The predictive and prognostic value of tumour necrosis in muscle invasive bladder cancer patients receiving radiotherapy with or without chemotherapy in the BC2001 trial (CRUK/01/004).
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Authors
Choudhury, A
West, CM
Porta, N
Hall, E
Denley, H
Hendron, C
Lewis, R
Hussain, SA
Huddart, R
James, N
West, CM
Porta, N
Hall, E
Denley, H
Hendron, C
Lewis, R
Hussain, SA
Huddart, R
James, N
Document Type
Journal Article
Date
2017-02-28
Date Accepted
2016-12-28
Date Available
Abstract
BACKGROUND: Severe chronic hypoxia is associated with tumour necrosis. In patients with muscle invasive bladder cancer (MIBC), necrosis is prognostic for survival following surgery or radiotherapy and predicts benefit from hypoxia modification of radiotherapy. Adding mitomycin C (MMC) and 5-fluorouracil (5-FU) chemotherapy to radiotherapy improved locoregional control (LRC) compared to radiotherapy alone in the BC2001 trial. We hypothesised that tumour necrosis would not predict benefit for the addition of MMC and 5-FU to radiotherapy, but would be prognostic. METHODS: Diagnostic tumour samples were available from 230 BC2001 patients. Tumour necrosis was scored on whole-tissue sections as absent or present, and its predictive and prognostic significance explored using Cox proportional hazards models. Survival estimates were obtained by Kaplan-Meier methods. RESULTS: Tumour necrosis was present in 88/230 (38%) samples. Two-year LRC estimates were 71% (95% CI 61-79%) for the MMC/5-FU chemoradiotherapy group and 49% (95% CI 38-59%) for the radiotherapy alone group. When analysed by tumour necrosis status, the adjusted hazard ratios (HR) for MMC/5-FU vs. no chemotherapy were 0.46 (95% CI: 0.12-0.99; P=0.05, necrosis present) and 0.55 (95% CI: 0.31-0.98; P=0.04, necrosis absent). Multivariable analysis of prognosis for LRC by the presence vs. absence of necrosis yielded a HR=0.89 (95% CI 0.55-1.44, P=0.65). There was no significant association for necrosis as a predictive or prognostic factor with respect to overall survival. CONCLUSIONS: Tumour necrosis was neither predictive nor prognostic, and therefore MMC/5-FU is an appropriate radiotherapy-sensitising treatment in MIBC independent of necrosis status.
Citation
British journal of cancer, 2017, 116 (5), pp. 649 - 657
Source Title
Publisher
ELSEVIER SCI LTD
ISSN
0007-0920
eISSN
1532-1827
Collections
Research Team
Clinical Trials & Statistics Unit
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Huddart)
Prostate and Bladder Cancer Research
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Huddart)
Prostate and Bladder Cancer Research