Shared insight on the potential roles of ctDNA and MRD testing in the monitoring and treatment of patients with colorectal cancer.
Aditya Bardia, MD, MPH: Continuing with the patient’s journey, how would you monitor the patient? What’s standard in terms of clinical follow-up imaging? If a patient has no evidence of disease on imaging but CA [cancer antigen] is elevated, how do you bring that in, in terms of decision-making, and finalize any role of ctDNA in this setting as well?
John H. Strickler, MD: The core components of surveillance included routine history and physical CEA [carcinoembryonic antigen] monitoring. Colonoscopy is part of that surveillance, with routine imaging, and there have been a number of studies showing limited utility to CEA. Additionally, there have been some provocative studies out of Europe showing that the aggressive use of imaging that we utilize in the United States may not provide value to the patients. It’s generally acknowledged that much of what we do in surveillance and colorectal cancer isn’t truly evidence based, yet it’s in our national guidelines.
An elevated CEA is 1 of the more challenging survivorship scenarios for us in the clinic, in that we know that a CEA that’s slightly positive is just as likely to be a false positive as a true positive. Our national guidelines advise us to perform repeat imaging at more frequent intervals in those scenarios and also to consider PET [positron emission tomography] scans. That can lead to overutilization of resources and is also remarkably challenging for patients because it can be very scary to have a slightly elevated CEA, even if that patient knows that it’s probably a false positive. Circulating tumor DNA has been quite helpful in these scenarios to help us understand whether this slightly elevated CEA is something to be worried about, if we need to do aggressive imaging or if we can treat it more as a false positive. Still, we’re doing all the routine surveillance but not escalating that surveillance above and beyond what we would normally do based on our guidelines.
Martin Dietrich, MD, PhD: This is a very exciting space that you’re working in. In terms of closing, in not only the adjuvant space but also the metastatic setting, how do you see the use of MRD [minimal residual disease] now and in the future? Where do you see the bigger unmet need for monitoring, and how MRD could fill in?
John H. Strickler, MD: The applications for ctDNA and MRD are evolving rapidly, and many of us are building comfort with this assay in the clinic. Right now, we’re seeing the greatest utilization of MRD monitoring in scenarios where we’re struggling with what to do next, specifically that elevated CEA with clear scans. How concerned do we need to be? Do we need to do a PET scan? Do we need to bring that patient back earlier than planned? That’s 1 aspect of that MRD testing that’s been helpful.
Additionally, this assay performs very well as a prognostic tool. We’re just starting to see it as a predictive tool in terms of how to incorporate that into our adjuvant decision-making. Already we’ve seen the provocative data of dynamic, which is a stage II clinical scenario, but what I’d like to see is more data in the stage III setting. Many patients in the stage III setting are being overtreated with chemotherapy. The chemotherapy we use, 5-FU [5-florouracil]–oxaliplatin, can have adverse effects. Oxaliplatin can have long-term peripheral neuropathy that has major quality-of-life implications for patients for years.
The question is, are we overtreating with oxaliplatin? Could we potentially spare some patients some of that lifetime of neuropathy? That would be an exciting development. We can expect to see those data come out of CIRCULATE-Japan and CIRCULATE-US, where the utility of the assay in the stage III setting is being evaluated. There are other unmet needs. For example, in the MSI [microsatellite instability]–high setting, pembrolizumab front line is our new standard of care. There’s a group of patients that have rapid progression on pembrolizumab and other immunotherapies. It would be helpful to know who those patients are earlier so we can potentially get them to a different therapy, maybe cytotoxic chemotherapy. There are a number of clinical scenarios where there’s tremendous unmet need for additional diagnostic tools to make us smarter as physicians, and I look forward to seeing the state unfold in the future so we can provide our patients better outcomes, better quality of life, smarter therapies, and more timely therapies.
Transcript edited for clarity.