Endocrine Abstracts

JOINT2684

Background: TERT promoter mutations are associated with poor long-term outcomes in papillary thyroid carcinoma (PTC), but their influence on short-term prognosis remains unclear. Understanding this association could enhance early risk stratification and support clinical decision-making. While the 2015 American Thyroid Association (ATA) guidelines acknowledge the potential prognostic value of TERT promoter mutations, they do not provide specific recommendations on their use or indicate when testing should be performed. This study evaluates the impact of TERT mutations on short-term clinical outcomes and proposes an enhanced risk stratification model integrating TERT mutation status.

Methods: This retrospective cohort study analyzed 3,078 patients who underwent thyroidectomy for PTC at Samsung Medical Center (2019–2021). Among them, 57 patients had TERT promoter mutations. Using propensity score matching (4:1) by age and sex, a matched cohort of 57 patients with TERT promoter mutations and 227 patients with wild-type TERT. Short-term outcomes were classified as no evidence of disease (NED), biochemical incomplete response, or structural incomplete response. Kaplan-Meier survival analysis and hazard ratios were used to assess recurrence risk. To improve risk prediction, we developed an alternative classification (RSS-T) that integrates TERT mutation status into the ATA risk stratification system.

Results: Patients with TERT promoter mutations had larger tumor, wider disease extent, and received more aggressive treatment. Short-term outcomes differed significantly (P < 0.001): NED was achieved in 95.6% of wild-type patients but only 64.9% of mutation carriers, with mutation carriers exhibiting higher rates of structural incomplete response (29.8% vs. 2.2%). When stratified by the ATA risk system, all low-risk patients achieved NED regardless of TERT status. However, in the intermediate- and high-risk groups, TERT mutations were associated with significantly poorer outcomes (P < 0.001 and P = 0.004, respectively). The RSS-T system categorized patients as RSS-T1 (low-risk, regardless of TERT status), RSS-T2 (intermediate/high-risk with wild-type TERT), and RSS-T3 (intermediate/high-risk with TERT mutation). RSS-T demonstrated superior predictive accuracy for structural persistence/recurrence compared to the ATA system (C-index 0.890 vs. 0.794, P = 0.03) and explained a greater proportion of variance (86% vs. 70%).

Conclusion: TERT promoter mutations are associated with worse short-term outcomes in PTC, particularly among intermediate- and high-risk patients. Integrating TERT status into the ATA risk stratification system (RSS-T) improves predictive performance and provides valuable guidance for clinical decision-making. Selective TERT testing in intermediate- and high-risk patients could refine risk assessment and enable more personalized, aggressive management strategies, ultimately improving patient outcomes.