Non-small Cell Lung Cancer with and without Spread Through Air Spaces: Which Therapies are Associated with Improved Survival?

Abstract

Spread through air spaces (STAS), defined as tumor cells within alveolar spaces beyond the main tumor, is associated with adverse outcomes in non-small cell lung cancer (NSCLC), but optimal management remains unclear. We evaluated whether extent of resection or adjuvant therapy was associated with improved survival in STAS-positive NSCLC. We conducted a retrospective cohort study of Veterans who underwent curative-intent resection for clinical stage I NSCLC within the Veterans Affairs (1/2018-3/2024). Overall survival (OS) and disease-free survival (DFS) were evaluated. Prespecified propensity score-matched (PSM) analyses assessed outcomes by STAS status, extent of resection among STAS-positive patients with tumors ≤2cm, and receipt of adjuvant systemic therapy among STAS-positive patients eligible for adjuvant treatment RESULTS: Of the 2,234 patients included, 37.7% were STAS-positive. In PSM analyses (683 pairs), STAS-positive patients had worse OS (p = 0.049; 5-year OS 64.9% vs. 71.3%) and DFS (p = 0.025; 5-year DFS 61.2% vs. 68.4%) compared with STAS-negative patients. Among STAS-positive patients with tumors ≤2cm (109 pairs), sublobar resection was associated with worse OS and DFS compared with lobar resection. In an exploratory analysis of STAS-positive patients eligible for adjuvant therapy (70 pairs), receipt of adjuvant systemic therapy was not associated with improved OS or DFS. STAS is associated with inferior survival in resected early-stage NSCLC. The adverse impact of STAS was mitigated by lobar resection, but not by adjuvant therapy. These findings support further investigation of strategies to identify STAS preoperatively or intraoperatively to better inform selection of resection extent.