Microwave ablation compared to thyroidectomy to treat benign thyroid nodules

Abstract

Objective: Benign thyroid nodules occur commonly but only require treatment when symptomatic. Surgical treatment, once routine, has been replaced by newer technologies, such as microwave ablation (MWA). The aim of this study was to assess the efficacy, tolerability and cost of MWA compared to surgery to treat benign thyroid nodules.

Methods: After obtaining ethical approval and informed consent, a prospective trial was conducted with 52 patients who had symptomatic benign thyroid nodules. Patients were randomly assigned to receive MWA or surgical treatment. The volume reduction ratio (VRR), thyroid function, complications, HRQoL, costs and some parameters were compared.

Results: MWA reduced mean nodule volume by 72.3% at 3 months, 84.5% at 6 months and 92.4% at 12 months as effective as surgery in inactivating nodules, and thyroid dysfunction did not occur during 12-month follow-up for those receiving MWA. Although both MWA and surgery were safe, patients undergoing MWA had fewer cases of complications and rarely reported pain. The MWA group was superior to the surgery group in length of stay, postoperative scar length and the operation time. Compared to patients who underwent surgery, those who underwent MWA had better general health and mental health scores at 6 months and 12 months. The mean total cost of the MWA group was lower than that of the surgery group.

Conclusion: MWA can significantly reduce nodule volume and nodule-related symptoms with more rapid recovery, more pleasing esthetic outcomes, less physiologic disruption and less expense compared to the surgery.

Keywords:

• Benign thyroid nodule
• microwave ablation
• thyroid surgery

Introduction

Thyroid nodules occur commonly, but only 4–8% of palpable nodules are associated with morbidity. Increased use of imaging technology has led to increased detection of thyroid nodules; high-resolution ultrasound (US) shows that 19–70% of randomly selected persons (and higher frequencies among women and elderly persons) have evidence of thyroid nodules [1–3]. Because most nodules are asymptomatic and benign, they are usually managed with follow-up only. Neither the American Association of Clinical Endocrinologists [4] nor the American Thyroid Association [5] recommends thyrotropin (TSH) suppressive therapy with levothyroxine for benign nodules. Radioactive iodine is used only as an adjuvant therapy in specific cases, such as hyperthyroidism secondary to a toxic nodule [6]. However, some nodules display compressive symptoms and require treatment. Surgical therapy has long been used as a primary treatment for these symptomatic nodules.

Although thyroid surgery is widely available and generally safe, there are still risks of complications. The high frequency of hypocalcemia requiring vitamin D treatment is a matter of continuing concern. It is occurred in 9.9% of the patients after total thyroidectomy and 5% of the patients after hemi-thyroidectomy [7,8]. At the same time, given that the incidence of postoperative hypothyroidism could be 22–56% [9–11], it is undoubtedly a common complication after hemi-thyroidectomy. And lifelong levothyroxine supplementation can be burdensome for patients. An important but often overlooked adverse effect of surgical treatment for benign nodules is patient quality of life, especially for women. Health-related quality of life (HRQoL) and general well-being may be significantly influenced by life-long dependence on thyroid hormone replacement, subtle metabolic changes and the presence of a neck scar [12,13].

The development of several nonsurgical, image-guided approaches for the treatment of thyroid nodules has led to increasing numbers of patients to choose minimally invasive, clinically effective treatments such as ethanol, percutaneous laser ablation (LA) and radiofrequency ablation (RFA) [2,14–16]. Particularly, LA and RFA may provide a less expensive and less invasive alternative to thyroid surgery without the risk of subsequent skin scarring or hypothyroidism [17]. Microwave ablation (MWA) is an important minimally invasive technique used for benign and malignant tumors of the liver, lung, kidney and thyroid [18–23] that has expanded the range of nonsurgical minimally invasive treatment options. However, there have been no studies to date comparing the clinical efficacy of surgery and MWA. In this study, we prospectively compared outcomes following surgery and MWA to treat benign thyroid nodules. We also compared surgery and MWA with respect to HRQOL and cost effectiveness.

