Thermal Ablation for Small Papillary Thyroid Cancer: A Systematic Review

Abstract

Background:

Although clinical studies indicate that thermal ablation is effective in treating low-risk papillary thyroid microcarcinomas (PTMCs), the effectiveness of this treatment in patients with low-risk PTMC has not yet been systematically evaluated.

Methods:

Ovid-MEDLINE and EMBASE databases were searched for studies published through May 1, 2019, which report the efficacy of thermal ablation in patients with low-risk PTMCs. Data were extracted and methodological quality was assessed independently by two radiologists according to PRISMA guidelines.

Results:

This systematic review identified 503 low-risk PTMCs in 470 patients treated by thermal ablation from 9 studies. During follow-up, no patient experienced local tumor recurrence or distant metastasis, whereas two patients (0.4%) experienced lymph node (LN) metastasis. One patient (0.2%) developed a new PTMC, which was successfully treated by additional ablation. Five patients (1.1%) underwent delayed surgery after ablation, including the two patients with LN metastasis and three additional patients with unknown etiology.

Conclusions:

Thermal ablation is an excellent local tumor control method in patients with low-risk PTMCs. Strict inclusion criteria and technical expertise are required to obtain favorable results.

Introduction

The incidence of papillary thyroid carcinoma (PTC) patients requiring subsequent surgery have markedly increased over the past 20 years. These increases are due primarily to the incidental detection of small subclinical PTCs and/or early ultrasound (US) screening (1 –3). The indolent characteristics of PTCs have reduced the need for immediate surgery, as surgery has several important drawbacks, including vocal cord paralysis, hypoparathyroidism, and postsurgical complications (4). Active surveillance (AS) is considered the alternative first-line option for patients with low-risk papillary thyroid microcarcinoma (PTMC), as it reduces overtreatment and unnecessary surgery, while showing favorable results, in these patients (5 –7).

Some patients with low-risk PTMCs undergoing AS may be concerned or anxious about the presence of cancer. Clinical trials have, therefore, evaluated thermal ablation of low-risk PTMCs, using methods such as radiofrequency ablation (RFA), laser ablation (LA), or microwave ablation (MWA) (8 –16). Although these thermal ablation methods have achieved good results with a low incidence of complications, inclusion/exclusion criteria and the completeness of treatment have varied (17,18). Therefore, a systematic evaluation about thermal ablation for low-risk PTMC is timely. This study, therefore, systematically reviewed the inclusion/exclusion criteria; efficacy of treatment; and rates of tumor recurrence, lymph node (LN) metastasis, distant metastasis, delayed surgery, and complications in patients undergoing thermal ablation for low-risk PTMC.

Materials and Methods

This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (19).

Literature search

The MEDLINE and EMBASE databases were searched systematically to identify primary studies of patients with PTMC who were managed by AS. Search terms included ([thyroid microcarcinoma] or [papillary thyroid microcarcinoma] or [papillary microcarcinoma] or [primary papillary thyroid carcinoma] and ablation). All relevant studies published through May 1, 2019, were included. The bibliographies of relevant articles were searched to identify other appropriate articles.

Inclusion criteria

Studies were included if they (1) involved patients with low-risk PTMCs satisfying at least one of the following criteria: (a) greatest tumor dimension ≤10 mm; (b) diagnosis by cytology or biopsy; and (c) absence of LN metastasis, distant metastasis, and gross extrathyroidal extension; (2) included evaluation of efficacy after thermal ablation; and (3) contained results of histopathological tests as reference standards. In this study, thermal ablation included MWA, LA, and RFA.

Exclusion criteria

Studies or subsets of studies were excluded if they (1) were case reports or case series; (2) were letters, editorials, conference abstracts, systematic reviews/meta-analyses, consensus statements, guidelines, or review articles; (3) did not focus on the efficacy of thermal ablation for low-risk PTMCs; (4) included patients with tumors >1 cm in size despite focusing on the efficacy of thermal ablation for PTC; (5) were articles with, or suspected of having, overlapping populations; or (6) were articles without reference standards based on histopathological tests.

The literature search and selection were independently performed by two radiologists, S.J.C. and J.H.B., with 5 and 25 years of experience, respectively, in thyroid imaging.

