MRD and Decision-Making in Early Stage Colorectal Cancer - Episode 5

Personalized MRD Testing in Early CRC

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An expert in CRC describes key findings from clinical trials related to personalized detection of molecular recurrence in early stage CRC.

Kristie L. Kahl: What has been the goal of the clinical trials looking at personalized MRD [minimal residual disease] testing in colorectal cancer?

Christopher Lieu, MD: We've discussed clinical trials looking at MRD testing in colorectal cancer. Regarding the trials that have been done, a lot of these were to assess how prognostic the MRD testing is, and what we have discussed is that it is incredibly prognostic. If it's ctDNA [circulating tumor deoxyribonucleic acid]-positive and remains ctDNA positive, those patients are going to have disease recurrence. Moreover, if they're ctDNA-negative or remain ctDNA-negative, those are the patients that are going to do the best. Of course, what we're really interested in is the next step. Can we act on this information and can that information then save lives? I think we're going to talk about in a little bit what some of those trials are.

Kristie L. Kahl: Can you describe the study’s aims, design, patients, endpoints, and the results from the Henriksen study?

Christopher Lieu, MD: There was a very important study presented at GI [gastrointestinal]-ASCO [American Society of Clinical Oncology] 2021 and that was from Henriksen and colleagues that looked a study of 265 patients with colorectal cancer. Specifically, this was stages I to III, but most were stage II and III. Notably, ctDNA was tested using a tumor-based profiling test called the Signatera assay and we've talked about that over the course of this talk. Only 9% of the patients were ctDNA-positive after surgery, and 75% of those patients relapsed. Overall, not very many patients were ctDNA positive, but when they were positive 75% of those patients did relapse. 

Five of the 20 that did not relapse even though they were ctDNA positive, did receive adjuvant chemotherapy. However, the study doesn't necessarily prove that the chemotherapy saved their lives, it's just an association. We talked about in that study that the detection of ctDNA to finding radiographically visible disease was approximately 8 months, so it does show you how quickly you can detect this compared to standard CT [computed tomography] imaging. 13.6% of the patients that were ctDNA negative postoperatively did relapse, but with longitudinal monitoring. If they remain negative over time, the relapse rate was only 3.4%, which showed the impact of this longitudinal testing. 

Kristie L. Kahl: What other evidence do we have from completed or ongoing trials for this approach?

Christopher Lieu, MD: We know that the Henrisken study fits in nicely with the other studies that have been done. We know how powerful of a prognostic test this is. Certainly, the trials that are currently underway and currently in development are really going to tell us whether we can act on this information. Currently, there are trials that are ongoing in stage II disease and there is going to be a nationwide trial coming in stage III disease in the next coming months. Additionally, there's some nice biomarker directed studies that are being conducted as well, and I think that these will really have the potential to tell us if there's something that we can do more for the patients with ctDNA positivity, and also if we can deescalate treatment for patients that are ctDNA negative.

Kristie L. Kahl: Lastly, what are the implications of the findings collectively for monitoring risk stratification and assessing treatment response after surgery in early-stage colorectal cancer? 

Christopher Lieu, MD: I think the main implication of not only the study the Henricksen study, but the other studies is that the overall impact of ctDNA testing in this MRD setting shows that the presence of ctDNA highly associated with relapse and that the absence of ctDNA, really a lower risk of relapse particularly with serial or longitudinal testing and cements ctDNA as the most impactful prognostic marker we've ever seen in colorectal cancer. In the future, we will have additional data to tell us how we might guide therapy with the use of these tests.

Transcript edited for clarity.