Methods

Patients

The authors had complete control over the data and methods for the study. This prospective trial was approved by the ethics committee of the Beijing Friendship Hospital and registered at www.chictr.org.cn (ChiCTR-INR-16008053) prior to patient recruitment. For the purposes of this investigation, consecutive patients with complex benign thyroid nodules referred to Beijing Friendship Hospital from October 2015 to February 2016 were invited to participate. Each participant was assigned by a computer-generated random list to either the (1) MWA group: one session of ablation in the outpatient setting; or (2) surgery group: operation performed by a single surgical team under general anesthesia according to the standard method of thyroidectomy [10,24].

Patients met inclusion criteria if thyroid nodules (1) were benign proven by two fine-needle aspiration biopsies (Bethesda class II at cytologic evaluation of material obtained during fine needle aspiration biopsy) [25] within the preceding 3 months and sonograph pattern consistent with low or very low suspicion of malignancy); (2) had a maximum diameter greater than 2 cm and were continuing to grow [26]; (3) were associated with structural symptoms or clinical concern for structural problems; [4] (4) were increasing rapidly in volume (more than double in 6 months); or if (5) patients were anxious about malignant transformation.

Patients were excluded if they had a history of (1) current pregnancy or lactation; (2) head or neck irradiation; (3) head or neck surgery; (4) medical conditions precluding intravenous sedation; (5) indeterminate or malignant findings at cytologic evaluation of FNAB specimen from thyroid nodule or (6) vocal cord palsy; or if they did not provide informed consent.

Patients satisfying the inclusion and exclusion criteria were invited to participate.

Procedures

Pretreatment evaluation

Patients first met with the clinic general surgeon, who divided patients into one of two groups according to the computer-generated random list. Nodule dimensions were measured with a US machine (Ascendus Color Doppler Ultrasound Diagnostic, Hitachi Medical Systems, Tokyo, Japan) using a 5 to 18-MHz linear matrix transducer. An independent, experienced sonographer who was blinded to patient treatment group performed all measurements.

The nodule volume (V) was calculated using the equation where V is volume, W is width, D is depth and L is length (all in centimeters) of the thyroid nodule.

Serum thyrotropin and free thyroxine levels were obtained and an FNAB was performed twice to check for evidence of malignant transformation. According to the US presentation of the internal nodule on color Doppler flow imaging (CDFI), the nodular vascular scores were classified into four grades: (1) no color signal in the nodule; (2) color signals in <25% of the nodule; (3) color signals in 25–50% of the nodule and (4) color signals in >50% of the nodule [21].

To compare the efficacy and tolerability of MWA to surgery, we took patient history, any current complaints (pressure symptoms in the neck and difficulty in swallowing, yes/no), cosmetic results (graded as poor, acceptable, good and excellent), drug history and TSH at baseline.

Patients in both groups were then asked to complete an HRQoL 36-Item Short Form Survey (SF-36). HRQoL can provide a subjective assessment of the impact of treatment across psychologic, physical, social and somatic status, and the comprehensive predictions of the intervention’s therapeutic effect is useful to clinicians and patients under specific conditions [27].

Contrast-enhanced ultrasounds (CEUs) were performed on patients in the MWA group to evaluate nodule blood supply.

Microwave ablation

MWA was performed in an outpatient setting by an experienced physician. Before ablation, intravenous access was obtained via the antecubital vein, and patient partial pressure of oxygen (PO₂), heart rhythm, respiratory rate and blood pressure were continuously monitored.

The MWA therapy instrument used was a KY-2000 (Kangyou Medical, Nanjing, China) that consists of a microwave generator, a flexible low-loss coaxial cable, and a cooled shaft antenna. The generator can produce 1 W to 100 W of power at 2450 MHz. The antenna (a 100-mm shaft coated with polytetrafluoroethylene) is 16 G, 3 mm long, needle-type, with a stable temperature of 28–32 °C. To prevent shaft overheating, distilled water was circulated continuously through dual channels inside the antenna shaft.

After determining the best puncture site using US, local anesthesia with 1% lidocaine was administered subcutaneously. For cases in which cystic components were detected on pre-ablation ultrasonography, fluid was aspirated using a percutaneous transhepatic cholangiography needle. Next, the capsule was rinsed repeatedly with 99% ethanol [28].

