Effect of MRD on Adjuvant Therapy and Monitoring Strategies in CRC


Specialists on colorectal cancer discuss the effect of MRD on monitoring strategies and adjuvant therapy decisions for patients with colorectal cancer.


Tanios S. Bekaii-Saab, MD: Let’s put all this in perspective. Joleen, thinking now about this emerging field of minimal residual disease [MRD] assessment and how we’re starting to integrate it in some aspects of our clinic globally, with the data we have, how do you think about MRD assessment and adjuvant therapy decisions?

Joleen Hubbard, MD: First, we don’t know that we’re helping patients live longer by doing this. I can’t stress enough the importance of enrolling patients on clinical trials that will help us answer these questions. From multiple studies, it’s clear that a ctDNA [circulating tumor DNA]–positive test is prognostic for recurrence, but it doesn’t predict who’s going to benefit from chemotherapy. That’s another reason for some of these clinical trials. If we detect minimal residual disease and intervene with something, whether that’s escalating therapy or monitoring more frequently, are we improving survival outcomes? That’s the question that we have to answer with these clinical trials. I’m all for using it as a risk stratification in stage II, where we need better strategies to identify the 15% of patients who will recur and not overtreat them. That’s 1 where I feel very comfortable using MRD to help make treatment decisions. In stage III, I’m more hesitant to de-escalate care for fear that we may miss a window of opportunity for cure. I can’t stress enough [the importance of] enrolling in these clinical trials that are ongoing to help decide how exactly we’re going to help patients live longer using a test looking for MRD.

Tanios S. Bekaii-Saab, MD: This is great. Thanks, Joleen. Dan, how about the MRD assessment, whether negative or positive. How would that, regardless of adjuvant therapy decisions, affect your willingness to monitor more or less aggressively? Or does it not affect it, integrating into the general monitoring schema?

Daniel H. Ahn, DO: To answer your question about how we should use ctDNA in our practice, I don’t think it should be used to replace our current standard, but it should be more used as an integrative tool. Some of my colleagues refer to ctDNA as a super CEA [carcinoembryonic antigen], which is a good way to describe it. It’s not meant to be better than CEA and CT scans but as an integrative tool, as a piece of a puzzle. If you have a positive ctDNA, if the CEA ends up being positive, and you have radiographic imaging, it confers well what the pathway is showing or what the disease course is manifesting. In terms of how I use it in routine practice and in the frequency I use it, that’s not clear. It’s reasonable to be integrated eventually into our standard practice. I use it between my other planned routine surveillance testing. I get CT scans and CEA every 6 to 12 months, and I use CEA between those time periods. If it comes back positive, I’ll go to a closer surveillance or regimen.

Tanios S. Bekaii-Saab, MD: Thanks, Dan. Aparna, this whole field of immune monitoring and helping with the decision points about the utilization of I/O [immuno-oncology] in colorectal [cancer] and beyond, are we there or does more work need to be done?

Aparna Parikh, MD, MS: A lot more work needs to be done. There are interesting data in the metastatic setting across different cancer types that changes in ctDNA early on are predictive of response. Although there are patients who have initial decline who may still have progressive disease and things too and vice versa, we’re getting there. One intriguing setting is in the MSI [microsatellite instable]–high patients who are first line, the standard of care is checkpoint inhibitors: pembrolizumab, given the KEYNOTE data. What’s interesting for those patients is that one-third don’t respond to immunotherapy. For the far majority of patients with colon cancer, we’re lucky in that it’s not metastatic gastric cancer, for example, where you may lose a window to treat a little sooner in those disease types and in colon cancer. There have been patients who have a high burden of disease even with microsatellite instability. Those are the patients for whom I find that monitoring is helpful because you start with immunotherapy, but you want to know if those are going to be responders or nonresponders. I’ve used it as an adjunct tool. If circulating tumor DNA is tracking up, then maybe you switch to chemotherapy. I hate anecdotes because we need prospective data to show that monitoring and switching early improve outcomes. From a toxicity perspective and a patient perspective, it’s important if you can spare a patient toxicity from an ineffective therapy. If you can know that early with a test like ctDNA, that’s certainly provocative, but we haven’t been using it as a routine part of monitoring.

Transcript edited for clarity.

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