The Adoption of Ultrasound-guided Radiofrequency Ablation of Thyroid Nodules in the United States

Thyroid nodules are a common clinical problem with up to 19% to 68%1 of the population having ≥1 lesions detected on examination or with high-resolution ultrasound. Fortunately, thyroid cancer is found in only 5% of all thyroid nodules, and of the approximately 130,000 thyroid operations performed each year, two-thirds are benign disease on final pathology.2 Although most benign nodules can be safely observed, a portion of these nodules requires definitive management due to significant size, continued growth, compressive symptoms, cosmesis, and/or autonomous function leading to hyperthyroidism. Surgical resection has been the mainstay of treatment for these benign, but problematic nodules. Although associated with excellent outcomes in experienced hands, thyroid surgery carries a low risk of complications that include recurrent or superior laryngeal nerve injury leading to voice changes, hypoparathyroidism, bleeding, infection, hypothyroidism with need for thyroid hormone supplementation, and unsightly scarring.2 In contrast to patients with thyroid cancer, these risks may be less acceptable to patients with benign disease. In an era when the medical field is treating thyroid cancer less aggressively, we are also considering ways to treat benign thyroid disease less invasively. Introduced in the early 2000s, ultrasound-guided percutaneous ablation of thyroid lesions has emerged as an alternative to surgery in patients with benign thyroid nodules. Of the myriad ablation methods, the most commonly used technique is radiofrequency ablation (RFA). An expanding body of evidence shows that RFA and other percutaneous interventions are effective treatments for benign solid thyroid nodules, toxic adenomas, and thyroid cysts resulting in overall volume reduction ranges of 40% to 70% with durable resolution of compressive and hyperthyroid symptoms.3–5 In addition, RFA has been used as an effective treatment for locally recurrent thyroid cancers in patients who are not good surgical candidates.6 These percutaneous techniques have been steadily gaining acceptance in Europe and Asia during the last 20 years, but adoption has been slow in the United States. However, in 2018, Hamidi et al7 published the first US institutional experience of 14 patients who received RFA, reigniting interest in the procedure. Since that time, the use of RFA has grown rapidly and at the time of the writing of this article, dozens of US physicians from various disciplines (endocrine surgery, otolaryngology, endocrinology, and interventional radiology) have started to offer RFA for the treatment of select benign thyroid nodules. Table 1 summarizes our single-institution experience with the RFA of 25 nodules in 16 patients since starting our program in August of 2019. Most of these patients had thyroid nodules that were benign on fine-needle biopsy and were either enlarging, symptomatic, or toxic nodules. One patient had a metastatic recurrent thyroid cancer. After an in-depth informed consent discussion, these patients were elected to have RFA over surgical resection or surveillance of their disease. The RFA procedures were performed in our outpatient procedure room under local anesthesia using internally cooled 18G electrodes (star RF electrode, STARmed, Seoul, Korea), 7 cm in length with a 5 to 10 mm active tip size according to nodule size, composition, and function, powered by the VIVA Combo RF generator (480 KHz; STARmed). All of the patients tolerated the procedure well with minimal pain and were able to complete the planned ablation session in full. With a mean follow-up time of 1.1 months, our mean nodule volume reduction at 1 month post procedure is 52.9%. Both of our patients with toxic adenoma(s) were euthyroid at 1 month and all of the patients who have had 3-month follow-up were euthyroid (n = 7). This is in contrast to an estimated rate of hypothyroidism requiring thyroid hormone supplementation of 30% after thyroid lobectomy.8 Of note, no patients have had complications outside the immediate periprocedure period listed in the table. TABLE 1 - Patients Who Have Undergone Radiofrequency Ablation at the Columbia Thyroid Center‡ Post-Procedure 1 mo Patient Indication No. Nodules Largest Diameter of Nodule, cm Nodule Volume, cc Cosmetic Score Immediate Complications Nodule Volume/VRR%∗ TSH mIU/L 37F Large solitary nodule 1 4.3 11.6 3 Dizziness 9.4/19.0† — 64F Toxic MNG in the setting of previous right hemithyroidectomy 1 1.7 1.7 0 None 0.5/72.7 0.51 59F Nontoxic MNG with large symptomatic nodule 1 4.0 11.5 2 Discomfort during RFA 4.7/58.9 — 45F Large solitary nodule 1 2.6 3.7 1 None 1.9/47.4 — 28F Large solitary nodule 1 6.4 53.5 3 None 30.4/43.1 1.29 36F Nontoxic MNG (right sided nodules) in the setting of left vocal cord paralysis from PDA ligation 2 2.62.7 5.74.7 2 None 2.9/37.62.3/58.7 — 54F Large solitary nodule 1 4.3 23.2 3 Discomfort during RFA 11.4/50.7 — 74F Toxic MNG 3 1.83.21.4 0.95.72.0 0 None 0.4/58.93.6/36.50.3/86.0 0.66 46F Large MNG 3 4.03.14.8 10.67.652.4 3 Mild swelling for 48 hours 2.2/79.35.5/27.411.9/77.2 25F Large solitary nodule 1 4.7 24.6 2 None 14.8/39.6 48F Large solitary nodule 1 3.4 6.4 2 Discomfort during RFA 3.6/43.1 57M Large solitary nodule 1 6.4 53.2 3 None 30.8/42.0 31F Recurrent PTC in thyroid bed 1 1.1 0.23 n/a None 0.07/67.9 45F Large MNG 2 4.31.9 9.441.95 2 Discomfort during RFA 3.6/61.70.8/56.4 50F Large MNG 2 3.32.8 10.93.75 3 None 3.19/70.71.18/68.6 42F Large MNG 3 2.23.43.9 3.113.612.3 3 None 2.7/12.06.55/46.75.5/59.2 MNG indicates multinodular ratio; PTC, papillary thyroid cancer.∗VRR, Volume reduction ratio = [1−(post-RFA volume/pre-RFA volume)] × 100%.†Evidence of marginal re-growth due to previously hidden inferior feeding artery; nodule volume/VRR% at 3 months is 5.7/50.9%.