A 1 to 2 mm skin incision was made and the ablation antenna was positioned under sonographic monitoring. During the MWA, a power output of 30–50 W and frequency of 2450 MHZ were used. Under US guidance, a moving shot technique was used [29,30] to release microwave energy from the moving electrode until the hyperechoic zone was filled with the treated portion of the nodule. A leverage and pry-off method was used during ablation to prevent heat energy damage to the recurrent laryngeal nerve, esophagus and other nearby structures [31]. For nodules located near the recurrent laryngeal nerve or large blood vessels, a mixture of 2% lidocaine (10 ml) and 0.9% physiologic saline (20 ml) were injected around the thyroid capsule to achieve a liquid isolation region. Patients remained under observation for a few hours following the procedure to monitor for complications.

Thyroid surgery

All operations were performed by a single surgical team. Patients, under general anesthesia, were placed in the supine position with the neck extended. Nerve monitoring was performed throughout the procedure. Thyroidectomy was performed through a single 2–4 cm arc incision at the neck midline above the sternal notch. Skin, subcutaneous tissue and the platysma muscle were incised. A freed skin flap was created from the cornu superius cartilaginis thyroideae down to suprasternal fossae, and both were joined to the middle line of suprasternal fossae. The linea alba cervicalis was incised and the cervical anterior muscles were retracted laterally to expose the thyroid.

The vessels of the thyroid medium vein were selectively ligated or closed by conventional vascular clipping, and the lesion was carefully explored. An incision was made longitudinally 2 cm ahead of the cervical sheath, and the vagus nerve was identified between the jugular vein and arteria carotis communis. During this time, the V1 nerve signal was monitored and confirmed normal. Next, the thyroid isthmus was removed to expose the trachea. The suspensory ligaments of thyroid were amputated and the cricothyroid artery and arteriae thyreoidea inferior were isolated and ligated while preserving the rami posterior. Next, the R1 signal was identified for the recurrent laryngeal nerve, which was then located using signal intensity. While ensuring normal R1 signal intensity, the recurrent laryngeal nerve and parathyroid gland were identified and preserved. The unilateral thyroid gland was completely resected and sent for pathologic examination. At that point, the V2 and R2 signals and laryngeal nerve were noted to have normal function. Following thyroid lobe and isthmus removal, the area was examined for bleeding. Once hemostasis was achieved, a drain was placed, and the incision was closed with sutures.

Follow-up evaluation

CEUs was performed in the MWA group immediately after ablation to determine treatment completeness and guide subsequent ablation of any residual viable tissue (as is performed with liver ablation and brain surgery) [32–34].

Patients in both groups underwent regiones thyreoidea measurement and peripheral lymph node examination with US at 3, 6 and 12 months. The percentage change in thyroid nodule volume was calculated using the following equation: where V_reduction is the change in nodule volume, V_initial is the initial nodule volume and V_final is the final nodule volume.

Therapeutic success was defined as a volume reduction greater than 50% [26]. At 1,6 and 12 months, thyroid function was measured using laboratory tests, and patients were asked to rate their pressure symptoms using a visual analog scale (VAS) to rate the improvement in their obstructive and local pressure symptoms compared to baseline. HRQOL surveys were re-administered at 1, 6 and 12 months.

Each complication was recorded during and after treatment until 18 months. Each patient had written and oral instructions that if there was any problem, they could contact medical staff directly. All the complications were classified according to SIR classification system [35].

Cost analysis

Cost analysis included the procedure (MWA or surgery) as well as pre-procedural and post-procedural exams. Direct costs were related to hospitalization for MWA or surgery plus any costs associated with adverse events. Pricing was obtained from the Beijing Friendship Hospital database. Indirect costs were evaluated using the human capital approach according to the Chinese guidelines for cost-effectiveness studies and using the standard formula

Indirect costs = Gross Domestic Product (GDP) per capita         × day × productive weight

where productive weight is based on the internationally weighted value, ages are divided into four groups (0–14 years, 15–44 years, 45–59 years and 60 years or older), and the weighted values were 0, 0.75, 0.80 and 0.10, respectively) [27]. The value of GDP per capita was based on the Beijing, China regional value estimate of Y292 per day.

