Mediastinal lymphadenectomy in non-small cell lung cancer: effectiveness in patients with or without nodal micrometastases — results of a preliminary study

Abstract
Objectives: So far it has not clearly been demonstrated that systematic mediastinal lymphadenectomy improves survival in patients with non-small cell lung cancer. One explanation might be that in some patients an early spread of tumor cells has occurred which might not be curable by surgical means. To test this hypothesis lymph nodes of patients which were treated either by lymph node sampling or systematic lymphadenectomy were screened for micrometastatic spread of tumor cells and the influence of nodal micrometastases on the efficacy of lymphadenectomy was analyzed. Methods: Lymph nodes from patients (n=94) which were included in a randomized trial of lymph node sampling (LS, n=41) versus radical systematic lymphadenectomy (LA, n=53) were screened by immunohistochemistry for disseminated tumor cells using the antibody Ber-Ep4. The median observation time was longer than 5 years and follow-up data were available from all 94 patients. Kaplan–Meier curves were calculated and tested for statistical significance using the log-rank test. Results: Standard histopathological analysis revealed no lymph node involvement (pN0) in 61 patients, pN1 disease in 13 patients and pN2 disease in 20 patients without significant differences between LA and LS with respect to T-stage, N-stage or age and sex of the patients. By immunohistochemistry a minimal nodal spread of tumor cells was detected in 21 out of 94 patients (LS, n=10 (24%); LA, n=11 (21%)). Similar to the entire group of patients also in the subset of patients with nodal micrometastases the type of lymphadenectomy did not significantly influence the long-term survival (P=0.27 and P=0.39, respectively). In contrast, in patients with a negative immunohistochemical analysis systematic lymphadenectomy resulted in an improved overall survival (P=0.044). Conclusions: Our data provide some evidence that systematic lymphadenectomy improves survival in patients without an early locoregional spread of cancer cells. As long as these patients can not be identified preoperatively all patients should undergo a systematic mediastinal lymphadenectomy.