Patient-Specific MRD Liquid Biopsy in Resected NSCLC: Plasma and Bronchial Washing ctDNA

This is a multicenter, prospective, observational pilot cohort study in patients with surgically resected non-small cell lung cancer (NSCLC, pathologic stage IA3-IIIA). Whole exome sequencing (WES) of each patient's resected tumor tissue and matched normal blood (buffy coat) is used to build a patient-specific (tumor-informed) minimal residual disease (MRD) panel, after excluding germline and clonal hematopoiesis variants. MRD is then assessed in paired plasma circulating tumor DNA (ctDNA) and bronchial washing fluid (BWF) ctDNA collected at 6, 12, 18 and 24 months after surgery. The study evaluates whether MRD positivity in plasma and/or BWF is associated with subsequent clinical or radiologic recurrence, compares MRD detection rates and quantitative values between plasma and BWF, and explores the lead time of MRD detection relative to standard surveillance with chest CT and serum CEA. MRD results are not used to confirm recurrence or to change treatment; all clinical decisions follow standard of care. Forty participants will be enrolled at three Severance hospitals in Korea.

Inclusion Criteria: * Adults aged 19 years or older * Pathologically confirmed non-small cell lung cancer who underwent curative-intent complete (R0) surgical resection * Final pathologic stage IA3 (tumor size \>2 cm) to IIIA after surgery * Able to attend the first outpatient visit within 1 month after surgery, and agrees to research blood sampling, provision of surgical tissue slides, and long-term follow-up * Provided voluntary written informed consent after adequate explanation of the study purpose and methods Exclusion Criteria: * Pathologic stage IA1 or IA2 (tumor size ≤2 cm), stage IV, or confirmed distant metastasis * Incomplete resection (non-R0) or clear residual tumor after surgery * History of other malignancy, including synchronous malignancy in another organ, that may confound interpretation of MRD results (cancers judged cured for more than 5 years may be included) * Poor performance status or other conditions making repeated blood sampling or bronchoscopy difficult * Unstable cardiopulmonary function, or high risk with sedation or additional procedures, in the judgment of the treating physician * Unable to provide informed consent, or judged unable to comply with regular follow-up during the study period