Integrating TERT promoter mutations into risk stratification of papillary thyroid cancer

Objective: The impact of telomerase reverse transcriptase (TERT) promoter mutations on short-term prognosis in papillary thyroid carcinoma (PTC) remains unclear. Clarifying this association may improve early risk stratification and guide timely management. This study aimed to evaluate the influence of TERT promoter mutations on short-term clinical outcomes in PTC and propose an enhanced risk stratification model incorporating TERT status. Methods: This study analyzed 3,078 patients who underwent thyroidectomy for PTC at a tertiary referral center in South Korea from 2019 to 2021. Among these, 57 had TERT promoter mutations. Using propensity score matching (4:1) by age and sex, 227 patients with wild-type TERT promoter were selected. Short-term outcomes were categorized as no evidence of disease (NED), biochemical incomplete, or structural incomplete response. A novel classification system (risk stratification system-TERT (RSS-T)) integrating TERT status into the 2015 American Thyroid Association (ATA) risk stratification system was developed to improve risk prediction. Results: Patients with TERT promoter mutations showed more aggressive disease and received more intensive treatments. Mutation carriers had poorer short-term outcomes, with lower NED rates and higher structural incomplete response rates. Among intermediate-and high-risk groups, TERT promoter mutations were associated with significantly worse outcomes. The RSS-T system demonstrated superior predictive performance over the ATA system. Conclusion: TERT promoter mutations are associated with poor short-term outcomes in PTC, especially among intermediate-and high-risk patients. Incorporating TERT status into risk stratification can refine initial risk stratification and facilitate the efficient allocation of medical resources for follow-up care after primary treatment.