Prognostic value of preoperative circulating tumor DNA in non-small cell lung cancer: a systematic review and meta-analysis

Background: Several recent studies have reported the increasing application of preoperative circulating tumor DNA (ctDNA) as a biomarker of tumor burden for guiding potential postoperative treatment strategies.

Methods: A meta-analysis of prospective/retrospective cohort studies was conducted to compare the prognosis of preoperatively genetically positive and genetically negative NSCLC patients. The endpoints used in the included studies were overall survival (OS) and recurrence-free survival (RFS). The objective of the meta-analysis was to comprehensively explore the prognostic value of preoperative ctDNA for patients with non-small-cell lung cancer (NSCLC) and its significance in guiding postoperative adjuvant therapy (AT) in patients with NSCLC.

Results: The preliminary analysis identified 1565 studies, among which only 11 studies fulfilled the eligibility criteria and were finally included in the present systematic review and meta-analysis. The statistical results revealed that the expression of preoperative ctDNA was associated with worse RFS (HR = 3.00; 95% CI 2.26-3.98; I² = 0%) and OS (HR = 2.77; 95% CI 1.67-4.58; I² = 0%), particularly in lung adenocarcinoma (LUAD) patients (RFS: HR = 3.46; 95% CI 2.37-5.05; I² = 0%; OS: HR = 3.52; 95% CI 1.91-6.49; I² = 0%) and patients with I-II stage of NSCLC (RFS: HR = 2.84; 95% CI 1.88-4.29; I² = 0%; OS: HR = 2.60; 95% CI 1.43-4.74; I² = 0%). Moreover, compared to patients with negative preoperative ctDNA, patients with positive preoperative ctDNA presented greater survival benefits (HR = 0.39; 95% CI 0.22-0.67; I² = 2%) from postoperative AT.

Conclusion: The evaluation of the prognostic value of preoperative ctDNA revealed that preoperative ctDNA might be used as a prognostic biomarker for patients with LUAD or those with stage I-II NSCLC. In addition, postoperative AT is recommended for NSCLC patients with positive preoperative ctDNA, regardless of the disease stage and subtype.