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

Ann Thorac Surg. 2019 Sep;108(3):945-954. doi: 10.1016/j.athoracsur.2019.02.045. Epub 2019 Mar 23.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Combined Modality Therapy
  • Disease Progression*
  • Disease-Free Survival
  • Female
  • Humans
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / therapy*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / pathology
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / physiopathology
  • Neoplasm Staging
  • Prognosis
  • Risk Assessment
  • Survival Analysis