Clinical application of minimal residual disease detection by ctDNA testing in non-small cell lung cancer: a narrative review

In recent years, significant advancements have been achieved in the treatment of non-small cell lung cancer (NSCLC), leading to prolonged patient survival; however, a subset of NSCLC patients may experience recurrence or distant metastasis following initial successful treatment. This phenomenon may be attributed to the presence of minimal residual disease (MRD) that remains undetectable by conventional imaging or laboratory techniques post-treatment. The potential sources of tumor recurrence (MRD), are significantly associated with adverse patient prognosis; therefore, the monitoring of these lesions is critically important in the management of NSCLC. This review seeks to examine the current evidence regarding the application of MRD in NSCLC clinical practice, as well as the challenges encountered in its role as a biomarker. We performed a narrative review by systematically searching the PubMed and Web of Science databases for pertinent literature published from 2005 to 2024, with the objective of identifying significant literature related to clinical research and detection techniques for MRD in NSCLC. The detection of circulating tumor DNA (ctDNA) for MRD has emerged as a significant focus in high-sensitivity genetic testing for monitoring NSCLC. This method may facilitate the assessment of recurrence risk in NSCLC and inform clinical decision-making to identify high-risk patients who are likely to benefit from treatment, thereby providing a rationale for treatment escalation or de-escalation. Nevertheless, the clinical application of ctDNA MRD continues to encounter several challenges, among which improving detection sensitivity and selecting the best detection timing are urgent issues that need to be addressed. ctDNA MRD testing offers robust evidence to assist clinicians in the early identification of NSCLC recurrence and in guiding clinical treatment. We recommend integrating ctDNA MRD with traditional biomarkers and imaging modalities for a comprehensive evaluation aiming at optimizing treatment strategies.