Circulating Tumor DNA Minimal Residual Disease Detection of Non-Small-Cell Lung Cancer Treated With Curative Intent

Abstract

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) is a powerful biomarker with the potential to improve survival outcomes for non-small-cell lung cancer (NSCLC). Multiple groups have shown the ability to detect MRD following curative-intent NSCLC treatment using next-generation sequencing-based assays of plasma cell-free DNA. These studies have been modest in size, largely retrospective, and without thorough prospective clinical validation. Still, when restricting measurement to the first post-treatment timepoint to assess the clinical performance of ctDNA MRD detection, they have demonstrated sensitivity for predicting disease relapse ranging between 36% and 100%, and specificity ranging between 71% and 100%. When considering all post-treatment follow-up timepoints (surveillance), including those beyond the initial post-treatment measurement, these assays' performances improve with sensitivity and specificity for identifying relapse ranging from 82% to 100% and 70% to 100%, respectively. In this manuscript, we review the evidence available to date regarding ctDNA MRD detection in patients with NSCLC undergoing curative-intent treatment and the ongoing prospective studies involving ctDNA MRD detection in this patient population.

FIG 1.

Proposed clinical trial designs for early-stage and locally advanced NSCLC using ctDNA as a biomarker for treatment personalization. CRT, chemoradiation; ctDNA, circulating tumor DNA; ICI, immune checkpoint inhibitor; MRD, minimal residual disease; NSCLC, non–small-cell lung cancer; PORT, postoperative radiotherapy.