New therapeutic challenges in advanced bladder cancer.

Treatment of advanced bladder cancer continues to be challenging. Despite initial high response rates with conventional cisplatin-based chemotherapy regimens, 5-year survival is suboptimal at 5% to 20%. Limited advances have been made in chemotherapy, including the design of the triplet regimen and the incorporation of dose intensification (dose-dense) formulations. Novel therapies are desperately needed for first- and second-line therapies and for both fit and unfit patients. Research efforts are now focused on several different areas of therapy, including new chemotherapeutic agents and targeted therapies. Although the use of targeted therapies has failed as of today to demonstrate benefit, a large list of new agents are being studied in properly designed and very promising phase II and III trials. A better understanding of tumor biology and identifying pathways critical for tumorigenesis can provide potential strategies for therapeutic intervention. Understanding the set of changes at the individual patient level hopefully will enable personalized treatment for patients with urothelial cancer.