Efficacy and Safety of RFA vs MWA for Treatment of Large Benign Thyroid Nodules, RCT

There is an estimated 10% lifetime probability for developing a thyroid nodule. Although up to 15% of these nodules will prove to be malignant, most thyroid nodules that are identified are benign nodules. However, even benign nodules can continue to grow to a size that start to cause compressive symptoms for patients, including neck pressure and discomfort, dysphagia, dyspnea, and dysphonia. Some nodules will become autonomously functioning causing hyperthyroidism. Traditionally the gold standard treatment for these benign, but problematic nodules, has been thyroidectomy. Although generally a low risk operation, thyroidectomy is associated with some risk for recurrent laryngeal nerve injury, bleeding, infection, and need for thyroid hormone supplementation.

Introduced in the early 2000s, ultrasound-guided percutaneous ablation of thyroid lesions has emerged as a potential 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 radiofrequency ablation and other percutaneous interventions are effective treatments for benign solid thyroid nodules, toxic adenomas, and thyroid cysts resulting in overall volume reduction ranges of 40-70% with durable resolution of compressive and hyperthyroid symptoms. However, RFA is not without its limitations. Radiofrequency waves can be limited by the heat sink effect and tissue char leading to longer procedure times and potentially less optimal outcomes in larger, hypervascular, and/or more cystic nodules.

Microwave ablation (MWA) is another ablative technique that uses electromagnetic energy waves to cause tissue hyperthermia and coagulative necrosis. It generally causes higher ablation temperatures than RFA and is less subject to the heat sink effect, and therefore can facilitate more efficient ablation procedures. Current evidence comparing RFA versus MWA for thyroid ablation were limited and were either retrospective or non-randomized, with focus mainly on small thyroid nodules of ≤10ml in volume. There is a lack of high quality evidence on the safety and efficacy of RFA versus MWA for the treatment of large thyroid nodules (≥20ml). Given the higher ablation temperatures, freedom from heat sink effect and no influence from impedance changes during ablation, MWA may achieve different treatment efficacy in large nodules.

The aim of this randomized controlled trial is to compare the safety and efficacy of RFA and MWA in the treatment of large, benign thyroid nodules. We hypothesize that MWA is not inferior to RFA in terms of complication rate and overall volume reduction of large, benign nodules, but will also be associated with overall decrease in procedure time and procedural discomfort. Patients with large benign thyroid nodules ≥20ml will be considered for recruitment. Suitable subjects will be randomized to receive either RFA or MWA according to a pre-generated block randomization list at a 1:1 ratio. The primary outcome of is the volume reduction rate at 6 months and one year after ablation. The secondary outcomes include safety, complication rates and quality of life after both procedures.

Inclusion criteria

• who have a solitary thyroid nodule ≥20ml in volume
• two benign fine needle biopsies, with the most recent biopsy performed within 1 year of enrollment in study or one benign fine needle biopsy and low suspicion characteristics on ultrasound
• Both functional and non-functional nodules are eligible

Exclusion criteria

• have multiple nodules and planned simultaneous ablation
• indeterminate nodules classified benign
• nodules with substernal extension or posterior extension that cannot be viewed sufficiently with ultrasound
• current pregnancy or cardiac arrhythmias