Critical role of spread through air spaces in prognosis of stage IA3 non-small cell lung cancer: insights from a real-world multicenter study

Background: Pathological stage IA3 non-small cell lung cancer (NSCLC) has higher recurrence rates and poorer prognosis than stages IA1 and IA2. This study systematically evaluates the prognostic impact of spread through air spaces (STAS) subtypes and related histomorphological factors, providing new insights for risk stratification in stage IA3 NSCLC. Methods: We analyzed 256 pathological stage IA3 NSCLC patients from multiple thoracic centers in Fujian Province between January 2013 and June 2019. Clinical and pathological data were collected, and Chi-squared tests identified factors associated with extensive STAS. Patients were stratified using various STAS assessment methods and other pathological features to evaluate risk factors for progression-free survival (PFS) and overall survival (OS). Results: STAS was observed in 115 patients (44.9%). Extensive STAS correlated with a family history of lung cancer, solid nodules, vascular invasion, micropapillary components, tumor budding, and STAS distance >1 mm. Multivariate analysis identified smoking history, tumor-stroma ratio, histopathological type, micropapillary components, and the STAS cell nest subtype as independent risk factors for PFS. Patients were categorized into low- (0 factors; 3.06%), medium- (1-2 factors; 9.66%), and high-risk groups (≥3 factors; 76.92%). For OS, significant risk factors included smoking history, tumor-stroma ratio, carcinoembryonic antigen (CEA) levels, and STAS cell nest subtype. Conclusions: The cell nest STAS subtype, tumor-stroma ratio, and smoking history are independent prognostic factors influencing PFS and OS in stage IA3 NSCLC. These findings underscore the need for detailed assessments of STAS subtypes and histopathological heterogeneity to refine prognostic evaluations and optimize clinical decision-making.