The Geriatrics and Genetics behind Bladder Cancer

Abstract

Bladder cancer is a disease of older patients who often have multiple comorbidities. Although cisplatin-based combination chemotherapy is the standard of care in the neoadjuvant and metastatic settings, outcomes remain poor, and approximately half of patients are ineligible for cisplatin where treatment options are severely limited. Recent comprehensive genome sequencing studies have defined the mutational spectra of high-grade urothelial carcinoma of the bladder. Although there is a high prevalence of potentially actionable genomic alterations, whether these events represent true oncogenic vulnerabilities has yet to be confirmed. Given the demographics and genetics, we propose that bladder cancer represents an ideal model to study the potential of targeted therapy in older patients who are too often unable to receive cisplatin-based therapy and where novel treatment strategies are desperately needed.KEY POINTSBladder cancer is a common malignancy that predominantly occurs in older patients with comorbidities.Cisplatin-based combination chemotherapy is the standard of care in the neoadjuvant and metastatic settings, but approximately half of patients are deemed ineligible for cisplatin.A number of highly targetable oncogenic mutations have been well described in urothelial carcinoma.Recent studies have identified a high rate of mutations in chromatin regulatory genes that may represent future targets for novel therapies.Given the demographics and genetics of bladder cancer, it represents an ideal opportunity to study targeted therapy in older patients who are too often unable to receive cisplatin-based therapy and where outcomes remain poor with standard treatment.