, No.	181
Unifocal	177 (97.8)
Unilateral multifocal	4 (2.2)
Mean (SD) age, y	45.8 (12.7)
<55	143 (79.9)
≥55	36 (20.1)
Sex
Female	118 (65.9)
Male	61 (34.1)
Tumor stage
T1a	167 (92.3)
T1b	14 (7.7)
Maximum diameter, median, mm	6.0 (3.0)
T1a	6.0 (3.0)
T1b	12.0 (2.0)
Volume, median, mm3	88.0 (163.2)
T1a	78.5 (123.6)
T1b	558.4 (167.3)
Thyroid background status
Normal	145 (81.0)
Hashimoto thyroiditis	34 (19.0)
Location
Right lobe	100 (55.2)
Left lobe	77 (42.6)
Isthmus	4 (2.2)
Composition
Solid or almost solid	179 (98.9)
Mixed cystic and solid	2 (1.1)
Echogenicity
Hypoechoic	179 (98.9)
Hyperechoic or isoechoic	2 (1.1)
Shape
Wider-than-tall	55 (30.4)
Taller-than-wide	126 (69.6)
Margin
Smooth	10 (5.5)
Ill defined	102 (56.4)
Lobulated or irregular	69 (38.1)
Echogenic foci
None or large comet tail artifacts	106 (58.6)
Macrocalcifications	33 (18.2)
Punctate echogenic foci	42 (23.2)
Vascularity
Absent	100 (55.2)
Present	81 (44.8)

Primary Outcomes

The primary outcomes are presented in Table 2. The overall incidence of disease progression was 6.1% (11 of 179 patients), and 10-year DFS was 93.9%. No distant metastases were detected. The differences in disease progression (10 of 165 patients [61.1%] vs 1 of 14 patients [7.1%]; difference, 1.0%; 95% CI, −6.5% to 25.6%) and 10-year DFS (93.9% vs 92.9%; difference, 1.0%; 95% CI, −6.5% to 25.6%) between patients with T1a and T1b tumors were small (Figure 2A). There were no significant differences in disease progression (8 of 139 patients who underwent RFA [5.8%] vs 3 of 40 patients who underwent MWA [7.5%]; difference, 1.7%; 95% CI, −5.4% to 14.4%) or DFS (94.2% vs 92.5%; difference, 1.7%; 95% CI, −5.4% to 14.4%) between the RFA and MWA group for T1N0M0 PTC (eTable 2 in Supplement 1).

Table 2. Disease Progression After Thermal Ablation for Treating T1N0M0 Papillary Thyroid Carcinoma.

Variables	No. (%)	Management
Total incidence	11 (6.1)	NA
LNM	4 (2.2)	NA
Location
Lateral compartment	1 (25.0)	Additional ablation
Central compartment	3 (75.0)	Additional ablation; surgery; active surveillance
Newly developed tumors	6 (3.3)	Additional ablation
Contralateral lobe	6 (100)	NA
Persistent tumors	1 (0.6)	Surgery
Distant metastasis	0	NA
10-y DFS, %	93.9	NA

Abbreviations: DFS, disease-free survival; LNM, lymph node metastasis; NA, not applicable.

Figure 2. Survival Curves.

A, Disease-free survival curves for thermal ablation in the treatment of T1a and T1b tumors (93.9% vs 92.9%; difference, 1.0%; 95% CI, −6.5% to 25.6%). B, Kaplan-Meier curves for tumor disappearance in T1a and T1b tumors (99.4% vs 71.4%; difference, 28.0%; 95% CI, 10.9%-54.0%).

