Some claim the new multi-cancer detection tests will “revolutionize” cancer screening. Others fear the “worried well” will succumb to slick marketing and subpar tests and overwhelm both primary care providers and cancer centers with requests for cancer scans following a positive tumor DNA result.
Multi-cancer detection tests, or MCDs, have already begun to enter the market even as the National Cancer Institute’s newly funded Cancer Screening Research Network (CSRN), coordinated by Fred Hutch Cancer Center, is studying their efficacy and clinical utility.
Is our health care system ready for this new cancer screening technology? Not even close.
MCED Tests at Fred Hutch
Learn more about Fred Hutch's patient care approach to MCED tests.
How do we get ready? That was the question Fred Hutch physician, health economist and CSRN co-principal investigator Scott Ramsey, MD, PhD, and others posed at the full-day Cancer Screening Intelligence for the Future symposium held Friday, September 12, at Bell Harbor Conference Center in Seattle.
The event drew approximately 200 PCPs, public health researchers, oncologists, health insurance representatives and patient advocates from around the country and provided a collegial forum to hash out the uncertainties surrounding this paradigm shift in cancer screening.
Cancer screening was widely introduced in the 1970s and it’s been an unequivocal public health win. According to the American Association for Cancer Research, or AACR, screening has helped avert 4.7 million deaths across five major cancer types between 1975 and 2020.
“The stated primary aim of cancer screening is to reduce deaths from cancer,” said Fred Hutch biostatistician and CSRN co-principal investigator Ruth Etzioni, PhD. “But cancer screening itself cannot save your life — it can only move your cancer diagnosis earlier.”
Colonoscopies — where precursor lesions are removed — come closest to preventing cancer. But mammograms and CT scans don’t remove tumors. Instead, we rely on these screening methods to find cancers early. An earlier diagnosis means earlier treatment. Earlier treatment usually means a much longer life.
But Americans tend not to think of cancer screening as an ongoing health behavior. Abnormal findings are ignored, and regular follow-ups are forgotten. The oft-tested screening tools we use — mammograms, colonoscopies or FIT tests, Pap smears, low-dose CT scans — could do much more if people just followed current guidelines.
“Right now, if the people eligible for lung cancer testing and colorectal cancer testing really got them, and did the follow-up after, that would have a huge impact on the burden of cancer,” said Fred Hutch biostatistician Carolyn Rutter, PhD.
All in attendance agreed that current screening rates could be better. But some cancers — think ovarian and pancreatic — don’t even have screening tests.
Is a single MCD test a better way to find cancer? That’s the nut the CRSN collaboration is trying to crack.
But here are just a few of the many unknowns:
“We want multiple approaches for detecting cancer early with these tests,” Ramsey told the audience. “And we don’t know what is best, so we need multiple companies exploring these new approaches. But we have standards and there are real problems that come with huge new technologies. We have to think differently about how we evaluate these tests. And we also have to acknowledge the strains the health care system is already under.”
Read on for a breakdown of MCD tests’ promise and pain points.
— Fred Hutch biostatistician Dr. Carolyn Rutter
Fred Hutch turns 50!
Take a look back at half a century of leading-edge research and compassionate care.
Also referred to as multi-cancer early detection tests, MCEDs, MCD assays or liquid biopsies, multi-cancer detection tests are quite different from other cancer screening methods. Instead of imaging tests (like a mammogram or low-dose CT lung scan), MCDs measure bits of tumor DNA that cancer cells shed, mostly in the blood.
“The current MCD tests are primarily based on circulating free DNA-based biomarkers,” said Fred Hutch researcher William “Bill” Grady, MD, who also serves as the medical director of the Gastrointestinal Cancer Prevention Program.
“Tumors shed DNA into circulation via blood and lymphatics,” he said. “We draw the blood, detect the tumor-free DNA, then analyze it for methylation, fragment patterns, sequence changes or genetic variants.”
MCDs are being studied as a cancer early detection tool for the general population — that is, asymptomatic healthy people who are mostly at average risk for cancer — which is why the discussion around cost is crucial.
Initially, MCDs would be used along with current screening methods. But there is also potential for the tests to be stratified and offered first to those in most need.
And what about early-stage cancer survivors? Are these tests being offered to them, too, to monitor metastatic recurrence?
“These types of tests are totally being investigated for early signs of recurrence, especially in breast cancer patients,” said Etzioni, holder of the Rosalie and Harold Rea Brown Endowed Chair. “But they are different tests, different analytes and have different performance criteria. Tests in the recurrence space are called liquid biopsy for minimal residual disease.”
The multi-center CSRN is the first large-scale U.S. scientific collaboration to focus on the new technology.
