The evolving role of MRD in solid tumors: Progress and potential

Molecular residual disease (MRD) testing is transforming cancer care by offering a more precise way to monitor treatment outcomes. MRD refers to trace amounts of tumor-derived materials, such as cells, nucleic acids, and proteins, that remain in the body after therapy. While MRD testing is well-established in hematologic malignancies, it is increasingly being explored for solid tumors to evaluate disease recurrence and treatment response. Recent advances in liquid biopsy and next-generation sequencing have enabled real-time, non-invasive MRD detection, allowing clinicians to assess disease status at levels undetectable by traditional imaging or pathology. These innovations open new possibilities for early intervention, ongoing monitoring and more informed treatment decisions across a broad spectrum of solid tumors.

Dr. Heidi Ko, a medical oncologist and director of medical affairs at Labcorp, shares how MRD is being applied in solid tumors, the challenges it presents and its future potential in cancer care.

How is MRD measured?

In solid tumors, MRD is typically assessed through next-generation sequencing of circulating tumor DNA (ctDNA). Tumor-informed MRD assays are tailored to an individual’s tumor profile, offering higher sensitivity but often requiring more time to develop, particularly when designed as bespoke panels. In contrast, tumor-agnostic assays use standardized panels that enable faster turnaround but may have reduced sensitivity.^1,2

MRD has been transformative in hematologic cancers. What’s driving its adoption in solid tumors?

Technological advancements, expanding clinical evidence and the shift toward personalized cancer care are driving the adoption of MRD testing in solid tumors. Prospective studies in colorectal and lung cancers have demonstrated that ctDNA-based MRD can detect recurrence months before it becomes visible on imaging. MRD testing also supports assessment of treatment response, informs therapeutic decisions and may enable de-escalation of therapy in patients who are MRD-negative. While the prognostic value of MRD has been established, its predictive utility, particularly in guiding treatment interventions, requires further validation through robust interventional studies.
 

How is MRD currently used in clinical trials?

ctDNA-based MRD could help identify high-risk patients and determine eligibility for a specific therapy (e.g., focusing only on MRD-positive cases). It can track treatment response and act as an early indicator of benefit, especially in early-stage cancers. FDA guidance supports its use in drug development, but more research is needed to link ctDNA changes to long-term outcomes.

Are there examples where MRD has directly influenced patient management in solid tumors?

Colorectal cancer is leading the way in MRD research. Trials such as GALAXY, BESPOKE CRC, and CIRCULATE-JAPAN  have shown that MRD positivity is prognostic, correlating with poorer survival outcomes.^3-5 Conversely, patients who are MRD-negative tend to have favorable prognoses and may be able to safely forgo adjuvant chemotherapy. However, using MRD predictively to guide treatment decisions still requires validation in randomized trials, such as the ongoing CIRCULATE-NORTH AMERICA  study. Experimental approaches, including treatment holidays in metastatic settings for patients with sustained MRD negativity, are being explored, though these strategies are not yet part of standard care.

What are the challenges to MRD implementation for solid tumors?

Key challenges to MRD adoption include inconsistent assay standards, limited prospective evidence of predictive clinical utility and the risk of false positives or negatives that may affect patient safety. There are also concerns about the psychological impact of MRD-positive results when no clear treatment path exists, as well as gaps in clinician education, particularly in community settings.

Where should future research focus to drive MRD progress?

Future research should aim to enhance assay precision, establish optimal testing intervals and demonstrate how MRD-guided decisions influence treatment strategies and long-term outcomes such as overall survival. Studies should also evaluate the impact of MRD testing on patient quality of life and its cost-effectiveness. To support broader adoption, integrating MRD’s clinical utility into trial design will be essential.

The molecular edge in cancer monitoring 

MRD testing offers a powerful tool for tracking residual disease and guiding personalized care in solid tumors. Continued research, standardization and clinician education will be key to unlocking its full potential in routine clinical practice.