Four patients (2.2%) developed LNM. Two patients with singly LNM (50.3mm³ and 67.1mm³) underwent additional ablation, and the LNMs disappeared at a mean (SD) of 16.5 (10.6) months after additional ablation. One patient with cervical LNM underwent total thyroidectomy with cervical lymph node dissection, and surgical pathology showed occult tumors in the contralateral lobe. One patient with cervical LNM underwent AS and showed stable lesions after a follow-up of 55 months. Six patients (3.3%) experienced newly developed tumors, and all underwent additional ablation. Four recurrent tumors were complete disappeared at a mean (SD) of 14.3 (6.6) months after additional ablation. A total of 73 ablated tumors were visible on ultrasonography at 12 months, and 44 underwent postablation CNB. One patient with a T1a tumor received a diagnosis of persistent tumor (0.6%) and underwent lobectomy with cervical lymph node dissection. Postablation CNB results of the other 43 ablated tumors showed degenerated and necrotic follicular epithelia with lymphocyte infiltration in the central zone, interstitial fibrous tissue hyperplasia with lymphocyte infiltration, and multinucleated giant cell reaction in the peripheral zone and follicular epithelia hyperplasia with lymphocyte infiltration in the surrounding thyroid parenchyma. Because of patients’ preferences, 29 ablated tumors did not receive postablation CNB; of them, 27 disappeared on ultrasonography during the subsequent follow-up and 2 shrank to a small volume, with a VRR of 99% in the last follow-up visit. A Cox analysis revealed that the isthmus location of tumor was associated with a large increase, young age with a medium increase, and presence of Hashimoto thyroiditis with a small increase risk of disease progression, while a small reduction in risk was associated with male sex and right lobe location of a tumor. The confidence intervals around all of the effect size estimates were quite wide; thus, no definitive conclusion can be drawn (Table 3).

Table 3. Univariable Hazard Ratios (HRs) and Associated 95% CIs Evaluating the Risk Factors for Disease Progression.

Characteristics	No. (%)	Disease progression, No. (%)	HR (95% CI)
Age, y
≥55	36 (20.1)	1 (2.8)	1 [Reference]
<55	143 (79.9)	10 (7.0)	2.584 (0.331-20.189)
Sex
Female	118 (65.9)	8 (6.8)	1 [Reference]
Male	61 (34.1)	3 (4.9)	0.719 (0.191-2.710)
Location
Left lobe	77 (42.6)	5 (6.5)	1 [Reference]
Right lobe	100 (55.2)	5 (5.0)	0.779 (0.225-2.689)
Isthmus	4 (2.2)	1 (25.0)	4.009 (0.468-34.345)
Thyroid background status
Normal	145 (81.0)	8 (5.4)	1 [Reference]
Hashimoto thyroiditis	34 (19.0)	3 (8.8)	1.614 (0.428-6.083)
Tumor size, mm3	NA	NA	0.919 (0.029-29.197)

Abbreviation: NA, not applicable.

Secondary Outcomes

All the patients were successfully treated in a single ablation session, with a technical success rate of 100%. The power, procedure time, and energy of RFA and MWA are listed in eTable 3 in Supplement 1. The volume and VRR at each follow-up point after ablation are presented in eTable 4 in Supplement 1. Because the enlarged ablation was used, the volume immediately increased after the procedure, and the volume during the first 3 months was larger than the initial volume, but gradually decreased after 6 months. At the last follow-up point, the median VRR was 100%, and 176 tumors (97.2%) had disappeared on ultrasonography. Of these, 99.4% (166 of 167 tumors) were T1a tumors, and 71.4% (10 of 14 tumors) were T1b tumors (difference, 28.0%; 95% CI, 10.9% to 54.0%; Figure 2B). There were no significant differences in tumor disappearance between RFA and MWA for T1N0M0 PTC (98.6% [139 of 141 tumors] vs 92.5% [37 of 40 tumors]; difference, 6.1%; 95% CI, −0.02% to 18.5%). eFigure 2 in Supplement 1 shows a representative case before and after ablation.

All of the patients tolerated the ablation procedure. Thirty-one patients (17.3%) experienced mild pain. Only 1 patient (0.6%) experienced voice hoarseness 30 minutes after MWA and recovered within 1 month after using mecobalamin. None of the patients developed hematoma or other nerve injury. One patient (0.6%) underwent lobectomy with prophylactic central neck dissection at 6 months because of anxiety. The ablation procedure did not affect the course of thyroid surgery, and no residual cancer cells, occult tumors, or cervical LNMs were found in the surgical pathology results.

Discussion

The outcomes of thermal ablation in patients with T1N0M0 PTC have not been well characterized because of the relatively short history of its clinical application. This multicenter study reported the 10-year outcomes of thermal ablation for T1N0M0 PTC treatment. During the mean (SD) follow-up period of 120.8 (10.8) months, the incidence of disease progression was 6.1% and 10-year DFS was 93.9%. Cox analysis revealed that isthmus location of tumor, young age, and presence of Hashimoto thyroiditis were associated with an increased risk of disease progression, and male sex and right lobe location were associated with a small reduction, although the width of the confidence interval prevented an ability to make any definitive conclusions. The tumor disappearance rate was much higher for T1a tumors than T1b tumors, but the differences in disease progression or 10-year DFS between the 2 types were very small and not clinically meaningful.

