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

Abstract Context The utility of thyroglobulin (Tg) in the follow-up of patients with differentiated thyroid cancer 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 2 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 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 Memorial Sloan Kettering Cancer Center protocol and ESMO Guidelines, yet demonstrating good predictive ability, with a negative predictive value of 98% and 0.84 ng/mL for patients receiving postsurgical RRA. High sensitivity and negative predictive value supported the potential of these thresholds in excluding structural disease. Conclusion 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.