Multicenter retrospective cohort study of TERT promoter variants, older age, and prognosis in papillary thyroid carcinoma

Older age at diagnosis is associated with worse outcomes in papillary thyroid carcinoma (PTC). TERT promoter variants are also associated with aggressive disease. A retrospective cohort study at 3 academic centers in the US evaluated the interplay between age, TERT promoter variants, and survival outcomes in PTC. The cohort included 169 PTC patients, who were integrated iwht publically available cohorts from The Cancer Genome Atlas (TGCA) and American Association of Cancer Research’s Project Genomics Evidence Neoplasia Information Exchange (AACR GENIE). Across all cohorts (n=1555), the prevalence of TERT promoter variants increased progressively with age (r=0.59; 95% CI 0.54-0.63), being rare in patients younger than 30 years (<2%) and reaching 32% to 70% in those older than 65 years. For survival analysis, 169 patients (median follow-up 13.7 years) were included. Among patients younger than 55 years without a TERT promoter variant, 10-year disease-specific survival (DSS, primary outcome) was 100%, and 10-year progression-free survival (PFS) was 83%. Among those 55 years or older, 10-year DSS was 91% for TERT wild-type tumors and 51% for TERT variant tumors (difference 40%; 95% CI 4-68). A similar trend was observed for PFS. In multivariable analysis, TERT promoter variants remained independently associated with worse DSS after adjustment for age and pathologic tumor, node, and metastasis categories. The authors conclude that in this analysis, the high prevalence of TERT promoter variants in older patients largely explains the association between age and worse prognosis in PTC. TERT promoter status offers more biologically grounded prognostic information than age and may improve risk stratification.