Spread through alveolar space predicts recurrence in epidermal growth factor receptor-mutated pathological stage IA...

We evaluated the significance of spread through alveolar space (STAS) as a predictor of cancer recurrence in epidermal growth factor receptor (EGFR)-mutated pathological stage IA lung adenocarcinomas.

Between 2011 and 2020, data from 856 patients with surgically resected pathological stage IA EGFR-mutated lung adenocarcinoma were evaluated to investigate the oncological and prognostic roles based on the presence of STAS. The cumulative incidence of recurrence (CIR) was estimated using the Fine-Gray test. Survival outcomes were assessed using Kaplan-Meier analysis and log-rank tests.

Seventy patients (8.2%) were STAS-positive, demonstrating a higher proportion of larger tumor size, lymphovascular invasion, nonlepidic predominant lesions, and the Ex19 subtype (P < .001). Postoperative cancer recurrence was significantly higher in the STAS-positive group (total: 18.6% vs. 5.7%, P < .001; locoregional: 10.0% vs. 3.8%, P = .015; distant: 15.7% vs. 3.7%, P < .001). Both CIR and recurrence-free survival (RFS) differed significantly according to the presence of STAS (5y-CIR: 14.4% vs. 4.2%, P < .001; 5y-RFS: 83.2% vs. 91.8%, P = .001). Multivariate analysis revealed that the presence of STAS (P = .028), lymphovascular invasion (P = .020), pathologic tumor size (P = .036), and absence of a lepidic component (P < .001) were independent significant factors for CIR. When combined with STAS, these factors further increased recurrence prediction (STAS and absence of a lepidic component, 5y-CIR: 26.8% vs. 4.0%, P < .001; STAS and larger tumor size, 18.1% vs. 4.3%, P < .001; STAS and lymphovascular invasion, 27.1% vs. 4.5%, P < .001).

STAS is an important risk factor for predicting postoperative cancer recurrence in EGFR-mutated pathological stage IA lung adenocarcinomas.