Fred Hutch is the Coordinating and Communications Center, or CCC, for this network. It’s also the Statistics and Data Management Center for the CSRN with a half dozen Fred Hutch researchers involved as co-principal investigators and many more scientists across multiple sites working with the data. The Public Health Sciences Division, which sponsored the symposium, has a long history of leadership in cancer screening research, acting as the coordinating center for the NCI’s Early Detection Research Network, EDRN, for 25 years. Etzioni holds an NCI Outstanding Investigator Award to study multi-cancer early detection tests and novel diagnostic technologies and has served on past cancer screening guidelines committees.
CSRN began its work in 2024 and launched its Vanguard study in July 2025, aimed at assessing the feasibility of using MCD tests in future larger trials. The goal is to enroll 24,000 participants at nine clinical sites (Fred Hutch is not an enrollment site).
Vanguard is testing two MCDs: the Avantect test by ClearNote Health and the Shield™ test by Guardant Health, but it’s not to compare the effectiveness of each test.
“This is a feasibility study,” said Etzioni. “We’re setting up the trial infrastructure with a later, larger, efficacy trial envisioned after this feasibility phase.”
The two selected MCDs both look for 10 different solid tumors including bladder, breast, colorectal, esophageal, stomach, liver, lung, ovarian, pancreatic and prostate cancers. Vanguard feasibility test results are expected in 2027.
Genomic DNA is most often the “meat of the assay,” said Grady, cofounder and director of another large Fred Hutch screening initiative, BEACON (Biomarkers for Early Assessment, Cancer detection and Outcome Navigation).
But the biotech companies developing these tests — and there are at least 50 — each have their own proprietary assay.
“Details of MCD test methods and assays are not available to scientists,” he said. “But mitochondrial DNA is also a thing. There are millions of DNA methylation features and millions of sequence changes that can be used in these assays. They allow us to identify healthy versus tumor cell DNA.”
One important note: methylated DNA, he said, “is often how we know the cancer site of origin.”
The short answer, per Etzioni: “We do not yet know.”
“These exciting new screening technologies have the potential to revolutionize cancer screening,” Ramsey told the audience. “But they’re at a very early stage. And it’s key for the general public to understand what MCDs are and what we know about how well they perform.”
Unfortunately, there’s not a lot of data on performance — or outcomes — right now.
“There’s a lot of hype and marketing from companies,” said Jane Lange, PhD, a biostatistician at Oregon Health and Sciences University. “But we have very little insight of clinical outcomes of MCD screening. Screening trials are key for determining the population impact.”
In addition to CSRN’s Vanguard study, the UK’s National Health Service is conducting a randomized trial of Grail’s Galleri test which looks for 50 different cancers. Grail has conducted studies in North America, as well, with its Pathfinder data published in The Lancet and Pathfinder 2 topline results released in June.
Some single-cancer blood-based assays, such as the FDA-approved blood-based test for colorectal cancer developed by Guardant Health and researched via clinical study by Fred Hutch’s Grady, have proven very effective.
A recent systematic review of MCDs, published in Annals of Internal Medicine, looked at 20 published studies on 19 different tests. Although MCDs were framed as “potentially transformative,” the authors concluded that at this time “no controlled studies are completed that report benefits of screening with MCDs tests” and that “evidence was judged insufficient to evaluate harms and accuracy.”
So, full information on the benefits and harms are still TBD.
But Fred Hutch’s Ziding Feng, PhD, another CRSN co-investigator, pointed to one obvious advantage.
“Early detection leads to less severe symptoms,” he said. “In some cancers, patients will have jaundice before the cancer is detected. But once they have jaundice, they can’t do chemotherapy. If you could give just four months of lead time, that’s a very good thing for the patients in terms of advanced symptoms because they can tolerate more aggressive treatment.”
Another big advantage: most MCD tests are aimed at finding cancers that have no screening alternative.
Unfortunately, there are potential harms, just as with current screening methods. Those include false positives (someone being told they do have cancer when they don’t) and false negatives (someone being told they don’t have cancer when they do).
Or as Etzioni put it: “These tests may give a wrong answer.”
The likelihood of a wrong answer often depends on the tests’ sensitivity and specificity.
“If the test is very sensitive, it has a low false negative rate — most cancers will be detected,” said Rutter. “But if the test has lower sensitivity, it has a higher false negative rate and will miss a high fraction of cancers, so you can’t believe that negative test.”
Other harms identified by panelists: unnecessary and expensive diagnostic odysseys driven by false positives; delayed diagnoses due to false negatives; incidental findings that lead to unnecessary interventions; overdiagnoses of indolent cancers that don’t cause harm; higher upfront costs; increased demand on diagnostic services and potential inequities in access.
