A definitive surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC). Research on genetic alterations, including epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC remains insufficient. We investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutations and recurrence after a complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resections at a single regional cancer center in Korea were recruited. We retrospectively compared the clinical and pathological data between the recurrence and non-recurrence groups. Among the 659 enrolled cases, the median age was 65.86 years old and the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutations was 43% (194/451). Among them, L858R point mutations and exon 19 deletions were 52.3% and 42%, respectively. Anaplastic lymphoma kinase (ALK) rearrangement was found in 5.7% of patients (26/453) and ROS proto-oncogene 1 (ROS1) fusion was found in 1.6% (7/441). The recurrence rate for the entire population was 19.7%. In the multivariate analysis, the presence of EGFR mutations (hazard ratio (HR): 2.698; 95% CI: 1.458–4.993;p= 0.002), stage II (HR: 2.614; 95% CI: 1.29–5.295;p= 0.008) or III disease (HR: 9.537; 95% CI: 4.825–18.852;p< 0.001) (vs. stage I disease), and the presence of a pathologic solid type (HR: 2.598; 95% CI: 1.405–4.803;p= 0.002) were associated with recurrence. Among the recurrence group, 86.5% of the patients with EGFR mutations experienced distant metastases compared with only 66.7% of the wild type (p= 0.016), with no significant difference in median disease-free survival (52.21 months vs. not reached;p= 0.983). In conclusion, adjuvant or neoadjuvant targeted therapy could be considered more actively because EGFR mutations were identified as an independent risk factor for recurrence and were associated with systemic recurrence. Further studies on perioperative therapy for other genetic alterations are necessary.
根治性手术切除是早期非小细胞肺癌（NSCLC）的首选治疗方法。目前针对早期NSCLC基因改变（包括表皮生长因子受体（EGFR）突变）的研究仍不充分。本研究旨在探讨早期NSCLC基因改变的流行情况，以及EGFR突变与完全切除术后复发之间的关联。研究纳入了2019年1月至2021年12月期间在韩国某区域性癌症中心接受根治性手术切除的659例NSCLC患者。我们回顾性比较了复发组与非复发组的临床及病理学数据。在659例入组病例中，中位年龄为65.86岁，最常见的组织学类型为腺癌（74.5%），其次为鳞状细胞癌（21.7%）。EGFR突变率为43%（194/451），其中L858R点突变和19号外显子缺失分别占52.3%和42%。间变性淋巴瘤激酶（ALK）重排发生率为5.7%（26/453），ROS原癌基因1（ROS1）融合发生率为1.6%（7/441）。总体复发率为19.7%。多变量分析显示，EGFR突变（风险比（HR）：2.698；95%置信区间（CI）：1.458–4.993；p=0.002）、II期（HR：2.614；95% CI：1.29–5.295；p=0.008）或III期疾病（HR：9.537；95% CI：4.825–18.852；p<0.001）（与I期疾病相比），以及存在病理实体型（HR：2.598；95% CI：1.405–4.803；p=0.002）与复发相关。在复发组中，EGFR突变患者发生远处转移的比例为86.5%，而野生型患者仅为66.7%（p=0.016），两组中位无病生存期无显著差异（52.21个月 vs. 未达到；p=0.983）。综上所述，由于EGFR突变被确定为复发的独立危险因素且与全身性复发相关，可考虑更积极地采用辅助或新辅助靶向治疗。针对其他基因改变的围手术期治疗仍需进一步研究。
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