Mediastinal Up-Staging During Surgery in Non–Small-Cell Lung Cancer: Which Mediastinal Lymph Node Metastasis Patterns Better Predict The Outcome? A Multicenter Analysis

Background: Unexpected N2 involvement occurs in approximately 10% to 20% of patients with non–small-cell lung cancer (NSCLC) and patients’ prognostic factors remain unclear. The aim of this study was to evaluate prognostic factors in these patients. Methods: From January 2002 to December 2012, we retrospectively analyzed data of 550 patients with NSCLC with preoperative negative, but pathologic positive N2 involvement, who underwent anatomical lung resection and hilo-mediastinal lymphadenectomy, obtained from 6 institutions. An established prognostic factor panel and N2-type involvement were correlated to overall (OS), cancer-specific (CSS), and disease-free survival (DFS) using multivariate Cox Regression model. The following lymph node patterns were analyzed: number of resected nodes (#RNs), metastatic nodes (#MNs), ratio between #MNs and #RNs (NR), N2 subgroups proposed for the eighth TNM edition, and lobe-specific versus nonspecific metastasis. Results: Regarding our cohort, 419 patients were staged IIIA (T1-2N2), 131 IIIB (T3-4 N2), 113 pT1, 306 pT2, 94 pT3, and 37 pT4; 5-year OS, DFS, and CSS were 34.1%, 20.1%, and 64.6%, respectively. Independent prognostic factor for OS, in the multivariable analysis, were as follows: NR <17% (P =.009), proposed N2 classification subgroups (P =.014), age <66 (P <.001), and pT (P =.005); for DFS: NR <17% (P =.003), adjuvant treatment (P =.026), and pT (P =.026); and for CSS: NR <17% (P =.008), grading (P =.001), and adjuvant treatment (P <.001). Conclusion: Our study confirms that adjuvant therapy is fundamental and NR, in patients with unexpected N2 involvement, has a strong prognostic factor. In particular, a NR cutoff value of 17% could predict OS, DFS, and CSS in patients with NSCLC.