TERT Promoter Mutation in Normal Urothelium Predicts Recurrence of Non-Muscle Invasive Bladder Cancer - Expert Commentary

There is a need for an accurate tool that predicts the recurrence and progression of non-muscle-invasive bladder cancer (NMIBC). A recent study published by Hayashi et al. in Molecular Oncology examined telomerase reverse transcriptase (TERT) promoter mutations in the non-malignant urothelium (NMU) as a prognostic tool for NMIBC. 

The study included 53 primary tumors and 428 systematic bladder biopsy specimens from 54 patients with NMIBC. The authors used digital droplet PCR (ddPCR) to detect TERT C228T and C250T mutations in these samples. For statistical analyses, they used the Kaplan–Meier method and Cox proportional hazards model. They found that 18/54 patients (33.3%) have TERT promoter mutations in NMU, 16/54 (29.6%) had a TERT C228T mutation, and 3/54 (5.6%) had a TERT C250T mutation.

During the follow-up period (median 3.7 years and range 0.8–4.8), 40.7% (22/54) had disease recurrence, and 9.3% (5/54) had disease progression. Interestingly, the presence of TERT C228T promoter mutation in NMU was significantly associated with bladder recurrence after adjusting for co-founding factors (P = 0.0128). The TERT C228T promoter mutation was an independent factor associated with NMIBC recurrence after adjusting for intravesical BCG therapy, EORTC score, and age (P = 0.018). In contrast, when TERT C228T promoter mutations were observed in primary tumors, it was not prognostic for recurrence (P = 0.265).

The role of genomic alterations in morphologically normal non-malignant urothelium in the initiation of bladder cancer is understudied. Understanding the role of these alterations as prognostic and predictive factors for clinical outcomes is critical.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

Reference:

  1. Hayashi Y, Fujita K, Nojima S, et al. “TERT C228T mutation in non-malignant bladder urothelium is associated with intravesical recurrence for patients with non-muscle invasive bladder cancer.” Mol Oncol. 2020 Jun 13. doi: 10.1002/1878-0261.12746. Online ahead of print. PMID: 32533903
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