If you mostly attend Precision Medicine conferences, the speed of adoption of new genomic technologies like minimal residual disease (MRD) seems breathtaking and probably every talk is positive.
If you go to another sphere, like radiology, they'll be talking about innovative new imaging biomarkers, important new AI imaging algorithms, and the speed of advance of THAT field.
If you look at current reviews articles from sources like ASCO and Nature Reviews, you'll get a vibe that's more circumspect that the precision medicine attendees, and that's a third forum that's worth paying attention to.
See a new review article for January 2025 at Nature Reviews Clinical Oncology, Normanno et al., which takes a comprehensive view of MRD in lung cancer.
Betteridge's Law says if a title has a question mark, the answer is "no."
And indeed, amidst a thorough review of the field, these authors summarize,
Owing to the limited number of patients enrolled and the different technologies used for ctDNA testing in most of the clinical studies performed thus far, their results are not sufficient to currently support the routine clinical use of ctDNA monitoring in patients with early stage or locally advanced NSCLC.
Therefore, we discuss the need for interventional studies to provide evidence for implementing ctDNA testing in this setting.
With this review in mind, we can look back at Decibio's recent update about payer coverage for use cases for MRD in oncology (here.) On the one hand, coverage for MRD has expanded. But on the other hand, MRD seems to be mostly MolDx and a still-easily-countable handful of tests and indications. Over at AMA, there's no general CPT code for MRD. And the CMS NCD for NGS in cancer, NCD 90.2, seems to create a barrier, if anything, by its emphasis on one-time testing for NGS (not serial monitoring). And it's five years old.
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I was reminded of the Natera JP Morgan deck, presented January 15, 2025. One of the slides highlights a trial in CRC, "CALGB/SWOG 80702," which is a big randomized RCT with 1,011 patients, all getting Signatera (bespoke MRD) testing. While the direct outcome will have some value (use of celecoxib, an NSAID), the overall picture of the 1000 CRC patients and their clinical pathways with their Signatera results, will provide a lot of data for MRD itself. My reading would be that Natera wants to invest to maintain a lead in large-scale trials and outcome data for MRD.
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See a quote from a Genomeweb article about a Br Ca trial ZEST using Signatera in 1,000 patients. There, Turner of Royal Marsden remarks,
- "We've shown here that ctDNA can pick up nearly all of the people who are going to relapse, but we don't really know yet how to use that information to guide therapy and whether identifying it early can improve outcomes," Turner said. "At the moment, if you do one of these tests, and you find ctDNA, but you can't see anything on the scan, we don't actually know how to use that information to treat those people."
- A positive ctDNA test when there is no evidence of radiological progression can be difficult for patients to understand, too, but lessons from trials like ZEST are helping the field better understand how to use ctDNA testing in precision oncology. "We're on the way to identifying the clinical situations where, hopefully, we can use these tests to improve outcomes in the future," Turner said.
