Tumor spread through air spaces (
STAS) is a newly recognized pattern of invasion in
lung adenocarcinoma. However, clinical significance of
STAS has not yet been characterized in lung
squamous cell carcinoma. In this study, we investigated whether
STAS could determine clinical outcome in Japanese patients with lung
squamous cell carcinoma. We reviewed
tumor slides from surgically resected lung
squamous cell carcinomas (n=216).
STAS was defined as
tumor cells within air spaces in the lung parenchyma beyond the edge of the main
tumor.
Tumors were evaluated for histologic subtypes,
tumor budding, and nuclear diameter. Recurrence-free survival (RFS) was analyzed using the log-rank test and the Cox proportional hazards model.
Tumor STAS was observed in 87 patients (40%), increasing incidence with
lymph node metastasis (P=0.037), higher pathologic stage (P=0.026), and lymphatic invasion (P=0.033). All cases with
STAS showed a solid nest pattern. The 5-year RFS for patients with
STAS was significantly lower than it was for patients without
STAS in all patients (P=0.001) and in stage I patients (n=134; P=0.041). On multivariate analysis,
STAS was an independent prognostic factor of a worse RFS (hazard ratio=1.61; P=0.023). Patients with
STAS had a significantly increased risk of developing locoregional and distant recurrences (P=0.012 and 0.001, respectively). We found that
tumor STAS was an independent predictor of RFS in patients with resected lung
squamous cell carcinoma, and it was associated with aggressive
tumor behavior.