Skip metastasis in mediastinal lymph node is a favorable prognostic factor in N2 lung cancer patients: a meta-analysis

Background: Skip metastasis is a common lymph node metastatic pattern in non-small cell lung cancer (NSCLC). The relationship between skip metastasis and specific clinicopathologic factors and the prognostic value of skip metastasis are controversial. Methods: A systematic search and analysis of skip metastasis in NSCLC was conducted in the databases of PubMed, EMBASE, and Web of Science up to Dec 2019. Summarized hazard ratio (HR), mean difference (MD), and odds ratio (OR) with associated 95% confidence intervals (CI) were evaluated to investigating the relationship between skip metastasis and overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and clinicopathological features in NSCLC. Results: 29 studies with a total of 1,806 skip and 4,670 non-skip N2 patients were included. The upper lobe tumor showed a higher rate of skip metastasis compared with lower lobe one (RR =1.16, 95% CI: 1.00-1.34, P=0.044, I-2=39.8%). The presence of skip metastasis correlated with superior overall survival (HR =0.74, 95% CI: 0.66-0.83, P<0.001, I-2=48.2%) and DFS or RFS (HR =0.71, 95% CI: 0.61-0.84, P<0.001, I-2=18.2%). Further subgroup analyses indicated similar results in articles that reported intrapulmonary lymph node dissection (HR =0.67, 95% CI: 0.57-0.77, P<0.001, I-2=0). Conclusions: The results indicate that the presence of skip metastasis is associated with a marked increase in survival of NSCLC patients compared to patients with non-skip N2 metastasis. These results suggest that skip metastasis might be a distinct subgroup for purposes of N staging of NSCLC patients, and intrapulmonary lymph node assessment is needed.