ERCC1 and XRCC1 expression predicts survival in bladder cancer patients receiving combined trimodality therapy

Combined trimodality therapy, including transurethral resection and platinum-based chemoradiotherapy, has shown promising results for muscle-invasive bladder cancer. However, this type of treatment may decrease survival as a result of delayed cystectomy in patients with non-responding tumors. DNA repair proteins may affect survival of bladder cancer patients receiving combined trimodality therapy, by affecting the perioperative nature of the tumor cells or by repairing DNA damaged by platinum agents and radiation. We investigated the associations of excision repair cross-complementing group 1 (ERCC1), X-ray repair cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with response and survival in 157 locally advanced bladder cancer patients receiving combined trimodality therapy, in order to determine the predictive value of the expression of these proteins in patient selection for therapy. We examined ERCC1, XRCC1 and APE1 expression in tumor specimens using immunohistochemistry. Patients positive for ERCC1, positive for XRCC1 and positive for either ERCC1 or XRCC1, exhibited significantly improved disease-specific survival rates (P=0.023, 0.025 and 0.0091, respectively). In multivariate analysis, combined ERCC1 and XRCC1 expression was independently associated with disease-specific mortality [risk ratio (RR): 0.64; 95% confidence interval (CI), 0.43-0.94 and P=0.024]. Thus, combined ERCC1 and XRCC1 expression may serve as an independent prognostic marker for survival in bladder cancer patients receiving combined trimodality therapy. Prospective studies with a larger sample size are required to confirm these results.