Neoadjuvant CMV chemotherapy for muscle-invasive bladder cancer: a new treatment paradigm?

The long term results of the EORTC/MRC trial 30894/BA06 show that neoadjuvant cisplatin, methotrexate, and vinblastine (CMV) chemotherapy improves outcome in patients with muscle-invasive urothelial cancer of the bladder treated by cystectomy and/or radiotherapy ¹. Two large randomized trials, this study and the Southwest Oncology Group intergroup study 0080 ², have confirmed a statistically significant and clinically relevant survival benefit for neoadjuvant chemotherapy as compared with cystectomy or radiotherapy alone in treating this disease.

In this international multicenter phase III trial which recruited 976 patients between 1989 and 1995, patients were randomized to receive either no neoadjuvant chemotherapy or three cycles of CMV. At a median follow-up of 8.0 years, a 16% reduction in the risk of death (hazard ratio 0.84; 95% CI, 0.72 to 0.99; P=0.037, corresponding to an increase in 10-year survival from 30% to 36%) was observed in the CMV arm.

In an editorial in the Journal of Clinical Oncology, Dean Bajorin and Harry Herr opine that the option of neoadjuvant chemotherapy before cystectomy should be given to all muscle-invasive cancer patients, so that they receive the best treatment that has been demonstrated through mature randomized clinical trials ³.

This is an extremely important study as it clearly shows the value of intergroup cooperation in conducting a large scale study that none of the individual groups would have been able to conduct in a similar period of time.

John Bean

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¹From the International Collaboration of Trialists on behalf of the Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group), the European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group, the Australian Bladder Cancer Study Group, the National Cancer Institute of Canada Clinical Trials Group, Finnbladder, Norwegian Bladder Cancer Study Group, and Club Urologico Espanol de Tratamiento Oncologico Group. International Phase III Trial Assessing Neoadjuvant Cisplatin, Methotrexate, and Vinblastine Chemotherapy for Muscle-Invasive Bladder Cancer: Long-Term Results of the BA06 30894 Trial. J Clin Oncol, Vol 29, 2011. doi: 10.1200/JCO.2010.32.3139.

² Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349:859-866, 2003.

3 Bajorin DF and Herr HW. Kuhn’s Paradigms: Are Those Closest to Treating Bladder Cancer the Last to Appreciate the Paradigm Shift? J Clin Oncol, Vol 29, 2011. doi: 10.1200/JCO.2010.34.0471