Data extraction

The following data were recorded using standardized forms according to PRISMA guidelines (19): (1) article characteristics, including institution, country of origin, authors, year of publication, duration of patient recruitment, number of patients, mean patient age, male-to-female ratio, and study design (prospective or retrospective); (2) details of the included tumors, including the total number of ablated tumors, the criteria for ablation (summary of inclusion and exclusion criteria), tumor multiplicity, and the methods of confirming tumor diagnosis; (3) the details of thermal ablation, including ablation methods and devices, power output, applicator, mean ablation time, techniques used [local anesthesia, hydrodissection (20), the moving shot technique (21,22), track-back coagulation], minimum extent of the margins over the tumor margins covering the ablation area, and methods to evaluate the completion of ablation; (4) the results of ablation and details of follow-up (FU), including mean FU duration, serial changes in the size of the index tumor (before and immediately after ablation and at last FU, including the maximum diameter and/or volume, with volume (V) calculated using the equation: V = a × b × c × 0.524, where a is the maximum length, and b and c are the other two perpendicular diameters), tumor disappearance rate (both complete tumor disappearance or the presence of residual scar-like changes), the volume reduction rate (VRR) during FU calculated as ([initial tumor volume − final tumor volume] × 100)/initial tumor volume), mean tumor size at last FU (maximum diameter and/or volume), VRR at last FU, local tumor recurrence (appearance of viable tumor at or around the ablated lesion), a new tumor separate from the target tumor, LN metastasis, distant metastasis, number and causes of surgery during FU after ablation, and complications associated with ablation.

Complications were evaluated using the reporting standards of the Society of Interventional Radiology (23). Major complications were defined as adverse events associated with substantial morbidity or disability, an increased level of care, hospital admission, or substantial prolongation of hospital stay. Minor complications were defined as all other complications, and side effects defined as untoward consequences that did not require therapy or medical treatment, as well as undesired consequences of the procedure according to previous studies (24,25). However, the occurrences after ablation, including transient voice changes, minimal or asymptomatic hematoma, bleeding, and parenchymal edema, and tolerable mild pain or discomfort not requiring medication were regarded as neither complications nor side effects. Early complications were defined as those occurring within 30 days after ablation, and delayed complications were those occurring after 30 days (26).

Quality assessment

Two reviewers independently extracted data and assessed quality using the risk of bias for nonrandomized studies (RoBANS) tool for nonrandomized controlled trials (27,28).

Results

Literature search

The article selection process is described in detail in Figure 1. The initial systematic literature search identified 367 articles. After removing 27 duplicates, screening of the remaining 340 titles and abstracts yielded 16 potentially eligible articles. Searching the bibliographies of these articles identified one additional article (10). The full texts reviews of the 17 provisionally eligible articles found that 3 articles did not assess the efficacy of thermal ablation for low-risk PTMCs (17,18,29), 2 were case reports or case series (30,31), 2 included populations that overlapped or were suspected of overlapping (32,33), and 1 was a review article (34): these 8 articles were excluded. Although two studies included PTCs with longest dimension >10 mm, these studies were included because raw data for low-risk PTMCs were accessible (8,10). Some of the data not included in one of the original articles were supplied by its first author (S.Y. Jeong) (8). Finally, nine studies were included for qualitative synthesis in the current systematic review.

FIG. 1.

Flow diagram of the study selection process.

Characteristics of the included studies

Table 1 gives the detailed characteristics of the 9 included studies, involving 503 tumors in 470 patients. Four studies evaluated patients who underwent MWA (11 –14), three evaluated patients who underwent RFA (8,10,16), and two evaluated patients who underwent LA (9,15). The sizes of the study populations ranged from 4 to 185 patients, with the patients having mean ages of 42.2–70.8 years. Eight studies included more women than men (9 –16), whereas one did not (8). Seven studies were retrospective in design (8 –13,15), whereas the other two were prospective (14,16). The criteria for ablation were generally similar across the studies; these included low-risk PTMCs diagnosed by cytology or biopsy, the absence of LN or distant metastasis, the absence of imaging-based gross extrathyroidal extension, and ineligibility for surgery. Three studies included some patients with multiple tumors (12,13,16), whereas the 6 other studies involved only patients with single tumors (8 –11,14,15), with the number of tumors in the 9 studies ranging from 4 to 206. In the 2 studies using LA, tumors were confirmed by cytology (or fine needle aspiration [FNA]) (9,15); in 2 studies using MWA and 2 using RFA, tumors were confirmed by either core needle biopsy (CNB) or FNA (8,10,12,13); and in the other 2 studies using MWA and 1 study using RFA, tumors were confirmed by CNB (11,14,16). The 2 studies using LA excluded tumors with coarse calcifications or isthmic location (9,15), whereas the 7 other studies did not consider calcification or isthmic location as criteria excluding ablation (8,10 –14,16). The other detailed criteria for ablation are described in Table 1.

