Keynote address: a critical assessment of trials of neoadjuvant (preemptive) chemotherapy for bladder cancer: lesson for future studies of combined modality treatment.

Abstract

The 5-year survival of patients with invasive, clinically non-metastatic bladder cancer (Stages T2-4N2Mo) is less than 50%, whether treated by radical radiotherapy, radical cystectomy, or combinations of the two modalities. Cytotoxic regimens, incorporating single agents or combination protocols, produce objective response rates of 10-30 and 10-70%, respectively. Hence, it has been postulated that the use of cytotoxics before or with radiotherapy or surgery ("neoadjuvant", "preemptive", or "concurrent" chemotherapy) could improve the cure rate of invasive bladder cancer. Initial Phase I-II clinical trials have shown such approaches to be feasible, with mild to moderate toxicity. To date, few randomized trials that compare conventional treatment with these new approaches have been initiated or completed, with the majority of eligible patients being treated in increasingly complex Phase II studies. Accordingly, progress has been retarded, and after a decade of investigation, the true role of preemptive or concurrent chemotherapy for invasive bladder cancer is not known. Patients should be entered into well designed, randomized clinical trials in which new approaches to treatment are compared to standard therapy.