Exploration on perioperative treatment strategies of driver gene–positive resectable non-small cell lung cancer.

e20071 Background: In recent years, multiple neoadjuvant treatment options have emerged for driver gene–positive, resectable Non-Small Cell Lung Cancer (NSCLC). However, the long-term prognosis of different treatment modalities and the specific populations that benefit most remain unclear. This study retrospectively compares multiple neoadjuvant and adjuvant strategies for driver gene–positive NSCLC, aiming to provide a reference for clinical decision-making. Methods: The medical records of patients with driver-gene-positive NSCLC who received neoadjuvant therapy and upfront surgery (US) with adjuvant targeted therapy (ATT) at Shandong Cancer Hospital and Institute from January 2021 to December 2023 were retrospectively reviewed. Patients were grouped into neoadjuvant targeted therapy (NTT), neoadjuvant chemoimmunotherapy (NCIT), neoadjuvant chemotherapy (NCT), and US+ATT. event-free survival (EFS) and overall survival (OS) were compared across the groups, and the subgroup analysis including pathological response and PD-L1 expression levels. Kaplan-Meier curves and log-rank tests were used to assess prognostic differences. Results: A total of 243 patients were included, and the median follow-up times for the NTT (n=39), NCIT (n=67), NCT (n=45), and US+ATT (n=92) groups were 23.05, 24.4, 24.9, and 23.7 months, respectively. NCIT significantly prolonged EFS compared with NCT (p=0.004). Focusing on patients with EGFR mutations, NTT combined with ATT showed no significant EFS or OS difference from NTT alone (p=0.124), but demonstrated a trend toward better EFS compared with US+ATT (after 1:1 propensity-score matching) (p=0.062). Compared with NCIT, NTT±ATT show no survival benefits; however, NCIT significantly improved EFS (p=0.001) over NCT without ATT with no OS benefit (p=0.234), and no major prognosis differences were observed between NCIT and NCT+ATT. Furthermore, among patients receiving NCIT, those who achieved a major pathological response (MPR) demonstrated significantly improved EFS (p=0.001) and OS (p=0.018). In the EGFR-mutant subgroup treated with NCIT, MPR status showed no significant impact on either EFS (p=0.128) or OS (p=0.221). Similarly, MPR status did not significantly influence survival outcomes in patients receiving NTT. Additionally, PD-L1 expression was not associated with survival outcomes. Conclusions: In patients with resectable, driver gene–positive NSCLC, NTT+ATT, NCT+ATT, and NCIT all demonstrate feasibility. Pathological response following NCIT was correlated with prognosis, suggesting it may serve as an important indicator for prognostic prediction. In the future, large-scale studies are warranted to further elucidate the long-term efficacy of different treatment strategies and to identify the patient populations most likely to benefit.