Semiquantitative Assessment of Tumor Spread through Air Spaces (STAS) in Early-Stage Lung Adenocarcinomas

Introduction: Tumor spread through air spaces (STAS) has recently been reported as a form of tumor invasion having an unfavorable prognosis, but the significance of a small amount of STAS is not known. The aim of this study was to perform a semiquantitative assessment of STAS.

Methods: Small (≤2 cm) stage I lung adenocarcinomas surgically resected at our institution between 2003 and 2009 were assessed semiquantitatively in the most prominent area as no STAS, low STAS (1-4 single cells or clusters of STAS), or high STAS (≥5 single cells or clusters of STAS) by using a 20× objective and a 10× ocular lens. A statistical analysis was performed to determine the impact of clinicopathologic parameters on STAS and to clarify the relationship between STAS and patient survival.

Results: STAS was assessed as no STAS in 109 of 208 cases (52.4%), as low STAS in 38 cases (18.3%), and as high STAS in 61 cases (29.3%). There were statistically significant associations between higher STAS and solid predominant invasive adenocarcinoma (p < 0.001), pleural invasion (p < 0.001), lymphatic invasion (p < 0.001), vascular invasion (p < 0.001), and tumor size of 10 mm or more (p = 0.037). There was a significant association between increasing STAS and shorter recurrence-free survival (RFS) in univariate analysis (no STAS, 154.2 months; low STAS, 147.6 months; and high STAS, 115.6 months). In a multivariate Cox proportional hazards model, only STAS (p = 0.015) remained a significant predictor of RFS.

Conclusions: We found that one-third of resected small adenocarcinomas had high STAS. Higher STAS was predictive of worse RFS.