LAUSR

Simple Summary Radioactive iodine treatment is the oldest targeted therapy for differentiated thyroid cancer. It can be used for normal thyroid remnant ablation (in order to increase the sensitivity and the specificity of the serum marker thyroglobulin), as an adjuvant treatment (in order to improve recurrence-free survival), or to treat radioiodine avid residual disease. Thanks to the use of sensible diagnostic tools, reliable prognostic classifications, and molecular profiling, the indication and modalities of radioiodine treatment are shifting from a one-size-fits-all to a tailored approach. This review provides insights into the most recent and high-quality evidence relating to radioactive iodine treatment. Abstract Radioiodine treatment (RAI) represents the most widespread and effective therapy for differentiated thyroid cancer (DTC). RAI goals encompass ablative (destruction of thyroid remnants, to enhance thyroglobulin predictive value), adjuvant (destruction of microscopic disease to reduce recurrences), and therapeutic (in case of macroscopic iodine avid lesions) purposes, but its use has evolved over time. Randomized trial results have enabled the refinement of RAI indications, moving from a standardized practice to a tailored approach. In most cases, low-risk patients may safely avoid RAI, but where necessary, a simplified protocol, based on lower iodine activities and human recombinant TSH preparation, proved to be just as effective, reducing overtreatment or useless impairment of quality of life. In pediatric DTC, RAI treatments may allow tumor healing even at the advanced stages. Finally, new challenges have arisen with the advancement in redifferentiation protocols, through which RAI still represents a leading therapy, even in former iodine refractory cases. RAI therapy is usually well-tolerated at low activities rates, but some concerns exist concerning higher cumulative doses and long-term outcomes. Despite these achievements, several issues still need to be addressed in terms of RAI indications and protocols, heading toward the RAI strategy of the future.