Advanced bladder and urothelial cancers.

After more than 40 years of use, cytotoxic chemotherapy has an evolving role in the management of advanced bladder cancer. Standard single-agent regimens, such as methotrexate, doxorubicin, vinblastine and cisplatin, have produced objective response rates of 15-25%, and combination chemotherapy causes objective regression in 50-75% of cases. Novel compounds such as ifosfamide, the taxanes and gemcitabine are now being incorporated into combination regimens, having shown activity in this disease, both in previously treated and untreated cases. The phenomenon of stage migration, with increased precision of imaging, leads to the inclusion of different populations of patients with advanced disease into protocols of assessment of chemotherapy. This may cause an artifact of improved outcome, when in fact the higher response rates and longer survival figures may reflect a reduced burden of disease and case selection. It is thus essential to validate novel approaches in well structured, randomised clinical trials that compare new strategies against established standard protocols. Historical comparisons serve only to confuse the issue by introducing errors from case selection bias, stage migration and differences in duration of follow-up and supportive technologies.