Background: Tumor spread through air spaces (STAS) has been proposed as a histopathological marker of aggressive tumor biology in adenocarcinoma of the lung (ADCL). Its independent prognostic significance and clinical implications regarding surgical strategy remain controversial. This study evaluated clinicopathological correlates and the prognostic impact of STAS in a homogeneous cohort of resected ADCL. Methods: We retrospectively analyzed 100 patients with primary ADCL resected between 2009 and 2018. STAS was classified as absent, low (1–4 clusters), or high (≥5) by an experienced pathologist. Associations between STAS and clinical, surgical, and pathological variables were tested with univariate analyses and multivariable logistic regression. Overall survival (OS) was evaluated using Kaplan–Meier and Cox regression. Results: STAS was present in 46% of tumors and was significantly associated with a higher pathological N category (pN0-pN3; p = 0.005), more advanced UICC stage (p = 0.049), lymphovascular invasion (LVI; p = 0.008), and perineural invasion (PnI; p = 0.012). In univariate survival analysis, patients with STAS had shorter OS than patients without STAS (p = 0.047). After limited resection, OS did not differ (p = 0.864), whereas after radical anatomical resection, patients with STAS showed reduced OS (p = 0.034). In multivariable Cox regression analysis, STAS did not retain independent prognostic significance. Conclusions: STAS is frequent in resected ADCL and correlates with adverse pathological features and reduced OS in univariate models. In multivariate analysis, STAS did not emerge as an independent prognostic factor. These findings support the interpretation of STAS as a marker of aggressive tumor biology rather than an independent determinant of prognosis or surgical decision-making.

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