Role of genetic alterations on outcomes for pulmonary resection in oligometastatic non-small cell lung cancer

Background: Local consolidative therapy (LCT) can improve survival outcomes for select patients with oligometastatic non-small cell lung cancer (NSCLC). While genetic alterations affect prognosis in NSCLC, their impact in oligometastatic patients undergoing lung resection as part of comprehensive LCT (cLCT) remains unclear. We sought to evaluate outcomes based on genetic alteration status in this population. Methods: We identified oligometastatic (≤3 synchronous sites) NSCLC patients from 2 centers who underwent cLCT to all disease sites from 1996-2023. Patients were stratified by genetic alteration status. Survival outcomes were evaluated with Kaplan-Meier and multivariable Cox regression models. Results: We identified 87 patients with the following genetic alterations: (1.2%, n=1), (13.8%, n=12), (12.6%, n=11), (5.7%, n=5), multiple alterations (6.9%, n=6), and no alterations (59.8%, n=52). The median overall survival (OS) was 88.9 months for patients with alteration [95% confidence interval (CI): 48.46-121.28], and 30.8 months for those with other alteration statuses (95% CI: 12.25-49.36, P=0.20). The median progression-free survival (PFS) for patients was 43.1 months (95% CI: 22.14-64.07) and 19.1 months for the other alteration status group (95% CI: 16.46-31.74, P=0.58). Multivariate Cox regression analysis failed to demonstrate any alteration status as an independent predictor of OS or PFS. Conclusions: mutation demonstrated a promising trend toward better outcomes among oligometastatic NSCLC patients undergoing lung resection. Whether these differences reflect dissimilarities in disease biology, targeted agent availability and/or efficacy, patient-related factors, or other elements remains unknown. Further efforts to understand the interplay among these variables are needed to advance multimodal treatment for oligometastatic NSCLC.