Tumor Spread through Air Spaces Affects the Recurrence and Overall Survival in Patients with Lung Adenocarcinoma >2 to 3 cm.

Objectives: Tumor spread through air spaces (STAS) is a novel invasive pattern in lung adenocarcinoma (ADC). The effects of the combination of STAS and tumor size on survival have not been well studied.

Methods: A total of 383 patients with ADC 3 cm or smaller (stage IA) and 161 patients with stage IB ADC were identified from 2009 to 2010. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients as stratified by STAS and tumor size. A validation cohort was included in this study.

Results: STAS was observed in 116 ADCs 3 cm or smaller (30.3%). In cases involving ADCs 3 cm or smaller, patients with STAS had worse RFS (p = 0.006) and OS rates (p < 0.001) than those without STAS. Furthermore, comparable RFS (p = 0.091) and OS (p = 0.443) rates were observed in patients with ADCs 3 cm or smaller with STAS present and those with stage IB ADC. Multivariate analysis revealed STAS to be an independent prognostic factor in ADCs 3 cm or smaller (RFS, p = 0.043; OS, p = 0.009). Among patients with ADCs larger than 2 to 3 cm, STAS still stratified the prognosis. Moreover, the unfavorable prognosis of patients with ADCs larger than 2 to 3 cm with STAS present was similar to that of patients with stage IB ADC. Among patients with ADCs 2 cm or smaller, STAS failed to stratify the prognosis significantly. Similar results were obtained in the validation cohort.

Conclusions: These results provide preliminary evidence that STAS could be considered as a factor in a staging system to predict prognosis more precisely, especially in ADCs larger than 2 to 3 cm.