Several studies have reported favorable outcomes of thermal ablation for T1N0M0 PTC, which ranged from 13.2 to 48 months.^{42,43,44,45,46} The pooled disappearance rate after ablation was 66% (95% CI, 52%-81%) at 12 months⁴⁷ and 98.5% (95% CI, 92.8%-99.7%) at 60 months.³² However, despite the indolent nature of PTC, evidence supporting this minimally invasive approach is still limited by studies having a single-center design and lacking long-term data. A recent Korean study reported 10-year outcomes of LA for treating 90 patients with solitary T1aN0M0 PTC; during a mean follow-up period of 112 months, all tumors disappeared completely, and the incidences of LNM and recurrent tumor were 1.1% and 5.5%, respectively.³³ Similar results were obtained in the present study. Although T1a tumors have a larger tumor disappearance rate than T1b tumors, there were no significant differences in disease progression or DFS between the 2 types, which was similar to previous findings.^{42,43,44,45,46,48} Tumor size was reported as an independent factor for tumor disappearance but was not associated with disease progression.⁴⁹ A few studies have reported favorable outcomes of thermal ablation for T1b tumors,^50,51 even for T2 tumors,⁵² because strict preablation evaluation, standardized ablation procedures, and adequate ablation margins were performed.

Postablation CNB was performed for 44 patients in the present study, and 1 persistent tumor was diagnosed, suggesting that the residual tumor may persist after ablation.⁵³ Similar results were also observed in a recent meta-analysis that reported results for 1770 patients treated with RFA⁴⁷; 21 patients did not experience completed disappearance on ultrasonography during the 34-month follow-up, and only 7 (0.4%) received a diagnosis of biopsy-confirmed residual PTC cells. The assessment of tumor response after treatment was complicated, and to our knowledge, there is no consensus about the criteria for degerming complete tumor response after thermal ablation.¹⁷ Tumor disappearance on ultrasonography indicates an excellent response to treatment,^54,55 and postablation biopsy can be valuable in increasing the certainty of complete tumor eradication if the ablated tumor does not disappear on ultrasonography during follow-up.⁵⁶ Most studies performed repeated biopsies at different follow-up visits within the first year to evaluate the ablated tumors. FNA and CNB were performed at 1 and 12 months after LA for an 81-year-old patient with T1aN0M0 PTC, finding necrotic material and inflammatory cells with no viable neoplasms.⁵⁷ Two previous studies used FNA to evaluate the ablation areas of T1aN0M0 PTC at 1, 6, and 12 months after ablation.^46,58 In a prospective study,⁵⁹ CNB was performed at 3 or 6 months after ablation, and no residual PTC cells were found. Compared with FNA, CNB has a higher diagnostic accuracy for detecting residual tumor cancer cells and could be valuable in increasing the certainty of tumor disappearance in case of residual tumor volume on ultrasonography after ablation.⁴⁷ In addition, CNB has been used to evaluate the ablation areas of recurrent thyroid cancer and benign nodules.^60,61,62,63 Because most tumors disappear during follow-up, biopsy at each visit or puncture time at the early stage of follow-up might be unnecessary. Additionally, commonly used thermal ablation modalities for PTC, including RFA, MWA and LA, are differentiated by their methods of generating heat,^19,64 leading to different ablation zone involution after treatment.^19,65 Therefore, the indication for postablation biopsy and appropriate puncture timing for biopsy require further investigation.

