Minimal Residual Disease: A New Cancer Biomarker

Minimal residual disease testing could transform cancer care—personalized therapies, early relapse detection, and improved outcomes. The technology is evolving, but its potential is limitless.

The term Minimal residual disease (MRD) was first introduced to describe the strong association between MRD detection after treatment and the risk of relapse. MRD is the least amount of cancer cells that remain in the body during or after treatment.

The technologies for detecting MRD have evolved along with its potential applications as these technologies are now used for studying MRD in multiple solid tumors.

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‘MRD positivity after treatment often signals cancer recurrence. It’s emerging as a powerful tool to guide therapy, adjust treatments mid-course, and monitor for relapse. #biomarker #cancerinnovation #medindia’

More assays are available even before their clinical use is proven. The assays or tests vary in sensitivity, detection limits and evidence that support their use.

Can all Liquid Biopsy Tests Detect MRD?

MRD, cell - free DNA(cfDNA) and circulating tumor DNA (ctDNA) are interchangeable under the field of liquid biopsy even though their meanings do not overlap. Their applications are different so it is important to know how they differ.

Most current tests detect ctDNA that detects the fraction of cfDNA released by tumor cells. In healthy persons the blood is rich in cfDNA released by dying cells and the ctDNA needs to be deducted from cfDNA. Not all ctDNA tests are MRD detectable tests.

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MRD tests are highly sensitive and will be able to detect even small traces of ctDNA. But most of the commercially available liquid biopsy tests focus on detecting druggable alteration and tumor features.

MRD tests are classified into 2 categories

Tumor-informed test : uses archival tumor tissue (tissue embedded in paraffin and stored) to detect tumor specific alteration which is then used to detect MRD in blood. Newer tumor-informed tests can detect thousands of mutations, lowering the limit of detection down to 1 part per million.
Tumor-naíve test : blood only tests that use tumor-intrinsic features such as epigenomic profiling and fragment length to identify minimal traces of ctDNA with cfDNA.

Tumor-informed tests have the highest sensitivity but their higher cost and longer turnaround times are disadvantages.

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Can MRD be Used as a Biomarker?

Almost all patients who test MRD positive after treatment experience recurrence. MRD can be a powerful prognostic biomarker that can find people with varying cancer risk recurrence.

Guiding adjuvant treatment : MRD detection after surgery can be used to personalize adjuvant or post surgery treatment. MRD-positive patients can be treated with targeting residual disease, while MRD-negative patients can avoid the potential toxicity.

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Adaptive treatment strategies during therapy: MRD clearance during neoadjuvant therapy is viewed as a supplement for treatment response. Researchers are exploring whether MRD status can help mid-treatment adjustments to improve therapy outcome.

Recurrence prevention: MRD monitoring during follow up offers advantage over traditional tumor markers by detecting recurrence rate. But it is not clear if early intervention based on this can alter the natural course of disease or if it is an advanced diagnostic sensitivity without changing outcomes.

Ultimately, as MRD assays become more advanced and data from ongoing trials become available, MRD has the potential to redefine treatment paradigms, offering more personalized and effective approaches across cancer types.

Reference:

NCCN Issues Updated Guidance on Genetic Testing for Several Cancers - (https:www.oncologynewscentral.com/article/nccn-issues-updated-guidance-on-genetic-testing-for-several-cancers )

Source-Medindia