Postoperative long-term survival of non-small cell lung cancer patients with skip-N2 metastases

Radical lymphadenectomy is crucial in operations for non-small cell lung cancer (NSCLC). Usually pN1 and pN2 lymph nodes are affected consecutively (N1N2). Nevertheless, pN2 metastases may also occur in the absence of pN1 as skip-N2 metastases (N0N2). Here we compare the long-term survival of N1N2- and N0N2 patients.

464 patients underwent surgery for NSCLC at our institution between 2012 and 2017. We retrospectively reviewed data of pN2 stage patients (n = 68). Patients with N1N2 (n = 39) were compared to N0N2 (n = 29) patients. 1-, 3-and 5-year survival rates were measured. Survival was assessed by Kaplan-Meier curves and the cox proportional hazards model was used to identify prognostic factors for overall survival. All patients received adjuvant chemoradiation therapy according to European guidelines.

The baseline characteristics did not differ between groups. We observed no differences in the histology, localization, or gender in our cohort. N0N2 patients showed significantly better 1- (N1N2: 82.4% vs. N0N2 100%; p = 0.001), 3- (14.7% vs. 63.6%; p=<0.001) and 5-year (9.4% vs. 43.8%; p = 0.001) survival rates. Tumor size (Hazard ratio (HR) 1.46, Confidence interval (CI 95%) 1.03-2.04; p = 0.03) and the occurrence of N1N2 (HR 4.26, CI 2.04-8.91; p < 0.0001) were independent prognostic factors for worse long-term survival. The Kaplan-Meier curves showed a reduced overall survival for N1N2 patients (log-rank N1N2, N0N2 p < 0.0001).

N1N2 patients have a significantly worse prognosis compared to N0N2 patients. This will aid to classify the heterogeneous pN2-NSCLC patient population more precisely. Further, multimodal therapy should be considered for N1N2 patients.