Chemotherapy, surgical and radiation options for metastatic bladder cancer

Many patients with locally advanced bladder cancer experience progression to metastatic disease in spite of aggressive local therapy. Furthermore, a subset of patients has metastatic disease at the time of presentation. For these patients, cisplatin-based multi-agent chemotherapy, namely M-VAC (Methotrexate, Vinblastine, Doxorubicin, and Cisplatin), has been the standard of care to which other combinations have been compared. The combination of Gemcitabine and Cisplatin has been widely accepted due to its improved toxicity profile compared to M-VAC yet both regimens can be difficult to administer due to various medical comorbidities and renal insufficiency. Dose dense chemotherapy regimens might yield improvements in disease response rates and currently are being evaluated in clinical trials. Novel targeted therapies are being studied as single agents or in combination with other traditional chemotherapeutics. The role of radiation therapy in the advanced setting is largely palliative whereas some patients with limited metastatic nodal disease might respond to surgical consolidation. Regardless of the currently available therapeutic options, the prognosis for most patients with metastatic or surgical unresectable urothelial cancer remains quite poor with few long-term survivors. There is an unmet need for more effective systemic therapy.