Two-year dynamic risk stratification and adjuvant radioiodine efficacy in initial non-distant metastatic papillary thyroid carcinoma harboring TERT promoter mutations.

Abstract

Background: The clinical utility of postoperative radioiodine (¹³¹I) ablation remains unclear for patients with initially diagnosed non-distant metastatic papillary thyroid carcinoma (PTC) with harboring TERT promoter(TERT-p) mutations, it is unknown whether ¹³¹I therapy reduces the risk of persistent or recurrent disease. This study investigated clinicopathological features, 2-year dynamic therapeutic responses and progression-free survival (PFS) in this specific patient cohort.

Methods: A single-center retrospective cohort study enrolled 113 eligible patients, allocated to the ¹³¹I ablation group (n=62) and non-¹³¹I group (n=51). Two-year dynamic risk stratification assessed treatment response. Kaplan-Meier curves and Cox regression models were used for survival analysis.

Results: The predominant TERT-p variant was C228T (89.4%), and most patients carried concurrent BRAF^V600E mutations. Only initial surgical approach remained an independent intergroup variable. Within 2 years, 46.0% achieved acceptable responses, associated with sex and primary surgery (p=0.036,p < 0.001). High baseline ATA risk was strongly correlated with structural residual lesions and unfavorable therapeutic response (p < 0.001).No significant between-group differences in response were observed across all ATA risk subgroups. The median follow-up was 4.6 years; 3- and 5-year PFS rates were 67.5% and 39.1%. Age ≥55 years, N1b stage and high baseline ATA risk were independent adverse predictors of PFS. Both 2-year therapeutic response and PFS at the end of follow-up exhibited no statistical differences between the ¹³¹I group and non-¹³¹I group.

Conclusions: In this retrospective observational cohort, postoperative ¹³¹I ablation was not associated with improved PFS among patients with non-distant metastatic TERT-p-mutant PTC. Advanced age, N1b lymphatic metastasis and high baseline ATA risk independently predict poor outcomes. Biologically, TERT-p mutations induce tumor dedifferentiation and impaired iodine uptake, diminishing ¹³¹I efficacy. Clinically, routine ¹³¹I yields no survival benefit for this high-risk molecular subgroup, guiding individualized surveillance and avoiding redundant ¹³¹I exposure.