Minimal Residual Disease in Oncology: From Cure to Longitudinal Patient Management

Minimal residual disease (MRD) refers to the persistence of low-level malignant cells or tumor-derived nucleic acids that remain after curative-intent therapy and are undetectable by conventional diagnostic methods. In oncology, MRD has emerged as a powerful biomarker with well-established prognostic value in hematologic malignancies and rapidly expanding relevance in solid tumors. Advances in sensitive detection technologies, including multiparameter flow cytometry, quantitative real-time polymerase chain reaction, next-generation sequencing, and digital polymerase chain reaction, have enabled the identification of residual disease at the molecular level, often preceding clinical or radiological relapse. Beyond its conventional role as a binary indicator of treatment response or cure, MRD is increasingly recognized as a dynamic longitudinal biomarker that supports personalized disease management. Within this evolving paradigm, patient-informed MRD strategies that incorporate tumor-specific molecular profiling and serial monitoring, particularly through circulating tumor DNA, offer the potential to guide treatment adaptation, including escalation, de-escalation, maintenance optimization, and surveillance strategies across both hematologic and solid malignancies. In this review, we summarize the biological basis of MRD, current and emerging detection methodologies, and clinical applications across cancer types, with a focus on patient-informed approaches. We also discuss key limitations, including assay standardization, biological variability in solid tumors, and the lack of clearly defined actionability thresholds. Finally, we highlight future directions for integrating MRD with multi-omics and AI-driven analytical frameworks to enable adaptive, risk-informed cancer management and advanced precision oncology.