Do skip-N2 metastases significantly impact overall survival and disease-free interval in N2 non-small-cell lung cancer patients? A multicentre analysis

OBJECTIVES: Skip-N2 metastasis (N0N2), thus N2 metastasis in the absence of N1 metastasis, occurs in similar to 20-30% of non-small-cell lung cancer patients. N0N2 patients have a better prognosis than continuous-N2 metastasis (N1N2) patients following surgery. However, this effect remains controversial. Therefore, we conducted a multicentre study to compare the long-term survival and disease-free interval (DFI) of N1N2- and N0N2 patients. METHODS: One- and 3-year survival rates were measured. Kaplan-Meier curves and a Cox proportional hazards model assessed survival and were used to identify prognostic factors for overall survival. In addition, we performed propensity score matching (PSM) to rule out confounding factors. All patients received adjuvant chemoradiation therapy according to European guidelines. RESULTS: Between January 2010 and December 2020, 218 stage IIIA/B N2 patients were included in our analysis. The Cox regression analysis revealed that N1N2 significantly influenced the overall survival rate. Before PSM, N1N2 patients showed significantly more metastatic lymph nodes (P < 0.001) and significantly larger tumours (P = 0.05). After PSM, baseline characteristics did not differ between groups. Before and after PSM, N0N2 patients showed significantly better 1- (P = 0.01; P = 0.009) and 3-year (P < 0.001) survival rates than N1N2 patients. Furthermore, N0N2 patients showed significantly longer DFI than N1N2 patients before and after PSM (P < 000.1). CONCLUSIONS: Prior and after PSM analysis, N0N2 patients were confirmed to have better survival and DFI than N1N2 patients. Our results demonstrate that stage IIIA/B N2 patients are heterogeneous and would benefit from a more precise subdivision and differential treatment.