Neutrophil-to-lymphocyte ratio and risk of nodal metastasis in early-stage lung adenocarcinoma: a brief report from a multicentric analysis

Introduction Nodal metastases in non-small cell lung cancer have a relevant prognostic role and may indicate neoadjuvant treatments. However, despite proper pre-operative mediastinal staging, still a remarkable percentage of patients has nodal upstaging at surgery. Neutrophil-to-Lymphocyte Ratio (NLR) may be a valuable and easily accessible tool to identify clinical N0 patients at risk for nodal metastases. Material and methods In this multicentric retrospective study, demographic, clinical and pathologic characteristics of all the patients undergoing anatomical resection and radical lymphadenectomy for cT1-3 cN0-1 lung adenocarcinoma in the period between Jan-2013 and Dec-2022 have been retrieved including preoperative biomarker of systemic inflammation and lymphadenectomy characteristics. Comparison was performed between upstaging and non-upstaging-group. Results Overall, 636 patients have been included in the analysis. Most of the patients were previous/active smoker males with right upper lobe stage I adenocarcinomas. Nodal upstaging was observed in 92 patients (14.5%). Median NLR was 2.4 (1.7 – 3.7). A 3.5 cut-off was chosen according to ROC-curve analysis for NLR. At univariate analysis cT, cN1 and NLR≥3.5 were predictive for upstaging (p=0.001;p=0.010;p=0.0001). Multivariate analysis confirmed the predictive role of cN1 status (OR=3.389, 95% CI 1.376-10.989; p=0.010) and NLR≥3.5 (OR=16.863, 95% CI 9.524-29.856; p=0.0001). Conclusion Clinical suspect of N1 disease as well as NLR ≥ 3.5 may predict unforeseen nodal metastases in early-stage lung adenocarcinoma. Implementation of NLR in the pre-operative assessment may help to identify patients at risk for upstaging.