First-line treatment options for metastatic urothelial carcinoma: balancing efficacy, safety, and individual values and preferences through shared decision making.

Abstract

Metastatic urothelial carcinoma (mUC) remains a disease with poor prognosis. While conventional platinum-based chemotherapy has long served as the standard first-line treatment, its survival benefit is limited, particularly in cisplatin-ineligible patients. The introduction of immune checkpoint inhibitors and antibody-drug conjugates as part of sequential treatment has improved outcomes, with pembrolizumab, avelumab, and enfortumab vedotin (EV) providing survival benefit in later lines. In 2024, the EV plus pembrolizumab (EV + P) regimen demonstrated a striking improvement in overall survival compared to chemotherapy followed by maintenance avelumab, representing a paradigm shift toward maximizing efficacy at the initial treatment stage. However, the safety profile of EV + P has specific safety concerns, including skin reactions, peripheral neuropathy, and immune-related adverse events. To fully realize the survival benefits of this combination, careful management and continued treatment are essential, especially in older adults, patients with poor general condition, or those with limited family support. In real-world practice, treatment decisions should be based not only on efficacy but also on safety, patient values and preferences, general condition, and social background. Therefore, shared decision making (SDM) has become increasingly important as a practical approach to adjust first-line treatment strategies. This review summarizes the developing landscape of first-line treatment options for mUC, evaluates the clinical and real-world implications of EV + P, and highlights the importance of SDM in balancing efficacy, safety, and personal values in routine clinical care.