As a minimally invasive technique, thermal ablation has been proposed as an outpatient therapy with a shorter procedure time, no need for general anesthesia, and a lower risk of complications compared with surgery.¹⁵ Previous meta-analyses have reported that the pooled complication rate was significantly lower in the ablation group than the surgery group (1.2%-3.3% vs 7.8%).^66,67 Voice hoarseness was the most common complication after treatment, with a reported rate of 0% to 3.3% in the ablation group and 1.6% to 4.3% in the surgery group.^66,68 For safe and effective ablation, accurate radiologic evaluation, understanding the ablation technique, and selecting the optimal treatment strategy are critical.⁶⁹ Communications with the patients is recommended to monitor the voice change during the procedure. When patients experienced voice hoarseness, a cold dextrose, 5%, solution injection can manage thermal nerve damage.¹⁶ Additionally, appropriate training and experience in ultrasonography evaluation and ablation techniques are recommended.^16,17,18 Although to our knowledge no objective corresponding indicators have yet been established, previous studies have defined an experienced physician as one who has successfully completed more than 50 cases of thyroid ablation.²² Because only the targeted tumor was treated using real-time ultrasonography monitoring, none of the patients in the present study had hypothyroidism. These results were consistent with that of a previous meta-analysis that reported that the incidence of hypothyroidism after ablation was only 0.04% (1 of 2245).⁷⁰ Thermal ablation may have an advantage vs surgery in terms of quality of life, as it has a lower risk of complications and does not cause persistent hypothyroidism or neck scars.^26,71

Although surgery remains the preferred treatment for patients with PTC, nonsurgical options, such as and thermal ablation, have gained increasing attention.^2,16 Although the patients included in the present study could be classified as ideal candidates for AS,² it was not recommended by the guidelines during the study period.¹ AS is a new conservative management option to immediate surgery for patients with PTC,^1,2 potentially reducing the drawbacks of unnecessary immediate surgery.^8,72,73,74 However, to our knowledge, direct compassions between these 2 managements are still unavailable. Recently, a meta-analysis involving 1329 patients from 13 studies reported a similar risk of recurrence and specific mortality among patients with PTC who underwent ablation or AS compared with surgery.⁷⁵ However, the anxiety experienced by patients during AS remained unresolved, which is the main reason motivating the decision to undergo delayed surgery.^6,76 In the present study, only 1 patient (0.6%) underwent delayed surgery because of anxiety, which was consistent with a previous study.⁷⁷ This suggests that thermal ablation may be a promising modality for treating PTC with similar efficacy to surgery and AS, and it may also be associated with reduced psychological anxiety and unnecessary surgery.

Limitations

This study had some limitations. First, it was a retrospective study with selection bias and a relatively small sample size, particular for T1b tumors. Prospective studies are warranted to confirm the results. Second, the health-related quality of life of the patients undergoing thermal ablation was not evaluated in the present study. Third, because only the targeted tumor was treated during ablation and most normal thyroid tissues were not damaged during the procedure, the present study did not evaluate the association between thyrotropin levels and disease progression for patients with T1N0M0 PTC. Fourth, tiny metastasis in cervical LNs or occult tumors that were not detected by preablated imaging modalities might have existed.⁷⁸ However, their association with overall survival was relatively small.¹ Fifth, thermal ablation is the local application of extreme temperature to induce irreversible cell injury, and surgical histology results could not be obtained during the procedure. The pathologic diagnosis of PTC only based on biopsy and the risk of an aggressive subtype of PTC could not be completely excluded. Moreover, we could not determine whether the newly developed tumor found during follow-up was a new primary tumor or recurrence that was associated with the initial treated cancer, and the same situations also exist in AS or thyroid lobectomy for managing PTC. Sixth, the comparison of surgery, AS, and RFA for treating PTC is still lacking and needs to be investigated further.

Conclusions

The results of this multicenter cohort study suggest that thermal ablation is an effective and safe alternative for patients with T1N0M0 PTC that may offer a minimally invasive curative treatment option for patients who elect to not undergo surgery or AS. For safe and effective treatment, accurate radiologic evaluation, an understanding of ablation techniques, and experienced physicians are recommended. Postablation biopsy could be performed to evaluate the complete tumor eradication, but its indication and appropriate puncture timing require further investigation.

Supplement 1.

eMethods.

eFigure 1. Images in a 36-year-old with papillary thyroid carcinoma who underwent radiofrequency ablation

eFigure 2. US image of a 32-year-old male with a papillary thyroid carcinoma treated with thermal ablation

eTable 1. The equipment of thermal ablation used in this study

eTable 2. Comparison between RFA and MWA for the treatment of T1N0M0 PTC

eTable 3. The treatment variables of RFA and MWA

eTable 4. Changes of the volume and VRR after thermal ablation at each follow-up

Supplement 2.

Data sharing statement