Patients with ERCC1-negative locally advanced esophageal cancers may benefit from preoperative chemoradiotherapy

Purpose: To assess the significance of excision repair cross-complementation group 1 (ERCC1) expression as a predictive marker, we analyzed the effects of preoperative chemoradiotherapy on survival relative to ERCC1 status in patients with locally advanced operable esophageal cancer. Experimental Design: Paraffin-embedded pretreatment tumor specimens, collected by endoscopic biopsy from patients treated with surgery alone or with preoperative chemoradiotherapy followed by surgery, were immunohistochemically assayed for ERCC1 expression. Results: Of the 175 patients, 152 biopsy specimens were available for immunohistochemical analysis. Based on a median ERCC1 expression score of 1, we divided the samples into ERCC1-positive (score >1; 71 patients, 47%) and ERCC1-negative (score <= 1; 81 patients, 53%) groups. No differences in patient and disease characteristics were observed between the two groups. However, among patients with ERCC1-negative tumors, those who received preoperative chemoradiotherapy had longer overall survival (OS) and event-free survival (EFS) than those treated with esophagectomy alone (median OS, 59.2 versus 25.4 months, P = 0.057; median EFS, 50.7 versus 19.7 months, P = 0.042). This difference was not observed among patients with ERCC1-positive tumors. In multivariate analysis, treatment modality was the major determinant of both EFS (P = 0.006) and OS (P = 0.008) for patients with ERCC1-negative tumors, whereas Eastern Cooperative Oncology Group performance status was the only significant predictor of outcome among ERCC1-positive patients. Among patients who received esophagectomy alone, those with ERCC1-positive tumors had a tendency toward longer OS and EFS (P = 0.085 and 0.094, respectively). Conclusions: Patients with ERCC1-negative operable esophageal tumors show a greater benefit from preoperative chemoradiotherapy followed by esophagectomy than those who undergo esophagectomy alone.