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Survival of Patients With Resected N2 Non–Small-Cell Lung Cancer: Evidence for a Subclassification and Implications

From the Departments of Medicine and Biostatistics, Institut Gustave Roussy, Villejuif; Department of Thoracic Surgery, Institut Mutualiste Montsouris, Paris; Department of Thoracic Surgery, Clinique des Cèdres, Bois Guillaume; Department of Thoracic Oncology, Hopital Arnaud de Villeneuve, Montpellier; Department of Thoracic Surgery, Hopital Michallon, Grenoble; Department of Thoracic Surgery, Hopital Purpan, Toulouse; Department of Pneumology, Hopital de Strasbourg, Strasbourg; Department of Pneumology, Hopital de Besançon, Besançon, France.

Address reprint requests to Fabrice Andre, MD, Department of Medicine, comité 031 Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France; email UIMMUNOC{at}igr.fr

PURPOSE: Patients who suffer from non–small-cell lung cancer (NSCLC) with ipsilateral mediastinal lymph node involvement (N2) belong to a heterogeneous subgroup of patients. We analyzed the prognosis of patients with resected N2 NSCLC to propose homogeneous patient subgroups.

PATIENTS AND METHODS: The present study comprised 702 consecutive patients from six French centers who underwent surgical resection of N2 NSCLC. Initially, two groups of patients were defined: patients with clinical N2 (cN2) and those with minimal N2 (mN2) disease were patients in whom N2 disease was and was not detected preoperatively at computed tomographic scan, respectively.

RESULTS: The median duration of follow-up was 52 months (range, 18 to 120 months). A multivariate analysis using Cox regression identified four negative prognostic factors, namely, cN2 status (P < .0001), involvement of multiple lymph node levels (L2+; P < .0001), pT3 to T4 stage (P < .0001), and no preoperative chemotherapy (P < .01). For patients treated with primary surgery, 5-year survival rates were as follows: mN2, one level involved (mN2L1, n = 244): 34%; mN2, multiple level involvement (mN2L2+, n = 78): 11%; cN2L1 (n = 118): 8%; and cN2L2+ (n = 122): 3%. When only patients with mN2L1 disease were considered, the site of lymph node involvement according to the American Thoracic Society numbering system had no prognostic significance (P = .14). Preoperative chemotherapy was associated with a better prognosis for those with cN2 (P < .0001). Five-year survival rates were 18% and 5% for cN2 patients treated with and without preoperative chemotherapy, respectively.

CONCLUSION: This study has identified homogeneous N2 NSCLC prognostic subgroups and suggests different therapeutic approaches according to the subgroup profile.

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