Clinicopathological Impact of the Spread through Air Space in Non-Small Cell Lung Cancer: A Meta-Analysis

This study aimed to elucidate the clinicopathological significance of spread through air space (STAS) in non-small cell lung cancer (NSCLC) through a meta-analysis. Using 47 eligible studies, we obtained the estimated rates of STAS in various histological subtypes of NSCLC and compared the clinicopathological characteristics and prognosis between NSCLC with and without STAS. The estimated STAS rate was 0.368 (95% confidence interval [CI], 0.336-0.0.401) in patients with NSCLC. Furthermore, the STAS rates for squamous cell carcinoma and adenocarcinoma were 0.338 (95% CI, 0.273-0.411) and 0.374 (95% CI, 0.340-0.409), respectively. Among the histological subtypes of adenocarcinoma, micropapillary-predominant tumors had the highest rate of STAS (0.719; 95% CI, 0.652-0.778). The STAS rates of solid- and papillary-predominant adenocarcinoma were 0.567 (95% CI, 0.478-0.652) and 0.446 (95% CI, 0.392-0.501), respectively. NSCLCs with STAS showed a higher visceral pleural, venous, and lymphatic invasion than those without STAS. In addition, anaplastic lymphoma kinase mutations and ROS1 rearrangements were significantly more frequent in NSCLCs with STAS than in those without STAS. The presence of STAS was significantly correlated with worse overall and recurrence-free survival (hazard ratio, 2.119; 95% CI, 1.811-2.480 and 2.372; 95% CI, 2.018-2.788, respectively). Taken together, the presence of STAS is useful in predicting the clinicopathological significance and prognosis of patients with NSCLC.