External validation of a microRNA thyroid classifier: a real-world prospective study.

Introduction: Thyroid nodules are common, affecting approximately 50% of individuals. These nodules are often discovered incidentally and exhibit benign characteristics. Following a suspicious ultrasound, a fine-needle aspiration biopsy (FNAB) is performed to assess the risk of malignancy. However, approximately 30% of cases are classified as indeterminate by cytology. In response, the development of molecular tests has refined malignancy risk assessment and reduced the need for diagnostic surgeries. Objective: To independently evaluate the real-world clinical utility and the diagnostic performance of a microRNA-based molecular test (mir-THYpe full) in improving diagnostic accuracy and avoiding unnecessary surgeries in indeterminate thyroid nodules. Methods: This is the first external, independent, prospective, real-world, observational, and non-interventional validation study of this molecular classifier. A total of 256 patients with nodules classified as Bethesda III/IV were analyzed. Results: The test was positive for malignancy in 90 patients, 79 (90%) of whom underwent surgery. Of the 158 test-negative nodules, 7 (4.4%) underwent thyroidectomy. The test demonstrated a sensitivity of 83.0%, a specificity of 83.5%, a positive predictive value of 62.8%, and a negative predictive value of 93.6%. Conclusions: The mir-THYpe full molecular test supported 95.5% of clinical decisions when negative and 89.8% when positive, reducing surgery rates by 79.5%. Therefore, the integration of this microRNA-based classifier into clinical practice represents a valuable tool in managing indeterminate thyroid nodules, reducing unnecessary thyroidectomies, and conserving valuable healthcare resources.