Abstract
Background: Radioiodine-refractory differentiated thyroid cancers (RAIR-DTCs) present a significant treatment challenge, with a dismal prognosis despite radioactive iodine (RAI) therapy and have limited treatment options.
Aim: To provide an overview of how the management of RAIR-DTC is evolving based on the 2025 American Thyroid Association Guidelines (ATA).
Methods: This focused review examines the 2025 ATA recommendations related to diagnostic criteria, molecular profile, systemic therapies, and new treatment approaches.
Results: RAIR-DTC is now redefined by the ATA as a dynamic spectrum of disease based on the biological characteristics of the tumors, the pattern of disease progression, and the total cumulative amount of RAI administered to a patient. Molecular profiling has become critical to the identification of actionable mutations in BRAF (V600E), RET, NTRK, and ALK, allowing for targeted therapy. The Diagnosis, Assessment, Treatment, and Response platform provides an organized framework for providing patient centered care. The two principal multikinase inhibitors (lenvatinib and sorafenib) will remain the most viable treatment options for systemic therapy, and redifferentiation therapy is an additional option for selected patients to restore iodine uptake.
Conclusion: Overall, the ATA 2025 Guidelines advance the fields of precision-based oncology and individualized treatment of RAIR-DTC patients to promote enhanced quality of life and improved outcomes among these patients.