Minimal residual disease in solid tumors: Clinical applications and future directions

Minimal residual disease (MRD) refers to the presence of residual cancer cells or tumor-derived fragments that persist after treatment and remain undetectable by conventional imaging or protein-based assays. Circulating tumor DNA (ctDNA) has emerged as a dynamic biomarker for MRD detection. It enables real-time disease monitoring, prognostication, and often therapeutic decision-making. Two major ctDNA approaches exist, tumor-informed and tumor-agnostic, and they differ in sensitivity, specificity, and clinical feasibility. Recent clinical trials have supported a prognostic and predictive utility of ctDNA MRD in gastrointestinal, lung, breast, and other malignancies, with positive postoperative or post-treatment MRD status correlating with higher recurrence risk and inferior survival outcomes. However, integration into clinical practice remains limited by challenges, including tumor heterogeneity, variable ctDNA shedding across tumor stage, location and timing, lack of standardized assay interpretation, and cost-effectiveness concerns. Emerging technologies such as methylation-based sequencing, ultra-deep next-generation sequencing, and machine learning-driven risk models hold promise for improving detection accuracy and clinical applicability. Ongoing clinical trials are expected to determine the impact of earlier MRD detection and intervention on patient outcomes, potentially supporting the broader adoption of ctDNA MRD. In this article, the authors reviewed the recent clinical applications, limitations and future directions of MRD in solid tumors.