New N1/N2 classification and lobe specific lymphatic drainage: Impact on survival in patients with non-small cell lung cancer treated with surgery

Objective: to validate the proposed N descriptor revision on a large cohort of patients and assess the impact of tumour location on the distribution pattern of lymph node metastases for patients with NSCLC. Methods: This is a retrospective review of a consecutive series of patients who had anatomical lung resections. Systematic lymph node dissection was done for all patients. Results: Between January 2009 and December 2019 2566 patients had surgical resection for NSCLC. 448 patients (17.5%) had histologically confirmed lymph node metastases: 257 (57.4 %) had pN1 and 191 pN2. Median age of the study population was 69.1 years. Overall survival (OS) for study population was 37.3 months with 5-year survival rate of 35.7 %. The survival analysis of the N subgroups showed the pN2 patients had a median OS of 27.9 months vs. 41.7 months for pN1 patients (p = 0.013). Analysis as per the new proposal of the N subgroups N1a vs N1b vs N2a1 vs N2a2 vs N2b showed that median survival OS was 41.7 vs. 39.2 mo vs. 33.3 mo vs. 28.9 mo vs. 24.6 mo (p = 0.099). There was statistically significant difference in survival between N2 patients with skip metastasis and N2 patients without skip metastases: OS 32.2 (95 % CI: 16.8-47.6) months vs. 24.2 months (p = 0.024). On multivariate analysis only pathological N (p = 0.011) and the new proposed N classification (p = 0.006) were independent prognostic factors for survival. Conclusions: N1 and N2 disease are heterogeneous groups and require further stratification. The number of N2 lymph node stations involved and the presence or not of N1 disease translated to significant differences in survival and therefore have to be included in N staging.

Automated summary

The proposed N descriptor revision and the impact of tumor location on lymph node metastases distribution have significant implications on survival prediction for NSCLC patients. A significant difference in survival was observed between N1 and N2 patients, especially with N2a2 and N2b subgroups showing poorer prognosis.