Statistical analysis

Continuous variables were expressed as means ± standard deviations, and chi-squared tests were used to compare categorical variables. Groups were compared using the Mann–Whitney U test. Post-treatment nodule volume was compared to pre-treatment volume using the paired samples t-test. Changes in HRQoL scores between groups over time and their interactions were evaluated using the Wilcoxon signed-rank test. All statistical analyses were performed using IBM SPSS Statistics 20.0 (Armonk, NY). p values of .05 or less were considered as statistically significant.

Results

Of the 74 eligible patients, 60 (81.1%) provided informed consent to participate in the study and were randomly divided into MWA group or surgery group, with 30 patients in each group. For patients with multiple nodules undergoing MWA, ablation was performed only for the largest or dominant nodule. For those with multiple nodules undergoing surgery, the surgeon chose hemithyroidectomy or total thyroidectomy based on thyroid nodule number, location, and size. In the case of unilateral nodules, surgeons performed hemi-thyroidectomy; however, total thyroidectomy was performed if a contralateral nodule exceeding 1 cm in diameter was found. In our study, 24 patients underwent hemithyroidectomy and 6 patients underwent total thyroidectomy. Due to the differences in postoperative complications and the effect of thyroid function on patients with hemi-thyroidectomy, 6 patients who underwent total thyroidectomy were excluded from the group. 2 patients in the MWA group whose VRR was less than 50% after 6 months were excluded from the group after the second ablation. Because their costs increased nearly twice as much as the one single treatment and the score on SF-36 also decreased. The above situation would result in the bias of statistical results. Therefore, in the end, MWA group was included in 28 patients, and the surgery group was included in 24 patients.

Patient characteristics are reported in Table 1. There were no differences between groups with respect to baseline age, sex, symptoms, nodule volume, TSH, free thyroxine, thyroid medication history, nodule type, nodule vascularity, autoimmunity or clinical nodule size (using the WHO grading system [36]). However, US imaging showed that baseline nodules in the surgery group were longer (3.76 cm vs. 4.38 cm, p = .031) on average. In MWA group, current complaints was positive in only 10 of 28 patients, while the cosmetic positive score was positive in 100% of the patients (Table 2). This may be due to the fact that many patients came to visit with the visible neck mass, and at this time they did not have the pressure symptoms or difficulty in swallowing. Our data showed that only when the volume of the nodule was larger than 17.8 ml, the patient would have the current complaints.

Table 1. Baseline patient characteristics.

	MWA group (n = 28)	Surgery group (n = 24)	p
Age (years)	53.61 ± 8.76	52.05 ± 11.95	.770^a
Sex (M/F)	20/8	14/10	.512^b
Nodule maximum diameter (cm)	3.76 ± 1.06	4.38 ± 0.84	.031^a^,c
Nodule volume (mL)	17.11 ± 14.41	20.79 ± 14.00	.165^a
Presence of symptoms (Y/N)	10/18	11/13	.697^b
Thyrotropin (µIU/ml)	1.85 ± 1.17	1.76 ± 0.83	1.000^a
Free thyroxine (ng/dl)	0.92 ± 0.18	0.89 ± 0.17	.565^a
Thyroid medication history	0 (0.0)	0 (0.0)
Nodule type			.099^b
Mainly solid nodules	5 (17.9)	10 (41.6)
Mainly cystic nodules	23 (82.1)	14 (58.3)
Nodule vascularity	1.87 ± 0.80	2.00 ± 0.89	.649^a
Anti-TPO and/or anti-TGAb (Y/N)	1/27	1/23	.897^b
Side			.606^b
Right	15	14
Left	13	10
Isthmus	0	0

Mainly solid nodules (solid components >50%); mainly cystic nodules (cystic components >50%).

^a Mann–Whitney U test.

^b x² test.

^c Indicates a significant difference.

Table 2. Efficacy of microwave ablation compared to surgery for the treatment of benign thyroid nodules.

