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

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.

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.

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).

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.