鉴于免疫疗法在晚期疾病中带来了显着的总生存 (OS) 益处，因此确定这些药物在早期非小细胞肺癌 (NSCLC) 中的有效性具有显着的意义。早期 NSCLC 的免疫治疗方法有可能模仿晚期 NSCLC 中的模式，其中生存率的提高使大多数患者显着受益。然而，它们在早期表皮生长因子受体（EGFR）突变非小细胞肺癌中的表现存在争议。在纳入 EGFR 突变状态患者的有限研究中，我们发现围手术期免疫检查点抑制剂 (ICIs) 对可切除 EGFR 阳性 NSCLC 具有意想不到的良好生存益处，这对于晚期 EGFR 突变 NSCLC 患者来说是有争议的。这可能是由于肿瘤进展过程中免疫环境发生了向免疫抑制的转变。在疾病早期阶段，抗肿瘤免疫反应可以在较少的障碍下被激活。在 EGFR 突变肿瘤的背景下，肿瘤内遗传异质性可以产生治疗敏感和耐药的亚克隆。耐药亚克隆的亚克隆性在治疗反应中至关重要，酪氨酸激酶抑制剂 (TKI) 选择性控制 EGFR 突变细胞增殖，“竞争性释放”可能解释辅助 TKI 试验中较低的病理反应。本综述深入研究了早期 EGFR 突变 NSCLC 围手术期治疗方式的新数据，探索独特的机制和预测生物标志物来指导围手术期管理策略。版权所有 © 2024。由 Elsevier B.V. 出版。

Given that immunotherapy has resulted in a significant overall survival (OS) benefit in advanced-stage disease, it is of notable interest to determine the effectiveness of these agents in early-stage non-small cell lung cancer (NSCLC). The potential exists for the immunotherapeutic approach in early-stage NSCLC to mirror the paradigm seen in advanced NSCLC, wherein survival enhancements have notably benefited the majority of patients. However, their performance in early-stage epidermal growth factor receptor (EGFR) mutant NSCLC is controversial. In the limited studies that included patients with EGFR mutation status, we found unexpected, good survival benefits of perioperative immune checkpoint inhibitors (ICIs) in resectable EGFR-positive NSCLC, which is controversial with those in advanced EGFR-mutant NSCLC. It is possible because of the shift toward immunosuppression that the immune environment undergoes during tumor progression. In the early disease stages, the anti-tumor immune response can be activated with fewer hindrances. In the context of EGFR mutant tumors, intratumor genetic heterogeneity can generate treatment-sensitive and -resistant subclones. The subclonality of the resistant subclone is pivotal in therapy response, with tyrosine kinase inhibitors (TKIs) selectively controlling EGFR-mutant cell proliferation and "competitive release" potentially explaining lower pathological responses in adjuvant TKIs trials. This review delves into emerging data on perioperative treatment modalities for early-stage EGFR mutant NSCLC, exploring unique mechanisms and predictive biomarkers to guide perioperative management strategies.Copyright © 2024. Published by Elsevier B.V.