OC50 - Not all microcarcinomas are low risk: identifying RAI resistance in pT1a differentiated thyroid cancer

Background Differentiated thyroid cancer (DTC) is generally associated with a favorable long-term outcome. Standard management includes surgical resection, often followed by radioactive iodine (RAI) therapy. In recent years, there has been a growing tendency to de-escalate treatment in patients with differentiated thyroid microcarcinomas (pT1a), based on their typically indolent clinical course. However, this group may also include individuals with biologically aggressive disease who ultimately develop resistance to RAI therapy. Identifying such patients early remains a clinical and therapeutic challenge. Purpose To identify prognostic factors associated with RAI resistance in patients with pT1a DTC and to evaluate clinical or biochemical parameters that may predict suboptimal response to treatment. Methods We retrospectively analyzed 693 patients diagnosed with DTC, including 310 with pT1a tumors. RAI resistance was defined using standard biochemical and imaging criteria. The potential impact of demographic, clinical, and histopathological features—including age, sex, tumor laterality, capsular invasion, presence of chronic lymphocytic thyroiditis, and thyroglobulin kinetics—was assessed. Statistical methods included univariate and multivariate analyses, as well as receiver operating characteristic (ROC) curve analysis. Results Among 310 patients with pT1a tumors, 23 (7.4%) were classified as RAI- refractory. RAI resistance showed no significant association with age, sex, tumor location, capsular invasion, or coexisting lymphocytic thyroiditis. The only variables significantly associated with treatment resistance were pre-RAI stimulated thyroglobulin (sTg) (p = 0.011) and the relative reduction in sTg at 12 months post- treatment (delta sTg) (p = 0.016). ROC analysis yielded AUCs of 0.657 for sTg and 0.666 for delta sTg. A cut-off of 6.5 ng/mL for sTg yielded sensitivity and specificity of 89.5% and 74.5%, respectively. Despite limited PPVs (15.1% and 12.6%), NPVs were high (98.4% and 95.5%), indicating strong exclusionary potential. Conclusions Although pT1a DTC generally follows an indolent course, a subset of patients may exhibit resistance to RAI therapy. Pre-treatment sTg and delta sTg at one year emerge as practical biochemical markers for risk stratification, supporting a more individualized approach to follow-up and management in this patient population.