Impact of Persistent N2 Disease and Lymph Node Ratio on Oncological Outcomes after Multimodal Treatment in Pre-Operative Histologically Proven N2 Disease Non-Small-Cell Lung Cancer

Objective: The objectives of our retrospective analysis were to estimate the oncological long-term results of patients with ypN2 and to evaluate the impact of lymph node ratio (LNR) on overall (OS) and disease-free survival (DFS). Methods: We analysed all consecutive patients (n=85) undergoing neoadjuvant chemotherapy (NAC) and surgery for pre-operative pathologically proven stage IIIA-B (N2) NSCLC from 2014 to 2020. Median LNR (0.29 or 29%) was selected as threshold for grouping. Survival was estimated using the Kaplan-Meier method. Cox regression was used to test the association between OS, DFS and covariates. Results: Post-operative mortality was 3.5%. The median follow-up was 21 months (range 6-69 months). The 5-year OS and DFS of the cohort were 41% and 20%. Patients with LNR>0.29 (n=13; 15.3%) showed a trend toward worse survival than patients with LNR0 (n=44; 51.8%) with a 5-year OS of 56% VS 14% (p=0.077), confirmed as a trend at the multivariable analysis (HR 2.28; p=0.066). At the univariate analysis a worse DFS was observed for ypN2 patients (n=58; 68.2%) compared with nodal downstaging (46% vs 25% 3-year DFS, p=0.039). DFS was different according to LNR: 3-year DFS was 14% in patients with LNR>0.29 while it reached 44% in patients with LNR 0 (p=0.043) and 62% in LNR<0.29 (p=0.03). LNR>0.29 was the only significant predictor (HR 2.89; p=0.047) of reduced DFS at the multivariable analysis. Conclusion: patients with ypN2 disease after NAC showed acceptable oncological outcomes and this finding is true for patients with low burden of nodal disease assessed by LNR.