Abstract

Urothelial carcinoma (UC) is one of the most common malignancies in the Western world. Historically, patients with advanced disease have had a poor prognosis and progress within months of completing upfront platinum-based chemotherapy. In the last two years, the treatment landscape for metastatic UC (mUC) has significantly shifted with the emergence of contemporary immunotherapy and targeted agents. The purpose of this review is to highlight the current and emerging systemic treatment options for mUC of the bladder. PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have demonstrated activity in the postplatinum and platinum-ineligible settings. Additionally, they have become a standard maintenance treatment option after avelumab demonstrated increased overall survival in patients with stable disease or better after first line platinum-based chemotherapy. Novel targeted therapies and antibody-drug conjugates (ADCs) have been granted Food and Drug Administration approval for subsequent line therapy based on promising results in phase II and III trials. There has been a considerable increase in the variety of effective therapies for mUC, including the utility of ICIs, novel targeted agents, and ADCs. Platinum-based chemotherapy remains an effective first-line option. As the role of novel therapies continues to shift toward earlier in the disease course, there remains an important need to develop feasible, globally accessible predictive biomarkers that can aid in patient selection and inform sequencing of therapeutic options.

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