Clinical Significance and Role of Lymphatic Vessel Invasion as a Major Prognostic Implication in Non-Small Cell Lung Cancer: A Meta-Analysis

Lymphatic vessel invasion (LVI) exerts an important process in the progression and local spread of cancer cells. However, LVI as a prognostic factor for survival in non-small cell lung cancer (NSCLC) remains controversial.A meta-analysis of published studies from PubMed and EMBASE electronic databases was performed to quantity the effects of LVI on both relapse-free survival and overall survival for patients with NSCLC. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the strength of these effects. This meta-analysis included 18,442 NSCLC patients from 53 eligible studies. LVI appeared in 32.1% (median; range, 2.8% to 70.9%) of tumor samples. In all, patients with LVI were 2.48 times more likely to relapse by univariate analysis (95% CI: 1.92–3.22) and 1.73 times by multivariate analysis (95% CI: 1.24–2.41) compared with those without LVI. For the analyses of LVI and overall survival, the pooled HR estimate was 1.97 (95% CI: 1.75–2.21) by univariate analysis and 1.59 (95% CI: 1.41–1.79) by multivariate analysis. Multivariate analysis showed a risk was 91% higher for recurrence (HR = 1.91, 95% CI: 1.14–2.91) and 70% higher for mortality (HR = 1.70, 95% CI: 1.38–2.10) in LVI-positive I stage patients compared with LVI-negative I stage patients. Subgroup analyses showed similar significant adjusted risks for recurrence and death in adenocarcinomas, and a significant adjusted risk for death in studies that utilized elastic staining with or without immunohistochemistry in defining LVI.The present study indicates that LVI appears to be an independent poor prognosticator in surgically managed NSCLC. NSCLC patients with LVI would require a more aggressive treatment strategy after surgery. However, large, well-designed prospective studies with clinically relevant modeling and standard methodology to assess LVI are required to address some of these important issues