DOI: 10.1177/17588359261472331 ISSN: 1758-8359

Real-world analysis of perioperative strategies for driver gene-positive resectable non-small cell lung cancer

Xingpeng Wang, Kaiyue Wang, Baiyang Huang, Jiarui Zhao, Min Li, Jingyu Zhu, Jing Xu, Chaoran Zhu, Zihan Liu, Xiaohan Wang, Menglin Bai, Xue Meng, Jinming Yu, Chenggang Wang, Guoxin Cai
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Background:

The optimal perioperative treatment strategy for driver gene-positive non-small cell lung cancer (NSCLC) remains unclear.

Objectives:

To compare the prognostic outcomes of different perioperative strategies for patients with resectable driver gene-positive NSCLC.

Design:

Multicenter retrospective observational cohort study.

Methods:

We retrospectively evaluated patients with resectable AJCC 8th clinical stage II–IIIB driver gene-positive NSCLC who underwent neoadjuvant therapy or upfront surgery with adjuvant targeted therapy (US + ATT) at two institutions between 2021 and 2023. Treatment was classified as neoadjuvant targeted therapy (NTT), neoadjuvant chemoimmunotherapy (NCIT), neoadjuvant chemotherapy (NCT), or US + ATT. The primary endpoints were event-free survival (EFS) and overall survival (OS). Survival was estimated using the Kaplan–Meier method and compared with the log-rank test.

Results:

In total, 290 patients were included; the median follow-up was 31.2 months. Compared with NCT, NCIT was associated with longer EFS ( p  = 0.048) and a nonsignificant favorable OS trend ( p  = 0.135). NCIT also achieved higher pathological complete response (29.8% vs 4.9%) and major pathological response (MPR; 52.1% vs 16.4%) rates and comparable R0 resection rates (96.8% vs 93.4%). Survival outcomes were comparable between NCIT and NCT for the epidermal growth factor receptor (EGFR)-mutant subgroup, but NTT showed better EFS ( p  = 0.093), without an OS advantage. NTT + chemotherapy achieved superior EFS ( p  = 0.038) and favorable OS trend ( p  = 0.146) versus NCT alone and longer EFS versus NTT alone ( p  = 0.062). Postoperative ATT did not confer survival advantage over no ATT in the NTT + chemotherapy subgroup. MPR to NCIT correlated with improved EFS ( p  = 0.001) and OS ( p  = 0.009), while MPR to NTT correlated with improved EFS ( p  = 0.049).

Conclusion:

NCIT was associated with improved EFS in resectable driver gene-positive NSCLC, although a corresponding OS improvement was not observed. NTT + chemotherapy may offer better prognosis than NCT alone in EGFR‑mutant NSCLC.

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