Table 1.

Characteristics of the Included Studies

Group	Source, publication	Study period	Institution	Patient no.	Mean age	Male: female	Study design	Tumor no.	Criteria for ablation (summary of inclusion and exclusion criteria)
LA	Zhang et al. (2018) (15)	November 2013–July 2016	Rui Jin Hospital, China	64	42.5	23:41	Retro.	64	(1) Single PTMC by cytology; (2) no LN or distant metastasis; (3) no contact or disruption of the thyroid capsule (4) no isthmic lesion; (5) no massive calcification (>2 mm), (6) no type of thyroid malignancy; (7) solid without cystic components; (8) unsuitable for or unwilling to undergo surgery
LA	Ji et al. (2019) (9)	May 2016–April 2017	Suzhou Hospital, Nanjing Medical University, China	37	43.9	12: 25	Retro.	37	(1) Single PTMC by FNA; (2) no LN or distant metastasis; (3) no invasion of the thyroid capsule, carotid artery, or trachea (4) no coarse calcification (<2 mm); (5) no contralateral vocal cord palsy; (6) no isthmic lesion; (7) no history of thyroid surgery or RT; and (8) unsuitable for or unwilling to undergo surgery
MWA	Yue et al. (2014) (14)	October 2010–February 2013	Yantai Affiliated Hospital, China	21	52.1	6:15	Pro.	21	(1) Single PTMC by biopsy and pathologic examination; (2) no LN or distant metastasis; (3) no contact or disruption of the thyroid capsule or invasion of extrathyroid organs (trachea or esophagus); (4) no anaplastic carcinoma or coexisting thyroid malignancies; and (5) ineligibility or refusal to undergo surgery for high thyroid surgical risk or other reasons
MWA	Li et al. (2018) (11)	February 2014–August 2017	Beijing Friendship Hospital, China	46	43.6	14:32	Retro.	46	(1) Single PTMC by CNB; (2) no LN or distant metastasis; (3) no contact or distortion of the thyroid capsule or extrathyroidal spread (trachea or esophagus); (4) no pregnancy, severe heart, respiratory, or liver disease, renal failure, or severe bleeding tendency; (5) no other type of or coexisting thyroid malignancies; (6) no history of neck irradiation
MWA	Teng et al. (2018) (12)	June 2013–June 2014	China–Japan Union Hospital of Jilin University, China	15	48	6:9	Retro.	21	(1) PTMC by FNA or CNB; (2) no LN or distant metastasis; (3) no invasion of tissues around the thyroid; (4) no serious organ failure, pregnancy, or severe bleeding tendency; and (5) unsuitable for or unwilling to undergo surgery
MWA	Teng et al. (2019) (13)	January 2015–June 2017	China–Japan Union Hospital, Jilin University, China	185	42.2	40:145	Retro.	206	(1) PTMC by FNA or CNB; (2) no LN or distant metastasis; (3) no severe cardiopulmonary abnormalities, pregnancy, severe coagulation dysfunction, or other malignant diseases; and (4) unsuitable for or unwilling to undergo surgery
RFA	Zhang et al. (2016) (16)	September 2013–October 2014	General Hospital of Chinese PLA, China	92	44.7	35:69	Pro.	98	(1) PTMC by CNB; (2) no LN or distant metastasis; (3) no extrathyroidal extension or tumor close to the danger triangle (i.e., within 5 mm of the tracheaesophageal groove); (4) no aggressive histological PTMC; (5) no contralateral vocal cord palsy; (6) no pregnancy, severe heart, respiratory, or liver disease, renal failure, conscious disturbance, cardiac pacemaker, or severe bleeding tendency; (7) no history of neck irradiation; and (8) medical contraindications to or refusal of surgery
RFA	Kim et al. (2017) (10)	2005–2009	Daerim St. Mary's Hospital; Seoul National University, Korea	4	70.8	0:4	Retro.	4	(1) PTC by FNA or CNB; (2) no LN or distant metastasis; (3) no extrathyroidal extension; (4) ineligibility or refusal to undergo surgery for high thyroid surgical risk or other reasons; (5) of the patients in this trial, only those with low-risk PTMCs were selected^a
RFA	Jeong et al. (2018) (8)	March 2011–April 2016	Asan Medical Center, Korea	6	56.3	3:3	Retro.	6	(1) PTC by FNA or CNB; (2) ineligibility or refusal to undergo surgery for high thyroid surgical risk or other reasons; (3) of the patients in this trial, only those with PTMCs without LN, distant metastasis, or invasion of extrathyroidal tissues (T1a, N0, M0) were selected^a