Outcome	MWA group (n = 28)	Surgery group (n = 24)
Current complaints	10	11
Remission of nodule-related symptoms	10	11
Patients with cosmetic concerns	28	24
Excellent cosmetic results	28	20

Thyroid nodule volume in the MWA group decreased over time, from 17.11 ± 14.41 ml at baseline to 3.01 ml ± 2.74 ml at 3 months (75.9%, p < .01), 1.70 ± 2.08 ml at 6 months (88.4%, p < .01), and 0.69 ± 0.89 at 12 months (95.2%, p < .01). The greatest volume reduction was observed within the first 3 months. The VRR (volume reduction rate) of mainly cystic nodules was significantly higher than that of mainly solid nodules at 3 months and 6 months (p < .05), but there was no significant difference at 12 months (p = .06) (Table 3).

Table 3. The changes in the nodule volumes before microwave ablation and at each follow-up period.

	No. of nodules	VRR after 3 months	VRR after 6 months	VRR after 12 months
Mainly solid nodules	5	0.34 ± 0.22	0.67 ± 0.20	0.84 ± 0.09
Mainly cystic nodules	23	0.84 ± 0.12	0.89 ± 0.12	0.97 ± 0.03
p		<.01	.03	.06

Mainly solid nodules (solid components >50%); mainly cystic nodules (cystic components >50%).

VRR: volume reduction rate.

All of the 24 patients in the surgery group were successfully treated with hemi-thyroidectomy, and all the nodules were benign nodules according to the postoperative pathological results.

With respect to treatment efficacy, MWA was associated with complete cure of nodule-related symptoms in 10 out of 10 patients; thus MWA was non-inferior to surgery (Table 2). Secondly, cosmetic results did not differ between groups and were excellent for most patients (28 out of 28 patients undergoing MWA and 20 out of 24 undergoing surgery). That is, most nodules that were clinically visible before treatment were not visible after treatment. Of the 24 patients who underwent surgery, 20 patients (83.3%) judged the cosmetic results to be ‘excellent’, whereas 3 patients (12.5%) rated the results as ‘good’, and a patient (4.2%) rated ‘acceptable’ because of scarring. In summary, the cosmetic benefit of thyroid nodule removal was felt to outweigh the presence of a scar by 20 of 24 patients, whereas the other 4 patients felt that the scar compromised the final cosmetic result.

Overall, the volume reduction achieved by MWA did not affect thyroid function, which remained unchanged throughout the 12-month follow-up period (Figure 1). Although serum TSH increased for one patient and TSH increased with a FT3 decrease in another patient at 1-month follow-up, these patients were not treated because they were asymptomatic and because thyroid function laboratory values normalized at 6-month follow-up. However, in the surgery group, there were 4 patients with subclinical hypothyroidism (elevated TSH but normal FT4), of which 1 patient had a normal lower limit of FT4 at 6 months after surgery. At the same time, the patient was in accordance with the diagnostic criteria of Hashimoto’s thyroiditis, so as to avoid its development into clinical hypothyroidism, the patient was given the treatment of hormone.

Figure 1. The volume reduction achieved by MWA did not affect thyroid function, which remained unchanged throughout the 12-month follow-up period. In contrast, the TSH level of the surgery group was significantly increased at 1 month, and was consistently higher than the baseline and MWA group during the 12-month.

MWA was well-tolerated compared to surgery. Post-ablation pain was rare (2 of 28 patients), mild and resolved without treatment by Day 5. In addition to pain, a patient experienced voice hoarseness, which resolved after 3 months of mecobalamin treatment [37,38]. No postoperative fever, infection, skin burn, neck damage or other important structural complications were observed. In contrast, patients in the surgery group commonly experienced postoperative pain (22 of 24 patients). This pain resolved spontaneously for most patients within 1 week; however, 3 patients required paracetamol treatment. In addition to postoperative pain, surgical complications included 2 cases of numbness, and 2 cases of voice hoarseness; all of these complications required medication. There was no bleeding significant enough to warrant repeat surgery. According to the SIR classification system, the complications of the two groups were graded as Class A-Class B (Table 4). As shown in Table 5, although the number of complications in the surgery group was more than that in the MWA group, there was no statistical difference between the two groups; however, the MWA group was superior to the surgery group in length of stay, postoperative scar length and the operation time (p < .001).

