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Clinical Trial
. 2017 Feb 28;116(5):649-657.
doi: 10.1038/bjc.2017.2. Epub 2017 Jan 26.

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)

Ananya Choudhury  1 , Catharine M West  1 , Nuria Porta  2 , Emma Hall  2 , Helen Denley  3 , Carey Hendron  4 , Rebecca Lewis  2 , Syed A Hussain  5 , Robert Huddart  6 , Nicholas James  4
Affiliations
Clinical Trial

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)

Ananya Choudhury et al. Br J Cancer. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The CONSORT diagram showing the flow of patients through the study.
Figure 2
Figure 2
Kaplan–Meier curves for locoregional control (A, B) and overall survival (C, D) after radiotherapy (RT) or chemoradiotherapy (RT+CT) and stratified according to absence (A, C) or presence (B, D) of necrosis. Test for interaction between necrosis and treatment yielded unadjusted P-value of 0.467 (locoregional control) and 0.0323 (overall survival).
Figure 3
Figure 3
Investigation of necrosis as a prognostic factor for locoregional control in all 230 patients (A) and in 109 patients receiving radiotherapy only (B), and for overall survival in all 230 patients (C) and in 109 patients receiving radiotherapy alone (D).
See this image and copyright information in PMC

References

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