A single blood draw that screens for more than 50 cancers substantially increased cancer detection when added to standard screening, identifying cancers that otherwise might have gone undetected until later stages, according to a new study from the Oregon Health & Science University Knight Cancer Institute.
The results from the PATHFINDER 2 study, published today in Nature Medicine, show the efficacy of GRAIL’s Galleri ® test, which uses a machine-learning algorithm to examine chemical patterns that distinguish cell-free DNA originating from healthy cells versus cancerous cells.
The findings arrive at a pivotal moment for the field of multi-cancer early detection. On Wednesday, Nima Nabavizadeh, M.D. , lead author of the study and professor of radiation medicine and director of early detection clinical research in the OHSU Knight Cancer Institute , is scheduled to present the results before a Food and Drug Administration advisory committee reviewing evidence supporting potential approval of the Galleri test.
“We screen for just five cancers, yet the ones we can't screen for cause up to 70% of cancer deaths in this country; that’s the gap this blood test helps close,” Nabavizadeh said. “It finds many of these cancers while they’re still asymptomatic and localized, when cure is still possible. It’s not a replacement for standard screening, but a powerful complement to it.
“Used together, we catch far more cancers early.”
Early detection
The PATHFINDER 2 trial — the study supporting GRAIL’s application for FDA approval of the Galleri test — enrolled 35,878 adults aged 50 and older across the United States and Canada, making it the largest interventional multi-cancer early detection study conducted in North America. OHSU was the study’s largest and leading enrollment site, with approximately 6,100 participants enrolled by the Knight Early Detection Clinical Research team.
The newly published results showed that adding Galleri to clinical recommendations for screening for breast, colorectal, cervical and lung cancers increased the number of cancers detected through screening 6.5-fold. Among cancers newly detected by the blood test, nearly half were diagnosed at stages 1 through 2, and nearly three-quarters were diagnosed at stages 1 through 3, when curative treatment is more often possible. Additionally, 70% were cancers that currently lack national screening recommendations.
The findings suggest the test could help address one of the biggest limitations in cancer screening today. While Americans are routinely screened for breast, colorectal, cervical, lung and prostate cancers, many of the deadliest cancers, including pancreatic, ovarian, liver and bile duct, are typically diagnosed only after symptoms appear.
For Franklin Weingarten , a retired Oregon physician who enrolled in the study at OHSU when he was 84, the study results are personal.
Galleri detected a cancer signal originating in his liver, ultimately leading doctors to diagnose cholangiocarcinoma, a rare and often deadly bile duct cancer that has no routine screening test and is frequently discovered only after symptoms develop.
Because his cancer was found early, surgeons were able to remove part of his liver. Now 88, Weingarten remains cancer-free.
“If I had waited until I had any symptoms, the disease would have been essentially incurable,” Weingarten said. “I have already been given a two-year life extension, and I expect to live quite a few more years. I have been told that no further testing is necessary. I am cured.”
Nabavizadeh said it’s become a welcome occurrence to be able to treat his patients in the early stages of disease, when he can still help them.
“Seeing what happened with Franklin was amazing. He had no symptoms, and the cancer was caught when still localized,” he said. “Without the blood test, the alternative for him might have been a jaundice presentation in the emergency department and likely advanced, surgically unresectable and incurable disease.”
Detecting more cancers
As described in the Nature Medicine study, seven in 10 cancers newly detected by Galleri in PATHFINDER 2 were cancers without national screening recommendations. That gap is precisely where multi-cancer early detection technology aims to make an impact, Nabavizadeh said. Galleri detected a cancer signal in 287 participants. Of those, 173 were ultimately diagnosed with cancer, yielding a positive predictive value of 60.3%. The test also demonstrated a specificity of 99.64%, translating to a false-positive rate of just 0.36%.
“What often gets misunderstood is the extraordinarily low false-positive rate due to the very intentional high specificity, which is by design,” Nabavizadeh said. “If a patient receives a positive Galleri result, there’s at least a 60% chance a cancer will be found. That confidence in a positive result is orders of magnitude higher than what we’re accustomed to with many traditional cancer screening tests.”
Researchers also reported that Galleri correctly predicted the cancer’s location in the body 91.3% of the time, helping clinicians focus diagnostic testing efficiently and avoid unnecessary procedures. Among more than 35,000 participants evaluated for safety, only 0.6% underwent an invasive procedure following a positive result, and most of those procedures were nonsurgical.
Leader in early detection
For the OHSU Knight Cancer Institute, PATHFINDER 2 represents more than a successful clinical trial.
Nabavizadeh says the study is likely the largest interventional clinical trial ever conducted through the Knight Cancer Institute and has positioned OHSU as a national leader in the rapidly evolving field of early cancer detection.
That scale, he said, was made possible through the dedication and expertise of the Knight Early Detection Clinical Research Team and its partners across Oregon, including the Oregon Rural Practice-based Research Network , operating in the Columbia River Gorge; the Knight’s Community Outreach and Engagement program; St. Charles Health System in Bend; Salem Hospital; and Bay Area Hospital in Coos Bay.
“A trial of this reach doesn't happen without an extraordinary team and true partners across the state,” Nabavizadeh said. “Every one of these sites and colleagues made it possible to bring this research to communities throughout Oregon. The roster of clinical research coordinators, regulatory managers and sub-investigators that worked on this trial throughout Oregon is 98 people deep.
