MRD and Decision-Making in Early Stage Colorectal Cancer - Episode 3

Role of ctDNA in Assessing Risk for Recurrence in Early CRC

Christopher Lieu, MD

Kristie L. Kahl

A leader in diagnosis and management of CRC reviews the role of MRD testing in early stage CRC.

Kristie L. Kahl: How does serial ctDNA [circulating tumor DNA] monitor capture tumor behavior over time?

Christopher Lieu, MD: We know that serial ctDNA monitoring, or drawing blood for ctDNA detection at regular intervals, can improve the sensitivity and specificity for recurrence. If you think about those patients who are ctDNA positive and remain ctDNA positive over time, those patients are going to have incredibly high risk for recurrence. If you see the patients who are ctDNA negative and remain ctDNA negative, those patients are going to remain very unlikely to have a recurrence. If patients are ctDNA negative and convert to ctDNA positivity, those patients are likely to have tumor recurrence because you’re detecting that ctDNA from the microscopic disease. The more recent studies that we’ll talk about in a little bit have shown that it takes a median of about 8 months from finding the ctDNA to actually finding radiographically visible disease. Overall, there is typically a decent amount of lead time before you see something on a CT scan.

Kristie L. Kahl: With that, what is the current standard of care for assessing risk for relapse and the need for adjuvant therapy in stage II colorectal cancer?

Christopher Lieu, MD: We quiz our fellows on this all the time. What are the traditional clinical high-risk features for stage II colon cancer? There are 5 that we always commit to memory: T4 stage, poor differentiation, lymphovascular and/or perineural invasion, any obstruction or perforation at the time of detection and surgery, and having fewer than 12 lymph nodes removed during surgery—we want a good sample size of lymph nodes to assess for disease. These high-risk features are typically used to assess the risk and the need for chemotherapy. However, we’re quickly finding that ctDNA is certainly more prognostic than any of these clinical features or any of the clinical features in combination.

Kristie L. Kahl: What percentage of patients with low clinical risk will eventually develop disease recurrence?

Christopher Lieu, MD: When we think about the percentage of patients with low clinical risk who will develop disease recurrence, we say that for low-risk stage II disease, the risk of recurrence is low, so percentages vary depending on what clinical trial you’re looking at or what group you’re looking at. However, the thought is that for low-risk stage II disease, the recurrence is roughly 10% or maybe even less. Therefore, when you think about the number of patients you actually have to treat just to prevent 1 recurrence, that number needed to treat is so high that the risk of chemotherapy outweighs any potential chemotherapy benefit. As such, that’s why we typically don’t offer these patients chemotherapy.

Kristie L. Kahl: What is the incidence of colorectal cancer recurrence in patients with vs without ctDNA after surgery?

Christopher Lieu, MD: We found that ctDNA is the most prognostic thing we’ve seen in early stage colorectal cancer. Regarding ctDNA, the studies show basically almost a 100% positive predicted value for disease recurrence if the ctDNA is present. If patients are ctDNA negative postoperatively, and more importantly remain ctDNA negative, we also know that those patients have an extremely good prognosis, and that the disease-free survival in that group is very high. We know that serial testing of ctDNA has a great positive predicted value and negative predicted value and is incredibly prognostic.

Transcript edited for clarity.