Recent therapeutic advances in urothelial carcinoma: A paradigm shift in disease management

Management of first-line advanced urothelial carcinoma (UC) has consisted during the past three decades in the administration of platinum-based chemotherapy followed by observation. Despite moderate to high response rates to first-line treatment, most patients will relapse shortly after and the outcomes with subsequent therapies are poor with 5-year overall survival rates of 5% in the pre-immunotherapy era. Nonetheless, recent therapeutic developments including the paradigm shift of first-line maintenance therapy with avelumab after response or stabilization on platinum-based chemotherapy, along with the incorporation of new drug classes in further lines of treatment such as antibody drug-conjugates and fibroblast growth factor receptor inhibitors have reshaped the field leading to better outcomes in this patient population. This article reviews the current state of the art with an overview on UC management, recent advances, and the upcoming strategies currently in development in advanced UC with an insight into the biology of this disease. •Several therapeutic strategies with CPIs are being developed in first-line mUC.•The JAVELIN Bladder 100 approach aimed to prolong the benefit of first-line CT.•Avelumab maintenance after non-progression to platinum-based CT increases OS in mUC.•CPI monotherapy may be an option for selected patients no candidates for upfront CT.•Avelumab maintenance is a first paradigm shift in the management of mUC in 20 years.