# Impact of STAS on Lung Resections for Adenocarcinoma: A Retrospective Analysis

## TL;DR

This study shows that spread through air spaces (STAS) in lung adenocarcinoma is linked to worse survival, but it does not independently predict outcomes after accounting for other factors.

## Contribution

The study clarifies that STAS is a marker of aggressive tumor biology but not an independent prognostic factor for survival in lung adenocarcinoma.

## Key findings

- STAS was present in 46% of lung adenocarcinoma tumors and was associated with advanced pathological features.
- Patients with STAS had reduced overall survival in univariate analysis but not in multivariable models.
- STAS did not independently influence survival after adjusting for other clinical and pathological variables.

## Abstract

Lung cancer is often treated by surgically removing the tumor. However, even patients with early-stage disease can experience recurrence after surgery. One histological feature that has gained increasing attention is spread through air spaces (STAS), a pattern in which tumor cells are found beyond the main tumor within the surrounding lung tissue. In this study, we analyzed patients who underwent surgical resection for non-small cell lung cancer and examined the association between STAS and long-term survival. We found that STAS was associated with worse survival outcomes, including in patients with early-stage tumors. These findings suggest that identifying STAS after surgery may help to better estimate individual risk and support discussions about the most appropriate surgical approach. Importantly, STAS cannot yet be reliably detected before or during surgery, and its role in guiding additional treatment remains unclear. Further prospective studies are needed to clarify how STAS should be integrated into clinical decision-making.

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.