Re-appraisal of N2 disease by lymphatic drainage pattern for non-small-cell lung cancers: By terms of nodal stations, zones, chains, and a composite

PURPOSE:N2 non-small-cell lung cancer (NSCLC) is a heterogeneous disease with an extremely wide range of 5-year survival rates. A composite method of sub-classification for N2 is likely to provide a more accurate method to more finely differentiate prognosis of N2 disease. METHODS:A total of 720 pN2 (T1-4N2M0) NSCLC cases were enrolled in our retrospective analysis of the proposed composite method. Survival rates were respectively calculated according to the N2 stratification methods: singly by "nodal stations", "nodal zones", or "nodal chains", or by combination of all three. Statistical analysis was carried out by Kaplan-Meier and Cox regression models. RESULTS:A total of 10,199 lymph nodes (8059 mediastinal; 2140 hilar and intra-lobar) were removed. By nodal station, there were 173 cases of single-station involvement and 547 multi-stations. By nodal zone, there were 413 single-zone involvement and 307 with multiple zones. By nodal chain, there were 311 cases with single-chain and 409 multi-chain involvements. The overall 5-year survival was 20% and median survival time was 27.52 months. The 5-year survival was significantly better for cases of single-zone involvement, as compared to multi-zones (29% vs. 6%, p<0.0001). The 5-year survival rates of single- and multi-chains involvement were 36% and 8%, respectively (p<0.0001). When taking all of the above grouping methods into consideration, the N2 disease state could be further sub-classified into two subgroups with respective survival rates of 36% and 7% (p<0.0001). Subgroup I was composed of individuals with single-chain involvement and having either one or two station metastasis; individuals with any other metastasis combinations formed Subgroup II. Multivariate analysis revealed that the composite sub-classification method, number of positive lymph nodes, ratio of nodal metastasis, and pT information were the most important risk factors of 5-year survival. CONCLUSIONS:By combining the three N2 stratification methods based on "stations", "zones", and "chains" into one composite method, prognosis prediction was more accurate for N2 NSCLC disease. Single nodal chain involvement, which may be either one or two nodal stations metastasis, is associated with best outcome for pN2 patients.