[Current Landscape of Sequential Treatment Strategy in Metastatic Urothelial Carcinoma]

In 2024, enfortumab vedotin plus pembrolizumab(EV+P)and nivolumab plus gemcitabine/cisplatin(Nivo+GC)were approved as first-line therapies for metastatic urothelial carcinoma(mUC), marking a major shift in treatment strategy.EV+P, in particular, demonstrated remarkable efficacy and has been assigned the highest level of recommendation in both the 2025 European Association of Urology(EAU)and National Comprehensive Cancer Network(NCCN)guidelines.By contrast, avelumab maintenance therapy following platinum-based chemotherapy-established since its approval in 2021-has long been practiced as a standard approach in Japan.Its major strength lies in the robust real-world evidence accumulated domestically, confirming both efficacy and safety across various patient populations.In the 2025 update of the Japanese Urological Association(JUA)bladder cancer guidelines lists EV+P, Nivo+GC, and avelumab maintenance therapy are all listed as Grade 1, Level A recommendations.However, there are no head-to-head trials directly comparing ICI-based combinations with sequential therapy, and no reliable biomarkers exist to predict treatment response to either platinum-based chemotherapy or subsequent avelumab maintenance.Therefore, careful consideration of efficacy, safety, and extensive real-world evidence available is required to guide optimal, individualized treatment selection for patients with mUC.