Definition of Radioactive Iodine Refractory Thyroid Cancer and Redifferentiation Strategies

Abstract Differentiated Thyroid Cancer (DTC) presents a 10-year survival rate of > 90% in case of localized disease while in case of distant metastases prognosis is poorer. Radioactive iodine is the first-line therapy for ablation, adjuvant intent, and for the treatment of distant metastases. In case of distant metastases, 50% of these patients obtain complete remission or stabilization of the disease over a long-term period with RAI therapy. Unfortunately, the remaining 50% of these patients, with the most aggressive and rapidly progressive disease, develop a RAI refractory disease thyroid cancer with loss of the ability to concentrate RAI or disease progression despite RAI uptake and with consequently poor outcomes (5-year disease-specific survival rates of 60–70% and a 10-year survival rate of 10%). In these patients, other treatment modalities including locoregional or systemic treatment by tyrosine kinase inhibitors (TKIs) should be preferred. Nevertheless, the definition of refractory thyroid cancer is still challenging and the decision to stop radioactive iodine and switch the therapeutic approach is still based on an individualized choice. Finally, a new approach by redifferentiation strategies combining TKI treatment and radioactive iodine is very promising for refractory and slowly progressive tumors.