Abstract LB-450: Necrosis predicts benefit from hypoxia-modifying therapy in urothelial cell carcinoma of the bladder

Abstract

Abstract To investigate the ability of tumor necrosis to predict benefit following radiotherapy with and without hypoxia-modifying treatment in high grade urothelial cell carcinoma of the urinary bladder. Background: There is no predictive marker of hypoxia-modifying therapy in cancer patients in routine clinical use. Methods: We identified 231 patients who participated in the BCON phase III randomised trial comparing radical radiotherapy (RT) with and without carbogen and nicotinamide (CON) in patients with urothelial cell carcinoma of the bladder who were suitable for this retrospective study. Tumor necrosis was scored on whole tissue sections as absent or present. Results: Tumor necrosis was identified in 121 of the 231 patients (52%). 5-year overall survival estimates were 41% for the RT arm and 48% for the CON arm (log rank p=0.14). When stratified using tumor necrosis, the 5-year overall survival estimates were 48% (RT) and 39% (CON) (log rank p =0.32) in patients with no evident tumor necrosis, and 34% (RT) and 56% (CON) (log rank p=0.004) in patients with tumor necrosis. Multivariate analyses showed that the presence of tumor necrosis was a significant predictor of benefit from CON with the risk of dying 57% lower compared to RT alone (HR 0.43, 95% CI 0.25-0.73, p=0.002). This trend was not observed when there is no evident tumour necrosis (HR 1.64, 95% CI 0.95-2.85, p=0.08). Test for heterogeneity in treatment effect by necrosis strata (p=0.007 unadjusted, p=0.001 adjusted). Conclusions: Tumor necrosis significantly predicts benefit from radiotherapy with hypoxia-modifying treatment. Independent validation in a prospective trial is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-450. doi:1538-7445.AM2012-LB-450