BRAFV600E-Informed TI-RADS Reclassification of Biopsy Eligibility in Thyroid Nodules: A Retrospective Oracle Decision–Simulation Study

Background/Objectives: We evaluated a hypothetical oracle strategy that assumes BRAFV600E status is known before fine-needle aspiration (FNA), although testing usually requires FNA-derived material.

Methods

This retrospective simulation included 4944 nodules from 4560 patients with linked ultrasound and molecular records following FNA evaluation. The cohort was selected for cytology and molecular testing and enriched for BRAFV600E positivity (42.4%) and TI-RADS 4C nodules (66.7%). The predefined rule combined BRAFV600E-positive upgrading with one-level downgrading of negative TI-RADS 4A/4B nodules. Outcomes were FNA-actionable classification changes and retention of originally FNA-actionable Bethesda V/VI nodules. Pre-FNA prediction was evaluated with patient-grouped cross-validation and training-fold calibration.