The sweet spot? Finding a test that minimizes false positive results while at the same time does not miss any cancers.
Some MCD tests are available in the U.S. now. But no multi-cancer detection tests have been approved by the U.S. Food and Drug Administration, or FDA.
And none of the major societies — the American College of Physicians, the American Society for Clinical Oncology, the American Cancer Society — recommend routine use of these tests at this point.
Also no insurance plan, including Medicare and Medicaid and commercial insurers, covers these tests. Additionally, the U.S. Preventive Services Task Force has yet to review MCD tests.
There are commercially available laboratory-developed tests on the market, though. These tests don’t require FDA approval if they’re conducted in a Clinical Laboratory Improvement Act (CLIA)-certified lab.
But the clinical pathway — the process of going from a positive test result to evaluation with additional tests, and for those who are diagnosed with cancer, starting treatment — has yet to be determined.
“We don’t have a guideline-based test now, but if we ultimately do have evidence-based MCD tests, we’ll need to think more about where people fall through the cracks,” said Fred Hutch pulmonologist and CSRN co-investigator Matthew Triplette, MD, MPH, who acts as medical director of the Lung Cancer Screening program. “We’ll want to think about the clinical pathway.”
Many agreed that a positive MCD test could lead, as Rutter put it, “to a harrowing journey.”
Eric Collisson, MD, a Fred Hutch translational researcher who treats pancreatic and other gastrointestinal cancers, said Fred Hutch is in the process of building a “clinical home” for people who receive a positive test on a multi-cancer detection test.
“This is a real-time question at Fred Hutch,” he said. “We’re actively working with nurse navigation and our service line managers and disease-specific experts to figure out how we can best support this population. They don’t come in as cancer patients — and we don’t have enough people to make these diagnoses immediately if they are indeed true positives. A lot of these patients will be in a diagnostic ‘No Man’s Land’ for longer than we want.”
Multiple factors go into calculating the costs of these tests and there’s not enough data yet to understand the cost-effectiveness, Ramsey stressed as he presented data on projected costs.
Annual cost of preventive screening currently runs about $43.2 billion in the U.S. Cost for screening with MCD would be approximately $26 billion to $32 billion.
“And that’s $26 billion to $32 billion more than we’re already paying,” he said. “Treatment cost savings from diagnosing cancer at an earlier stage would be about $1 billion. But we’re not going to completely offset the cost of MCDs by shifting everything to an earlier stage. We will save money, but we won’t offset the cost.”
Yet, the potential price tag does not appear to be detracting from the tests’ apparent promise, Etzioni said.
Congress is also following the rapidly evolving science of MCD tests. H.R. 842 and S. 339, the Nancy Gardner Swell Medicare Multi-Cancer Early Detection Screening Coverage Act, was reintroduced in early 2025 and seeks to establish a new coverage and payment pathway for Medicare beneficiaries for certain FDA-approved MCD tests starting in January 2028.
Absolutely not, experts agreed. At least not yet.
“These tests will not replace current screening — but physicians and patients want that,” said family physician Alex Krist, MD, MPH, part of the Virginia Commonwealth University, one of the CSRN sites. “We should expect high enthusiasm and high uptake for these tests. It’s just a blood test and much easier than a colonoscopy, mammogram, CT scan or even a Pap smear.”
Those standard-of-care tests are still necessary, though, due to false negatives.
“We encourage patients and providers to stick with standard-of-care cancer screening tests,” said Rutter. “It would be awful for someone to have an MCD test that’s negative and decline standard screening or even ignore symptoms thinking they’re cancer free.”
The NCI agrees. “Standard-of-care cancer screenings for breast, cervical, colorectal and lung cancers are recommended regardless of whether or not a person has an MCD test.”
The bottom line: watch this space.
Funding for the Cancer Screening Intelligence for the Future was provided by the Dillon Family Foundation.
Diane Mapes is a senior editor and writer at Fred Hutch Cancer Center, who's written for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor and patient advocate, you can reach her at dmapes@fredhutch.org or doublewhammied.com / @double_whammied / @doublewhammied.bsky.social. Just diagnosed and need information and resources? Visit our Patient Care page.
Are you interested in reprinting or republishing this story? Be our guest! We want to help connect people with the information they need. We just ask that you link back to the original article, preserve the author’s byline and refrain from making edits that alter the original context. Questions? Email us at communications@fredhutch.org
Are you interested in reprinting or republishing this story? Be our guest! We want to help connect people with the information they need. We just ask that you link back to the original article, preserve the author’s byline and refrain from making edits that alter the original context. Questions? Email us at communications@fredhutch.org
Every dollar counts. Please support lifesaving research today.
For the Media