The Evolution of Immune Checkpoint Inhibitors in Advanced Urothelial Carcinoma

SIMPLE SUMMARY: Urothelial carcinoma is an aggressive cancer with a high risk of metastatic progression. Chemotherapy plays a key role in the management of metastatic urothelial carcinoma, with, however, no possibility of cure. Immune checkpoint inhibitors have significantly improved the outcomes of patients, delaying progression of disease and improving quality of life. However, many questions remain concerning the optimal use of immunotherapy in urothelial carcinoma: When to start? Which biomarker of sensitivity/resistance to use? Which of the available options will increase the efficacy of immune checkpoint inhibitors? We review the mechanisms of immune checkpoint inhibitors as well as the current management of patients with metastatic urothelial carcinoma in the era of immunotherapy. ABSTRACT: Urothelial carcinoma is an aggressive cancer and development of metastases remains a challenge for clinicians. Immune checkpoint inhibitors (ICIs) are significantly improving the outcomes of patients with metastatic urothelial cancer (mUC). These agents were first used in monotherapy after failure of platinum-based chemotherapy, but different strategies explored the optimal use of ICIs in a first-line metastatic setting. The “maintenance” strategy consists of the introduction of ICIs in patients who experienced benefit from first-line chemotherapy in a metastatic setting. This allows an earlier use of ICIs, without waiting for disease progression. We review the optimal management of mUC in the era of ICIs, based on the key clinical messages arising from the pivotal trials.