Necrosis predicts benefit from hypoxia-modifying therapy in patients with high risk bladder cancer enrolled in a phase III randomised trial.

Abstract

BACKGROUND AND PURPOSE:

Addition of carbogen and nicotinamide (hypoxia-modifying agents) to radiotherapy improves the survival of patients with high risk bladder cancer. The study investigated whether histopathological tumour features and putative hypoxia markers predicted benefit from hypoxia modification.

MATERIALS AND METHODS:

Samples were available from 231 patients with high grade and invasive bladder carcinoma from the BCON phase III trial of radiotherapy (RT) alone or with carbogen and nicotinamide (RT+CON). Histopathological tumour features examined were: necrosis, growth pattern, growing margin, and tumour/stroma ratio. Hypoxia markers carbonic anhydrase-IX and glucose transporter-1 were examined using tissue microarrays.

RESULTS:

Necrosis was the only independent prognostic indicator (P=0.04). Necrosis also predicted benefit from hypoxia modification. Five-year overall survival was 48% (RT) versus 39% (RT+CON) (P=0.32) in patients without necrosis and 34% (RT) versus 56% (RT+CON) (P=0.004) in patients with necrosis. There was a significant treatment by necrosis strata interaction (P=0.001 adjusted). Necrosis was an independent predictor of benefit from RT+CON versus RT (hazard ratio [HR]: 0.43, 95% CI 0.25-0.73, P=0.002). This trend was not observed when there was no necrosis (HR: 1.64, 95% CI 0.95-2.85, P=0.08).

CONCLUSIONS:

Necrosis predicts benefit from hypoxia modification in patients with high risk bladder cancer and should be used to select patients; it is simple to identify and easy to incorporate into routine histopathological examination.

• Authors: Amanda Eustace, Joely J Irlam, Janet Taylor, Helen Denley, Shailesh Agrawal, Ananya Choudhury, David Ryder, Jonathan J Ord, Adrian L Harris, Ana M Rojas, Peter J Hoskin, Catharine M L West
• Journal: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology (Radiother Oncol) Vol. 108 Issue 1 Pg. 40-7 (Jul 2013) ISSN: 1879-0887 [Electronic] Ireland
• PMID: 23773411 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Chemical References

• Glucose Transporter Type 1
• SLC2A1 protein, human
• Carbon Dioxide
• Niacinamide
• carbogen
• Carbonic Anhydrase IV
• Oxygen

Topics

• Aged
• Aged, 80 and over
• Carbon Dioxide (therapeutic use)
• Carbonic Anhydrase IV (analysis)
• Cell Hypoxia
• Female
• Glucose Transporter Type 1 (analysis)
• Humans
• Male
• Middle Aged
• Necrosis
• Niacinamide (therapeutic use)
• Oxygen (therapeutic use)
• Risk
• Urinary Bladder Neoplasms (chemistry, mortality, pathology, radiotherapy)