Radioiodine refractory differentiated thyroid cancer

Differentiated thyroid cancer (DTC) is usually curable with surgery, radioactive iodine (RAI), and thyroid-stimulating hormone (TSH) suppression. However, local recurrence and/or distant metastases occur in approximately 15% of cases during follow-up, and nearly two-thirds of these patients will become RAI-refractory (RR-DTC) with a poor prognosis. This review focuses on the most challenging and rapidly evolving aspects of RR-DTC, and we discuss the considerable improvement in more accurately defining RR-DTC, more effective therapeutic strategies, and describe the diagnosis, pathogenesis, and future prospects of RR-DTC. Along with the detection of serum thyroglobulin and anatomic imaging modalities, such as ultrasound and computer tomography, radionuclide molecular imaging plays a vital role in the evaluation of RR-DTC. In addition, continual progress has been made in the management of RR-DTC, including watchful waiting under appropriate TSH suppression, local treatment approaches, and systemic therapies (molecular targeted therapy, redifferentiation therapy, gene therapy, and cancer immunotherapy). These all hold promise to change the natural history of RR-DTC.