Could Tumor Spread Through Air Spaces Benefit From Adjuvant Chemotherapy In Stage I Lung Adenocarcinoma? A Multi-Institutional Study

Background:The benefit of adjuvant chemotherapy (ACT) remains unknown for patients with stage I lung adenocarcinoma (ADC) with spread through air spaces (STAS). This study investigated the effect of adjuvant chemotherapy in stage I ADC/STAS-positive patients.Methods:A total of 3346 patients with stage I ADC from five institutions in China were identified from 2009 to 2013, of whom 1082 were diagnosed with STAS (32.3%). By using the Kaplan-Meier method and Cox proportional hazard regression model, we explored the impact of STAS on prognosis, and determined if the use of adjuvant chemotherapy was associated with improved outcomes in patients with stage I ADC/STAS-positive. A validation cohort was also included in this study.Results:Patients with stage I ADC/STAS-positive in the primary cohort had unfavorable overall survival (OS) and disease-free survival (DFS). A multivariate Cox regression model confirmed the survival disadvantages of STAS in patients with stage I ADC [OS: hazards ratio (HR) = 1.877, 95% confidence interval (CI): 1.579-2.231; p < 0.001; DFS: HR = 1.895, 95% CI: 1.614-2.225; p < 0.001]. Lobectomy was associated with better OS and DFS than sublobar resection (SR) in both stage IA and IB ADC/STAS-positive. Similar results were observed in the validation cohort. For patients with stage IB ADC/STAS-positive, ACT was revealed as an independent factor for favorable survival (OS: HR = 0.604, 95% CI: 0.397-0.919; p = 0.018; DFS: HR = 0.565, 95% CI: 0.372-0.858; p = 0.007). However, among patients with stage IA ADC/STAS-positive, ACT was associated with improved outcomes only for those undergoing SR (OS: HR = 0.787, 95% CI: 0.359-0.949; p = 0.034; DFS: HR = 0.703, 95% CI: 0.330-0.904; p = 0.029).Conclusion:The presence of STAS was correlated with poor prognosis in patients with stage I ADC. Our study suggested that ACT might be considered for patients with stage IB ADC/STAS-positive and those with stage IA ADC/STAS-positive who underwent SR.