Table 4. Definitions of SIR class and percentage incidence.

		Microwave group (n = 28)		Surgery group (n = 24)
SIR class	Description	Number of patients	Percentage of patients with complications	Number of patients	Percentage of patients with complications
A	No therapy, no consequences	2	6.7%	18	75%
B	Nominal therapy, observation, no consequences	1	3.3%	4	16.7%
C	Required therapy, minor hospitalization (<48 h)	0	0	0	0
D	Major therapy, unplanned increase in level of care, prolonged hospitalization (>48 h)	0	0	0	0
E	Permanent adverse sequelae	0	0	0	0
F	Death	0	0	0	0

SIR: Society of Interventional Radiology.

Table 5. Comparison of the complications and procedures condition of the MWA group and surgery group.

	MWA group (n = 28)	Surgery group (n = 24)	p
Numbness	0	2	.208
Voice hoarseness	1	2	.891
Total complication	1	4	.110
Postoperative pain	2	22	<.001
Postoperative scar >3cm	0	24	<.001
Length of stay (day)	0.05 ± 0.00	4.04 ± 0.79	<.001
The operation time (min)	20.4 ± 7.2	106.5 ± 20.5	<.001

SF-36 scores for patients undergoing microwave ablation or surgery at 6 months and matched general population scores are shown in Figure 2 [39]. Compared to patients who underwent surgery, those who underwent MWA had better general health, vitality and mental health scores. Moreover, compared to the general population, patients in the surgery group had lower scores for general health, and mental health, whereas patients in the MWA group did not differ with respect to SF-36 scores at 6 months. The 12 months after treatment are shown in Figure 3, not much different from the results in 6 months. The surgery group was slightly elevated on mental health, but still lower than the MWA score.

Figure 2. Compared to patients who underwent surgery, those who underwent MWA had better general health and mental health scores. Moreover, compared to the general population, patients in the surgery group had lower scores for general health and mental health, whereas patients in the MWA group did not differ with respect to SF-36 scores at 6 months.

Figure 3. The 12 months after treatment were not much different from the results in 6 months. The surgery group was slightly elevated on vitality, but still lower than the MWA score.

The average direct cost was Y12 293per MWA patient and Y11 983 per surgery patient. The extra cost of Y7,560 per MWA patient was due primarily to the high purchase price for the microwave needle (Table 6). The mean length of hospitalization was shorter for MWA patients compared to surgery patients (1 day versus 4 days, p < .001); thus, indirect costs were lower for the MWA group compared to the surgery group (Y411 versus Y981, p < .001). In general, the mean total cost of the MWA group was lower than that of the Surgery group (Y12 704 versus Y12 964, p < .001).

Table 6. The direct costs for microwave ablation versus surgery to treat benign thyroid nodules.

	MWA group	Unit cost (Y)	Surgery group	Unit cost (Y)
Medical nursing	Second-grade nursing (per day)	20	Special nursing (per day)	60
			First-grade nursing (per day)	26
			Second-grade nursing (per day)	20
Hospitalization			Room (per day)	80
Doctor visit		42		42
Medical procedure	Ultrasound-guided operation (>60 min)	300	Thyroidectomy (or hemi-)	437
	Microwave ablation	1466	General anesthesia	435
	Biopsy (superficial)	78	Post-anesthesia nursing	220
Examination and laboratory  testing	Electronic laryngoscope	150	Electronic laryngoscope	150
	Electrocardiogram	20	Electrocardiogram	20
	Chest X-ray	150	Chest X-ray	150
	Cytologic examination	110	Pathologic examination	200
	Contrast-enhanced ultrasound	480	Thyroid function	226
	Thyroid function	226	Coagulation function	296
	Coagulation function	296	Infectious disease	401
	Infectious disease	401	Routine blood test	51
	Routine blood test	51	Hepatic and renal function	261
Medications	Lidocaine hydrochloride	1.4	Levothyroxine	11
			Methoxamine hydrochloride	63.9
			Atropine sulfate	0.65
			Esmolol hydrochloride injection	32.35
			Urapidil hydrochloride injection	50.7
			Remifentanil hydrochloride	90.92
			Sufentanil citrate	50.2
			Midazolam injection	10.48
			Propofol injection	349.44
			Hydroxyethyl starch 130/0.4 and sodium chloride injection	101.86
			Compound lidocaine cream	71.83
			Flumazenil injection	36.8
Instruments and materials	Biopsy needle	264	High-frequency electrotome	60
	Microwave needle	7560	Negative plate	99
			Absorbable suture	517
			Nerve monitor	4925
			Ablation electrode	748
			Ultrasonically activated scalpel	600
Follow-up costs	Thyroid function(×3)	226	Thyroid function (×3)	226
	Ultrasound	free	Ultrasound	free
Total		12,293		12,357