Results of RFA in patients with low-risk PTMCs.

CNB, core needle biopsy; FNA, fine needle aspiration; LA, laser ablation; LN, lymph node; MWA, microwave ablation; NA, not available; Pro., prospective; PTC, papillary thyroid carcinoma; PTMC, papillary thyroid microcarcinoma ≤10 mm in greatest dimension; Retro., retrospective; RFA, radiofrequency ablation; RT, radiation therapy; US, ultrasonography.

Characteristics of the ablation methods

The detailed characteristics of the ablation methods are reported in Table 2. The mean ablation times were variable without tendency according to the type of ablation ranging from 165.9 to 500 seconds. In 5 studies, 2% lidocaine was used for local anesthesia (8,10,11,14,15), whereas the other 4 studies used 1% lidocaine (9,12,13,16). Three of 185 patients were converted to general anesthesia, 2 because they could not bear the pain of the intervention, and 1 because of a vasovagal reflex (13). Hydrodissection was not used in 2 studies (8,10), but was used in the other 7 on a case-by-case basis (9,11 –16). Hydrodissection was performed with lidocaine (1–2% lidocaine diluted 1:8 in normal saline) in 4 studies (9,11,14,15) and with normal saline in 3 studies (12,13,16). The moving shot technique was performed in 6 studies (8,10 –13,16), but details were not available for the other 3 studies (9,14,15). Two studies used a track-back coagulation technique at the final stage of ablation to prevent track seeding (11,14). The minimum covering ablation margin extent over the tumor margin was 5 mm in 4 studies using MWA and 1 using RFA (8,11 –14) and 1–2 mm in 1 study using LA (9), but details were not available for the other 4 studies (15,16). Seven studies used both conventional US and contrast-enhanced ultrasonography (9,11 –16), whereas two used conventional US and Doppler US (8,10) as conformation methods for completion of ablation.

Table 2.

