Immunotherapy in metastatic urothelial carcinoma: focus on immune checkpoint inhibition

Immunotherapy has been used in localized urothelial carcinoma for decades, especially in the treatment of superficial disease, in which instillation of BCG is a commonly used treatment option. Clinical investigations based on new insights into the immunogenic potential of metastatic urothelial carcinoma have led to the accelerated FDA approval of the immune checkpoint inhibitors atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab. Preliminary findings suggest additional benefits of combinations of immunotherapeutic agents as a future treatment approach in metastatic urothelial carcinoma. Treatment experience with immunotherapy suggests that these drugs are associated with a unique spectrum of immune-related adverse events and specific immune-related patterns of response, including cases of pseudoprogression, which could impede the optimal use of immune checkpoint inhibitors in the clinic. Appropriate management of immune-related adverse events and a greater awareness of immune-mediated response patterns will help to inform treatment decisions and improve patient outcomes; predictive biomarkers of response might facilitate selection of patients who are most likely to respond to and benefit from these exciting new treatments.