Abstract
Advanced bladder cancer, both muscle-invasive localized disease and metastatic disease, is managed with systemic chemotherapy. Cisplatin-based multi-agent chemotherapy remains the cornerstone for systemic therapy. MVAC (methotrexate-vinblastine-doxorubicin-cisplatin) has been most rigorously studied, both neoadjuvantly and for palliation of metastatic disease. For metastatic disease, cisplatin-gemcitabine (GC) has compared favorably to MVAC due to improved tolerability with similar efficacy. GC has been adopted as standard therapy. Neoadjuvant chemotherapy for muscle-invasive bladder cancer improves survival among those patients eligible to receive cisplatin. Adjuvant chemotherapy is difficult to administer effectively given morbidity of radical cystectomy, and studies have shown mixed results about its benefit. Non-cisplatin regimens have been investigated but remain experimental and reserved for those not candidates for cisplatin in the metastatic setting. While multiple agents have been studied after metastatic disease progression after cisplatin-based therapy, there remain no FDA-approved therapies for the second line. Future trials with anti-VEGF therapy and immunotherapy are actively being investigated. This review examines the systemic therapy available to oncologists with current evidence and future directions.