Treatment strategies for cisplatin-ineligible metastatic bladder cancer: Emerging therapies and future perspectives.

Recently, the combination of enfortumab vedotin and pembrolizumab has been recommended as the preferred first-line therapy for metastatic or locally advanced urothelial carcinoma owing to its substantial survival benefits. However, its high-cost limits accessibility, leading to many patients receiving cisplatin-based chemotherapy as a more practical alternative. Therefore, cisplatin-based combination chemotherapy remains a widely used first-line treatment for metastatic bladder cancer (MBC). Nonetheless, nearly half of the patients are ineligible for cisplatin owing to factors such as renal impairment, poor performance status, or other comorbidities. The definition of cisplatin ineligibility, which is often based on the Galsky criteria, lacks robust scientific validation, and limited pharmacokinetic data on the effects of cisplatin in patients with renal impairment are available. This review explored alternative treatment strategies for cisplatin-ineligible patients, including immune checkpoint inhibitors, carboplatin-based regimens, antibody-drug conjugates, and novel combination therapies. Notably, recent advancements, such as the combination of enfortumab vedotin and pembrolizumab, have shown promising survival benefits in this patient population. Additionally, emerging targeted therapies, such as fibroblast growth factor receptor inhibitors, are reshaping the treatment landscape of cisplatin-ineligible patients with MBC, emphasizing the need for personalized approaches that balance efficacy and safety.