ctDNA Alone ‘Not Sufficient’ When Monitoring Patients With Colorectal Cancer

Circulating tumor DNA (ctDNA) has been found to have limited clinical benefits when added to standard recommended surveillance among patients with stages 2 to 4 colorectal cancer who underwent curative-intent surgery, researchers have found.

“You're going to miss recurrences if you do ctDNA alone — that's not sufficient,” said Dr. Marwan Fakih of City of Hope Comprehensive Cancer Center in Duarte, California in an interview with CURE®.

Fakih, one of the co-author of the study published in JAMA Network Open, is a professor in the Department of Medical Oncology and Therapeutics Research, co-directs the Gastrointestinal Cancer Program and is the Judy and Bernard Briskin Distinguished Director of Clinical Research. Fakih discussed the study’s findings and their significance for patients.

The retrospective study included data from 184 patients treated at City of Hope Comprehensive Cancer Center and were monitored with a serial ctDNA assay and National Cancer Center Network-guided radiographic imaging surveillance between Sept. 20, 2019 and April 3, 2024, with a median follow-up of 26 months. ctDNA assays were performed every three months for two years and every six months for the following three years.

ctDNA, according to the National Cancer Institute, is made up of small pieces of DNA released into a patient’s blood by tumor cells, and it can be used as a biomarker to help diagnose some cancers, help plan treatment or determine how well treatment is working or if cancer has returned.

Researchers reported that 45 patients (24.5%) had ctDNA or imaging-confirmed recurrence, and of those patients 14 had radiographic recurrence with negative ctDNA and 11 had concurrent ctDNA and imaging recurrence, while 20 patients had ctDNA positivity with negativing imaging at first ctDNA positivity.

Eleven of the 20 patients with ctDNA recurrence without initial concurrent imaging recurrence had subsequent mastectomy, and three (1.6%) of the surveilled population, were disease-free at the data cutoff in April 2024.

“If you're in the [other] 98% of patients, you can argue that strategy was not helpful for those patients, and cost the health care system a lot of dollars,” Fakih said.

Fakih discussed the study’s findings and their significance for patients.

Transcript:

At the end of the day, we found about three cases in the [approximately] 180 patients that we followed that eventually had surgery, and where the surgery so far had been beneficial, and so that's why, at the end of the day we say that when you survey these 180-plus patients at the end of the day, 1.6% of the patients who were surveyed by Signatera [ctDNA assay], eventually, that led to a curative surgical intervention down the road.

Now, if you're the 1% of patients, that is great. If you're in the [other] 98% of patients, you can argue that strategy was not helpful for those patients, and cost the health care system a lot of dollars. And so those are questions that we have to ask ourselves as a society as to what is important to do and at what cost.

I think the other big question, frankly, is that even those three patients who eventually had surgery, those patients would have anyway, even if you hadn't done Signatera, continued to have some form of imaging on an every six months basis or on a yearly basis. Eventually, you probably would have found those tumors, and eventually you probably could have resected those tumors and probably it could have still have been a curative outcome. And so we don't even know that those less than 2% of patients who eventually had curative surgical intervention would have really not have had the same option, had they continued without Signatera.

Now you could argue this the other way around, and say, 'Hey, what if they had waited for CT imaging, and a year later, and now the cancer has spread even further, and you can't resect it.' So those are unknowns.

And so I think the importance of this study is that, number one, it confirms what we have said before. You're going to miss recurrences if you do ctDNA alone. That's not sufficient. When we look at the patients who had recurrence by CT and the ctDNA was negative, there was a higher proportion of those patients who actually had a curative surgical intervention. So CT imaging is standard of care and continues [to be so].

Transcript has been edited for clarity and conciseness.

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