Completely Resected Non-Small Cell Lung Cancer: Reconsidering Prognostic Value and Significance of N2 Metastases

Background: Non-small cell lung cancer (NSCLC) mediastinal (N2) metastases are indicators of poor prognosis. Survival rates decrease with increasing number of N2 stations and involved lymph nodes as well as lymph node size and capsular invasion. Our purpose was to elucidate the impact lymph node-related variables on the outcome after surgical resection. Methods: We reviewed data of 2344 NSCLC patients who underwent curative resections with mediastinal lymphadenectomy, and 586 (25%) had N2 metastases. We studied the overall survival of N2 patients according to some important covariates. Results: Metastases involved single N2 stations in 386 patients (66%) and two or more in 200 (34%). Survival was not related with histology or pathologic tumor (pT), but was better when only one N2 station was involved (5-year overall survival 28.5% [median, 24 months] versus 17.2% [median, 14 months] respectively; p = 0.0002. For single N2 stations, capsular rupture, number, and size of lymph nodes were not significant prognostic factors. When the size of lymph node was analyzed (micrometastases, 53; nonbulky, 207; or bulky metastases, 126), overall survival differences between nonbulky and bulky N2 were significant: 5-year overall survival was 34% (median, 28 months) versus 23% (median, 23 months), respectively (p = 0.026). Presence of micrometastases was associated with a poor prognosis: 5-year overall survival of 21.4% (median, 23 months). Conclusions: Prognosis was better for patients with single N2 stations when metastatic lymph nodes were not enlarged. However, the presence of lymph nodes micrometastases does not seems associated with a better outcome.