Tumor spread through air spaces (STAS): prognostic significance of grading in non-small cell lung cancer

Tumor spread through air spaces (STAS) is an invasive pattern of lung cancer that was recently described. In this study, we investigated the association between the extent of STAS and clinicopathological characteristics and patient outcomes in resected non-small cell lung cancers (NSCLCs). STAS has been prospectively described from 2008 and graded its extent with a two-tiered system (STAS I: <2500 μm [one field of ×10 objective lens] from the edge of tumor and STAS II: ≥2500 μm from the edge of tumor) from 2011 in Seoul National University Bundang Hospital. We retrospectively analyzed the correlations between the extent of STAS and clinicopathologic characteristics and prognostic significance in 1869 resected NSCLCs. STAS was observed in 765 cases (40.9%) with 456 STAS I (24.4%) and 309 STAS II (16.5%). STAS was more frequently found in patients with adenocarcinoma (ADC) (than squamous cell carcinoma), pleural invasion, lymphovascular invasion, and/or higher pathologic stage. In ADC, there were significant differences in recurrence free survival (RFS), overall survival (OS), and lung cancer specific survival (LCSS) according to the extent of STAS. In stage IA non-mucinous ADC, multivariate analysis revealed that STAS II was significantly associated with shorter RFS and LCSS (p < 0.001 and p = 0.006, respectively). In addition, STAS II was an independent poor prognostic factor for recurrence in both limited and radical resection groups (p = 0.001 and p = 0.023, respectively). In conclusion, presence of STAS II was an independent poor prognostic factor in stage IA non-mucinous ADC regardless of the extent of resection.