New Advances in Metastatic Urothelial Cancer: A Narrative Review on Recent Developments and Future Perspectives

The standard of care for advanced or metastatic urothelial carcinoma (mUC) was historically identified with platinum-based chemotherapy. Thanks to the advances in biological and genetic knowledge and technologies, new therapeutic agents have emerged in this setting recently: the immune checkpoint inhibitors and the fibroblast growth factor receptor inhibitors as the target therapy for patients harboring alterations in the fibroblast growth factor receptor (FGFR) pathway. However, chasing a tumor’s tendency to recur and progress, a new class of agents has more recently entered the scene, with promising results. Antibody–drug conjugates (ADCs) are in fact the latest addition, with enfortumab vedotin being the first to receive accelerated approval by the U.S. Food and Drug Administration in December 2019, followed by sacituzumab govitecan. Many other ADCs are still under investigation. ADCs undoubtedly represent the new frontier, with the potential of transforming the management of mUC treatment in the future. Therefore, we reviewed the landscape of mUC treatment options, giving an insight into the molecular basis and mechanisms, and evaluating new therapeutic strategies in the perspective of more and more personalized treatments.