New gadgets for thyroid ablation—what’s the promise?

Introduction

Thyroid nodules are present in a large proportion of the population (1). Most often their discovery is incidental, at the time of imaging studies performed for non-thyroidal pathology. In the vast majority of these cases evaluation and, hopefully, reassurance regarding their benign and non-functional status are the essential elements. However, there are a subgroup of thyroid nodules that require further evaluation and management: malignant, toxic or compressive nodules. For the vast majority of malignant nodules surgical management is the mainstay of therapy (2) but that is no longer the case for the other two categories. The toxic and compressive nodules are usually detected by patients or they surface during work-up for symptoms of thyrotoxicosis or local compressive symptoms (most commonly neck pressure and/or dysphagia). The option of non-surgical management has supplanted surgical therapy for a significant proportion of these benign and yet, clinically consequential nodules (3).

For toxic nodules the option of radioactive iodine therapy has been an acceptable choice over many decades. That has also been tried for non-toxic yet compressive nodules with synthetic TSH stimulation but the results have been plagued by increase rates of hypothyroidism and an initial increase in the size of the thyroid, concerning for patients with preexistent compressive symptoms (4,5). Currently for both categories of these benign nodules the option of percutaneous ablation with non-radioactive local energy delivery has generated considerable enthusiasm (3,6,7) and in practices like ours it captures roughly half of these patients. Multiple modalities for delivering the energy have been explored over the past few decades (e.g. Laser, radiofrequency ablation (RFA), high-intensity focused ultrasound, microwave) with the RFA being the dominant technique over the last few years (8). RFA has demonstrated efficacy in normalizing thyroid levels in more than 90% of toxic nodules (9,10) as well as decreasing the volume of compressive thyroid nodules on average by more than 75% at 12 months (11), with best efficacy in nodules that are less than 20 mL total volume (11,12).

While ultrasound-guided thermal ablation applies to suprasternal nodules entirely visible on ultrasound (and fully accessible to the ablation electrode), there are known, even though rare, complications that need to be considered: injury to the recurrent laryngeal nerve and/or parathyroid glands, thermal injury to the skin, trachea or esophagus and nodule rupture (11).

To minimize collateral tissue injury while preserving ablative efficacy, nanosecond pulsed field ablation (nsPFA) (13) has been proposed as an approach to the treatment of benign thyroid nodules. In September 2025, Spiezia et al. (14) published in the journal Thyroid the first-in-human results of thyroid nodule ablation using this approach, reporting rapid nodule volume reduction accompanied by improvement in patients’ symptoms. We aim to put these results in perspective using, where possible, the lens of existing thermal ablation therapies.

Main clinical aspects

This was a prospective open-label, single arm feasibility study of nsPFA for predominantly solid thyroid nodules. conducted at a single institution (Ospedale del Mare, ASLNA1Centro, Naples, Italy). All procedures were performed by the main investigator who has extensive experience in thyroid ablation. The first five cases had the procedure performed just prior to a thyroidectomy and then the specimens were evaluated for both macro- and microarchitectural changes. All remaining patients (second and third groups) were treated under local anesthesia. The second group (20 patients) was treated in a dose-escalating fashion, with ten patients having a second procedure 12 months later, while the third group (5 patients) was treated with the goal of full nodule ablation using overlapping ablation zones. Most participants (75%) were women with a mean age of 51 years and the nodules had a mean volume of 17 mL. The treat-and-resect group provided immediate, objective feedback on the impact of the intervention on to surrounding structures, as those were examined intraoperatively. Histologic evaluation confirmed absence of any injury to neurological, vascular, or tracheoesophageal structures. A sharp demarcation between treated and untreated tissue was notable; however, the authors also observed congestion, hemorrhagic extravasation, and colloid leakage, raising the possibility of transient thyrotoxicosis. Thyroid function data are not reported in this manuscript. The inflammatory response was minimal and there was no necrosis at this early stage.

Volume reduction was rapid and stabilized after the first three months. In the subgroup of patients that received a second ablation at 12 months, further rapid volume response was observed. In cohort 3 (complete ablation intent) the volume reduction improved from 48% at two weeks to 71% at four weeks after the procedure, with stability documented through one year. Importantly, volume reduction was associated with rapid resolution of compressive symptoms and with high patient’s satisfaction.

Reassuringly, no serious adverse events were reported. Minor local pain with swelling and/or bruising were present only for few days, without any scar formation. Transient dysphonia occurred in two of the twenty cohort 2 cases (10%) and resolved spontaneously within 24 hours. However, by comparison, the rate of this complication with RFA therapy is 0.9–1% (15), a notable difference.

Main technical aspects

In this report, Spiezia and colleagues describe performing the nsPFA procedure under ‘light sedation’ or local anesthesia only. This would be similar to the RFA treatment, routinely performed under local anesthesia alone, well-tolerated by awake patients, and typically allowing discharge after 1–2 hours of observation. The utility of having patients awake during these interventions relates to the ability of continuous voice monitoring as a real-time safety check for recurrent laryngeal nerve injury. Unfortunately, there remains some uncertainty in this area, with some recent public comments (16) suggesting the need for deep sedation or general anesthesia, while reports from the cardiac ablation field suggesting that the procedure could be well tolerated under local anesthesia alone by most (but not all) patients (17). The level of sedation required to perform a thyroid ablative procedure warrants careful consideration, as it directly affects the time, cost, and institutional resources required. It would be interesting to know nsPFA post-procedure observation time, discharge criteria, or duration of facility stay for a broader understanding of the process.

