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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Genetic Alterations and Risk Factors for Recurrence in Patients with Non-Small Cell Lung Cancer Who Underwent
Hwa Kyung Park1,2, Yoo Duk Choi1,3, Ju-Sik Yun1,4
1Lung Cancer Center, Chonnam National University Hwasun Hospital, Gwangju 58128, Republic of Korea.
Abstract:
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.
Insights
Epidermal growth factor receptor (EGFR) mutations are linked to recurrence in early-stage non-small cell lung cancer (NSCLC) after surgery. These mutations indicate a higher risk of distant metastasis, suggesting targeted therapy may be beneficial.
Area of Science:
- Oncology
- Genetics
- Thoracic Surgery
Background:
- Surgical resection is standard for early-stage non-small cell lung cancer (NSCLC).
- Limited research exists on genetic alterations, like epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC.
- Understanding these alterations is crucial for predicting recurrence and optimizing treatment.
Purpose of the Study:
- To investigate the prevalence of genetic alterations in early-stage NSCLC.
- To determine the association between EGFR mutations and cancer recurrence post-resection.
- To explore the impact of EGFR mutations on recurrence patterns and outcomes.
Main Methods:
- Retrospective analysis of 659 patients with NSCLC who underwent curative surgery from 2019-2021.
- Clinical and pathological data were compared between recurrence and non-recurrence groups.
- Prevalence of EGFR, ALK, and ROS1 alterations was assessed.
Main Results:
- EGFR mutations were found in 43% of patients, with L858R and exon 19 deletions being most common.
- The overall recurrence rate was 19.7%.
- EGFR mutations (HR: 2.698), advanced stage (II/III), and pathologic solid type were independent risk factors for recurrence.
- Patients with EGFR mutations experiencing recurrence had higher rates of distant metastasis (86.5% vs. 66.7%).
Conclusions:
- EGFR mutations are an independent risk factor for recurrence in early-stage NSCLC.
- EGFR mutations are associated with a higher likelihood of systemic recurrence.
- Adjuvant or neoadjuvant targeted therapy should be considered more actively for patients with EGFR mutations.
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