Tumor Spread Through Air Spaces Is a Survival Predictor in Non-Small-Cell Lung Cancer

Tumor spread through air spaces (STAS) is a newly recognized invasion pattern in non-small-cell lung cancer (NSCLC). However, the clinical application value of STAS in NSCLC remains to be clarified. We aimed to comprehensively explore the potential role of STAS as a prognostic indicator in NSCLC.

A systematic search was performed in PubMed, Embase, Cochrane Library, and Web of Science until April 15, 2018. A quantitative meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

A total of 3231 patients from 8 studies were included. STAS was observed in 1204 cases (37.3%). A significant association was found between STAS and poor progression-free survival (PFS) (hazard ratio [HR], 1.789; P < .001) and overall survival (OS; HR, 1.488; P < .001). STAS was also an independent prognostic factor for PFS (HR, 1.632; P < .001) and OS (HR, 1.475; P < .001) without obvious heterogeneity. Subgroup analyses and meta-regression showed histology type, tumor, node, metastases (TNM) stage, publication year, sample size, region, and quality score did not alter prognostic value of STAS. Tumor STAS was associated with male sex (P < .001), history of smoking (P < .001), tumor budding (P = .038), vascular invasion (P < .001), lymphatic invasion (P < .001), pleural invasion (P < .001), T stage (P < .001), N stage (P < .001), and TNM stage (P < .001). The publication bias was observed. After adjustment using a nonparametric "trim-and-fill" method, corrected HRs had no significant change.

Tumor STAS is associated with clinicopathologically aggressive features and could be exploited as a novel prognostic predictor in NSCLC.