Spread through air spaces may predict early progression after salvage surgery for EGFR-mutant advanced lung adenocarcinoma treated with targeted therapy.

Objective: Salvage resection for residual lung cancer harboring epidermal growth factor receptor (EGFR) mutations following EGFR-tyrosine kinase inhibitor (TKI) treatment is gaining traction for its survival benefits. However, the impact of pathological factors on survival remains unclear.

Methods: Between 2013 and 2023, we retrospectively reviewed 34 patients with advanced lung adenocarcinoma who received EGFR-TKI therapy. After a median TKI treatment duration of 9.1 months, all patients demonstrated either partial response (n = 27) or stable disease (n = 7) before salvage surgery. Demographic, pathological outcomes, progression-free survival (PFS), and overall survival (OS) were analyzed.

Results: Among the 34 patients, six (17.6%) achieved a pathological complete response (pCR) and nine (26.5%) had a major pathological response (MPR). Additionally, 11 patients (32.4%) exhibited spread through air spaces (STAS), and lymphovascular invasion (LVI) was observed in nine patients (26.5%). The 3-year PFS and OS rates were 55.8% and 60.5%, respectively. No significant differences in PFS or OS were observed regarding mutation type, TKI generation, pCR, MPR, or LVI. However, Kaplan-Meier analysis revealed that STAS was associated with shorter PFS compared to non-STAS cases (p = 0.01). In multivariate analysis, STAS was identified as an independent prognostic factor for PFS (hazard ratio: 2.83, 95% CI: 1.35-28.54, p = 0.02). No significant prognosticators were found for OS in univariate or multivariate analyses.

Conclusion: While salvage surgery following TKI treatment is feasible and prolongs survival by removing residual primary tumor with potential TKI resistance, STAS may contribute to a higher risk of early progression. This finding warrants further investigation and tailored treatment strategies.