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.