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 (PPV) of 62.8%, and a negative predictive value (NPV) 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.