Pharmacotherapy of bladder cancer--practice and prospects

In contrast to the US, the incidence and mortality rates of bladder cancer are still increasing in some European countries, despite the fact that most new cases are diagnosed as early, superficial tumours. The standard of care of superficial tumours consists of cytoscopic electroresection of the tumour followed by intravesical immunotherapy or chemotherapy. Immunotherapy with bacillus-Calmette Guerin (BCG) prevents recurrence in most treated patients and has a positive impact on survival; however, approximately 30% are BCG-refractory, progressive tumours. Pharmacogenomics will enable to distinguish those high-risk patients in clinical practice soon. New immunotherapy approaches, such as BCG combined with low-dose interferon or recombinant BCG strains, are promising approaches which need to be explored in prospective trials. The use of neoadjuvant or adjuvant chemotherapy is still controversial but the results of recent trials of neoadjuvant chemotherapy in locally-advanced bladder tumours convinced some leading centres to implement neoadjuvant chemotherapy in selected groups of patients. By far, the four-drug methotrexate-vinblastine-doxorubicin-cisplatin regimen was widely used in metastatic and locally-advanced disease. Recently, two-drug combination gemcitabine-cisplatin proved to be equally effective and less toxic. New chemotherapies tested in clinical trials include gemcitabine, taxanes and new drugs that interfere with signal transduction. Individualisation of established and investigational treatment options based on molecular tumour characteristics, such as p53 status, is probably the future of bladder cancer pharmacotherapy.