Prognostic Value and Clinical Outcomes of Spread through Air Spaces in Lung Adenocarcinoma: A Single-Center Retrospective Study in Türkiye

Background: Spread through air spaces (STAS), first described in lung adenocarcinomas in 2013, has been identified as a prognostic factor in numerous studies. We investigated the prognostic effect of STAS positivity and its potential role in staging and treatment strategies. Methods: We retrospectively reviewed prospectively collected data from patients who underwent surgery at our hospital and were diagnosed with adenocarcinoma between 2018 and 2021. Patients were classified into 2 groups, STAS-negative and STAS-positive. Overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS) were compared between the groups. Results: Of the 480 patients, 123 (25.6%) were STAS-positive. STAS positivity was associated with significantly worse survival outcomes in early-stage disease, although this association diminished in stage III. Mean DFS was 50.1 months (95% confidence interval [CI], 47.7-52.4) in the STAS-negative group and 35.1 months (95% CI, 31.2-39.1) in the STAS-positive group (p<0.001). In multivariable Cox regression analysis, STAS positivity was an independent adverse prognostic factor for both OS and DFS, with hazard ratios of 1.574 and 2.345, respectively. Analyses stratified by stage showed that the prognostic impact of STAS positivity was strongest in stage I disease, in which it was associated with worse OS, DFS, and LRFS; formal interaction testing supported this finding. Conclusion: In early-stage disease, STAS is a significant adverse prognostic factor. This finding suggests that early-stage STAS-positive tumors may warrant upstaging in future staging systems and that STAS status may help individualize surgical and follow-up strategies.