Characteristics of the Ablation Methods

Group	Source, publication	Ablation device	Power output, W; mean energy, J	Applicator	Mean ablation time (range), seconds	Technique					Confirmation methods
Group	Source, publication	Ablation device	Power output, W; mean energy, J	Applicator	Mean ablation time (range), seconds	Lidocaine for local anesthesia (%)	Hydrodissection	Moving shot	Tract-back coagulation	Covering extent (from margin), mm	Confirmation methods
LA	Zhang et al. (2018) (15)	Nd-YAG laser operating at 1.064 lm with an optical beam-splitting device (EchoLaser X4, Esaote, Florence, Italy).	3–4 W; 994.0 ± 310.7 J	300 μm plane-cut optic fiber	271.6 ± 86.7 (125.0–474.3)	2	Yes	NA	NA	NA	Conventional US; CEUS
LA	Ji et al. (2019) (9)	Nd-YAG laser operating at 1.064 μm with an optical beam-splitting device (EchoLaser X4, Esaote, Florence, Italy).	3–4 W; 989.4 ± 417.6 J	—	165.9 ± 92.8 (150–500)	2	Yes	NA	NA	1–2	Conventional US; CEUS
MWA	Yue et al. (2014) (14)	KY2000 (Kangyou Medical Instruments, Nanjing, China).	40 W; NA	16G cooled shaft antenna	500 (400–650)	2	Yes	NA	Yes	5	Conventional US; CEUS
MWA	Li et al. (2018) (11)	NA	30 W at 2450 MHz; NA	17G antenna	NA (20–120)	1	Yes	Yes	Yes	5	Conventional US; CEUS
MWA	Teng et al. (2018) (12)	Ego ECO-100A1 machine (YIGAO Microwave System Engineering, Nanjing, China)	20 W, 4686.0 ± 3365.5 J	ECO-100AI superficial organ ablation antenna	234.3 ± 168.3 (92–808)	1	Yes	Yes	NA	5	Conventional US; CEUS
MWA	Teng et al. (2019) (13)	Ego ECO-100A1 machine (YIGAO Microwave System Engineering, Nanjing, China) and ECO-100AI superficial organ ablation needle	Initiated at 20 W; NA	ECO-100AI superficial organ ablation antenna	NA	1	Yes	Yes	NA	5	Conventional US; CEUS
RFA	Zhang et al. (2016) (16)	A bipolar RFA generator (CelonLabPOWER; Olympus Surgical Technologies Europe, Hamburg, Germany)	3–5 W; 1404.7 ± 822.0 J	18G bipolar electrode; 0.9 cm active tip	450.8 ± 230.2 (91–902)	1	Yes	Yes	NA	NA (exceeded the tumor edge)	Conventional US; CEUS
RFA	Kim et al. (2017) (10)	Cool-Tip, Radionics, Burlington, MA	10–35 W	Thyroid-dedicated straight-type internally cooled electrode: 0.5 active tip	NA	2	No	Yes	NA	NA	Conventional US; Doppler
RFA	Jeong et al. (2018) (8)	VIVA RF generator, STARmed, Goyang, Korea, and M-2004; RF Medical, Seoul, Korea	10–30 W (mean 16 W)	Thyroid-dedicated straight-type internally cooled electrode: 0.5 and 0.7 cm active tip	300 ± 127 (NA)	2	No	Yes	NA	5^a	Conventional US; Doppler

Original data communicated by the first author (S.Y. Jeong) of the study.

CEUS, contrast-enhanced ultrasonography; NA, not available; Nd-YAG, Neodymium yttrium–aluminum–garnet.

Results of ablation

The mean FU duration after ablation ranged from 7.8 months to >53 months (Table 3). The mean size of the index tumor before and immediately after ablation and at last FU ranged from 4.3 to 7.5 mm (41–157 mm³), 11.8 to 14.1 mm (517.6–3099.4 mm³), and 0 to 4 mm (0–70 mm³), respectively. Disappearance rates ranged from 33.7% to 100%. Although disappearance rate was defined as complete tumor disappearance or the presence of residual scar-like changes, the latter was not evaluated in four studies (8,11 –13). The VRR conversion period from negative to positive ranged from 1 to 3 months in 1 study (14), from 3 to 6 months in 3 studies (9,15,16), and from 6 to 12 months in 3 other studies (11 –13); this factor was not available in 2 other studies (8,10). The VRR at last FU ranged from 47.8% to 100%. No local tumor recurrence or distant metastasis was observed during FU. One study reported a new tumor separate from the primary ablated tumor, but this tumor disappeared completely 18 months after additional ablation (13). Two patients from 2 studies using LA showed LN metastasis: 1 patient out of 37 (2.7%) at 24 months after ablation (9) and 1 of 64 patients (1.5%) at 30 months after ablation (15). Both of these patients (9,15), and three patients from one another (14%) study for causes that are not specified (14), underwent delayed surgery during FU. There were no major complications in any of the included studies, with five studies reporting no significant complications. The rate of minor complications per tumor in the other four studies were 3.4%, 4.3%, 5.4%, and 19%, respectively, with the most common complication being transient hoarseness (11/15, 73.3%).

Table 3.

