Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists

Medical Research Council Advanced Bladder Cancer Working Party, EORTC Genito-Urinary Group, Australian Bladder Cancer Study Group, National Cancer Institute of Canada Clinical Trials Group, Finnbladder, Norwegian Bladder Cancer Study Group and Club Urologico Espanol de Tratamiento Oncologico (CUETO) group (1999) Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. International collaboration of trialists. The Lancet, 354 (9178), 533-540. (doi:10.1016/S0140-6736(99)02292-8).

Abstract

BACKGROUND: Several non-randomised trials have shown that transitional-cell carcinoma of the bladder is a moderately chemosensitive tumour. We investigated whether the addition of neoadjuvant cisplatin-based chemotherapy to radical surgery or radiotherapy would improve survival.

METHODS: Patients with T2 G3, T3, T4a, N0-NX, or M0 transitional-cell carcinoma of the bladder undergoing curative cystectomy or full-dose external-beam radiotherapy were randomly assigned three cycles of neoadjuvant chemotherapy (cisplatin, methotrexate, and vinblastine, with folinic acid rescue, n=491) or no chemotherapy (n=485). When possible, clinical tumour response was assessed cytoscopically after completion of chemotherapy but before cystectomy or radiotherapy; histopathologically assessed response was on cystectomy samples. We recorded every 6 months locoregional persistence or relapse of tumour, appearance of distant metastases, survival, and cause of death.

FINDINGS: Median follow-up of patients still alive was 4.0 years. 485 patients died, and 78.6% of deaths were due to transitional-cell carcinoma. Chemotherapy mortality was 1% and operative (cystectomy) mortality was 3.7%. Kaplan-Meier curves compared by means of the log-rank test gave a calculated absolute difference between groups in 3-year survival of 5.5% (95% CI -0.5 to 11.0, p=0.075; 55.5% for chemotherapy, 50.0% for no chemotherapy). Median survival in the chemotherapy group was 44 months compared with 37.5 months for the no-chemotherapy group. 32.5% of cystectomy samples contained no tumour after neoadjuvant chemotherapy.

INTERPRETATION: Three cycles of neoadjuvant chemotherapy before cystectomy or radiotherapy did not give the 10% improvement in 3-year survival that was judged to be necessary for introduction into routine use. The chemotherapy regimen was associated with a higher pathological complete-response rate in primary tumours, but there was no clear evidence that it would increase survival.

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Contributors

Author: Gareth Griffiths

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