Prognostic significance of tumor spread through air spaces and lymphovascular invasion in stage I non-small cell lung cancer: implications for adjuvant chemotherapy.

Objective: Tumor spread through air spaces (STAS) and lymphovascular invasion (LVI) have been associated with poor prognosis in stage I non-small cell lung cancer (NSCLC). This study aimed to evaluate the prognostic significance of STAS and LVI, and to investigate the impact of adjuvant chemotherapy (ACT) on survival outcomes in this patient population.

Methods: A retrospective cohort study was conducted including 392 patients with pathological stage I NSCLC who underwent surgical resection at two Kaohsiung Medical University-affiliated hospitals between 2016 and 2019. Patients were stratified into three groups: STAS-positive without LVI (STAS + LVI-), STAS-positive with LVI (STAS + LVI+), and STAS-negative (STAS-). Survival outcomes were analyzed using Kaplan-Meier methods and Cox proportional hazards models. Associations between tumor size, STAS, and LVI were evaluated using chi-square tests.

Results: STAS was identified in 101 patients (25.8%), of whom 20 (19.8%) also exhibited LVI. The prevalence of both STAS and LVI increased significantly with tumor size (p < 0.0001 for both). STAS positivity was independently associated with inferior recurrence-free survival (RFS) (hazard ratio [HR] = 2.33, p = 0.021). Overall, ACT did not significantly improve survival in STAS-positive patients (p = 0.63). However, among patients with concurrent STAS and LVI, a trend toward improved 5-year RFS was observed with ACT (54.5% vs. 44.4%; p = 0.43). In contrast, ACT was associated with significantly worse RFS in STAS-negative patients (p = 0.024).

Conclusions: STAS represents an independent adverse prognostic factor in stage I NSCLC, and conventional ACT appears to offer limited benefit in this group overall. Patients harboring both STAS and LVI may derive potential benefit from ACT, whereas STAS-negative patients may require careful evaluation to avoid overtreatment. These findings support the need for personalized, risk-adapted postoperative management strategies and warrant further prospective investigation.