Results of Ablation

Group	Source, publication	Mean FU duration, months (range)	Tumor diameter, mm (volume, mm³)			Disappearance rate^a	Conversion of VRR to plus, months	VRR at last FU	Local tumor recurrence	New dancer	LN metastasis	Distant metastasis	Surgery during FU	Complications
Group	Source, publication	Mean FU duration, months (range)	Index tumor	Immediate ablation	At last FU	Disappearance rate^a	Conversion of VRR to plus, months	VRR at last FU	Local tumor recurrence	New dancer	LN metastasis	Distant metastasis	Surgery during FU	Complications
LA	Zhang et al. (2018) (15)	25.7 ± 8.2 (12–42)	4.6 ± 1.5 (41.0 ± 40.4)	14.1 ± 2.4 (517.6 ± 262.9)	0.6 ± 1.3 (1.8 ± 6.7)	64/64 (100%)	3–6	100	0	0	1	0	1^b	No significant complication
LA	Ji et al. (2019) (9)	16.5 ± 6.9 (12 –24)	5.1 ± 3.45 (52.8 ± 30.6)	12.9 ± 4.1 (726.5 ± 187.2)	1.1 ± 0.6 (2.1 ± 1.3) at 24 months	36/37 (97.3%)	3–6	NA	0	0	1	0	1^c	Early minor Cx.: 1 pain; Delayed minor Cx.: 1 transient hypothyroidism
MWA	Yue et al. (2014) (14)	10.5 (3 –22)	7.3 ± 3.0 (89.5 ± 20.1)	NA	0.3 ± 1.9 (8.7 ± 9.3)	9/18 (50%)	1–3	90 ± 14% at 10.5 months	0	0	0	0	3^d	Early minor Cx.: 4 transient hoarseness
MWA	Li et al. (2018) (11)	NA, at least 42	4.34 ± 1.37 (53.61 ± 48.43)	11.81 ± 2.42 (978.23 ± 605.74)	1.73 ± 1.19 (4.84 ± 6.55) at 42 months	NA (over 7/46, (15%))	6–12	81.33 ± 36.87% at 42 months	0	0	0	0	0	Early minor Cx.: 2 transient hoarseness
MWA	Teng et al. (2018) (12)	NA, at least 36, (36–48)	6.3 (134.3 ± 129.8)	NA (3099.4 ± 3004.5)	NA (2.3 ± 10.5) at 36 months	NA (over 20/21(95%))	6–12	98.78 ± 5.61% at 36 months	0	0	0	0	0	No significant complication
MWA	Teng et al. (2019) (13)	20.7 ± 8.8 (12 –36)	5.3 ± 1.91 (100.1 ± 92.9)	NA (2421.9 ± 1279.0)	NA (2.2 ± 5.6) at 36 months	NA (over 174/206 (84.5%)	6–12	98.65 ± 3.60% at 36 months	0	1	0	0	NA	Early minor Cx.: 5 transient hoarseness, 2 bleeding with additional hemostasis
RFA	Zhang et al. (2016) (16)	7.8 ± 2.9 (3 –18)	5.8 ± 2.2 (118.8–106.9)	NA (749.8 ± 594.4)	NA; 0	33 (33.7%)	3–6	100% at 18 months	0	0	0	0	0	No significant complication
RFA	Kim et al. (2017) (10)	53 ± 13.6 (36–65)	7.5 ± 2 (157 ± 116.1)	NA	0,0	100%	1–6	100	0	0	0	0	0	No significant complication
RFA	Jeong et al. (2018) (8)	20 (17–24)	7.3 ± 1.3 (160 ± 80)	NA	4 ± 4.8 (70 ± 120)	3/6 (50%)	NA	47.8%	0	0	0	0	0	No significant complication

Including complete disappearance and residual scar-like change.

One of 64 (1.5%, 30 months after ablation due to LN metastasis).

One of 37 (2.7%, 24 months after ablation due to LN metastasis).

Three of 21 (14% with unclear etiology).

Cx., complication; FU, follow-up; LA, laser ablation; NA, not available; VRR, volume reduction rate.

Assessment of the study quality

Assessment of the qualities of the included studies according to RoBANS criteria (Fig. 2) showed that all nine studies had a low risk of bias in the selective reporting, incomplete outcome data, outcome data, measurement of exposure, confounding variables, selection of participants, and participant comparability domains. However, eight of the studies showed an unclear risk of bias in the blinding of outcome assessment domain, as they did not clearly report patient/investigator blinding (8 –15).

FIG. 2.

The quality assessment of the included studies according to the RoBANS. RoBANS, risk of bias for nonrandomized studies.