Discussion

Although most cytologically benign thyroid nodules do not require intervention, some do become large enough to cause obstructive or local pressure symptoms [40,41]. Although surgery is the most effective therapeutic option for those patients, some are reluctant to pursue this intervention [42]. The risk of surgical complications, high cost, need for general anesthesia and permanent loss of thyroid parenchyma are thought to be some reasons for patient reluctance [36]. Thus, in these cases, a minimally invasive alternative treatment, such as MWA, is often preferred. There are many publications proving the effectiveness and safety of MWA which showed positive results [28,30,31]. Many studies have also compared the clinical outcomes of MWA with other minimally invasive treatments [21,43,44]. Although MWA has been extensively studied, there are no works comparing it to surgery for the treatment of benign thyroid nodules. For this reason, our present study was designed to compare the efficacy, safety, HRQoL and cost between these two treatments.

Our data show that MWA can reduce thyroid nodule volume and alleviate nodule-related symptoms and cosmetic concerns as effectively as surgery. In this study, thyroid nodule volume decreased 92.4% 12 months after MWA. Our finding is in line with that of a previous study showing 90% nodule volume reduction 12 months after MWA [31]. That study also showed that nodule volume continued to decrease beyond 12 months [31]. Furthermore, VRR of mainly cystic nodules was better than mainly solid nodules at 3 months and 6 months which is in consistent with the literature [31,45]. It might be that the heat conduction was homogeneous, after removing the internal fluid, the nodules were shrunk and the unit area received more heat energy. However, there was no significant difference during the 12 months follow-up, which may indicate that the nodule component had only the effect of speed without affecting the final VRR.

The goal of MWA is complete thyroid nodule inactivation and cure, as incompletely inactivated nodules in residual tissue may recur. Although Color Doppler Flow Imaging, CEUs, and other methods are used to identify residual tissue during the MWA procedure to add ablation during the ablation process, but the extent of ablation is sometimes limited to nodules to avoid damage to adjacent structures. Therefore, postoperative residual tissue is common, especially for larger nodules, which may require multiple ablations to completely inactivate the target [46]. During follow-up, 2 patients in this study did require a second ablation, which ultimately resulted in nodule inactivation and cure. In contrast, all nodules were completely inactivated in the surgery group. Overall, MWA was as effective as surgery in completely inactivating nodules.

Volume reduction did not affect thyroid function in patients undergoing MWA. In this study, the two patients with evidence of thyroid dysfunction at 1 month had normalization of thyroid function at 6 months. This thyroid function recovery may reflect the thyroid tissue preservation that occurred with MWA, in which only the target nodules were affected [30]. Hemi-thyroidectomy had a slight influence on the thyroid function of the patients. 4 patients had subclinical hypothyroidism (elevated TSH but normal FT4), which may be accompanied by an increased risk of atherosclerosis and myocardial infarction [47,48] and eventually progress to overt hypothyroidism. Therefore, for patients with subclinical hypothyroidism, we need to give regular follow-up to avoid adverse events. One of the patients needed to be treated with levothyroxine, which may be due to the history of Hashimoto’s thyroiditis, so the thyroid hormone secretion was low.

