Abstract
Urothelial carcinoma, the most common malignancy of the urinary tract, presents a significant challenge, particularly in its metastatic stage, where prognosis remains poor despite advancements in treatment. Historically, platinum-based chemotherapy has been the standard first-line therapy, achieving moderate response rates but limited long-term survival. Recent breakthroughs have introduced immune checkpoint inhibitors, antibody-drug conjugates (ADCs), and targeted therapies as more effective alternatives. Enfortumab vedotin plus pembrolizumab has demonstrated superior efficacy as a first-line treatment, improving overall survival (OS) and objective response rates compared to chemotherapy. Maintenance therapy with avelumab has further prolonged survival in patients responding to initial platinum-based chemotherapy. Additionally, sacituzumab govitecan, an ADC targeting Trop-2, and erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor, have provided promising options for patients with refractory disease or FGFR alterations. The evolving treatment paradigm now prioritizes biomarker-driven, personalized approaches over traditional chemotherapy-based regimens. However, challenges remain in optimizing treatment sequencing and managing toxicity. Future research should focus on refining patient selection criteria and exploring novel combination therapies to enhance efficacy and durability of response.