Efficacy of Adjuvant Chemotherapy in Stage IA Lung Adenocarcinoma with Tumor Spread Through Air Spaces: A Multi-Center Real-World Study.

Background: The role of adjuvant chemotherapy (ACT) for stage IA lung adenocarcinoma (LUAD) with tumor spread through air spaces (STAS) remains inconclusive. This study aimed to evaluate the efficacy of ACT in stage IA STAS⁺ LUAD patients and to identify subpopulations that might derive clinically significant benefits from ACT.

Methods: Consecutive pathological stage IA (T1a-cN0M0) STAS⁺ LUAD patients who underwent surgery, with or without ACT, between 2012 and 2020 across 6 high-volume centers were retrospectively reviewed. Propensity-score matching (PSM) was performed to minimize selection bias. The primary endpoint was overall survival. Clinically significant survival benefits were predefined as a hazard ratio (HR) < 0.70, or HR < 0.75 with an absolute 5-year survival improvement > 5%.

Results: Among 3026 eligible cases, 2619 patients (873 ACT and 1746 no ACT) were matched by PSM, achieving well-balanced clinicopathological characteristics. Over a median follow-up of 6.88 years, ACT did not confer clinically significant improvements in overall survival (hazard ratio = 0.795, P = .010) in the overall cohort. Cox regression analyses identified age, histology subtype, lymphovascular invasion (LVI), resection extent, and pathological stage as independent prognostic factors. Interaction analyses further revealed that histology subtype, LVI, and resection extent, but not age or pathological stage, modified ACT's effect on survival. Exploratory stratified analyses demonstrated that ACT may be associated with clinically significant survival benefits among patients undergoing sub-lobectomy, those with LVI⁺ tumors, and those with solid/micropapillary-predominant histology.

Conclusions: Although ACT demonstrated limited clinical survival benefit for the overall stage IA STAS⁺ LUAD population, it may be necessary for selected high-risk subgroups, specifically those undergoing sub-lobectomy, with LVI⁺ tumors, or with solid/micropapillary-predominant histology.