Minimal Residual Disease (MRD) and CRC

June 2022

Minimal residual disease (MRD) is a term that refers to cancer cells that remain after treatment has ended, cause no symptoms, and cannot be detected by routine clinical tests, such as CT scans or blood tests. It is a term that is commonly used in blood cancers like leukemia and lymphoma, but it is now increasingly used in solid tumours such as colorectal cancer (CRC). In solid tumours, MRD can refer to remaining cancer cells in the blood, small metastases in the body, or a small amount of the primary tumour that remains after treatment. MRD is a predictor or biomarker for worse prognosis (disease outcomes), which highlights the importance of early detection of MRD and subsequent treatment to eliminate any remaining cancer cells.

How is MRD used for patients with colorectal cancer?

Patients with locally advanced (stage II or III) or resectable (able to be removed by surgery) metastatic (stage IV) CRC are typically treated first with chemotherapy, followed by surgery, and usually additional chemotherapy (adjuvant chemotherapy). After adjuvant therapy, the cancer is monitoring by testing the blood for the CEA tumour marker, and conducting scans at regular intervals. This approach, however, is unable to effectively detect small amounts of remaining cancer cells and in the instance that the CEA marker or scans show that the cancer has returned, it is usually at a more advanced stage. The failing of these detection methods to effectively find cancer cells when they are more treatable has been the impetus for the search for more accurate and efficient detection methods.

Currently, MRD is being studied in clinical trials to determine its effectiveness as a prognostic biomarker. Studies aim to answer the following questions:

• ·  Can MRD effectively determine if a patient needs additional chemotherapy after surgery?
• ·  Can MRD be used to detect cancer recurrences earlier, allowing clinicians to intervene earlier and improve patient outcomes?

Prognostic biomarker: a biomarker that indicates an increased (or decreased) likelihood of a future clinical event, disease recurrence or progression in an identified population (National Center for Biotechnology Information).

How is MRD measured?

MRD is measured by the amount of tumour DNA that is found in the blood, also known as circulating tumour DNA (ctDNA). Special tools are used to determine what DNA is from the patient’s normal healthy cells, and what DNA comes from the tumour cells. If these ctDNA levels are monitored over time, such as before treatment and at regular intervals after treatment, clinicians can get an idea of whether residual cancer is present in the body that is not showing up on standard scans.

Many clinical trials are underway that are examining whether safe treatment decisions can be made based on the levels of tumour DNA in the blood. For example, studies are examining the necessity of additional treatments if a patient has already undergone chemotherapy, surgery and more chemotherapy, and signs of MRD are found in the blood. Click here for a list of MRD clinical trials that are currently recruiting.