Prognostic Implications of Tumor Spread Through Air Spaces in Patients with Resected Lung Adenocarcinoma

Background: Spread through air spaces (STAS) consists of micropapillary clusters, solid nests, and/or single neoplastic cells into the air spaces of the lung parenchyma beyond the edge of the primary tumor. To date, its prognostic role in patients with lung adenocarcinoma is crucial, resulting in an independent negative factor for both overall survival (OS) and disease-free survival (DFS). The study aims to assess the prognostic impact of STAS in patients with lung adenocarcinoma undergoing curative resection. Methods: A retrospective, observational single-center study enrolling consecutive patients who underwent lung resections for adenocarcinoma from January 2018 to December 2023 was performed. OS and DFS were analyzed. Univariable and multivariable Cox proportional hazard models, along with the inverse probability of treatment weight-adjusted Kaplan-Meier curves, were used to evaluate the prognostic impact of STAS. A logistic regression model was used to estimate the odds ratios and 95%-confidence intervals for clinical variables associated with the STAS status. Results: In total, 329 patients were enrolled, and two different groups were defined (STAS-present: 30; STAS-absent: 299). No statistically significant differences were observed in OS and DFS when comparing patients according to their STAS status. Conversely, STAS-present patients were more frequently associated with pN2-nodal involvement (22.7% vs. 77.3%, p = 0.022), stage IIIA disease (p = 0.003), and the presence of an adenocarcinoma-predominant micropapillary-pattern (p < 0.001). Female patients were associated with better outcomes than male patients in survival analysis, while stage IIIA disease and micropapillary-pattern emerged as statistically significant after the logistic regression. Conclusions: Our study provides relevant information on the relationship between STAS and clinicopathological characteristics, demonstrating its potential aggressive histological feature, due to the significant correlation with stage IIIA disease, and the adenocarcinoma micropapillary pattern. Therefore, STAS may identify a subgroup of patients in whom the prognostic implications should be further investigated.