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

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

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.

Aged, Antineoplastic Combined Chemotherapy Protocols, Australia, Canada, Carcinoma, Transitional Cell, Cisplatin, Combined Modality Therapy, Cystectomy, Europe, Female, Humans, Male, Methotrexate, Middle Aged, Neoadjuvant Therapy, Neoplasm Invasiveness, Survival Analysis, Treatment Outcome, Urinary Bladder Neoplasms, Vinblastine, Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial
0140-6736
533-540
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
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
Club Urologico Espanol de Tratamiento Oncologico (CUETO) group
Griffiths, Gareth
7fd300c0-d279-4ff6-842d-aa1f2b9b864d

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).

Record type: Article

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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Published date: 14 August 1999
Keywords: Aged, Antineoplastic Combined Chemotherapy Protocols, Australia, Canada, Carcinoma, Transitional Cell, Cisplatin, Combined Modality Therapy, Cystectomy, Europe, Female, Humans, Male, Methotrexate, Middle Aged, Neoadjuvant Therapy, Neoplasm Invasiveness, Survival Analysis, Treatment Outcome, Urinary Bladder Neoplasms, Vinblastine, Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial
Organisations: Clinical Trials Unit

Identifiers

Local EPrints ID: 406318
URI: http://eprints.soton.ac.uk/id/eprint/406318
ISSN: 0140-6736
PURE UUID: cc4bcb94-4b5c-4c95-8f82-7fab3bb396a6
ORCID for Gareth Griffiths: ORCID iD orcid.org/0000-0002-9579-8021

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Date deposited: 10 Mar 2017 10:44
Last modified: 17 Dec 2019 01:35

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Contributors

Corporate Author: Medical Research Council Advanced Bladder Cancer Working Party
Corporate Author: EORTC Genito-Urinary Group
Corporate Author: Australian Bladder Cancer Study Group
Corporate Author: National Cancer Institute of Canada Clinical Trials Group
Corporate Author: Finnbladder
Corporate Author: Norwegian Bladder Cancer Study Group
Corporate Author: Club Urologico Espanol de Tratamiento Oncologico (CUETO) group

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