Prognostic impact of spread through air spaces and its association with KRAS mutation and histopathologic factors in resected colorectal lung metastases.

Spread through air spaces (STAS) represents an independent prognostic factor for poor overall survival (OS) in patients with colorectal carcinoma who underwent pulmonary metastasectomy.

This study aims to evaluate the prognostic impact of STAS and explore its associations with histopathologic features and KRAS mutation status/subtypes.We retrospectively analyzed 61 consecutive patients with colorectal cancer (CRC) who underwent pulmonary metastasectomy at a single tertiary center (May 2016 - July 2024). Histopathologic review assessed STAS and other histopathologic features. KRAS mutations were tested using a real-time polymerase chain reaction assay detecting 19 variants (codons 12, 13, 59, 61, 117, 146). Spread through air spaces was present in 37/61 cases (60.7%).

Median OS was 1702 days (95% CI: 1495-NA) in STAS-negative and 1288 days (95% CI: 523-NA) in STAS-positive patients (log-rank p = 0.041). In univariable analysis, STAS remained an independent predictor of poorer OS in multivariable modeling (hazard ratio: 2.37; 95% CI: 1.17-4.80; p = 0.017). KRAS mutations (present in 44.3% of tested cases; common subtypes G12V and G12D) showed no significant association with STAS (p = 0.34) or with OS. Spread through air spaces is an independent poor prognostic factor in resected CRC pulmonary metastases, whereas KRAS mutation status and subtypes were not prognostic in this cohort.