In order to improve the results obtained by cystectomy alone and to determine the possibilities of conservative treatment in invasive bladder cancer, we designed a prospective study using a combination of 5-FU--Cisplatin and concomitant radiation therapy, followed either by cystectomy or additional chemoradiotherapy. Sixty six patients (pts) with T2-T4 operable untreated invasive bladder cancer were entered into the study. Treatment was begun in all patients by trans-urethral resection (complete in 30 pts) and followed by 5-FU-Cisplatin combination with concomitant bifractionated split course radiation therapy. The neo-adjuvant irradiation dose was 24 Gy delivered in 8 fractions over 17 days, according to a modified bifractionated split course schedule. Each fraction delivered 3 Gy, twice on day (D1, D3, D15 and D17. The patients received concomitant Cisplatin (15mg/m2/d) and 5-FU (400mg/m2/d) on day D1, D2, D3 and D15, D16, D17. A control cystoscopy was performed six weeks after completion of the neoadjuvant program. Patients with persistent tumor underwent cystectomy. Complete responders were treated either by additional chemoradiotherapy (group A) or cystectomy (group B). At control cystoscopy, 51 of the 66 patients (77%) had histologically documented complete response. Among the 51 patients with complete tumor regression 31 were treated by conservative chemoradiotherapy and 20 underwent cystectomy. With a mean follow-up of 35 months, five responders developed recurrent pelvic disease (4/31 in group A and 1/20 in group B). Metastatic disease, which developed in 22 patients, occurred more frequently in the non responders (93%) than in responders (16%). Disease free survival at 5 years was 51%; it was significantly better in responders than in non responders. There was no difference in survival between groups A and B. This neoadjuvant chemoradiotherapy combination, easy to implement and well-tolerated even in elderly patients, provides a high CR rate. It may prove to be effective in inoperable patients and may be proposed as conservative treatment in patients with a complete response to the initial course of chemoradiation.