Tumor Spread Through Air Spaces in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

A series of studies have assessed the clinicopathological features and prognostic impact of spread through air spaces (STAS) in non-small cell lung cancer (NSCLC) bringing conflicting findings so far. We performed a systematic review and meta-analysis to synthesize the available evidence regarding to the prognostic value of STAS in NSCLCs.

Studies were identified by searching databases including PubMed, EMBASE, Web of Science, and Cochrane Library up to August 2018 without language restrictions. Results of these searches were filtered according to a set of eligibility criteria and analyzed in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

A total of 3,754 patients from 14 studies were selected for the present study. The pooled results suggested that presence of STAS was associated with worse recurrence-free survival (hazard ratio [HR], 1.975; 95% confidence interval [CI], 1.691 to 2.307; p < 0.001) and overall survival (HR, 1.75; 95% CI, 1.375 to 2.227; p < 0.001) in NSCLCs. Subgroup analysis by histology type indicated the presence of STAS was significantly associated with inferior recurrence-free survival in resected lung adenocarcinoma (n = 7; HR, 2.288; 95% CI, 1.843 to 2.840; I² = 7.80%), lung squamous cell carcinoma (n = 3; HR, 1.622; 95% CI, 1.279 to 2.056; I² = 0%), and lung pleomorphic carcinoma (n = 1; HR, 4.76; 95% CI, 1.168 to 19.398). Additionally, a number of clinicopathological characteristics indicating STAS in NSCLCs are summarized.

Our study indicates that tumor STAS was a potentially significant prognostic predictor for surgical patients with NSCLCs. The prognostic impact of STAS present in the resection margin remains undetermined. Further large-scale prospective studies are warranted to confirm the prognostic significance of STAS in patients with NSCLCs.