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

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.

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.

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.

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.