ABSTRACT: The present study investigated the prognostic role of extranodal extension (ENE) in stage III-N2 non-small-cell lung cancer (NSCLC) following curative surgery. From January 2005 to December 2018, pathologic stage III-N2 disease was diagnosed in 371 patients, all of whom underwent anatomic pulmonary resection accompanied by mediastinal lymph node dissection. This study included 282 patients, after excluding 89 patients who received preoperative chemotherapy or incomplete surgical resection. Their lymph nodes were processed; after hematoxylin and eosin staining, histopathologic slides of the metastatic nodes were reviewed by a designated pathologist. Predictors of disease free survival (DFS), including age, sex, operation type, pathologic T stage, nodal status, visceral pleural invasion, perioperative treatment, and the presence of ENE, were investigated. Among the 282 patients, ENE was detected in 85 patients (30.1%). ENE presence was associated with advanced T stage (p = 0.034), N2 subgroups (p < 0.001), lymphatic invasion (p = 0.001), and pneumonectomy (p = 0.002). The multivariable analysis demonstrated that old age (p < 0.001), advanced T stage (p = 0.012), N2 subgroups (p = 0.005), and ENE presence (p = 0.005) were significant independent predictors of DFS. The DFS rate at five years was 21.4% in patients who had ENE and 43.4% in patients who did not have ENE (p < 0.001). The presence of ENE, coupled with tumor-node-metastasis staging, should be recognized as a meaningful prognostic factor in stage III-N2 NSCLC patients.
