Cancer esearch ical Studies E 11 Expression Is Predictive of Cause-Specific Survival wing Radical Radiotherapy for Muscle-Invasive R der Cancer

nloaded ical radiotherapy and surgery achieve similar cure rates in muscle-invasive bladder cancer, but the of which treatment would be most beneficial cannot currently be predicted for individual patients. rimary aim of this study was to assess whether expression of any of a panel of DNA damage signaling ns in tumor samples taken before irradiation could be used as a predictive marker of radiotherapy re, or rather was prognostic. Protein expression of MRE11, RAD50, NBS1, ATM, and H2AX was studied by nohistochemistry in pretreatment tumor specimens from two cohorts of bladder cancer patients (valcohort prospectively acquired) treated with radical radiotherapy and one cohort of cystectomy paIn the radiotherapy test cohort (n = 86), low tumor MRE11 expression was associated with worse r-specific survival compared with high expression [43.1% versus 68.7% 3-year cause-specific survival P = 0.012] by Kaplan-Meier analysis. This was confirmed in the radiotherapy validation cohort (n = .0% versus 71.2%, P = 0.020). However, in the cystectomy cohort (n = 88), MRE11 expression was not ated with cancer-specific survival, commensurate with MRE11 being a predictive marker. High 1 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival red with the high-expression cystectomy cohort (69.9% versus 53.8% 3-year CSS, P = 0.021). In this valimmunohistochemistry study, MRE11 protein expression was shown and confirmed as a predictive associated with survival following bladder cancer radiotherapy, justifying its inclusion in subsequent factor trial designs. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy, thus improving overall cure rates. Cancer Res; 70(18); 7017–26. ©2010 AACR.

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