Multi-cancer early detection (MCED) tests are emerging blood-based screenings designed to detect multiple cancers by analyzing cell-free DNA and methylation patterns. While these tests are already available (despite lacking FDA approval), current evidence shows high specificity (~99%) but relatively low sensitivity (~40%), meaning false reassurance from negative results is a real concern. Additional challenges include lengthy diagnostic follow-up, unclear clinical pathways, and significant out-of-pocket costs. MCED tests have not yet demonstrated a clear mortality benefit and are not recommended in current screening guidelines. Clinicians should be prepared to discuss both the promise and limitations of MCED testing, emphasizing that these tests do not replace standard cancer screening.
You’re seeing a patient in clinic for a preventive care visit, and they ask you about cancer screening. You run through the usual age-appropriate cancer screening, and then they hit you with the big question: “Can’t you just do a test for everything?” A few years ago, the simple answer to this question would have been “No.” However, multi-cancer early detection (MCED) tests are here.
Despite lacking FDA approval, MCED tests are available to order, and companies that produce these tests are advertising directly to consumers. It’s no longer a matter of if a patient will ask you about this; it’s when. So how do we make sense of these tests? Are they the future of cancer screening… or a well-marketed work in progress?
Let’s walk through what these tests are, what the data actually shows, and why many clinicians are feeling both intrigued and uneasy.
At its core, an MCED test is designed to do something we’ve never really been able to do before: screen for multiple cancers at once, many of which currently have no recommended screening strategies.
These tests use a blood sample to look for cell-free DNA (cfDNA), which are tiny fragments of DNA shed by tumors into the bloodstream. Some tests also analyze DNA methylation patterns, which can act like molecular fingerprints, suggesting the possible tissue of origin of a cancer.
In theory, that’s powerful. Because right now, our screening toolbox is limited to a handful of cancers: breast, colorectal, cervical, lung (in select patients), and prostate. That leaves a long list of cancers that we typically diagnose only after symptoms appear. MCED tests are trying to fill that gap.
These tests are not FDA-approved but are marketed under a regulatory loophole that permits the sale of certain tests without FDA review. These are currently available by prescription only for patients over age 50.
The appeal of these tests is obvious. Imagine being able to catch aggressive cancers at an earlier, more treatable stage. Or simply offer patients a single cancer screening strategy that requires zero preparation.
In theory, this is the “holy grail” of cancer screening: earlier detection leading to earlier treatment and thus better outcomes.
But as we’ve learned from decades of screening debates (PSA, mammography, thyroid cancer, etc), finding cancer earlier doesn’t automatically translate to improved survival. And that’s where things get complicated.
In the PATHFINDER study evaluating one MCED test, specificity was ~99% (few false positives), but sensitivity was ~40% (many cancers missed). Said another way, this test was pretty good at detecting cancer, but a negative result doesn’t rule out cancer.
That’s a tricky combination. Patients may feel reassured by a negative test result even when they shouldn’t be.
The number needed to screen (NNS) to detect one cancer was ~189 in PATHFINDER.
In PATHFINDER, the median time to diagnostic resolution for all positive tests was 79 days. This was shorter for true positives (57 days) and longer for false positives (162 days). And the workup isn’t trivial ~92% of patients with a positive test underwent imaging, and ~49% underwent procedures. In this study, all workups were paid for by the study. In the real world, this raises immediate questions about cost, access, and prior authorization headaches. There are no guideline recommendations for how to evaluate further after a positive result.
A large randomized trial of one MCED test failed to show a reduction in late-stage cancer diagnoses compared to usual care. That’s not the same as proving no benefit, but it does highlight the central issue that we still don’t know if these tests actually help patients live longer.
Very few insurance providers cover these tests, which can range from $600 up to $1000. It is unclear how willing insurance providers will be to cover downstream costs after a positive test result.
There are currently no recommendations for how often these tests should be repeated.
MCED tests are available right now to order for patients. While these tests are exciting and may someday be recommended screening for cancer, they are not FDA-approved and are not currently recommended in any guidelines. Additionally, there are no guideline recommendations for follow-up after a positive result. These tests are highly specific but not very sensitive, so a negative test result does not rule out the presence of cancer.
Patients will begin asking clinicians about these tests if they haven’t already. And even if we, as clinicians, may feel hesitant about them, we need to be prepared to discuss the risks and benefits with our patients. You might start the conversation by reviewing what these tests detect and their limitations. It’s important to discuss that the follow-up after a positive test result could involve imaging, additional blood work or even procedures. Patients should be cautioned that insurance approval for additional evaluation after a positive result may be frustrating, as these tests are not supported by any guidelines. Patients should also be cautioned that a negative result does not rule out cancer, so if something feels off to them, we still need to evaluate that. Most importantly, patients should be reminded that these tests do not replace routine cancer screening.
MCED tests are an exciting area in medicine and could be the future of cancer screening. But not quite yet! At the moment, we don’t have clear data that these tests help to detect cancers at earlier stages or provide a mortality benefit. While typically that means these tests could only be accessed through participation in a study, that’s not the case for MCED tests. These can be ordered right now, so we all need to be prepared to discuss the risks and benefits of these tests with our patients.
To learn more, listen to the Primary Care Reviews and Perspectives podcast segment, "Your Body's Check Engine Light? Multi-Cancer Early Detection Tests."