Bladder cancer: can we move beyond chemotherapy?

Since the advent of cisplatin-based chemotherapy, cytotoxic combination chemotherapy remains the mainstay of treatment for locally advanced and metastatic urothelial malignancies. The current paradigm of combining novel agents with cytotoxic chemotherapy without any understanding of the underlying biology of urothelial cancer has limited the impact of developing novel agents for this disease. Current research investigating the biology of bladder cancer, including the role of p53, EMT, EGFR-related pathways, and anti-angiogenic pathways, may potentially impact the future development of novel agents targeting urothelial malignancies. Additionally, the use of novel gene therapy to mediate enhanced interferon expression in the bladder using adenoviral vectors, and enhancing tumor recognition strategies using the immune system with vaccines and anti-CTLA4 antibodies, are of interest. It is hoped that through these efforts we may soon move beyond the traditional cytotoxic chemotherapy paradigm, developing combinations that are more active and less toxic for all patients with urothelial cancer.