Spread Through Air Spaces (STAS) Is an Independent Prognostic Factor in Resected Lung Squamous Cell Carcinoma

SIMPLE SUMMARY: There is no histoprognostic grading for lung squamous cell carcinoma (LUSC). The objective of this work was to identify prognostic factors from a retrospective cohort study of pulmonary squamous cell carcinomas. In this single-center retrospective study of 241 patients, all patients with LUSC who underwent surgical excision over a 12-year period were included. The presence of Spread Through Air Spaces (STAS) was correlated with tumor location (p < 0.001), pathological stage (p = 0.039), tumor differentiation (p = 0.029), percentage of necrosis (p = 0.004), presence of vascular and/or lymphatic emboli, budding (p = 0.02), single cell invasion (p = 0.002) and tumor nest size (p = 0.005). On multivariate analysis, only STAS > 3 alveoli (HR, 2.74; 95% CI, 1.18–6.33) was related to overall survival. In conclusion, extensive STAS is an independent factor of poor prognosis in LUSC. STAS is correlated with the presence of other poor prognostic factors such as emboli and pleural invasion and would reflect greater tumor aggressiveness. ABSTRACT: Objective: There is no histoprognostic grading for lung squamous cell carcinoma (LUSC). Different prognostic factors have been described in the recent literature and are not always studied in parallel. Our objective was to search for morphological histopathological prognostic factors in LUSC. Materials and Methods: In this single-center retrospective study of 241 patients, all patients with LUSC who underwent surgical excision over a 12-year period were included. The primary endpoint was 5-year overall survival. Results: STAS was present in 86 (35.7%) patients. The presence of Spread Through Air Spaces (STAS) was correlated with tumor location (p < 0.001), pathological stage (p = 0.039), tumor differentiation (p = 0.029), percentage of necrosis (p = 0.004), presence of vascular and/or lymphatic emboli, budding (p = 0.02), single cell invasion (p = 0.002) and tumor nest size (p = 0.005). The percentage of tumor necrosis was correlated with the overall survival at 5 years: 44.6% of patients were alive when the percentage of necrosis was ≥50%, whereas 68.5% were alive at 5 years when the necrosis was <30% (p < 0.001). When vasculolymphatic emboli were present, the percentage of survival at 5 years was 42.5% compared to 65.5% when they were absent (p = 0.002). The presence of isolated cell invasion was correlated with a lower 5-year survival rate: 51.1% in the case of presence, versus 66% in the case of absence (p = 0.02). In univariate analysis, performance status, pathological stage pT or pN, pleural invasion, histopathological subtype, percentage of tumor necrosis, vasculolymphatic invasion, single-cell invasion, budding and tumor nest size correlated with the percentage of survival at 5 years. On multivariate analysis, only STAS > 3 alveoli (HR, 2.74; 95% CI, 1.18–6.33) was related to overall survival. Conclusion: In conclusion, extensive STAS is an independent factor of poor prognosis in LUSC. STAS is correlated with the presence of other poor prognostic factors such as emboli and pleural invasion and would reflect greater tumor aggressiveness.