[Research Progress on Circulating Tumor DNA Status and Postoperative Central Nervous System Recurrence Risk and...

Lung cancer is one of the malignancies with the highest incidence and mortality rates worldwide, with non-small cell lung cancer (NSCLC) accounting for the vast majority. Patients with postoperative central nervous system (CNS) metastasis have a dismal prognosis, highlighting the urgent need for more precise molecular biomarkers. Although circulating tumor DNA (ctDNA)-based molecular residual disease (MRD) testing can predict postoperative recurrence, its utility in detecting CNS metastasis remains debated. This review examines the association between MRD status and CNS recurrence risk, synthesizes evidence linking MRD status to overall survival (OS), and explores mechanisms underlying false-negative results of peripheral blood MRD in CNS metastasis detection alongside potential clinical strategies. Current evidence indicates that MRD positivity correlates with increased overall recurrence risk and shortened OS; some studies suggest a potential increase in CNS recurrence, yet direct evidence specifically targeting intracranial recurrence-free survival (iRFS) remains insufficient. MRD-negative patients generally have favorable prognosis; however, a subset of high-risk patients - those with epidermal growth factor receptor (EGFR) mutations, stage III disease, or adenocarcinoma - may still develop isolated CNS metastases, primarily due to the blood-brain barrier limiting ctDNA release. Adjuvant Osimertinib reduces CNS recurrence risk, though recurrence remains high within the first year after treatment discontinuation. MRD status serves as an important prognostic stratification tool after NSCLC resection, but negative peripheral blood MRD does not completely exclude CNS recurrence risk. Comprehensive assessment integrating imaging, risk factors, and cerebrospinal fluid testing is therefore warranted.
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