New Developments in Urothelial Cancer

Abstract

Overview: Urothelial cancer is among the most chemotherapy-sensitive neoplasms of all the solid tumors. However, for the majority of patients with advanced disease, response durations with conventional treatment are relatively short. Second-line systemic treatment regimens are associated with modest response rates and poor outcomes. Trials in both the first- and second-line settings have demonstrated that a ceiling in efficacy has likely been reached with cytotoxic drugs, particularly in unselected patient populations. Promising areas of investigation include integrating predictive biomarkers to optimize patient selection for specific therapies, disrupting driving oncogenomic mutations, and associated signaling pathways and cotargeting both tumor and the immune system or tumor stroma. In addition, expanded sources of evidence generation are of interest in an effort to refine treatment for the general population of patients with advanced urothelial cancer, not only those who meet the narrow eligibility criteria used in most clinical trials.