Lymph node isolated tumor cells and micrometastases in pathological stage I non-small cell lung cancer: prognostic significance

Objective: To determine the prevalence and prognostic significance of lymph node micrometastases and isolated tumor cells (ITC) in patients submitted for radical resection for pathological stage I non-small cell lung cancer (NSCLC). Methods: From January 1998 through December 2005, 87 consecutive pT1-2, pN0 NSCLC patients were enrolled. Surgical specimens were submitted to pathological routine examinations to define histotype, grade, stage, vascular invasion, necrosis and tumor proliferative index. A total of 694 regional lymph nodes were examined by means of serial sections stained with hematoxylin and eosin and labelled by immunohistochemistry (antibody AE1/AE3, DAKO). Relationships between these parameters and patients' prognosis were investigated. Results: By histological examination, there were 36 squamous-cell carcinoma, 38 adenocarcinoma and 13 large-cell carcinoma. Micrometastases and ITC were detected in 19 lymph nodes (2.7%) of 14 patients (16%). Significant correlation was observed between micrometastases or ITC and adenocarcinoma (p = 0.03) and the absence of necrosis (p = 0.05). No relationship was demonstrated between micrometastases or ITC and T-status, vascular invasion or proliferative index (p > 0.05). Median follow-up was 3.2 (range 0.25-8.6) years. Two- and 5-year disease-free survival was similar for patients with and without micrometastases or ITC (79% and 64% vs 81% and 64%, respectively). Recurrence occurred in three patients with (two local, 66%) and in 21 patients without micrometastases or ITC (three local, 14%) (p = 0.186). By multivariate analysis only T-status was demonstrated to be a significant prognostic factor. Discussion: Micrometastases or ITC to regional lymph nodes are demonstrated to be not a rare aspect of pathological stage I resected lung cancer. In our series, the presence of lymph nodes micrometastases does not affect long-term disease-free survival.