A real-world experience of active surveillance in Bethesda IV thyroid nodules

PURPOSE: Management of Bethesda IV thyroid nodules is challenging due to their indeterminate nature and potential overtreatment. The aim was to evaluate the long-term outcomes of an active surveillance (AS) strategy for Bethesda IV nodules using clinical and ultrasound-based selection criteria in a middle-income setting without access to molecular testing. METHODS: Retrospective analysis of a multicenter observational cohort. Patients were enrolled between January 2016 and December 2024. Adults with cytologically confirmed Bethesda IV thyroid nodules < 4 cm, TI-RADS 2-4, and no high-risk clinical or radiologic features were offered AS. Patients with prior head and neck cancer, prior radiation, or suspicious lymphadenopathy were excluded. AS with structured clinical and ultrasound follow-up. Surgery was considered for significant growth (≥ 3 mm), new suspicious features, or by clinical/patient decision. RESULTS: A total of 184 patients (88.6% women, 52.7% <55 years) were included. At 48 months, 87.6% of nodules remained growth-free and 89.0% had not required surgery. Overall, 36 nodules (19.6%) showed growth; 26 patients (14.1%) underwent surgery. The malignancy rate was 7% for the full cohort and 46% among operated patients. Most malignant tumors were low-risk papillary carcinomas. No variable significantly predicted growth, but initial nodule size was associated with surgery (HR 1.06; 95% CI, 1.00-1.12; P = 0.04). CONCLUSIONS: In this cohort, AS for Bethesda IV nodules demonstrated high stability, low malignancy rates, and low surgical conversion, supporting its feasibility in selected patients. In resource-limited settings, AS guided by clinical and ultrasound criteria may safely reduce unnecessary surgeries.