# Spread Through Air Spaces in Colorectal Lung Metastases Signals Local Recurrenece and Reflects Morphologic Aggressiveness of the Primary Tumor

## TL;DR

This study shows that spread through air spaces in lung metastases from colorectal cancer is linked to worse survival and higher recurrence rates, and is connected to aggressive features in the primary tumor.

## Contribution

The study identifies STAS as a prognostic marker in CRC pulmonary metastases and links it to tumor budding in the primary tumor.

## Key findings

- STAS was present in 33.1% of patients and was associated with significantly shorter 5-year recurrence-free survival.
- High tumor budding grade in the primary tumor correlated with a higher STAS-positive rate in metastases.
- Quantitative STAS metrics correlated with intrathoracic recurrence and enhanced prognostic precision.

## Abstract

Tumor spread through air spaces (STAS) is a histological feature associated with poor prognosis in primary lung cancer, but its relevance in colorectal cancer (CRC) pulmonary metastases remains unclear. This study evaluated the prognostic impact of STAS in CRC pulmonary metastases and its association with histologic features of the primary tumor. A total of 124 patients who underwent pulmonary resection for CRC metastases were retrospectively analyzed. Quantitative STAS parameters, including density and maximum spread distance, were assessed histologically. Survival outcomes were analyzed using Kaplan–Meier and Cox proportional hazards models, and logistic regression identified predictors of STAS. STAS was present in 33.1% of patients and was associated with significantly shorter 5‐year recurrence‐free survival (18.7% vs. 53.0%, p = 0.002) and overall survival (p = 0.001). Quantitative STAS metrics correlated with intrathoracic recurrence. Patients with high tumor budding grade had a significantly higher STAS‐positive rate than those with none or low grade (60% vs. 31.2%, p = 0.036). Tumor budding independently predicted STAS (odds ratio: 3.19, 95% confidence interval: 1.05–9.69, p = 0.040). STAS independently predicted poor prognosis, particularly intrathoracic recurrence. Quantitative STAS assessment enhanced prognostic precision, and tumor budding grade may serve as a preoperative marker for predicting STAS.

STAS in colorectal cancer (CRC) pulmonary metastases was significantly associated with worse overall survival and higher recurrence rates, particularly intrathoracic recurrence. Furthermore, this study showed that high tumor budding grade in the primary CRC was significantly correlated with the presence of STAS in the pulmonary metastases.