“Our clinical research team now has arguably the most robust experience in the world providing multi-cancer early detection tests, discussing the meaning of the results and evaluating patients with signal-positive findings,” he added. “This field is still developing. We’re helping define how these patients are evaluated and communicated to, how diagnostic pathways are designed and how health systems can efficiently manage this new type of cancer screening.”
That experience has included working through both straightforward and complex patient journeys.
One PATHFINDER 2 participant, Bart Dawkins , 68, of The Dalles, Oregon, received a positive cancer signal that led to the diagnosis of early-stage hepatocellular carcinoma, the most common type of primary liver cancer. Following a rapid and efficient diagnostic workup guided by the cancer signal origin returned by the test, Nabavizadeh was able to promptly connect Dawkins to the multidisciplinary liver team at OHSU for prompt treatment. After later developing a separate cancer in another area of his liver, Dawkins continues to receive care at OHSU, where he is being evaluated for liver transplantation.
“Catching Bart’s cancer at the stage we did is what allowed him to be a candidate for curative therapy, up to and including a liver transplant,” Nabavizadeh said. “Early detection didn’t just find the cancer — it preserved his options for a cure.”
Next: REACH and INFORM
As federal review continues, OHSU is looking ahead.
The Knight Early Detection Clinical Research team is enrolling participants in the REACH study, which is evaluating annual multi-cancer early detection testing among Medicare beneficiaries. Enrollment is underway at OHSU and has expanded to community sites across Oregon, including the Columbia River Gorge, Astoria and Coos Bay.
OHSU is also preparing to launch a study called INFORM, a collaboration with the Dana-Farber Cancer Institute and Jackie Shannon, Ph.D., associate director of community outreach and engagement in the OHSU Knight Cancer Institute and professor in the Division of Oncological Sciences (population science) in the OHSU School of Medicine. The INFORM study will evaluate multi-cancer early detection testing among people identified through the Healthy Oregon Project as having inherited cancer risk, strong family histories of cancer or genetic cancer predisposition syndromes. The study is expected to provide at-home access to testing through telehealth, mobile phlebotomy and community laboratory partners.
Together, the programs reflect growing momentum behind a technology many researchers believe could fundamentally change cancer screening.
“We’re at a watershed moment,” Nabavizadeh said. “The promise of finding dozens of cancers through a single blood test is real — but promise isn’t proof, and rigorous clinical trials are how a technology like this earns its place before commercialization.
“PATHFINDER 2 and complementary studies in the United Kingdom are advancing that evidence, and our team at OHSU will keep doing the work to move the early detection field forward.”
Patients like Dawkins say that possibility is what makes the technology so compelling.
“Thank God for that test,” Dawkins said. “I think everybody needs to do this bloodwork. It will potentially save their life.”
Nabavizadeh has served in a consulting/advisory role for GRAIL, Inc. and Exact Sciences and has received honoraria from Roche Diagnostics and MJH Life Sciences. N.N. has no stock nor equity interests related to this work.
The study was designed and funded by GRAIL, Inc. The funder also participated in data curation, data analysis and interpretation, and drafting and approval of the publication
Wider Context: Galleri in the United Kingdom
PATHFINDER 2 was designed to measure how well the test performs in a U.S. population — how many cancers it finds, and how accurately and safely — in a study where all participants received the test. Whether finding those cancers earlier ultimately shifts diagnoses away from late-stage disease is a question of randomization, and it is being explored by NHS-Galleri, a separate randomized controlled trial across United Kingdom’s National Health Service.
The results of those studies were published today in the New England Journal of Medicine and Nature Medicine . NHS-Galleri enrolled nearly 140,000 participants in 10.5 months.
While the trial did not find a statistically significant reduction in the combined number of stage 3 and stage 4 cancers, a favorable trend emerged over time. Its secondary findings were notable: Across 12 of the deadliest cancers, stage 4 diagnoses fell substantially — by more than 20% in the second and third rounds of screening — alongside a marked increase in cancers caught at stages 1 and 2, and an overall detection rate that was approximately four-fold higher when the blood test was added to standard screening.
Nima Nabavizadeh, M.D., who led Oregon Health & Science University’s PATHFINDER 2 effort but was not involved in NHS-Galleri, said the combined stage 3 and 4 result likely reflects a feature of any first year of population screening — a reservoir of previously undetected, asymptomatic stage 3 cancers that the test surfaces all at once.
“What struck me most was the previously unknown magnitude of asymptomatic stage 3 cancers in the general population, which NHS-Galleri swept up in its first round of screening,” Nabavizadeh said. “Many are curable, and finding them at stage 3 is not a loss — especially given recent advances in immunotherapy, radiation and other novel therapies. The combined stage 3 to 4 shift is only one of many endpoints needed to assess clinical utility for guideline recommendations, and longer follow-up will be essential to answer that question.”
Nature Medicine
Randomized controlled/clinical trial
People
Performance and safety of a multi-cancer early detection test: the PATHFINDER 2 study
22-Sep-2026
Nabavizadeh has served in a consulting/advisory role for GRAIL, Inc. and Exact Sciences and has received honoraria from Roche Diagnostics and MJH Life Sciences. N.N. has no stock nor equity interests related to this work.