By Aureole Medical Communications

The oncology landscape is being reshaped by groundbreaking advances in liquid biopsy techniques and molecular diagnostics. Among these, minimal residual disease (MRD) testing using circulating tumor DNA (ctDNA) is emerging as a leading innovation. This approach facilitates early detection of cancer recurrence, tailors treatment plans, and enhances patient outcomes1. By addressing critical gaps in cancer care, ctDNA-based MRD testing is proving invaluable to physicians, researchers, and patients. 

The Significance of MRD Testing

MRD testing identifies persisting cancer cells post-treatment that may lead to relapse. Traditionally, this has been assessed through invasive biopsies or imaging techniques2. In contrast, ctDNA analysis offers a less invasive, more accurate, and dynamic alternative3. 

ctDNA consists of small DNA fragments released into the bloodstream by tumor cells. Advanced sequencing technologies allow these fragments to be detected and analyzed, providing actionable insights. 

MRD Testing After Surgery: A Paradigm Shift in Cancer Care

Post-surgical minimal residual disease (MRD) testing using circulating tumor DNA (ctDNA) analysis represents a significant advance in cancer management, providing crucial insights that can directly influence patient outcomes and treatment strategies.

Confirming Remission

•  ctDNA testing plays a pivotal role in confirming complete remission following surgery. When ctDNA is undetectable (MRD-negative), it indicates the absence of residual cancer cells, helping clinicians avoid unnecessary adjuvant treatments such as chemotherapy or radiation. This approach not only minimizes the risk of side effects but also enhances patients’ quality of life. The GALAXY study4,5, conducted with patients who had surgically resectable colorectal cancer (CRC), reinforces this benefit. It demonstrated that patients with MRD-negative results post-surgery experienced significantly better long-term outcomes, with an impressively low spontaneous clearance rate of just 1.9% in those without recurrence.

Improving Recurrence Detection Beyond Imaging

• Traditional imaging methods, such as CT or MRI scans, are often limited in detecting recurrence until the tumor has reached a substantial size. In contrast, ctDNA testing offers a far more sensitive approach, detecting molecular relapse much earlier. This earlier detection facilitates timely therapeutic intervention, potentially improving survival rates. The updated GALAXY study demonstrated that ctDNA positivity during the MRD window was strongly associated with poor disease-free survival (DFS) and overall survival (OS), with hazard ratios (HR) of 11.99 for DFS and 9.68 for OS (P<0.0001). These results highlight ctDNA as a superior tool for detecting relapse and optimizing treatment decisions early.

Early Detection of Relapse and Tailored Treatment

• ctDNA monitoring can identify molecular relapse before clinical or radiological symptoms appear, allowing for more precise and early interventions. This is especially valuable in patients with a higher risk of recurrence. The GALAXY study further demonstrated that sustained ctDNA clearance following adjuvant chemotherapy (ACT) was strongly correlated with better long-term outcomes. Patients who achieved sustained ctDNA clearance had a 24-month DFS of 89.0%, while those with transient clearance had only a 3.3% DFS at the same time point. This underlines the importance of ongoing ctDNA monitoring to assess treatment effectiveness and adjust strategies as needed.

The growing body of evidence from studies like GALAXY supports the integration of ctDNA-based MRD testing into routine clinical practice. By enabling earlier detection of recurrence, confirming remission status, and guiding personalized treatment plans, ctDNA testing represents a powerful tool in post-surgical cancer care. The potential of ctDNA as a biomarker to stratify patients based on relapse risk, and inform therapy choices, could redefine how we approach cancer treatment in the post-surgical setting. As this technology evolves, it holds the promise of significantly improving outcomes by tailoring treatment to individual patient needs, enhancing survival, and reducing unnecessary interventions.

Aureole’s analysis on the future of MRD testing in Oncology: potential Gaps and Opportunities

Gaps in Current Oncology Approaches

Despite significant advances in cancer therapies, gaps remain in detecting and monitoring MRD after treatment. Traditional methods, such as imaging, often miss early signs of recurrence, detecting tumors only once they have reached a detectable size. This delay can result in missed opportunities for early intervention, which may impact survival outcomes. Moreover, patients can be overtreated with unnecessary chemotherapy or radiation, leading to avoidable side effects. ctDNA-based MRD testing offers a non-invasive, highly sensitive alternative, detecting molecular traces of residual disease well before recurrence becomes visible through conventional imaging or symptoms. By identifying the disease at earlier stages, ctDNA testing can improve decision-making, minimize unnecessary treatments, and ultimately enhance patient outcomes.

Opportunities for Advancing Personalized Care

The integration of ctDNA-based MRD testing holds immense potential for advancing personalized cancer care. By providing a clearer picture of a patient’s molecular profile, ctDNA testing enables more precise treatment strategies. Clinicians can identify patients at high risk of recurrence and tailor their treatment plans accordingly, administering adjuvant therapies only to those who need them, while sparing others from unnecessary side effects. Furthermore, ctDNA can monitor real-time changes in the tumor’s molecular profile, allowing for adaptive therapy. This personalized approach shifts oncology from a one-size-fits-all model to one that’s individualized, optimizing therapy and improving both survival rates and quality of life. As the technology becomes more widely adopted, ctDNA could become a cornerstone of personalized oncology, offering patients more tailored, effective treatment options.

Final Remarks: Tapping into the Full Potential of ctDNA

The future of ctDNA-based MRD testing in oncology looks promising, with the potential to revolutionize cancer care by enabling earlier detection, more personalized treatment, and real-time monitoring. As technology evolves and clinical trial data continues to grow, ctDNA testing is poised to expand across a wider range of cancers, including colorectal, breast, lung, and pancreatic cancers. However, the successful integration of ctDNA into routine clinical practice requires clear regulatory frameworks and FDA guidelines to ensure test reliability, sensitivity, and uniformity. As these guidelines take shape, ctDNA-based MRD testing will likely become a fundamental tool in the fight against cancer, enhancing both early detection and treatment precision. The shift toward personalized cancer care driven by ctDNA testing promises to improve patient outcomes and move oncology toward a more targeted, efficient, and effective future.

"Every blood sample holds the potential to save lives—ushering in a new era of hope, healing, and healthier future"

References:

1.  Pantel, K., & Alix-Panabières, C. (2025). Minimal residual disease as a target for liquid biopsy in patients with solid tumours. Nature Reviews Clinical Oncology, 22, 65–77. https://doi.org/10.1038/s41571-024-00967-y

2.  Honoré, N., Galot, R., et al. (2024). Liquid biopsy to detect minimal residual disease: Methodology and impact. Cancers, 13(21), 5364. https://doi.org/10.3390/cancers13215364

3.  Martínez-Castedo, B., Camblor, et al. (2024). Minimal residual disease in colorectal cancer: Tumor-informed versus tumor-agnostic approaches—unraveling the optimal strategy. Annals of Oncology. https://doi.org/10.1016/j.annonc.2024.12.006

4.  Nakamura, Y., Watanabe, J., et al. (2024). ctDNA-based molecular residual disease and survival in resectable colorectal cancer. Nature Medicine, 30, 3272–3283. https://doi.org/10.1038/s41591-024-03254-6

5.  Yukami, H., Nakamura, Y., et al. (2024). Circulating tumor DNA (ctDNA) dynamics in patients with colorectal cancer (CRC) with molecular residual disease: Updated analysis from GALAXY study in the CIRCULATE-JAPAN. Journal of Clinical Oncology. https://doi.org/10.1200/JCO.2024.42.3_suppl.6