Negative to positive lymph node ratio is a superior predictor than traditional lymph node status in stage III colorectal cancer

Negative lymph node counts has recently attracted attention as a prognostic indicator in colorectal cancer (CRC). But little is known about prognostic significance of negative to positive lymph node ratio (NPR) in CRC. Our aim was to determine impact of NPR on oncological outcomes in patients with stage III CRC. This retrospective study included 2,256 patients with stage III CRC under curative resection at Fudan university Shanghai cancer center. Kaplan-Meier methods and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. Accuracy of the NPR was assessed with the Harrell's concordance-index(C-index).X-tile program identified 2.38 or 0.55/2.38 as the optimal cutoff value for NPR to divide the cohort into high/low risk or high/middle/low risk subsets in terms of CRC cause specific survival (CCSS). In a multivariate analysis, NPR was significant independent prognostic factors for CCSS (P<0.05), notably, N classification was not an independently prognostic factor (P>0.05). Further analysis found NPR could give detailed prognostic classification for both N1 and N2 stage (P<0.05). Interestingly, patients in N2+ NPR >2.38 stage have similar survival outcome with N1+ NPR >2.38 stage (χ2=0.030, P=0.863), and better than those at N1+ NPR ≤2.38 and N2+ NPR ≤2.38 stage (P<0.001). The TN(NPR)M stage was more accurate for predicting CCSS (C-index = 0.659) than current TNM stage system(C-index = 0.628) (P<0.001). Collectively, NPR was an independent prognostic factor for stage III CRC patients, it could provide more accurate prognostic information than the current node stage system.