Impact of Radioactive Iodine Treatment on Long-Term Relative Survival in Patients with Papillary and Follicular Thyroid Cancer: A SEER-Based Study Covering Histologic Subtypes and Recurrence Risk Categories

For patients with differentiated thyroid cancer (DTC), that is, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC), the American Thyroid Association and European Thyroid Association generally recommend radioactive iodine (RAI) therapy after surgery only for high-risk patients. For intermediate-risk patients, RAI therapy is recommended only as a should-be-considered option. For low-risk patients, RAI therapy is not routinely recommended. Other countries, such as Germany, are more in favor of using RAI. Thus, RAI therapy remains a matter of controversial debate, because prospective long-term data on survival are scarce. <b>Methods:</b> We retrospectively compared long-term relative survival in DTC cohorts treated with and without RAI. From the Surveillance, Epidemiology, and End Results Program database, 101,087 patients harboring DTC were identified between 2000 and 2020. Patient cohorts were subdivided based on histology (classical PTC, aggressive variants of PTC, FTC, and minimally invasive FTC). These cohorts were stratified into the following categories: very low risk, low risk, intermediate risk, and high risk. Relative survival was determined for each subgroup. Statistics included a <i>z</i>-test specifically developed for comparison of relative survival, testing the long-term effect of RAI therapy (3, 5, and 10 y). <b>Results:</b> The relative survival rate is higher or tends to be higher in most subgroups undergoing RAI therapy than in subgroups not undergoing RAI therapy. Even for low-risk minimally invasive FTC, the 10-y relative survival rate tends to be higher by 2.0% (<i>P</i> = 0.055). For larger tumor size or lymph node involvement in classical PTC, a 10-y relative survival benefit of 1.3%-2.0% (<i>P</i> = 0.045) in the RAI subgroup prevails. In high-risk DTC, benefits in relative survival of up to 30.9% (<i>P</i> < 0.05) were observed. Relative survival is not negatively affected in any RAI subgroup. <b>Conclusion:</b> In patients with DTC, depending on histology subtype, a benefit in relative survival prevails in low-, intermediate-, and high-risk subgroups that underwent RAI therapy compared with patients who did not undergo RAI therapy. Even in low-risk minimally invasive FTC, a clear trend toward higher survival rates is observed. For PTC, a survival benefit prevails in the presence of lymph node involvement, larger tumor size, or distant metastasis.