The number of metastatic lymph nodes is more predictive of prognosis than Location-based N stage for Non-small cell lung cancer: a retrospective cohort study

The eighth edition of nodal classification is defined only by anatomical location of metastatic lymph nodes and has limited prognostic discrimination power. We aimed to evaluate the prognostic significance and discriminatory capability of the number of metastatic lymph nodes (nN) in resected non-small cell lung cancer.Patients with stage IA to IIIB resected non-small cell lung cancer between January 1, 2009 to December 31, 2013 were analyzed as Chinese cohort. Optimal thresholds for the nN classification were determined by X-tile. The receiver operating characteristic curve, net reclassification improvement and standardized net benefit calculated by decision curve analysis was estimated to quantify the nN classification's performance in prognostic stratification. External validation in the Surveillance, Epidemiology, and End Results database was performed to test the robustness of nN classification.Both cohorts showed a stepwise prognosis deterioration with increasing nN. One to three, four to six, and more than six were selected as optimal thresholds of nN classification in the Chinese cohort which included 4,432 patients, then validated in the SEER cohort (n=28,022 patients). Multivariate Cox analysis showed the nN classification was an independent predictive factor for overall survival in both cohorts (Chinese cohort and SEER cohort: N0 vs. N1-3, P<0.001; N0 vs. N3-6, P<0.001; N0 vs. N>6, P<0.001). And prognostic discriminatory capability was improved in the nN classification compared with location-based N classification [5-year NRI score, 0.106 (95% CI, 0.049-0.132) and 5-year time-independent AUC, 0.593(95% CI, 0.560-0.625) vs. 0.554(95%CI, 0.520-0.588), P<0.001].The nN classification tended to be a superior prognostic indicator than location-based N classification. The number of metastatic lymph nodes should be considered in the future revision of TNM system.