ThyroidPrint: Thyroid Genetic Classifier Long‐Term Follow‐Up of Benign Called Lesions

BACKGROUND: The management of indeterminate thyroid nodules (ITNs) remains challenging, with molecular classifiers emerging as valuable tools for risk stratification. ThyroidPrint is a novel quantitative PCR-based 10-gene classifier designed to predict benignity in ITNs, enabling more informed clinical decision-making. OBJECTIVE: To evaluate the long-term follow-up (≥ 5 years) of patients with a benign ThyroidPrint result managed via active surveillance, assessing the safety, durability and clinical utility of the test in a real-world setting. METHODS: This prospective, single-centre study included 104 patients with indeterminate cytology (Bethesda III/IV) and a previous benign ThyroidPrint result, followed for a median of 5.3 years. Ultrasound monitoring and clinical assessments guided management, with surgery reserved for significant nodule growth or patient preference. Outcomes included the proportion of patients remaining under surveillance, nodule growth and surgical pathology. RESULTS: Of the 104 patients with benign ThyroidPrint results, 94.2% remained under active surveillance at 5 years, with only 5.8% undergoing surgery, all of which confirmed benign or low-risk histology. The false-negative rate was minimal among resected nodules supports the test's safety as a rule-out tool. Ultrasonographic monitoring proved effective for early detection of changes in warranting intervention. CONCLUSIONS: Long-term follow-up demonstrates that ThyroidPrint provides a reliable, safe and durable approach to managing ITN, significantly reducing unnecessary surgeries while maintaining a low rate of missed malignancies. These findings reinforce its role in personalised patient management and support structured surveillance protocols for selected patients.