Novel therapies in urothelial carcinoma: a biomarker-driven approach.

Urothelial malignancies, including carcinomas of the bladder, ureters, and renal pelvis comprised ∼8% of new cancer cases in the USA in 2016. In the metastatic setting, 15% of patients exhibit long-term survival following cisplatin-based chemotherapy and in patients with recurrent disease, response rates to second-line chemotherapy are generally 15%-20% with a 3-month progression-free survival. However, recent advances in immunotherapy represent an opportunity to significantly improve patient outcomes. Moreover, the advent of next-generation sequencing has resulted in both an improved understanding of the fundamental genetic changes that characterize urothelial carcinoma (UC) and identification of several candidate biomarkers of response to various therapies. Incorporation of prospective genotyping into clinical trials will allow for the identification and enrichment of patients most likely to respond to specific targeted therapies and chemotherapy. Combining different therapeutic classes to enhance outcomes is also an area of active research in UC.