mutations predict shorter overall survival in urothelial cancer.

BACKGROUND

Mutations of DNA repair genes, e.g. , are frequently found in urothelial cancer (UC) and have been associated with better response to cisplatin-based chemotherapy. Further external validation of the prognostic value of mutations in UC can inform clinical decision making and trial designs.

RESULTS

In the discovery dataset, mutations were present in 24% of patients and were associated with shorter OS (adjusted HR 2.67, 95% CI, 1.45-4.92, = 0.002). There was a higher mutation load in patients carrying mutations (median mutation load: 6.7 versus 5.5 per Mb, = 0.072). In the validation dataset, mutations were present in 22.2% of patients and were non-significantly associated with shorter OS (adjusted HR 1.87, 95% CI, 0.97-3.59, = 0.06) and higher mutation load (median mutation load: 8.1 versus 7.2 per Mb, = 0.126).

MATERIALS AND METHODS

Exome sequencing data of 130 bladder UC patients from The Cancer Genome Atlas (TCGA) dataset were analyzed as a discovery cohort to determine the prognostic value of mutations. Results were validated in an independent cohort of 81 advanced UC patients. Cox proportional hazard regression analysis was performed to calculate the hazard ratio (HR) and 95% confidence interval (CI) to compare overall survival (OS).

CONCLUSIONS

mutations may be a biomarker of poor prognosis in unselected UC patients and may correlate with higher mutational load. Further studies are required to determine factors that can further stratify prognosis and evaluate predictive role of mutation status to immunotherapy and platinum-based chemotherapy.