Clinical guidance for Radioiodine Refractory Differentiated Thyroid Cancer

Summary Prognosis from differentiated thyroid cancer is worse when the disease becomes refractory to radioiodine. Until recently, treatment options have been limited to local therapies such as surgery and radiotherapy, but the recent availability of systemic therapies now provides some potential for disease control. Multi-targeted kinase inhibitors (TKIs) including lenvatinib and sorafenib have been shown to improve progression free survival in Phase III clinical trials, but are also associated with a spectrum of adverse effects. Other TKIs have been utilised as “redifferentiation” agents, increasing sodium iodide symporter expression in metastases and thus restoring radioiodine avidity. Some patients whose disease progresses on initial TKI therapy will still respond to a different TKI and clinical trials currently in progress will clarify the best options for such patients. As these drugs are not inexpensive, care needs to be taken to minimize not only biological but also financial toxicity. In this review we examine the basic biology of radioiodine refractory disease, and discuss optimal treatment approaches, with specific focus on choice and timing of TKI treatment. This clinical field remains fluid, and directions for future research include exploring biomarkers and considering adjuvant TKI use in certain patient groups. This article is protected by copyright. All rights reserved.