Telomerase reverse transcriptase (TERT) promoter mutations are known to be associated with aggressive clinicopathological features in papillary thyroid cancer (PTC). However, their independent prognostic value remains uncertain. This study aimed to evaluate the clinical significance of TERT promoter mutations in predicting early disease outcomes in PTC.

We retrospectively analyzed a prospective cohort of PTC patients who underwent initial surgery at a single tertiary center. Patients with available TERT promoter and BRAF V600E mutation data were matched 1:1 using propensity scores adjusting for key clinicopathological factors. Associations between TERT promoter mutations and early outcomes, including American Thyroid Association (ATA) response-to-therapy classification and recurrence, were evaluated.

Among 10,642 PTC patients with available molecular data, 115 (1.1%) harbored TERT promoter mutations. Due to imbalances in baseline characteristics, a matched cohort of 90 patients per group (TERT-wild vs. TERT-mutant) was analyzed. One year after total thyroidectomy and radioactive iodine ablation, biochemical incomplete response (BIR) occurred in 12.2% of TERT-wild and 10.4% of TERT-mutant patients, while structural incomplete response (SIR) was observed in 2.0% and 8.3%, respectively. The mean follow-up duration was comparable between groups (45.9 vs. 42.6 months, P = 0.119), but recurrence or death events were significantly more frequent in the TERT-mutant group (7 vs. 1, P = 0.022).

Even after propensity score matching, TERT promoter mutations were significantly associated with higher rates of SIR, recurrence, and mortality in PTC. These findings suggest that TERT promoter mutations are an independent prognostic marker and may aid in early risk stratification.