Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy

Purpose: Excision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy. Materials and methods: Thirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival. Results: Pathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012-0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2-11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. <= 60 years) (HR 3.4, 95% CI 1.2-9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014-0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9-19.9, P = 0.002) were significantly associated with OS. Conclusions: Our results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer. (C) 2013 Elsevier Inc. All rights reserved.