Proposal of a New Prognostic Model for Differentiated Thyroid Cancer with TERT Promoter Mutations

SIMPLE SUMMARY: In a cohort study involving 393 patients with differentiated thyroid cancer, we incorporated the TERT mutational status into AJCC TNM staging 8th edition (TNM-8), proposing a new prognostic system, termed TNM-8T. We demonstrated that the new prognostic system is superior to the existing TNM-8 staging system and its contents are not very complicated. This study is the first to present a new model that combines the mutational profile with the AJCC TNM stage to improve the predictability of cancer-specific survival with long-term follow-up. ABSTRACT: The role of telomerase reverse transcriptase (TERT) promoter mutations as an independent poor prognostic factor in differentiated thyroid cancer (DTC) patients is well known, but there is no prognostic system that combines the TERT promoter mutation status with tumor-node-metastasis (TNM) stage to predict cancer-specific survival (CSS). A total of 393 patients with pathologically confirmed DTC after thyroidectomy were enrolled. After incorporating wild-type TERT and mutant TERT with stages I, II, and III/IV of the AJCC TNM system 8th edition (TNM-8), we generated six combinations and calculated 10-year and 15-year CSS and adjusted hazard ratios (HRs) for cancer-related death using Cox regression. Then, a new mortality prediction model termed TNM-8T was derived based on the CSS and HR of each combination in the four groups. Of the 393 patients, there were 27 (6.9%) thyroid cancer-related deaths during a median follow-up of 14 years. Patients with a more advanced stage had a lower survival rate (10-year CSS for TNM-8T stage 1, 2, 3, and 4: 98.7%, 93.5%, 77.3%, and 63.0%, respectively; p < 0.001). TNM-8T showed a better spread of CSS (p < 0.001) than TNM-8 (p = 0.002) in the adjusted survival curves. The C-index for mortality risk predictability was 0.880 (95% CI, 0.665–0.957) in TNM-8T and 0.827 (95% CI, 0.622–0.930) in TNM-8 (p < 0.001). TNM-8T, a new prognostic system that incorporates the TERT mutational status into TNM-8, showed superior predictability to TNM-8 in the long-term survival of DTC patients.