MCED: Tests May Have a Role in Health Equity, but We’re Not There Yet

If you ask experts about low rates of next-generation sequencing (NGS) and what can be done to improve testing levels to fulfill the promise of precision medicine, it's a good bet someone will bring up multicancer early detection (MCED), the blood tests that offer the possibility of finding the first cells of cancer in the body.

Jonathan M. Marron, MD | Image credit: Harvard

This is a concept that many like in theory, but the US oncology care system is a long way from offering these tests to patients on a widespread basis, according to panelists of the session, “Multicancer Detection: Is it Ready for PrimeTime?” The packed session took place on the first day of the 2024 American Society of Clinical Oncology annual meeting.

The reality of MCED's status was borne out when moderator Jonathan Marron, MD, MPH, FAAP, Dana-Farber/Boston Children’s, polled the audience on whether someone had ordered an MCED test for any of their patients in the last year—75% of the respondents said no.

This is so even though cancer is showing up at earlier ages in young adults, so much so that the United States Preventive Services Task Force has lowered the recommended screening age for colorectal cancer and now breast cancer. These screening methods remain the gold standard and there is no suggestion they should be replaced; MCED would augment existing screening or perhaps provide extra comfort for a person with a significant family history of cancer.

Robert A. Smith, MD | Image credit: American Cancer Society

Panelist Robert A. Smith, PhD, senior vice president, American Cancer Society, noted that most tests are in research and development—more than 2 dozen by some estimates. He discussed the decision by GRAIL, which developed the Galleri test, to launch the REACH study following the FDA’s approval for the investigational device exemption and CMS’ approval for Medicare coverage of the study. Panelist Chyke Doubeni, MD, MPH, chief health equity officer, Ohio State University, noted the Galleri test has achieved breakthough status and can test for up to 50 cancers—quite an achievement—but is only offered in settings out of reach of many patients.

A separate study of these tests, called the Vanguard study, is “being driven by” the National Cancer Institute; this is a 3-arm pilot involving 24,000 people. Other research is under way in the United Kingdom.

Smith noted that the Galleri test is available commercially, and often ordered as a laboratory-developed test since it is not covered by insurance. As scenarios the panel outlined showed, what patients want may not matter—what technology can provide and what payers will cover may matter a lot more.

Can MCED Tackle Equity?

MCED has been viewed by some as a way to bring greater equity to genomic testing. But the problem is that the tests are not covered, so for now, the lack of access does not support this argument, some panelists argued.

Audience members weighed in on a scenario involving a Miss Johnson, age 45, and whether an MCED test might help address her interest in keeping regular tabs on her cancer status, as she has Lynch syndrome and several family members have developed Lynch-related cancers. Would MCED help, given her difficulty getting to visits? The room was divided: half did not want to test due to “incomplete knowledge about risks and benefits,” 30% said it should be Miss Johnson’s preference, and 22% said testing might provide useful information. No one in the audience selected the option regarding cost, but the panelists did.

Jamie Renee Brewer, MD | Image credit: FDA

Said panelist Jamie Renee Brewer, MD, of the FDA, “If a patient is having trouble with access [and] if a patient is dealing with issues of financial toxicity, the MCED test in itself is probably not going to solve those problems. There's a cost component associated with the test itself,” she said. And if the test comes back positive, “A patient has to go on what a lot of people are calling a ‘diagnostic odyssey’ to figure out what's the origin of this particular cancer signal.”

The optimism surrounding the tests, Brewer said, is offset by the need “to be really intentional” about how cost affects access. When designing clinical trials, she said, stakeholders must be “thinking about access and equity there and ensuring that we're enrolling patients to those trials that represent the US population.”

The cost of MCED testing would be a nonstarter for Doubeni, who is a family physician. “I've had the opportunity and privilege of having to discuss these with patients in my clinical practice. The cost is real. And so, I do not think I'll be able to recommend this for this patient just because of the cost issues.,” which would be $1000.

The tests may have a role at some point, “but I do think that equity as an argument for this test may be a stretch. But I don't want to say that it doesn't have a role in potentially addressing equity issues.”

What Are the Risks?

Marron noted that MCED cannot be seen as a replacement for certain well-known cancer screens with decades of evidence. Brewer, as a regulator, notes that testing sensitivity varies with the type of test, and the prospect of a new testing paradigm raises a host of questions for the

Chyke Doubeni, MD, MPH | Image Credit: Ohio State

clinician. Doubeni worries that the convenience of a blood test could make it easy for busy clinicians to lean on MCED if they lack an understanding of the appropriateness of which test to use in which circumstance.

Other concerns are lack of specificity and the risk of overdiagnosis or false positives, which could increase anxiety and costs, Smith said. Doubeni noted that finding an indolent cancer creates challenges with current screening methods. Brewer said the numbers of potential false positives creates cost concerns that must be considered.

“In some ways, it will come down to patient preferences,” he said.

“One of the things that we've observed over the years is that we don't do a very good job of preparing the clinician for what they should do,” Smith said. Brewer is correct about the need for guidance, he said. “It's a little early in the game to answer some of these questions. But the fact that we're bringing them up now, I think, is important because we want to be cautious and not just presume that they any patient would understand the different circumstances where they might think, well, ‘Maybe I don't need to keep getting mammograms.’”