Discussion

This systematic review evaluated the efficacy and safety of thermal ablation of 503 low-risk PTMCs in 470 patients. None of these patients experienced local tumor recurrence or distant metastasis. However, two patients developed LN metastasis during FU. In addition, one patient developed a new cancer, which completely disappeared after additional ablation. Of the 470 patients, only 5 (1.1%) underwent delayed surgery after ablation, including the 2 patients with LN metastasis and 3 patients for reasons that were not specified. Therefore, this systematic review reveals that thermal ablation is a safe and effective local tumor control method for patients with low-risk PTMCs.

Incidental detection or US screening has resulted in marked increases in the incidence of PTC and the number of operations over the past 20 years (1 –3). Because immediate surgery has more disadvantages than advantages (4), AS has become the alternative first-line option for low-risk PTMCs and shows favorable results (5 –7). The 2015 ATA guidelines recommend AS for the first-line management of low-risk PTMCs (5). Based on this background, many trials have treated a small proportion of patients at high surgical risk and those who refuse to undergo surgery using thermal ablation techniques (8 –16). According to a recent systematic review and meta-analysis, AS shows acceptable size enlargement and LN metastasis during 5-year FU (pooled proportion of 5.3% and 1.6%, respectively). However, a large proportion (ranging from 8.7 to 32%) of patients underwent delayed surgery. Among them, a substantial proportion (ranging from 50 to 69%) of the reasons for delayed surgery were distinct from size enlargement or LN metastasis. We believe that anxiety is one of the main reasons for delayed surgery (35). In contrast, in this systematic review, we show that after thermal ablation, only two patients developed LN metastasis without local tumor recurrence or distant metastasis. Moreover only 1.1% of patients in this study underwent delayed surgery after thermal ablation, with none undergoing delayed surgery because of the patient's anxiety about tumor progression. By treating the primary tumor, thermal ablation may alleviate or eliminate patient anxiety.

A recent study showed results conflicting with those of this systematic review (18). That study described the results in 12 patients with PTCs who underwent thermal ablation followed by surgery. Postsurgical results were unsatisfactory, with residual tumor in 11 patients and multifocality in 9 patients. Nine patients had T1b stage tumors, and eight had LN metastases. In contrast, the current systematic review did not identify local tumor recurrences or distant metastasis in the small number of patients who underwent delayed surgery after ablation. This discrepancy may be due to differences in patient inclusion criteria, the extent of the ablation zone, and qualities of the treatment center. Acceptable inclusion criteria may be adopted from those used for AS. It can, for example, be based on the clinical framework for risk stratification in determining whether AS is appropriate for PTMC categorized patients as ideal, appropriate, or inappropriate for AS based on imaging findings, and the characteristics of the patient and/or medical team (36). Based on strict stratification, the patients classified as inappropriate for AS should not be considered for thermal ablation. However, patients with a fear of undergoing surgery can be considered for thermal ablation. Because the ablation procedure is totally operator dependent, the qualities of the operator and the treatment center are essential. The finding that most of the complications were minor, with transient hoarseness being the most frequent complication, indicates that the operator should be thoroughly trained in US-based anatomy, especially in the evaluation of the danger triangle, that is, the tracheoesophageal groove including the RLN, trachea, and esophagus (37). In addition, the operator needs to be fully competent with the technical aspects of thermal ablation, including the use of a small active tip, the moving shot technique, and hydrodissection, thereby maximizing the efficacy and minimizing complications associated with thermal ablation (38).

This study has several limitations. First, some of the included studies were case–control studies, which varied in cohort size and mean FU duration. Additional well-designed multicenter studies comparing ablation with surgery or observation, with long-term FU, in large-sized populations are needed to clarify the efficacy of thermal ablation for low-risk PTMCs. Second, the criteria for ablation in the included studies were not identical, despite all of these studies assessing patients with low-risk PTMCs. The definitions of disappearance also differed among studies, as four of the included studies did not define scar-like changes as disappearances (8,11 –13).

In conclusion, this systematic review shows that thermal ablation methods are safe and effective for local tumor control in patients with low-risk PTMCs, minimizing the delayed surgery rate. Strict inclusion criteria and technical proficiency are required to maximize favorable results.

Footnotes

Author Disclosure Statement

All authors declare no competing financial activities relating to this article. Financial activities not related to this article are J.H.B. is a patent holder for a unidirectional ablation electrode. J.H.B. has been a consultant to two radiofrequency companies, STARmed and RF Medical, since 2017.

Funding Information

No funding was received for this article.

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