Efficacy and Safety of Thermal Ablation for Indeterminate Thyroid Nodules: A Systematic Review of the Literature and Meta-Analysis

Background: The management of indeterminate thyroid nodules (ITNs), classified as Bethesda III and IV, is challenging due to biopsy limitations in distinguishing benign from malignant nodules. While diagnostic lobectomy is the standard, thermal ablation (TA) is increasingly considered for patients ineligible or unwilling to undergo surgery. This systematic review and meta-analysis therefore evaluate the efficacy and safety of TA for ITNs. Methods: A comprehensive search of MEDLINE, EMBASE, and COCHRANE databases was conducted through May 11, 2025, for studies on ITNs treated with TA, with ≥12 months of follow-up and reported clinical or safety outcomes. Case reports, abstracts, and reviews were excluded. Two radiologists independently performed data extraction and quality assessment. Outcomes included volume reduction rate (VRR), regrowth, delayed surgeries, malignancy detection, and complications. The Risk of Bias for Nonrandomized Studies (RoBANS) tool was used for quality assessment. A random-effects model synthesized pooled estimates, with heterogeneity quantified by Higgins' I². Results: A total of 15 studies with 1149 nodules were analyzed, showing progressive VRR increase, plateauing at 48 months. The pooled 12-month VRR was 81.0% (confidence interval: 76.0-85.9%). Hydrodissection significantly improved VRR at 6 months (p = 0.03), while larger nodules were more prone to regrowth. Major complications occurred in 1.8% (21/1149), with no reported metastasis. Regrowth and delayed surgery occurred in 2.3% (26/1149) and 0.3% (4/1149), respectively, with three malignancies upon delayed surgery. Conclusions: TA may be considered a minimally invasive alternative for ITNs who are not candidates for or decline surgery, demonstrating favorable efficacy and safety. However, study limitations, short follow-up, and residual malignancy risk necessitate careful follow-up, particularly for larger nodules. Advanced TA techniques such as hydrodissection may enhance outcomes by increasing the likelihood of complete ablation. Long-term prospective studies and randomized trials are needed to confirm TA's role in clinical practice.