The Multi-Cancer Early Detection Test
Every year, more than 600,000 Americans die from cancer. But here’s an equally disturbing statistic—seven out of 10 of those deaths are from cancers that don’t have a recommended screening test. In fact, there are only four cancers—lung, breast, colorectal and cervical—with screening tests that receive either an “A” or “B” grade from the US Preventive Services Task Force and the American Cancer Society (two of the most trusted organizations when it comes to cancer screening recommendations—A and B grade recommendations are given to services that the task force recommends implementing for preventive care). But there are more than 100 types and subtypes of cancer, ranging from acute lymphoblastic leukemia to vulvar cancer, including many common cancers that are rarely diagnosed before they’ve spread to an untreatable, lethal degree, such as ovarian, pancreatic and bladder cancers.
Does modern medicine have anything to offer for the early detection of the vast majority of cancers? Bottom Line Personal asked Nima Nabavizadeh, MD, a doctor at Oregon Health & Science University, who is on the front line of researching and testing a new and remarkable type of cancer screening—the multi-cancer early detection (MCED) Test.
Each type of cancer has unique characteristics—what scientists call its phenotype. Despite their differences, all cancers have a similar molecular underpinning and commonality…and that is what is detected by an MCED test. The MCED test is likely to revolutionize the field of early detection—from one test for one cancer to one test for many cancers. It can detect all types of cancer at any stage of advancement, and it is not limited to one specific organ, as are mammograms or colonoscopies.
An MCED test is a blood test, also called a liquid biopsy, so it doesn’t require any advanced equipment or specialized skills on the part of the practitioner. An MCED test uses the unprecedented analytical power of artificial intelligence (AI) to compare each test finding to a massive database of findings and identify a cancer signal origin—a biomarker that indicates the type of cancer. After early detection, the next steps are confirming that a cancer exists and, if it does, treating it. As we all know, the earlier a cancer is detected and treated, the greater the likelihood of survival.
There are many MCED tests in development, and any one of them may prove to be the best. But two tests are furthest along in development—the Galleri test from GRAIL…and CancerGuard from Exact Sciences. Large clinical trials in healthy populations have supported the efficacy of both these tests…and those trials have allowed the FDA to grant “breakthrough device” designation status to Galleri, allowing the company to market the test.
This test screens for more than 50 cancers by identifying the cancer biomarker circulating free DNA (cfDNA). Everyone has microscopic fragments of DNA floating in the bloodstream from dead cells, including people with cancer. But the DNA of cancer cells has unique markers on it, called methylation patterns, that block, or “silence,” the activity of genes. These patterns are like QR codes for specific cancers—the Galleri test can read those patterns and identify dozens of cancers.
The first clinical trial on Galleri was conducted at leading cancer centers in the UK and the US, including Mayo Clinic, Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center. The trial involved nearly 6,700 participants, who had and did not have cancer. The results, published in Annals of Oncology in 2020, showed that the Galleri test had a “specificity” of 99%—that is, it correctly identified people who did not have cancer 99% of the time. The results also showed that the test had a “sensitivity” of 70% for 12 designated cancer types—meaning that it correctly identified a person with cancer in seven out of 10 cases.
That initial study was followed by the Pathfinder study by Oregon Health & Science University and other US institutions, in which more than 6,600 healthy adults, average age 63, who had not been diagnosed with cancer were given the Galleri test. Once again, the test had a specificity of 99%—it detected cancer in 92 participants, leading to 36 cancer diagnoses in 35 people (26 of those cancers were of the type that lacked standard screening). Of note, the cancer signal—the predicted origin of the cancer—was shown to be correct about nine out of 10 times, which helped direct diagnostic workups for the cancers. The positive conclusion of the researchers—“It is feasible to detect cancers early using blood tests.” The results were first reported at the 2022 European Society for Medical Oncology Congress and subsequently published in The Lancet.
Currently, a second study—Pathfinder 2—is enrolling 35,000 healthy people in the US to hopefully confirm the results of the first Pathfinder study. If you’re interested in enrolling in this clinical trial: Go to ClinicalTrials.gov/study/NCT05155605 to find a participating institution near you. (To find a state-by-state list of dozens of study locations, click the “Contacts and Locations” link.) You also can initiate the enrollment process at Oregon Health & Science University and its subsites in Oregon and southern Washington by sending an e-mail to Pathfinder@ohsu.edu.
Criteria for enrollment in the Pathfinder 2 clinical trial: You must be over the age of 50…not have a history of cancer…or have had cancer that was treated and cured (it must be three years since your last cancer treatment).
Another study—the NHS-Galleri study—is underway in the UK and involves 140,000 healthy people. Its goal is to determine whether early detection with the test can reduce the number of diagnosed (and more deadly) Stage 3 and Stage 4 cancers.
You don’t necessarily have to participate in a clinical trial to get the Galleri test. It is available with a doctor’s orders, but it costs nearly $1,000 and is not covered by insurance (Galleri.com). Currently, there is not enough scientific data to know who is the ideal candidate for this test—in other words, who will benefit the most in terms of early detection and potentially cancer-curing, life-saving treatment.
Keep in mind: The Galleri test is not a replacement for standard screening tests, such as mammogram or colonoscopy. It is an additional test that could be used to further refine existing cancer screening. Additionally, the personal and societal harms of these multi-cancer early detection tests—unnecessary and harmful workups for false-positives or overdiagnosis of nonlethal cancers—has yet to be fully elucidated.
From Exact Sciences, the CancerGuard MCED test looks at four biomarkers—DNA methylation…DNA mutation…aneuploidy (an abnormal number of chromosomes)…and various proteins linked to cancer. A study of more than 4,000 people reported at the 2022 European Society for Medical Oncology Congress showed that the test had a specificity of 98.2% and sensitivity of 61%. This test is not yet FDA-approved, but you can find out more about it at
ExactSciences.com/Pipeline-and-Data/cancerguard.
20/20 GeneSystems Inc. markets a single-test combo of about a dozen cancer tests called OneTest (OneTest ForCancer.com) and branded as an MCED test. The test requires a doctor’s prescription and costs $189. It is not covered by insurance but might be eligible for coverage under your HSA plan. It can detect a signal for 20 cancers, including lung, breast, prostate, colorectal, ovarian, pancreatic and kidney cancers. Research shows that the specificity for OneTest is 80%, and the sensitivity for cancer is 82% in men and 62% in women.
MCED tests have gotten the government’s attention. President Biden included funding for the National Institutes of Health to study MCED tests as part of his “Cancer Moonshot” program to “end cancer as we know it.” In 2023, the Medicare Multi-Cancer Early Detection Screening Coverage Act was introduced to establish a Medicare benefit category for MCED tests once they are approved by the FDA. With positive results from the many studies on MCED tests underway, the timeline for that approval may be years rather than decades.
