ABSTRACT: Abstract ABSTRACT Background: Up to now, there are no direct prospective studies comparing Laser (LA) and radiofrequency ablation (RFA). We aimed to compare, in a head- to-head clinical trial, the efficacy and safety of both techniques in a population affected by solid or predominantly solid benign non-functioning thyroid nodules (BNTN). Methods. LARA is a six-month, single-use, randomized, superiority, open-label, parallel trial. We enrolled subjects with a solitary BNTN or dominant nodule characterized by pressure symptoms/cosmetic problems or patients without symptoms who experienced a volume increase >20% in one year. Nodules underwent core needle biopsy (CNB) to evaluate the histological architecture. Patients were randomly assigned (1:1) to receive treatment with either LA or RFA. The primary endpoint was to evaluate the difference in nodule volume reduction between the RF and the LA group at six months. Moreover, we aimed to assess the differences between groups in the rate of nodules with greater than 50% base volume reduction (successful rate) at six months after treatment. ClinicalTrials.gov: number NCT02714946. Findings: From January 2016 to November 2018, 60 patients were randomly assigned (30 participants per group). In the whole study population, the average volume of nodules was 25 ml. The two groups were similar in terms of basal nodule volume, thyroid function, histology, symptoms/cosmetic score and procedure time. At six months, participants in the RFA group showed a reduction volume of 64·3% (95% CI: 57·5% - 71·2%) compared to 53·2% (95% CI: 47·2% - 59·2%) in the LA group (p= 0·015) and this difference was also confirmed in a linear regression model adjusted for age, baseline volume and proportion of cellular component (Laser vs. RFA percent change Delta= -12·8, P=0·018).We have not recorded any significant difference in terms of successful rate at six months after treatment between the two groups (86·7% in the RFA vs 66·7% in the LA, p=0·127). At six months, both symptoms and cosmetic scores improved (compressive symptom score: 2·13 vs 3·9 for RFA, p < 0·001; 2·4 vs. 3·87 for LA, p < 0·001; cosmetic score: 1·65 vs 2·2 for RFA p <0·001, 1·85 vs 2·2 for LA p <0·001) without any statistically significant difference between the two groups. No statistical difference between the two groups was detected at six months as regards the TSH level. High rate of cellularity negatively affects the volume reduction in RFA group (r coefficient -0·41, p=0·034) while histological features did not affect the efficacy of the LA. The adverse event rates were 37% and 43% for RFA and LA, respectively, with no requirement for hospitalization. Interpretation: Both techniques are very effective in reducing the volume of thyroid nodules. RFA appears to be more effective than LA, but both techniques showed no difference in terms of success rate six months after treatment. The safety of the two techniques is very satisfactory.
