This multi-institutional retrospective cohort study (1993–2020, 3 US academic centers + TCGA + AACR GENIE) evaluated the relationship between age at diagnosis, TERT promoter variant status, and survival outcomes (disease-specific survival [DSS] and progression-free survival [PFS]) in 1,555 patients with papillary thyroid carcinoma (PTC), with long-term survival analysis in a subset of 169 patients (median follow-up 13.7 years).
TERT promoter variant prevalence rose sharply with age (r = 0.59; <2% in patients <30 years vs. 32–70% in those >65 years). Among patients ≥55 years, 10-year DSS was 91% for TERT wild-type vs. 51% for TERT-variant tumors (difference 40%; 95% CI, 4–68); 10-year PFS was 75% vs. 23% (difference 52%; 95% CI, 9–82). TERT variant status remained independently associated with worse DSS on multivariable analysis after adjusting for age and pTNM categories.
- Survival analysis was limited to 169 patients from 3 academic centers, which may limit generalizability. - Retrospective design introduces selection and ascertainment bias. - TERT promoter testing was not uniformly applied across all cohorts, and integration of heterogeneous datasets (TCGA, AACR GENIE) may introduce variability.
TERT promoter testing in PTC — especially in patients ≥55 years — may offer more biologically precise risk stratification than age alone, given the dramatic difference in 10-year DSS (91% vs. 51%) based on variant status. Clinicians should consider incorporating TERT promoter status into prognostic discussions and staging decisions for older PTC patients.
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