‡All RFA procedures performed with internally cooled 18G electrodes (star RF electrode, STARmed, Seoul, Korea) powered by the VIVA Combo RF generator (480 KHz; STARmed). Our preliminary experience with RFA mirrors the generally good outcomes reported in the significant international experience. However, there are several factors that should be considered before widespread adoption of these percutaneous techniques. Although conceptually simple, ultrasound-guided RFA is a technique that requires a unique blend of skills- proficiency with ultrasound, expertise conceptualizing lesions in 3 dimensions, precise fine-motor skills, and the ability to interpret and react to multiple data streams at once (ie, real-time imaging, fluctuating impedance values, tactile feedback, and patient movement and symptoms). Regardless of training background and experience, even clinicians who are already facile with diagnostic ultrasound and fine needle aspiration biopsy will be required to learn a new skillset. They will need to master the new ablation technology and think about aspects of a nodule that may not have been of concern before (eg, feeding arteries and marginal veins, relationship with the isthmus to plan a trans-isthmic technique, and hydro-dissection of planes to create a safety barrier to protect critical structures like the recurrent laryngeal nerve). In addition, they will have to learn how to ablate while the electrode is in motion. This so-called "moving-shot technique" is different from the standard ablation technique of other tumors where the electrode is inserted into the middle of the tumor and kept still during the ablation. These considerations make learning and mastering RFA of thyroid nodules a challenging proposition that requires careful training. Although RFA of thyroid nodules is generally regarded as a safe procedure, it is not without risk. Complications have been reported in 4% to 30% of patients in which RFA has been performed by experienced physicians and include pain, nerve injury and voice change, hematoma, skin burns at the puncture site, thyrotoxicosis, edema, and fever.9 The rare incidence of more severe complications including esophageal or tracheal perforation, infection, abscess formation, and permanent recurrent nerve injury is likely higher in less experienced hands. In addition, it is likely that undertreatment of individual nodules with RFA may be more of an issue in less experienced hands. Several studies with longer follow-up periods of 2 to 3 years have reported regrowth of previously ablated nodules in up to 35% of patients.10 Regrowth happened more frequently in larger nodules, nodules that were ablated with too low energy, and in nodules with inadequate ablation of the margins of the nodule. Certain techniques can help prevent this regrowth, but generally require a more advanced technical skill and experience. As more and more clinicians explore this technique, it will be critical for experienced operators to ensure adequate training protocols and best practices to maximize patient safety. Although there is a clear learning curve to obtain the technical mastery of this combination of skills, even more nuanced is understanding the clinical indications for the procedure, appropriate patient selection, and proper counseling of patients. Acceptable indications for RFA are quickly evolving, but are best established for symptomatic benign nonfunctioning solid nodules (>75% solid) that have been confirmed to be benign on fine needle aspiration biopsy, or autonomously functioning thyroid nodules, especially for patients who may not be good candidates for radioactive iodine ablation or surgery. RFA can also be performed on recurrent thyroid cancers in the thyroid bed and cervical lymph nodes for patients at high surgical risk or who refuse surgery, although proximity to the recurrent laryngeal nerve does increase the risk for nerve injury and may require some advanced techniques (ie, hydrodissection). There is also emerging preliminary data that RFA may also be an acceptable option for treatment of papillary microcarcinomas. Appendix A, https://links.lww.com/SLA/C164; https://links.lww.com/SLA/C165 summarizes the international experience and existing literature for these various indications. Although there are no absolute contraindications to RFA, ethanol ablation is likely a more cost-effective treatment of predominantly cystic thyroid nodules with similar good outcomes, and there is some scant evidence that RFA may promote faster growth of follicular neoplasms and therefore should not be used to treat indeterminate nodules. Additionally, the use of monopolar electrodes (only ones available in the United States) for pregnant women or patients with electrical devices such as a cardiac pacemaker is not recommended because there is insufficient evidence regarding safety of monopolar electrodes in these patients. Future availability of bipolar electrodes may be a safer option for these patients. An appropriate informed consent must discuss the short- and long-term advantages and disadvantages of both radiofrequency ablation and surgery in order for the patients to make informed decisions regarding which approach is best suited for them. Given the complexities of such decision-making, patients are likely best served in tertiary referral or high-volume centers that have a multidisciplinary team that works together to counsel patients regarding the appropriate indications, benefits, and hazards of the procedure. Equally important is the ability of the multidisciplinary team to be able to effectively address potential complications, and to provide follow-up to fully evaluate the safety of the procedure and long-term outcomes. RFA, as well as other percutaneous interventions, offer a promising alternative treatment for benign thyroid nodules. A wealth of international and a growing US experience have shown that RFA can be safe and effective. As we expand our experience with percutaneous ablation of thyroid lesions, we must determine how best to fit these interventions into management algorithms and standards of care for our patients. As with any new technology or therapy, patients are best served by a cautious and judicious adoption process that prioritizes safety and excellent outcomes.