Clinical application value of postoperative ctDNA detection in minimal residual disease monitoring of lung cancer based on liquid biopsy technology

Objective To evaluate the clinical application value of circulating tumor DNA (ctDNA) detection in postoperative minimal residual disease monitoring of lung cancer and analyze the relationship between ctDNA dynamic change patterns and patient prognosis. Methods A single-center retrospective cohort study was conducted, including 279 patients with stage I-IIIA lung cancer who underwent curative surgical treatment from January 2022 to June 2024. The exclusion rate was modest at 10.6% (33/312), and baseline characteristics showed no significant differences between excluded and included patients (Supplementary Table S1). ctDNA was detected using next-generation sequencing technology combined with unique molecular identifiers, using a customized panel containing 168 genes with a detection limit of 0.01% variant allele frequency. UMI error-correction efficiency achieved 99.7% duplicate consensus rate; median sequencing depth was 18,500× (range: 15,200-24,800×); positive controls (0.1% VAF) showed 100% detection across 45 batches; negative controls maintained 0% false-positive rate; and LOD validation demonstrated 95% reproducibility at 0.01% VAF. Blood samples were collected preoperatively, on postoperative days 7, 14, 30, and every 3 months during follow-up. The primary endpoints were minimal residual disease status and disease-free survival (DFS). Kaplan-Meier method was used for survival analysis, and Cox regression model was used to analyze independent factors affecting prognosis. Results With a median follow-up of 26.8 months, the postoperative ctDNA positive rate was 21.9% (61/279). Overall, 55.9% of patients received adjuvant therapy, with higher rates in MRD-positive patients (70.5% vs. 51.8%, P=0.008). A total of 48 cases (17.2%) experienced recurrence and 24 cases (8.6%) died. The sensitivity of ctDNA detection for predicting recurrence was 89.6%, specificity was 92.2%, and area under the curve was 0.909, detecting recurrence signs an average of 3.2±1.8 months earlier than imaging examinations. Exploratory analysis showed that among 28 ctDNA-positive patients receiving early adjuvant therapy (median lead time: 3.1 months), 2-year DFS was 52.3% versus 18.2% without early intervention (P=0.019). According to ctDNA dynamic change patterns, the 2-year DFS rates for the persistently negative group, early clearance group, intermittent positive group, and persistently positive group were 98.4%, 93.3%, 65.2%, and 7.9%, respectively (P