A comprehensive overview of minimal residual disease in the management of early-stage and locally advanced non-small cell lung cancer

Abstract

Novel therapies have significantly improved survival for non-metastatic non-small cell lung cancer (NSCLC), however recurrence remains a challenge. Current treatment and surveillance strategies rely on imaging and clinical assessments with limited sensitivity in early detection of disease progression. Liquid biopsy-mediated detection of minimal residual disease (MRD) allows monitoring of tumor activity at the molecular level before clinical and radiologic progression. Here, we review the current evidence for MRD in the adaptive management and surveillance of non-metastatic NSCLC, focusing on the missing links that prevent its widespread clinical adoption.

Fig. 1. Hypothetical schematic workflow for MRD-guided management of early-stage (or locally-advanced, inoperable) NSCLC in the near future.

Question marks denote areas of uncertainty that warrant further investigation. Insets (right side) illustrate the gross differences between the existing therapeutic approach and a potential future MRD-based strategy. Created in BioRender. Boukouris, A. (2025) https://BioRender.com/1fk6hfs.