Clinical implication of tumor spread through air spaces in stage IA lung adenocarcinoma: prognostic impact and association with the International Association for the Study of Lung Cancer (IASLC) grade.

Tumor spread through air spaces (STAS) and a new histological grading system proposed by the International Association for the Study of Lung Cancer (IASLC) have been studied for risk stratification and prognostic assessment in patients with lung adenocarcinoma (LUAD). This study aimed to clarify the association between STAS and IASLC grade and to assess the prognostic significance of STAS in patients with pathological stage (p-stage) IA LUAD as stratified by the IASLC grading system. This study included 789 patients with resected p-stage IA LUAD treated between 2018 and 2020. Logistic regression analysis was performed to assess the association between STAS and clinicopathological characteristics. A Cox proportion hazards model was used to assess the risk factors related to recurrence-free survival (RFS) and overall survival (OS). STAS was present in 242 patients (30.7%). The independent factors associated with the presence of STAS were nodule type [odds ratio (OR) =3.89; 95% confidence interval (CI): 2.69-5.62; P<0.001], IASLC grade (grade 2: OR =12.41, 95% CI: 3.83-40.23; P<0.001; grade 3: OR =27.35, 95% CI: 8.24-90.82, P<0.001), and lymphovascular invasion (OR =3.30; 95% CI: 1.72-6.35; P<0.001). For all patients (N=789), STAS and IASLC grade were independent prognostic factors for RFS and OS. For grade 2 LUAD, p-stage T1c was an independent prognostic factor for RFS [hazard ratio (HR) =4.30, 95% CI: 1.07-19.08; P=0.045] and OS (HR =4.95, 95% CI: 1.14-21.54; P=0.03). STAS was significantly correlated with unfavorable RFS (HR =2.81; 95% CI: 1.32-5.97; P=0.007) and OS (HR =2.04, 95% CI: 1.40-7.75; P=0.006) in patients with grade 3 tumors. The presence of STAS was not only directly correlated with the IASLC grading system, but was also a prognostic factor for worse RFS and OS in grade 3 LUAD patients.