Absence of survival benefit from radioactive iodine therapy in T3b differentiated thyroid cancer: A Surveillance, Epidemiology, and End Results-Based cohort study.

Abstract

The role of adjuvant radioactive iodine therapy in patients with T3b differentiated thyroid cancer remains contentious. This study aimed to evaluate the association between radioactive iodine and disease-specific survival in this intermediate-risk group. We analyzed 6,638 patients with T3b differentiated thyroid cancer from the Surveillance, Epidemiology, and End Results database (2004-2022). Variable importance was assessed using the SHapley Additive exPlanations and permutation methods from the random survival forest model. The association of radioactive iodine with disease-specific survival was evaluated using multivariable Cox regression, with the proportional hazards assumption formally tested by Schoenfeld residuals. Restricted cubic splines examined whether tumor size modified the radioactive iodine-survival association. Sensitivity analyses included propensity score matching with optimal matching, restriction to papillary thyroid cancer, restriction to T3N0 patients, and a Fine-Gray competing-risk model. Variable importance analysis identified age, tumor size, and N stage as the dominant prognostic factors, whereas radioactive iodine ranked low. Radioactive iodine was not associated with improved disease-specific survival in the overall cohort (adjusted hazard ratio, 0.89; 95% confidence interval, 0.63-1.25; P = .502; Schoenfeld P = .156). The 10-year disease-specific survival was 96.9% in the radioactive iodine group versus 97.2% in the no-radioactive iodine group. The restricted cubic spline analysis demonstrated no association between radioactive iodine and survival across the tumor size spectrum. Stratified analyses and sensitivity analysis further suggested the absence of benefit across all subgroups, including patients with large tumors (>40 mm), older age (≥55 years), or N1b disease. Radioactive iodine therapy was not associated with improved disease-specific survival among patients with T3b differentiated thyroid cancer, and this lack of association was consistent across clinically relevant subgroups defined by tumor size, age, and nodal status. These findings inform the survival outcome of radioactive iodine use in T3b differentiated thyroid cancer and underscore the need for prospective studies that capture recurrence outcomes to guide individualized treatment decisions.