The presence of isolated tumor cells and micrometastases in the intrathoracic lymph nodes of patients with lung cancer is not associated with decreased survival

Abstract

The prognostic role of small intrathoracic nodal metastases in primary patients with lung cancer has been controversial, and it is unclear how their presence should be used for pathologic staging and treatment planning. The intrathoracic lymph nodes from 266 clinical stage I non-small cell carcinoma patients treated at Cedars Sinai Medical Center from 1992 to 2006 were evaluated with immunohistochemistry for keratin AE1/AE3 for the presence of isolated tumor cells and micrometastases, as defined by American Joint Commission on Cancer criteria, correlated with survival using the Kaplan-Meier method and analyzed with power analysis. The English literature from 1995 to 2008 was reviewed to identify best available evidence regarding the prognostic value of isolated tumor cells and micrometastases detected with various immunohistochemistry and molecular methods in non-small cell carcinoma patients. Results were combined with our own data and evaluated with meta-analysis using Comprehensive Meta-analysis 2.0 software (Biostat Inc, Englewood, NJ). Isolated tumor cells and micrometastases were detected in 8 and 67 of 4148 lymph nodes, respectively, and their presence was not significantly associated with survival. Power analysis showed that 3060 cases followed up for 60 months would be needed to achieve 80% power in a study designed to detect survival differences between patients with negative nodes and micrometastases. Meta-analysis of 835 non-small cell carcinoma patients reported in 13 studies showed scanty data to evaluate patients with isolated tumor cells, no significant association between micrometastases and survival and significant data heterogeneity. Current best evidence suggests that non-small cell carcinoma patients should probably not be "upstaged" in the presence of isolated tumor cells and micrometastases. There is no data demonstrating survival benefits for patients treated with adjuvant chemotherapy and/or radiation therapy because of the presence of small nodal metastases.