Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer:: A combined analysis of two Nordic studies

Objectives: A Nordic collaborative group assessed the effectiveness of cisplatinum based combination chemotherapy prior to cystectomy in two consecutive trials. We analyzed overall survival in all patients and in prespecified subgroups defined by preoperative T-stage, gender and age. Methods: The studies included in 1985-1997 620 patients with clinically T1G3, T2-T4aNXM0 urothelial bladder cancer and WHO performance status less than or equal to 2. Platinum was combined with adriamycin in the first and with methotrexate in the second trial. In the first of the studies, preoperative radiotherapy was used in both arms. Individual patient data were used. No patients were lost to follow-up. The median follow-up was 4.7 years. A fixed effect model was used to combine the results of the two trials. Subgroup analyses were performed for T-stages, gender and age groups. All analyses were done according to intention to treat. Results: The combined study results showed a hazard ratio of 0.80 (95% confidence interval 0.64-0.99) for overall survival in favor of neoadjuvant treatment. Survival was 56% at five years in the experimental group versus 48% in the control group, thus corresponding to an eight percent absolute risk reduction after neoadjuvant chemotherapy. We could not substantiate any differences in effect by subgroup. Conclusions: In a combined analysis of two trials within the same study organization and the same clinical and biological domain, neoadjuvant platinum based combination chemotherapy was associated with a 20% reduction in the relative hazard in probability of death. (C) 2003 Elsevier B.V. All rights reserved.