Systemic Therapy for Advanced Urothelial Carcinoma: Current Standards and Treatment Considerations

Urothelial carcinoma is the sixth most common malignancy in the United States. Although most are diagnosed with non-muscle-invasive malignancy, many patients will develop recurrent disease within 5 years, with 10% to 20% developing advanced muscle-invasive or more distant incurable disease. For such patients, clinical outcomes have remained suboptimal, although recent therapeutic advances have brought new hope to the field. Here, we discuss the main systemic treatment options available for the treatment of patients with advanced disease. This review begins with traditional chemotherapy, which remains a first-line treatment option for many patients. The second section focuses on the evolving landscape of immunotherapy, specifically on approved checkpoint inhibitors and future challenges. Last, we address advances in targeted treatments, including angiogenesis and fibroblast growth factor receptor (FGFR) inhibitors as well as antibody-drug conjugates. As the number of available treatment options continues to expand, ongoing trials to investigate the best sequence and combination strategies to incorporate these drugs into clinical practice will help delineate the future.