Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome

BACKGROUND: Lymph node (LN) status after surgery for rectal cancer is affected by preoperative radiotherapy. The purpose of this study was to perform a population-based evaluation of the impact of pathologic LN status (ypN) after neoadjuvant radiotherapy on survival. METHODS: Patients undergoing radical resection for rectal adenocarcinoma were identified from the Surveillance Epidemiology and End Results registry (1991-2004). Patient characteristics, overall survival, and cancer-specific survival (CSS) by ypN stage after surgery and use of preoperative or postoperative radiotherapy were compared. RESULTS: Of the 23,809 patients identified, 12,513 received preoperative (n = 5367) or postoperative (n = 7146) radiotherapy and resection. Preoperative patients were more likely to be younger (P < .001) and histopathologically free of detectable nodal metastasis (ypN0) than postoperative (51.8% vs 31.7%, P < .001). Median total numbers of LNs (6 vs 10) and positive LNs (2 vs 3) were lower among preoperative than postoperative (P < .001 for both). OS and CSS were similar among pN0 patients. However, on proportional hazards regression, ypN+ stage was associated with an increase in relative risk for death by 21% overall (hazard ratio [HR] = 1.21; 95% confidence interval 1.09-1.35, P < .001) and 23% cancer-specific (HR = 1.23; P = .001) for preoperative compared with postoperative. CONCLUSIONS: Pathologic LN status after neoadjuvant radiotherapy for rectal cancer is a biologic marker of prognosis. Patients who are ypN+ after preoperative are a subgroup of LN positive patients with adverse outcome. These high-risk patients should be targeted for studies of novel multidisciplinary approaches, including expanded chemo- and biologic therapies.