The duration of this procedure is best assessed in the cohort treated with therapeutic intent (Cohort 3). For a mean of 55.4 discrete ablation positions in a mean nodule volume of 15.8 cc. the authors reported a mean treatment time of 28 minutes. This is certainly an element that varies with procedure volume and experience. At this stage it seems to be slightly longer than the reported RFA times, without a clear advantage in procedural efficiency—Shin et al. (18) reported a mean of 17.6 minutes for a mean pre-treatment nodule volume of 13 cc, while Park et al. (19) reported a mean duration of 13 minutes for nodules averaging 21 cc in.

Unlike RFA, nsPFA does not produce pronounced microbubbling during treatment, which may limit immediate visual confirmation of tissue effect. However, this characteristic conversely preserves real-time visibility of adjacent critical structures throughout the procedure—a meaningful consideration in the thyroid given the proximity of the recurrent laryngeal nerve, trachea, and major vessels. Contrast-enhanced ultrasound can be employed immediately post-procedure to verify ablation completeness.

Clinical implication

These are encouraging results of a novel ablation technology that should be explored further in several areas of thyroid pathology. First, it suggests a more rapid reduction in nodule volume than thermal ablation techniques in predominantly solid nodules. However, the patient subgroup most likely to benefit from nsPFA’s volume reduction characteristics, the appropriate clinical setting, and a rigorous comparison to existing thermal ablation techniques remain beyond the reach of this pilot study. These are important questions that prospective comparative studies will need to address before broader adoption can be recommended. Rapid volume reduction can certainly benefit patients who need timely debulking but remain unable or unwilling to pursue surgical management. This advantage in solid nodules is further supported by the absence of a significant inflammatory component post-nsPFA, whereas thermal ablation can transiently increase nodule volume. Second, nsPFA generates a distinct margin between treated and untreated areas. Such a sharp area of ablation should also enhance the safety of the procedure overall. While the authors claim that “this novel energy spares nerves and blood vessels”, the transient dysphonia experienced by two patients and the small number of patients treated so far behoove us to be cautious in evaluating this aspect more extensively. Third, the process of nsPFA-induced cell damage leads to regulated cell death, rather than the large cellular infiltrate followed by scarring and necrosis associated with the thermal ablation procedures. The lack of necrosis could prevent significant calcium deposition that can render a nodule “suspicious” on subsequent ultrasound imaging and lead to unnecessary biopsies. Whether the consistency of such a nodule (described by the authors as softer than the “fibrotic ball” induced by RFA) will be reflected in any better local perception by the patient or different technical challenges for surgeons operating in that area later remains unknown. Fourth, the authors attempted to characterize as precisely as possible the volumetric impact of an individual ablation and thus hopefully predict the number of required ablations for a given nodule volume, which could help to estimate the time needed for the procedure. This could certainly be of benefit to practices that aim to improve procedural efficiency.

The uncertainties that will need to be defined by further work with nsPFA relate to the reproducibility of these results in large cohorts and with operators having a more variable level of experience. There is a need to ascertain the long-term durability of the results reported here. We know with RFA that there is a rate of regrowth of 10–20% over 1.5–3 years (19,20). We do not know if, like with thermal ablation, there is a volume inflexion point, with larger nodules having a lower volume reduction rate than smaller nodules. Will this mechanism be effective also for toxic thyroid nodules and, the most intriguing question, will it be effective at treating thyroid malignancy? The answer to the latter questions seems to be an exciting “yes” for low-risk papillary thyroid microcarcinoma, based on a very recent publication (21). Financial considerations will certainly play a role in the future of nsPFA. The cost of a system will have to be considered in comparison with the thermal ablation systems, while acquiring such a system may not be feasible in the immediate future for centers that have recently invested in thermal ablation technology. The process of regulated cell death, associated with this ablation, involves dendritic cells, which are known to be antigen presenting cells to the immune system. Few cases of thyroid autoimmunity developing after thermal ablation have been reported (22) and it will be important to consider this aspect if nsPFA is utilized more broadly. On that note it is surprising that this report does not describe the impact of nsPFA on thyroid function. Transient thyrotoxicosis was reported in the majority of patients treated with nsPFA for papillary thyroid microcarcinoma (21), lesions of considerably smaller volume than those treated in the present study.

Additional considerations

This is an evolving field with some of the authors actively involved in the development process, as their disclosures clearly outline. As with evolution everywhere, there is inherent heterogeneity in technical aspects of this study. Cohorts 1 and 2 were treated with a 13G electrode while for Cohort 3 an 18G electrode was utilized. Furthermore, within Cohort 3 the first two patients were treated ‘conservatively’, with deliberate avoidance of capsule-adjacent tissue, while the final three were treated more completely. Pooling these five patients into a single efficacy endpoint challenges the interpretation of the reported volume reduction.

Summary remarks

Technical advances in energy delivery are clearly influencing the management of thyroid pathology, and nsPFA deserves further exploration based on several of the benefits described in this publication. However, thermal ablation is well established among clinicians and investigators, and a head-to-head trial—perhaps randomized by center—would be the optimal means of defining the relative strengths and limitations of each approach. The ideal study would plan complete treatment of the target nodule, as would occur in standard clinical practice; reevaluate and report the level of sedation required along with patient tolerance; provide a detailed account of total episode-of-care; report thyroid function data before and after treatment and, ultimately, document the generalizability of such results across multiple investigators. Such work can only enrich the options available to our patients and allow us to further individualize their care.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gland Surgery. The article has undergone external peer review.

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0141/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-2026-0141/coif). J.J.S. reports honorarium from Midwest Endocrinology Society for giving a lecture on Thyroid RFA at the MWES annual meeting in 2025. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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