Learn about MRD and ctDNA

What is colorectal cancer and how does it recur?

Colorectal cancer (CRC) is the second leading cause of cancer death in the US for men and women. A major problem is that patients with colorectal cancer can have recurrence even after surgical resection and chemotherapy. This recurrence is typically in distant parts of the body, which we term metastatic disease. While treatable, metastatic disease is not able to be cured in most patients. Therefore, we may be able to improve outcomes in colorectal cancer patients by more aggressively treating early stage colorectal cancer patients after surgery. However, there is a risk of overtreating patients who may never have recurrence.

What is the risk of recurrence and how can it be reduced?

Early stage colorectal cancer is treated predominantly with surgery with or without the addition of further chemotherapy to try to eradicate any microscopic disease. This chemotherapy is called adjuvant chemotherapy and it is administered either before or after surgery. When the chemotherapy is administered before surgery, the term neoadjuvant is used to describe the treatment.

Despite our best available therapies and surgery, the risk of recurrence can be as high as 30 to 50% depending on characteristics of the colorectal cancer. On average, it takes about two years until the cancer cells radiographically appear on surveillance CT scans or routine blood work. For some patients, however, this may be 6 months up to 7 years after surgery and chemotherapy. This means that the cancer cells have survived the prior surgery and chemotherapy but are too small to be detected by standard of care testing over the surveillance time until they grow large enough.

How can residual cancer cells be detected earlier?

New technology enabled by improvements in DNA sequencing has enabled blood tests that are much more sensitive than traditional CT scans and bloodwork. This website is designed to educate patients and patient advocates on this new technology and its opportunities to improve outcomes in patients.

Minimal residual disease is a term that has been developed to define and describe patients who don’t have any evidence of disease remaining in their body by routine bloodwork and CT scan, but where higher sensitivity tests using circulating tumor DNA detect microscopic disease that remains behind. We use the term “minimal” to describe disease that is not apparent through other methodologies, and “residual” to note that this is reflective of tumor cells that remain behind despite surgery and potential adjuvant chemotherapy.

Currently, minimal residual disease can only be detected by the use of circulating tumor DNA or ctDNA. This technology is now available as standard of care testing in the US for colorectal cancer patients. It is in the process of being approved and adopted in other tumor types, although this set of resources will focus on colorectal cancer.

What is circulating tumor DNA, or ctDNA?

Circulating tumor DNA (ctDNA) are fragments of DNA that are present in the bloodstream. These fragments are released from cancer cells wherever they are in the body. This is different from circulating tumor cells, where the tumor cells themselves are detected in circulation. Instead, one can think of circulating tumor DNA as fragments of DNA released from tumor cells and other parts of the body that are swept up and in the process of being filtered out of the blood by the kidneys.

We can tell that these fragments of DNA come from cancer cells because of the unique mutations that are only present in the cancer cells and not in other healthy tissues in the body.

Where to go next