The availability of newer effective therapies in the therapeutic landscape of bladder cancer has offered intriguing opportunities to clinical investigators to improve the cure rate of patients with limited/early disease stage, while simultaneously providing new opportunities to design organ-sparing locoregional therapies to achieve cure. These advances are likely to impact the way we define the disease states, currently based on conventional diagnostic tools, and inform management, which currently relies on disappointing standard therapeutic options without validated biomarkers.