MWA was safe and well-tolerated, with only one case of postoperative pain and one case of transient voice hoarseness. This favorable outcome may have been due in part to the use of the moving shot technique, which is intended to minimize thermal nerve injury [29]. Postoperative analysis showed that patient who had transient voice hoarseness had a larger nodule prior to treatment (70.3 ml), the ablation time was relatively long, the fluid was not added in time to achieve ‘liquid isolation region’, and the ablation range is too large to cause heat damage to the recurrent laryngeal nerve. However, previous studies demonstrated that using an artificial liquid isolation region is a safe and effective adjunct to MWA when thyroid nodules are near the esophagus, trachea or recurrent laryngeal nerve [45]. Such isolation can prevent heat stimulation of the trachea and esophagus, which could otherwise cause cough or pain that decreases treatment tolerability [31].

In contrast, surgery was associated with postoperative pain in 93.3% of patients. Although there were more cases of complications in the surgery group, there was no statistical difference with MWA group. It may be that with the advances in surgical techniques, including the use of intraoperative nerve monitors [49], the complications of hemi-thyroidectomy were also decreasing. As with other studies of surgery for thyroid nodules [50], no patient in this study developed life-threatening complications such as hemorrhage, laryngeal edema or tetany.

Although most patients were very satisfied with surgical results, as in previous reports [51], some study patients were concerned about the risk of complications and cosmetic problems caused by scarring. MWA does not carry the risks of general anesthesia, so it may be preferred for treating weak or elderly patients or those with clinical or social contraindications to surgery.

Our results also showed that HRQoL was better for patients undergoing MWA compared to surgery in two aspects of SF-36 domains at 6-month follow-up. With respect to mental health, lower scores in the surgery group may be related to the cosmetic effects of scarring. The score was slightly elevated 12 months after surgery. I asked about the reasons for the increase in scores, in some of patients it was due to scars decreased, and others it was due to a decrease in their care over time.

Although in our study, we did not find hidden microcarcinoma. Some benign nodules still may hide small malignancies, which can be missed during FNAB due to sampling error. Wang et al. found that, on average, 6% of clinically benign nodules were found to be malignant on postoperative cytopathology [52]. The clear advantage of surgery is tissue removal for pathologic diagnosis and cure. However, it has been suggested that low-risk thyroid cancer, such as microcarcinoma, is presently overtreated, as no patients with microcarcinoma who underwent surgery had carcinoma recurrence, metastasis, or death due to thyroid carcinoma in a study with a 5-year follow-up. These findings suggest that low-risk microcarcinoma is generally indolent and does not require immediate surgery [53]. Although MWA can successfully treat nodule-related symptoms for patients unwilling to undergo surgery, there are no long-term studies about outcomes after MWA for clinically benign nodules that harbor malignant cells. Thus, it would be important to monitor patients following MWA for thyroid nodules for at least 5 years.

Our study has some limitations. Firstly, we included a small number of patients and followed them for only 12 months. The incidence of thyroid dysfunction and SF-36 score changes during the first year may not reflect final outcomes, and patients undergoing MWA may experience larger thyroid nodule volume reduction over time. A larger follow-up study with longer follow-up would address this limitation. Secondly, compared with MWA, RFA and LA are recommended for minimally invasive treatment of symptomatic benign thyroid nodules because of lots of strong data, especially for non-surgical candidates, high-risk groups for surgery or those refusing surgery [2,3,16,21]. For MWA, there had been some retrospective trails and prospective multicenter study [21,28,31]. But there was no prospective randomized controlled study of MWA and other minimally invasive treatment, or other strong evidenced-based data. Thus, further clinical studies are needed. Thirdly, the SF-36 was not designed to assess HRQoL in patients with thyroid nodules, so a questionnaire tailored to thyroid disease may more accurately assess patient outcomes.

Conclusions

In conclusion, our comparative study shows that, for benign thyroid nodules, MWA is an effective alternative to surgery, which may be undesirable in cases of limited local symptoms or cosmetic concerns. MWA can significantly reduce nodule volume and nodule-related symptoms with more rapid recovery, more pleasing esthetic outcomes, less physiologic disruption and less expense. However, our findings do not support replacement of surgery with MWA for all cases of thyroid nodules. Surgery appears to be a more effective treatment for patients with multiple nodules and a better choice for obtaining conclusive pathologic results.

Disclosure statement

No potential conflict of interest was reported by the authors.