[Clinical Frontiers and Applications Progress of ctDNA in Precision Treatment
of Non-small Cell Lung Cancer]

Circulating tumor DNA (ctDNA) enables minimally invasive, repeatable assessment of tumor burden and molecular evolution and is an important candidate biomarker for precision management of non-small cell lung cancer (NSCLC). This review summarizes current evidence on assay strategies, perioperative dynamics, molecular residual disease (MRD) after curative-intent treatment, relapse surveillance, and applications in unresectable stage III disease. The most consistent evidence shows that detectable ctDNA after definitive treatment is associated with a substantially increased risk of recurrence, whereas longitudinally undetectable MRD identifies lower-risk populations more reliably than a single negative result. ctDNA clearance during neoadjuvant therapy is associated with pathological response and long-term outcomes but cannot replace pathology or imaging. In oncogene-driven disease, epidermal growth factor receptor (EGFR)-mutated NSCLC has MRD evidence from samples collected in a randomized trial; a small prospective postoperative study has provided direct MRD evidence in early-stage anaplastic lymphoma kinase (ALK)- or ROS proto-oncogene 1, receptor tyrosine kinase (ROS1)-fusion-positive disease, although the evidence base remains limited; Kirsten rat sarcoma viral oncogene homolog (KRAS), GTPase specific postoperative MRD studies remain insufficient. When pathology, imaging, and ctDNA are discordant, assay validity should first be confirmed and lesion-directed imaging or tissue confirmation pursued according to the suspected relapse pattern; ctDNA alone should not trigger deviation from standard therapy. ctDNA has substantial clinical validity, but routine treatment decisions still require standardized analytical performance, cross-platform reproducibility, and prospective evidence of clinical utility.
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