The treatment landscape for patients with advanced urothelial carcinoma (UC) has evolved rapidly in recent years. In current guidelines, combination treatment with enfortumab vedotin plus pembrolizumab is the first-line (1L) standard of care, and other recommended 1L treatment options are platinum-based chemotherapy followed by avelumab as switch-maintenance treatment in patients without progression, or combination treatment with nivolumab, cisplatin, and gemcitabine for cisplatin-eligible patients only. Individual patients differ in terms of their health status, disease characteristics, expected toxicities, and treatment preferences
thus, a "one-size-fits-all" approach to treatment is unlikely to be optimal. The availability of several treatment options creates the potential for individualized treatment. In this review, we discuss factors that may be considered when selecting 1L treatment for patients with advanced UC, including efficacy and safety data from phase 3 trials and real-world studies, quality of life, patient priorities for treatment, patient and disease characteristics, treatment sequencing, biomarkers, and treatment access and cost. Patients and physicians should discuss the benefit-risk balance of all available 1L options to enable shared decision-making. Longer follow-up from clinical trials and additional real-world studies are needed to further inform treatment selection.