Lymph-node ratio predicts survival among the different stages of non-small-cell lung cancer: a multicentre analysis†

Abstract

Objectives: The prognostic role of the number of resected and metastatic lymph nodes in non-small-cell lung cancer (NSCLC) is still being debated. The aim of this study was to evaluate the impact of lymphadenectomy in addition to the already validated variables in NSCLC survival.

Methods: From January 2002 to December 2012, data on 4858 patients with NSCLC undergoing anatomical lung resection and hilomediastinal lymphadenectomy in 6 institutions were analysed retrospectively. Established prognostic factors in addition to the number of resected lymph nodes and the ratio between the number of metastatic lymph nodes and the number of resected lymph nodes (NR) were correlated to overall survival (OS) and disease-free survival (DFS) using the multivariable Cox regression model. Harrell's C-statistic with the 95% confidence interval (CI) was determined. Analysis by means of maximally selected log-rank statistics was performed to find optimal cut-off points in order to split patients into groups with different outcome probabilities.

Results: The median numbers of resected lymph nodes and of metastatic lymph nodes were 17 (range 6-85) and 2 (1-36), respectively. Hilar (N1) and mediastinal (N2) metastases were identified in 21.3% and 20.0% of cases, respectively. Overall, the 5-year OS and DFS rates were 54.6% and 44.8%, respectively. At multivariable analysis, age, gender, pathological stage, R0 resection, type of surgery and NR correlated with longer OS rates; the same variables plus tumour grading were further related to DFS. C-statistics were 66.0 (95% CI 62.7-69.4) for DFS and 60.5 (95% CI 58.3-62.6) for OS. An NR <40% significantly correlated with a higher 5-year survival rate in the total sample (OS 57.6% vs 23.8%, P < 0.001; DFS 48.2% vs 11.4, P < 0.001) and in patients with N1 (OS 47.9% vs 36.1%, P = 0.03; DFS 39% vs 24.2%, P = 0.02) and N2 (OS 36.9% vs 21.8%, P < 0.001 DFS 23.9% vs 9.1%, P < 0.001).

Conclusions: Our study confirms that the number of resected lymph nodes is a strong prognostic indicator in NSCLC. In particular, an NR cut-off value of 40% may predict both OS and DFS.

Keywords: Lung surgery; Lymph nodes metastasis; Lymph-node ratio; Non-small-cell lung cancer.