NEW YORK – Researchers, oncologists, and other physicians gathered at a session of the American Society of Clinical Oncology's annual meeting on Friday to discuss their experiences with and expectations for emerging blood-based multi-cancer screening assays.
The field has been debating the implications of multi-cancer early detection (MCED) tests for about as long as these technologies have been in development, but the tenor of these conversations has begun to change with the clinical availability of at least one test, Grail's Galleri, and the anticipation that others will soon join it.
Jonathan Marron, a pediatric oncologist and bioethicist at the Dana-Farber Cancer Institute, opened the webcast session by noting that while MCED testing "carries great promise," there is still much more uncertainty than certainty about the role such tests can and should play in patient care.
MCED tests "may have value both now and in the future for some patients, but the value … remains to be clearly demonstrated at this time," he said, adding that ongoing international efforts to build well-designed studies will be of "incredible importance" in understanding these benefits and potential harms.
Polling meeting attendees, Marron asked if any in the audience had yet experienced caring for a patient who had an MCED test sent or ordered by another provider. Only about 25 percent indicated "yes," reflecting the fact that this area of testing is still relatively nascent but that clinicians are indeed encountering it.
Robert Smith, an epidemiologist with the American Cancer Society, said that the field is fortunate to have a number of larger studies underway, highlighting the NCI's Vanguard study, a three-arm pilot that is comparing two yet-to-be-determined MCED tests against one another with individuals randomized to one of the two tests or a control arm with no testing.
The UK also has a trial of the Galleri test that has already enrolled 140,000 adults for three rounds of testing and is currently in its second round with anticipated completion in 2026. Last week, the NHS said that it had declined an option of accelerating the implementation of Galleri following a review of data from the first year of their clinical study, opting instead to wait for the full results before implementing the test nationwide.
Smith said the decision most likely reflects the fact that screening studies rarely show a significant stage-shift in their first year, so the longer-term results will be needed to bear out that endpoint.
Even if Galleri does demonstrate a notable shift toward detection of earlier-stage cancers in the trial, that doesn't necessarily mean that will translate to improved outcomes, said Jamie Brewer, a medical oncologist and a clinical team lead at the US Food and Drug Administration.
"We are really trying to figure out what the optimal endpoint for these studies is going to be [and] I get a sense that there may be some reticence to look at survival endpoints or to look at endpoints that may require long readouts," Brewer said. "But we are talking about a cancer screening prevention test, so we need to ensure that … you are either decreasing cancer incidence or improving cancer-specific survival."
Finally, Smith highlighted that the US Centers for Medicare and Medicaid Services recently announced a planned investigational device exemption study of the Galleri test called REACH, which will collect real-world evidence with an emphasis on inclusion of marginalized populations.
Chyke Doubeni, Ohio State University's chief health equity officer and a practicing primary care physician, said that he views the technology being advanced in MCED tests — based largely on genome-wide epigenetic signals sometimes coupled with complementary biomarkers — as "quite fascinating." The fact that such tests can be performed with a simple blood draw has been highlighted as a potential tool to overcome healthcare inequities. However, Doubeni said, it remains to be seen whether that actually holds true.
To further take the temperature of attendees at the session, the panelists presented two additional multiple-choice questions to the audience, each describing a hypothetical patient case.
The first featured a patient with Lynch syndrome, who had frequent issues obtaining insurance coverage for recommended screening tests and difficulty obtaining transportation to office visits, and had read about MCED testing in the news and wondered if they should get one.
Asked how they would handle this patient, a little under half of responding audience members said that they would not recommend a MCED test due to the fact that studies have not yet sufficiently defined their risks and benefits.
Another 30 percent said they would defer to the patient's preference after offering advice, and 22 percent said they would offer the test based on the potential for it to provide helpful information.
Interestingly, no one responded that they would avoid MCED testing due to cost, despite the patient being described as having struggled with insurance coverage in the past. Grail's Galleri is not currently covered by payors.
"We certainly have a lot of sessions over the course of the meeting talking about financial toxicity, so that's interesting," Marron said.
Brewer also focused on the question of health equity. "If a patient is having trouble getting to visits … having trouble with access … [or] dealing with issues of financial toxicity, the test in itself is probably not going to solve those problems," she said.
"There's a cost component associated with the test itself. And as we'll talk about throughout this session, there will be more than likely continued access issues if the test is positive and the patient has to go on what a lot of people are calling a diagnostic odyssey," Brewer added. "I think there is a lot of optimism about what [MCEDs] can do, potentially, and we want them to solve that access problem, but I think that by themselves, they won't, so we need to be really intentional in thinking about that."
Doubeni said he didn't think he'd be able to recommend MCED testing for the hypothetical patient, primarily because of the issue of cost.
"Nearly $1,000 is clearly outside of this patient's means," he said. "Clearly, if we're doing a test that is easily accessible at the time of our appointment, it's an important advancement. But I do think that most people who experience inequities do not actually get meaningful access to care, so while this test may hold some promise in making it easier for patients to get tested … I do think that equity as an argument for [these tests] may be a stretch."
Brewer raised the issue of a future with multiple available tests with different performance characteristics in specific tumor types. In the case of Lynch syndrome, which features a risk of multiple types of cancer, he wondered whether clinicians would need to order multiple MCEDs and how they would choose.
"Even if you participate in shared decision-making and you want to honor the patient's decision because you feel they are well informed, there's also that practical component that we really just don't know enough yet from the clinical trials to really figure out where to start," she said.
Panelists also questioned the potential impact that blood-based tests may have on patients' willingness to complete other recommended screening.
Smith said that in his opinion it is still "a little early in the game to answer some of these questions." But he said the fact that they are coming up now is important.
"We want to be cautious and not just presume that the patient would understand the different circumstances [and they] need to be prepared for the importance of continuing with standard-of-care screening and especially regular standard-of-care screening" if they also undergo MCED testing, Smith said.
Panelists then challenged the audience with a second hypothetical case, a healthy man in his 30s, interested in optimizing his health, who had a test ordered and is now seeking counsel from an oncologist regarding potential next steps if the result were to come back positive.
Respondents were split, with 40 percent saying they'd send him back to his primary care physician and would only see him if the MCED result were positive, and another 40 percent saying they'd see him either way, but only after the result came in.
About 16 percent said they'd only consult with the patient if the result led to a "clear oncological diagnosis."
Regarding the potential of false positives in widespread MCED testing of the general population, Brewer said that while these tests have been shown to have a false-positive rate of less than 1 percent, 1 percent of a million is still a significant number.
"While I don't think that we should let costs dictate our pursuit of trying to find a better way to diagnose cancer, this is something that will potentially have an impact on the healthcare system," she said.
"On the flip side of that, I think we don't always think about the false negative aspect of these tests. What we're seeing with some of these assays is that the sensitivity is not very high," she added.
"You really need to look at the incorporation of [these tests] in a longitudinal perspective to get an idea of what the impact is of all of these different results the patients can get," Brewer said, further noting that the best scenario in which to order or recommend MCEDs would likely be in the context of a clinical trial.
As a final nod, Marron turned the question back to the panel itself, prompted by an audience question regarding whether the doctors would consider ordering an MCED test for themselves.
Doubeni's answer was no. Brewer's was the same, though she said that her brain fought her a bit on the question because "there's a part of me that's inherently curious." Marron also said he would not order himself a test, while Smith said he'd have to think about it longer.
"I don't know anybody who's had the test yet. At the same time, I'm curious about these sorts of things and what it would be like and what the results would be," Smith said. "I do feel that all of us on this panel are in a better position to know what to do with these results and know how to deal with the response from the people who would be working us up, though," he added.