Aug. 20, 2025
Multi-cancer detection (MCD) testing's promise of potentially intercepting cancer at earlier stages all but guarantees it will play a significant role in population screening in years to come. Yet the murkiness that can accompany positive test results has some community healthcare professionals concerned about how to manage the emerging technology.
Steven W. Ressler, M.D., an internist at Mayo Clinic in Arizona, is working to bridge the gap between the benefits MCD testing can provide and the uncertainty that subsequent diagnostic testing can create. He has helped launch an enterprisewide, dedicated clinic — called the MCD Clinic — designed to help people with positive MCD results find answers.
"We're wading into this ambiguity to get people to a place of certainty," says Dr. Ressler.
Addressing the challenges of a positive MCD test
The purpose of MCD testing is to screen for multiple cancers at once, leveraging strength in numbers. Guideline-directed cancer screening options currently look for less than 30% of the cancers that people ultimately die of. MCD technology is particularly relevant to that group of cancers that do not have existing screening options. With a single blood draw, these tests can detect the majority of potentially life-threatening cancers by looking for biomarkers in the blood. Sometimes, the testing can also point to the likely origin or origins of disease.
The emerging field of MCD testing, based primarily on methylation patterns identified in cell-free DNA in the blood, has many top genetic sequencing companies vying to succeed in this space. However, no true MCD tests have received FDA approval yet.
While MCD tests show potential, one of their biggest challenges is false-positives. In fact, a positive MCD test is not a diagnosis of cancer but simply means further testing is needed, Dr. Ressler says, and that can mean additional costs and anxiety for the patient, as well as potentially unnecessary invasive tests.
And the people who aren't confirmed to have cancer, Dr. Ressler notes, are put into "this kind of uncomfortable surveillance category."
It's an uncomfortable area where Dr. Ressler and the enterprise team feel comfortable. As the founder of the Undiagnosed Mass Clinic (UMC) at Mayo Clinic, Dr. Ressler assembles teams to address gaps in the early diagnostic phase of the cancer care continuum for people with potential malignancies. Many of those working in the MCD Clinic bring their prior UMC experience.
"We've developed a platform across all three of our sites that puts the patient at the center," says Dr. Ressler. "Because of our multidisciplinary approach, every specialist is just a phone call away. It allows us to diagnose these challenging cases in a timely manner."
Detection rates that surpass the average
In early 2024, Dr. Ressler and colleagues saw an opportunity to leverage the clinical, operational and research model of the UMC to help people with positive MCD tests navigate the nuances of undiagnosed disease. The MCD Clinic relies heavily on integrated care, skilled internists and disease group engagement. Because diagnosis is critical, Dr. Ressler enlisted radiology champions from each campus to help create diagnostic protocols that can evolve with time based on the team's iterative experience.
Dr. Ressler says early findings from Mayo Clinic's MCD experience are serving as a lightning rod in the MCD world so far.
The MCD experience in the Executive Health Program at Mayo Clinic's Rochester, Minnesota campus — the first of the three clinic sites to initiate population MCD testing — confirmed a cancer diagnosis in 73% of patients who had a positive MCD test result. That outcome is about 25 percentage points higher than anything reported in the global literature thus far, Dr. Ressler says. The MCD experience at Mayo Clinic's campus in Arizona is showing almost identical detection rates, making the case that there appears to be unique advantages to how the Mayo Clinic Model of Care is being leveraged to provide MCD testing and diagnostic evaluations.
One of the team members, Aditya K. Ghosh, M.D., presented these findings at the 2025 American Society of Clinical Oncology Annual Meeting. The results were also published in the Journal of Primary Care & Community Health in March 2025.
"The attention this early manuscript is receiving is confirmation that we're in the right space," says Dr. Ressler. "There's something about Mayo Clinic in this area that's unique. We've been able to recognize this gap in MCD testing that makes community providers nervous — and rightly so — and then use our existing expertise and infrastructure to meet the need by creating a regional resource."
The need for regional expertise around MCD testing is made evident by the numbers. If a community physician or an advanced practice provider runs 100 tests a year in the clinic — a high number comparatively — that healthcare professional will only evaluate one or two positive results a year, which is hardly enough to accrue expertise. Dr. Ressler says the Mayo Clinic team hopes to codify the knowledge from the MCD Clinic experience to create diagnostic algorithms with help from Mayo Clinic Platform. This would allow the broader community to access Mayo Clinic's accumulated knowledge, thereby extending the team's impact.
To help advance that goal and learn from those who participate in MCD testing, researchers have created an MCD observational cohort study in conjunction with the MCD Clinic and with support from Mayo Clinic Comprehensive Cancer Center. The research protocol allows higher level analytics and insights from biobanking blood samples for people with positive test results.
For more information
Hurt R, et al. Implementation of a multicancer detection (MCD) test in a tertiary referral center in asymptomatic patients: An 18-month prospective cohort study. Journal of Primary Care & Community Health. 2025;16:21501319251329290.
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