Predictors of progressive disease in intermediate to high risk differentiated thyroid cancer patients with biochemical incomplete response after initial radioiodine therapy

Background A subset of intermediate- to high-risk differentiated thyroid cancer (DTC) patients achieves only a biochemical incomplete response (BIR) after initial radioiodine (RAI) therapy. These patients have variable clinical outcomes, with some remaining stable and others developing progressive disease (PD). Early identification of BIR patients at high risk for PD is essential for personalized follow-up and treatment decisions. Methods We retrospectively enrolled 183 intermediate- or high-risk DTC patients with BIR after initial RAI therapy at our institution between December 2008 and July 2023. Clinicopathological characteristics, post-operative stimulated thyroglobulin (ps-Tg) levels, BRAF V600E mutation status, and therapeutic responses were evaluated. Univariate and multivariate Cox regression analyses were performed to identify independent predictors of PD. Results After a median follow-up of 51.1 months, 38 patients (20.8%) developed PD. Multivariate Cox regression showed that age (<55 years/≥55 years; HR = 1.176, 95%CI: 0.547 - 2.528, P = 0.017), T stage (T1-T3a vs. T3b-T4; HR = 2.023, 95%CI: 0.766 - 5.344, P = 0.025), ps-Tg level (<55.7 vs. ≥55.7 ng/mL; HR = 5.205, 95%CI: 2.043 - 13.265, P < 0.001), and BRAF V600E mutation (No/Yes; HR = 1.201, 95% CI: 0.580 - 2.488, P = 0.044) were independently associated with the risk of PD. Conclusion In intermediate to high-risk DTC patients with BIR after initial RAI therapy, Age ≥55 years, ps-Tg ≥55.7 ng/mL, advanced T stage (T3b–T4), and BRAF V600E mutation were independently associated with a higher risk of PD. These readily available parameters can guide risk-adapted follow-up and individualized management strategies.