Tumor Spread Through Air Spaces Is a Predictor of Occult Lymph Node Metastasis in Clinical Stage IA Lung Adenocarcinoma

In patients with stage IA lung adenocarcinoma (ADC), sublobar resection and tumor spread through air spaces (STAS) are associated with high rates of locoregional recurrence, half of which occur within the regional lymph nodes (LNs). Our objectives were to investigate the association between occult LN metastasis (ONM) and STAS and to assess their prognostic value in patients with clinical stage IA lung ADC. The association between STAS and ONM was analyzed in patients who underwent lobectomy and LN dissection for clinical stage IA lung ADC (n = 809). Multivariable logistic regression analysis was carried out to identify predictors of ONM. Site-specific recurrence by surgical procedure was investigated in patients with pathologic node-negative disease (n = 1055) using a competing risk approach. ONM was identified in 129 patients (16%)—one-third of ONMs were located only in intrapulmonary nodes. STAS was more common in patients with ONM than in those without ONM (67% versus 39%; p < 0.001) and in patients with multiple ONMs than in those with a single ONM (86%–89% versus 60%–67%). STAS was a significant predictor of ONM (p = 0.004) on multivariable analysis, independent of tumor size, maximum standardized uptake value, and lymphovascular invasion. In patients with STAS-positive ADC (high ONM risk), the risk of recurrence in the treated lobe and regional LNs increased as the extent of resection decreased (recurrence risk: lobectomy < segmentectomy < wedge resection). In patients with STAS-negative ADC, the risk of locoregional recurrence did not differ by procedure type. Presence of STAS predicts ONM in patients with clinical stage IA lung ADC and can help stratify risk of recurrence by extent and type of resection.