TSH Stimulation Methods Are Associated With Comparable Outcomes in Radioiodine-Avid Metastatic Differentiated Thyroid Cancer: Single Center Retrospective Observational Study

Background: To enhance sodium-iodide symporter expression and, thereby, radiopharmaceutical uptake/retention in differentiated thyroid carcinoma (DTC) metastases, radioiodine therapy (RAIT) can be stimulated by recombinant human TSH (rhTSH) or thyroid hormone withdrawal (THW). We investigated the association of thyrotropin (TSH) stimulation methodology with treatment outcomes in patients with radioiodine-avid distantly metastatic DTC. Methods: Single-center retrospective cohort study involving 189 consecutive eligible patients initiating RAIT from 2005 to 2015, a period allowing sufficient follow-up to adequately assess long-term outcomes. Patients were dichotomized into “rhTSH only” or “mixed stimulation” subgroups (respectively, all RAIT activities prepared by rhTSH or ≥1 activity prepared using THW; n = 81, n = 108). Patients given only THW ( n = 5) were excluded due to low numbers for statistical analysis. Endpoints comprised radiological/biochemical response and time-to-progression (TTP) and overall survival (OS) estimated via the Kaplan–Meier method. Unadjusted inter-subgroup differences underwent log-rank testing; multivariable Cox modeling assessed independent associations with TTP and OS of disease/treatment characteristics, including stimulation methodology. Propensity score matching was performed to reduce baseline differences between the stimulation groups. Results: Median (minimum–maximum) follow-up was 123 (3–182) months. The best radiologic response consisted predominantly of stable disease (49%), with complete and partial responses observed in 23% and 18% of patients, respectively, and progressive disease in 10%, without significant differences between the TSH stimulation subgroups. Unadjusted analyses favored the mixed subgroup regarding TTP (141 vs. 42 months; p < 0.05) and OS (116 vs. 68 months; p < 0.01). However, after adjustment, TSH stimulation method was not independently associated with these outcomes; metastatic burden (macrometastasis) and age at DTC diagnosis were the strongest independent predictors. Consistent results were observed in the propensity score-matched cohort, with no significant differences in TTP or OS between stimulation groups. Conclusions: In radioiodine-avid metastatic DTC, rhTSH or mixed rhTSH/THW preparation is associated with comparable adjusted outcomes. Prognosis appears to be chiefly driven by metastatic burden and age. Clinical Implications: In patients with radioiodine-avid metastatic DTC, the choice between rhTSH and THW should be individualized based on comorbidities, logistics, and patient preference rather than an assumed difference in oncologic efficacy.