Blood test finds seven times more cancers than standard screenings
Screening, diagnosing and curing cancer at its earliest, most treatable stages has become a welcome and regular occurrence for radiation oncologist Nima Nabavizadeh, M.D. This has been made possible by a simple blood test that can not only detect more than 50 types of cancer, but also pinpoint where it's coming from with striking accuracy.
Chief medical officer for the Knight Cancer Institute's Cancer Early Detection Advanced Research Center, or CEDAR, Nabavizadeh is the principal investigator for the PATHFINDER 2 study. PATHFINDER 2 is the largest interventional multi-cancer early detection, or MCED, trial in North America. It is examining the safety and efficacy of Grail's Galleri MCED blood test in an intended-use population.
Oregon Health & Science University was the top-enrolling site for the ongoing PATHFINDER 2 study's initial phase. The team enrolled 6,125 of the 35,000 participants—all adults older than 50 with no suspicion of cancer—making it the highest-enrolling interventional study in the history of the Knight Cancer Institute.
In October, Nabavizadeh traveled to the European Society for Medical Oncology conference in Berlin, Germany, to present initial PATHFINDER 2 results. He highlighted key findings, which found that the Galleri blood test:
- Increased the number of screen-detected cancers by more than seven-fold when added to standard-of-care screenings for breast, colorectal, cervical and lung cancers;
- Has a 62% positive predictive value, which means it accurately identified cancer in 6 out of 10 participants with a positive cancer signal;
- For true positives, accurately identified the cancer's origin 92% of the time;
- Found cancer in early stages a majority of the time, most of which had no recommended screenings;
- Had a false-positive rate of just 0.4%;
- Was safe, with less than 1% of all participants undergoing an invasive procedure because of the test.
"It's actually been really thrilling," Nabavizadeh said of the PATHFINDER 2 experience. "Having a blood test that detects a signal for a cancer in somebody with no symptoms and then seeing it confirmed on imaging? It's a game-changer. It's completely revolutionary."
Multi-cancer early detection tests
Cancer leaves clues—molecular traces—in the blood. Researchers developed the MCED test to analyze this circulating cell-free DNA, or cfDNA. Using a machine-learning algorithm, the test examines methylation patterns to distinguish cfDNA originating from healthy cells versus cancerous cells.
Methylation is a natural chemical process that is essentially the body's way of using tiny chemical tags to manage its operations. It acts like an "on" and "off" switch for genes, helping cells decide which instructions to follow and when, and keeping many crucial body processes running smoothly.
The Galleri MCED test screens for more than 50 types of cancer. It works in three steps:
- Analyzing blood for circulating cfDNA;
- "Reading" specific methylation patterns on the cfDNA to identify if it came from a cancer cell;
- If cancer is detected, using pattern recognition technology to predict which organ the cancer may have originated in.
Positive predictive value improves
OHSU was one of seven health care organizations that worked with Grail, Inc. from 2019 to 2023 on the original PATHFINDER clinical trial, in which OHSU also led recruitment nationally. PATHFINDER 2 results show the updated test has improved performance over the version used in the first PATHFINDER trial, with its positive predictive value, or ability to accurately predict cancer, increasing from 43% to 62%.
"OHSU's Knight Cancer Institute is one of the premier cancer institutions in the world, both from a research and a patient care perspective," said Eric Fung, M.D., Ph.D., senior vice president of clinical development at Grail, Inc. "We are honored to partner with OHSU in the development of clinical evidence for our groundbreaking MCED program. Our partnership reflects our commitment to innovation and scientific rigor, and a shared mission to improve outcomes from cancer."
Fung said data from PATHFINDER 2 will be submitted to the Food and Drug Administration as part of the Galleri premarket approval application in the first quarter of 2026, with a potential decision expected in 2027. For those not eligible for clinical trials, the test is commercially available at OHSU as a laboratory-developed test.
For PATHFINDER 2, OHSU deliberately expanded enrollment beyond the Portland area, reaching rural and urban communities across Oregon. The Oregon Rural Practice-based Research Network, known as ORPRN, helped deliver the Galleri blood test to The Dalles and Hood River, while an OHSU coordinator living in southern Oregon enrolled patients through sites like Bay Area Hospital in Coos Bay and Roseburg. Strategic partnerships with Salem Health in Salem and St. Charles Hospital in Bend further broadened the geographic reach.
This multi-site approach, coupled with support from OHSU's Knight Community Outreach and Engagement team, ensured representation from underserved and minority populations.
REACH trial for Medicare beneficiaries
Rural outreach will continue as OHSU embarks on its third clinical trial with Grail, a study called REACH that examines the benefit the Galleri blood test can have in the Medicare population. To be eligible, participants must be 50 or older, on Medicare, and have no history of cancer within the last three years. With REACH, patients will be tested annually for three years at potentially no cost to the patient.
Building on the robust statewide engagement of PATHFINDER 2, the REACH study—currently enrolling at OHSU—will expand in early 2026 to serve the Columbia Gorge, Oregon Coast, and southern and central Oregon.
"With age being the most significant risk factor for cancer, Medicare beneficiaries face a critical unmet need for early cancer detection," Fung said. "REACH is a first-of-its-kind study comparing up to 50,000 Medicare beneficiaries who have received usual care plus an annual Galleri MCED test with a matched comparator arm of beneficiaries. This study could provide evidence for a clinical benefit to a Medicare beneficiary population in Oregon, and we are excited to partner with OHSU in this program."
If Grail's MCED test is approved by the FDA, it could fundamentally change the way clinicians approach cancer screenings. There are more than 200 types of cancer, 70% of which have no screening test. This means most people won't know they have cancer until they're symptomatic, and likely in stages three or four.
"MCED tests have the potential to fill one of the biggest gaps in cancer screening today," Nabavizadeh said. "While we have effective screening tools for a handful of cancers like breast, colon and cervical, the vast majority of cancers are discovered only after symptoms develop—often when they are much harder to treat. MCED tests allow us to look across dozens of cancer types simultaneously through a simple blood draw, offering the possibility to detect cancers earlier and save lives where no screening options currently exist."
And Nabavizadeh sees another benefit: offering cancer survivors peace of mind.
"When my patients reach five years cancer-free, I usually tell them they no longer need to come in for annual surveillance," he said. "But that moment can be anxiety-provoking—for them, and honestly for me too—because we both know there's still a small risk of recurrence or even a new, therapy-related cancer. For survivors who are at least three years out from treatment, I'm excited to offer enrollment in the REACH study as part of their long-term survivorship care."
UK study
PATHFINDER 2 results are promising, and MCEDs are being developed and studied by dozens of companies around the world. But payor and large health system adoption will require evidence that the use of the test improves outcomes across a population, and the benefits outweigh potential harms.
To understand whether Galleri provides a meaningful benefit at population scale and improves outcomes in real-world practice, Grail is conducting the NHS-Galleri study in the United Kingdom.
This study aims to demonstrate a reduction in the proportion of late-stage cancer, with 140,000 participants who were randomized after their first blood draw to either have their blood tested with Galleri annually, or have their blood collected and banked for potential future analysis. Results are anticipated in mid-2026.
Nabavizadeh, who is also the principal investigator for the REACH clinical trial, said he envisions a future where MCED blood tests are approved by the FDA and commonplace—part of routine health care given alongside standard cancer screenings like colonoscopies and mammograms.
"MCED tests fill an unmet need. We have all of these cancers that are causing cancer-related mortality every single year, but we don't know about them until it's often too late," Nabavizadeh said. "This test gives us a way to potentially screen for those cancers, find it early and give our patients a much greater chance of being cured."
Provided by Oregon Health & Science University
