Data-Driven Thyroglobulin Cutoffs for Low- and Intermediate-Risk Thyroid Cancer Follow-Up: ITCO Real-World Analysis

Context: The utility of thyroglobulin (Tg) in the follow-up of differentiated thyroid cancer (DTC) patients has been well-documented. Although third-generation immunoassays have improved accuracy, limitations persist (interfering anti-Tg antibodies and measurement variability). Evolving treatment strategies require a reevaluation of Tg thresholds for optimal patient management. Objective: To assess the performance of serum Tg testing in two populations: patients receiving total thyroidectomy and radioiodine remnant ablation (RRA), or treated with thyroidectomy alone. Design: Prospective observational study. Setting. Centers contributing to the Italian Thyroid Cancer Observatory (ITCO) database. Patients: We included 540 patients with 5 years of follow-up and negative anti-Tg antibodies. Interventions: Serum Tg levels assessed at 1-year follow-up visit. Main outcome measure: Detection of structural disease within 5 years of follow-up. Results: After excluding 26 patients with structural disease detected at any time point, the median Tg did not differ between patients treated with or without radioiodine. Data-driven Tg thresholds were established based on the 97th percentile of Tg levels in disease-free individuals: 1.97 ng/mL for patients undergoing thyroidectomy alone (lower than proposed by the MSKCC protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value (NPV) of 98%) and 0.84 ng/mL for patients receiving post-surgical RRA. High sensitivity and NPV supported the potential of these thresholds in excluding structural disease. Conclusions: This real-world study provides evidence for the continued reliability of 1-year serum Tg levels. The data-driven Tg thresholds proposed offer valuable insights for clinical decision-making in patients undergoing total thyroidectomy with or without RRA.