Background: Radical cystectomy remains the gold standard treatment for invasive non metastatic transitional cell cancer of the bladder. Perioperative chemotherapy (adjuvant ou neoadjuvant) has been developed to increase overall survival. However, the chemotherapy administration time and optimal chemotherapy regimen are not yet determined. As DD-MVAC has been shown to be associated with higher response rates in bladder metastatic disease, also a better efficacy can be suspected in the perioperative setting. Methods: We designed a randomized phase III study to compare the efficacy of GC and DD-MVAC in term of progression-free survival in patients for whom chemotherapy has been decided, before or after radical cystectomy (disease defined by a T2, T3 or T4a N0 M0 stadification for patients receiving neoadjuvant chemotherapy or pT3 or pT4 or pN+ and M0 for patients receiving adjuvant chemotherapy). Secondary endpoints include overall survival, side effects, response rate in the neoadjuvant setting. Main exclusion criteria were histological variants (pure adenocarcinoma or pure epidermoid carcinoma or pure or mixed small-cell neuro-endocrine carcinoma) and ventricular ejection fraction under 50%. The total number of patients projected was 500 based on the median progression-free survival rate of 50% at 3 years observed in patients treated with GC (standard arm A) in the perioperative setting. An absolute improvement of 10% (HR = 0.74) was expected with DD-MVAC (experimental arm B) with a = 0.05 and b = 0.20. In October 2017, 460 patients have been included. An interim analysis is planned after the occurrence of 174 events. With an estimated uniform accrual rate of 140 patients per year for 3.5 years and exponential survival, the final analysis is expected to occur 8 years after the start of the trial. Concomitant ancillary study has also started, focusing on the identification of subgroups for muscle invasive bladder tumors sensitivity to neoadjuvant chemotherapy, as suggested by the recent MDA classification. Clinical trial information: NCT 018 12369.