In 2021, Clinical Cancer Research (Impact Factor 10.4) published a study titled "Perioperative ctDNA-based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1)", led by Prof. Lunxu Liu's team from West China Hospital, Sichuan University in collaboration with Sichuan Provincial People’s Hospital, Chengdu Shangjin Nanfu Hospital, and Genecast.

The LUNGCA study is a large-scale, multicenter, prospective investigation on molecular prognostic biomarkers for lung cancer, led by Prof. Liu’s team. LUNGCA-1, focusing on the perioperative phase, demonstrated that perioperative ctDNA analysis effectively predicts postoperative recurrence in NSCLC patients, identifies high-risk individuals, and serves as a reliable indicator for early molecular residual disease (MRD) detection.

In March 2025, the authoritative oncology journal JNCI (Journal of the National Cancer Institute) (Impact Factor 10.0) published the full-course findings of the LUNGCA study titled "Dynamic ctDNA Informs Whole-course Postoperative Precise Management of NSCLC (LUNGCA Study)". Below we present an overview of these research findings.

Background: Circulating tumor DNA (ctDNA) is valuable for detecting minimal residual disease (MRD). However, studies involving long-term blood sampling are required to comprehensively interpret the clinical use of ctDNA analyses.

Methods: We conducted a prospective multicenter cohort study (LUNGCA) for dynamic ctDNA monitoring in lung cancer patients receiving curative-intent surgery. ctDNA analysis was conducted on preoperative plasma samples, at postoperative three days and one month, and then every three-six months for up to three years.

Results: 233 non-small cell lung cancer (NSCLC) patients and 2336 longitudinal plasma samples were included; the median follow-up was 51.4 months. Post-comprehensive treatment (after radical surgery + necessary adjuvant therapy) MRD status was better at predicting relapse than postoperative MRD status (positive predictive value: 100% vs 90.0%; negative predictive value: 90.3% vs 90.1%). Patients with positive pre-adjuvant ctDNA and targetable mutations in tumor tissues had improved recurrence-free survival (RFS) with corresponding adjuvant TKI treatment [hazard ratio (HR) = 0.01, P = .005], but adjuvant chemotherapy failed to improve RFS (HR = 0.6, P = .491). Of patients receiving adjuvant therapies, patients with a negative- or positive-negative ctDNA change pattern had favourable and similar RFS (P = .419), whereas patients with a positive- or negative-positive pattern had worse RFS (P < .001). TKI therapy was more effective than chemotherapy in clearing ctDNA. Post-relapse ctDNA negativity was associated with favorable OS (HR = 0.4; P = .029).

Conclusions: Comprehensive interpretation of dynamic ctDNA monitoring data can inform precise whole-course postsurgical management of NSCLC patients.