Non-Small Cell Lung Cancer Patients with Skip-N2 Metastases Have Similar Survival to N1 Patients—A Multicenter Analysis

<b>Introduction:</b> Nodal involvement is one of the most important prognostic factors in NSCLC. Skip-N2 metastasis (N0N2), which is N2 metastasis in the absence of N1 metastasis, occurs in approximately 20-30% of patients. According to the International Association for the Study of Lung Cancer, N1 and N0N2 patients may have comparable long-term survival, considering their similar tumor stages. However, this conclusion remains controversial. Therefore, we carried out this multicenter study to examine the long-term survival and disease-free interval (DFI) of N0N2- and N1 patients. <b>Methods:</b> One-, three-, and five-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. <b>Results:</b> Between January 2010 and December 2020, 273 N0N2 and N1 patients were included in our analysis. Of those patients, 77 showed N0N2 and 196 N1. Baseline characteristics did not differ significantly between groups. Between N0N2 and N1 patients, there were no significant differences in one- (<i>p</i> = 0.67), three- (<i>p</i> = 0.20), and five-year (<i>p</i> = 0.27) survival. Furthermore, DFI did not differ between groups (<i>p</i> = 0.45). <b>Conclusions:</b> Our findings indicate that N0N2 patients have a prognosis comparable to that of patients with N1 disease. These results indicate that patients with N0N2 have a similar prognosis to N1 patients. N2-NSCLC is heterogeneous and would benefit from a more precise subdivision and differential treatment in the upcoming UICC 9 classification. The following question remains: are we overtreating N0N2 patients or undertreating N1 patients?