Urothelial carcinoma (UC) is the most common cancer of the urinary tract and the sixth most frequently diagnosed cancer in the United States.[SEER] Historically, patients with unresectable locally advanced or metastatic urothelial UC (mUC) have had a poor prognosis, particularly if they are platinum-ineligible or if their cancer progresses after platinum-based chemotherapy. However, new treatments and therapeutic combinations are becoming available in first and later-line settings and offer promise for improved clinical outcomes. In this update, I highlight recent results from clinical trials, noting which findings are practice changing and which are worthy of further investigation.
Bladder cancer is common and challenging to treat. A thorough assessment of the molecular biology and immunology background has pinpointed potential biomarkers, “drivers” and promising therapeutic targets. The advent of immune checkpoint inhibitors (ICI) has heralded a new era after approximately two decades of a “stagnant landscape”.  As single agents in patients with advanced urothelial carcinoma, ICI can induce rapid and durable responses, with a very small proportion of patients achieving long term remission. However, most patients do not achieve response, while a proportion may have immune-related adverse events. Therefore, there is an urgent need for additional therapies that raise the bar, improve quality of life, and prolong the life of our patients.

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