Impact of delayed first radioiodine therapy on response evaluation in intermediate risk differentiated thyroid cancer

Differentiated thyroid cancer (DTC) generally has a favorable prognosis; however, intermediate- and high-risk DTC may not progress positively. The optimal timing for radioactive iodine (RAI) after total thyroidectomy in intermediate-risk patients remains uncertain. we evaluated whether delaying RAI by > 6 months affected early treatment responses in 132 consecutive intermediate-risk patients with DTC treated between 2018 and 2022. Patients were grouped by surgery-to-RAI interval: ≤6 months (Group 1, n = 69) and > 6 months (Group 2, n = 63). Administered activities were 3,700 MBq or 5,550 MBq. The primary outcome was excellent response (ER) at 6‑month post‑treatment, per ATA‑2015 criteria. Multivariable logistic regression and 1:1 propensity score matching (age, sex, histology, multifocality, nodal status, and extrathyroidal extension) were used to address confounding factors. Sensitivity analyses included dose-stratified models. At 6 months, ER was more frequent in Group 1 than in Group 2 (35.6% vs. 21.2%; p = 0.049), while incomplete biochemical responses were higher in Group 2 (15% vs. 9.8%). After multivariable adjustment and in the propensity‑matched cohort (63 pairs), an RAI delay > 6 months remained associated with lower odds of ER (adjusted odds ratio 1.98; 95% confidence interval 1.05-3.74; p = 0.035). Aggressive histology and nodal metastasis independently reduced the likelihood of ER. The adverse effect of the delay appeared stronger among patients receiving 3,700 MBq, although the dose-time interaction was not statistically significant. The median follow‑up was 18 ± 6 months. In this cohort, RAI administration beyond 6 months was associated with a lower probability of excellent early response in intermediate-risk DTC, particularly in patients with nodal disease or aggressive histology.