Multicancer blood tests have for years been hyped as a potential breakthrough in early cancer detection. But with news that one of the big names in the field, the Galleri test, failed to meet its primary endpoint in a major clinical trial, the future looks uncertain.

On February 19, Galleri maker Grail Inc. announced results from the closely watched National Health Service (NHS)-Galleri trial, which compared annual screening with the blood test against standard cancer screenings alone among 142,000 adults aged 50-77 years. The major finding: Adding Galleri to conventional screening failed to reduce stage III-IV cancer diagnoses over 3 years.

The Galleri test is not approved by the FDA, but it has been commercially available as a laboratory developed test for about 5 years. It promises to screen for over 50 cancers with a single blood test, at a list price of $949, which most people pay for out-of-pocket. Grail said it sold over 185,000 Galleri tests in 2025 alone. Meanwhile, numerous other companies are developing or marketing their own multicancer early detection (MCED) tests.

But given the NHS-Galleri findings, experts interviewed by Medscape Medical News warned against recommending any MCED test to patients, at least for now.

What Did NHS-Galleri Show?

In announcing the trial results, Grail aimed for a positive spin. While the primary endpoint was not met, the company said the blood test led to a “substantial and clinically meaningful” reduction in stage IV diagnoses across a prespecified group of 12 cancers, increased detection of stage I and II cancers, and yielded a fourfold higher cancer detection rate vs standard screenings alone.

But according to H. Gilbert Welch, MD, the company’s take is off-base.

“Talk about putting lipstick on a pig,” said Welch, of the Center for Surgery and Public Health at Brigham and Women’s Hospital, in Boston.

He asserted that the fourfold increase in cancer detection is, in fact, “worrisome” because it suggests there was overdiagnosis in the trial’s intervention group.

Grail didn’t share data beyond the summary in the press release, saying that detailed results will be submitted for presentation at the American Society of Clinical Oncology’s annual meeting later this year.

For now, the available information raises more questions than it answers, said Richard M. Hoffman, MD, MPH, lead author of a recent American Cancer Society (ACS) consensus statement on discussing MCED tests with primary care patients.

Without full study results, Hoffman said, descriptors like fourfold improvement and “substantial” reduction are impossible to meaningfully interpret.

Richard Houlston, MD, PhD, of the Institute of Cancer Research in London, England, concurred.

Grail’s take on the findings highlights “the familiar misconception that a favorable trend is almost as persuasive as a statistically robust result,” Houlston said in a statement shared via Science Media Centre.

“When the main outcome is not met,” he added, “selectively highlighting secondary or subgroup findings should be seen as hypothesis-generating, not proof of benefit.”

What Are the Implications of the Findings for Clinicians?

Both Welch and Hoffman said the findings should give physicians pause when it comes to MCED testing in routine practice.

“I’d say that docs should not use or recommend these tests,” Welch said. “They only add expense and trigger more testing and anxiety, as well as some overdiagnosis [and] overtreatment.”

Hoffman agreed, noting that the ACS statement already stresses caution. “I hope that practice will not move ahead of evidence,” he said.

While no MCED test has been approved by the FDA yet, the recently passed Nancy Gardner Sewell Medicare MCED Screening Coverage Act authorizes Medicare to cover any FDA-approved MCED test beginning in 2028.

Hoffman pointed out that, in determining such coverage, the Centers for Medicare & Medicaid Services is supposed to consider whether a test has demonstrated clinical benefit.

“I would expect that they would recognize that a negative study using a surrogate endpoint does not demonstrate clinical benefit,” he said.

What’s Next for Galleri and Other MCEDs?

According to Grail, additional analyses of the NHS-Galleri data are underway. But the experts interviewed by Medscape Medical News said that more — and different — studies are needed.

“If more patients had been enrolled and followed for a longer period of time, perhaps the reduction [in stage III-IV cancers] would become statistically significant,” Hoffman said.

The major caveat, though, is that reduction in late-stage diagnoses is a controversial primary endpoint.

“We don’t know that this stage shift will translate into a mortality reduction — which is the ultimate goal of screening,” Hoffman said, noting that ongoing studies at the National Cancer Institute are being designed to measure cancer mortality as an endpoint.

Welch and Houlston agreed that stage shift is a suboptimal measure.

For cancer mortality to go down, Welch noted, there must be a decrease in late-stage incidence. But, he added, “a stage-shift can occur without lowering cancer mortality.”

Similarly, Houlston said that stage shift may be an “unreliable surrogate for real patient benefit,” because — like Welch pointed out — an increase in early-stage detection can reflect overdiagnosis of indolent disease that would never have caused harm.

“Without mortality data and a transparent account of harms, including false positives, unnecessary procedures, and opportunity cost, claims of population benefit from multi-cancer early detection remain speculative,” Houlston said.

Still, Hoffman predicted that MCED development will continue to move forward. And he said it may be possible to improve the tests’ performance by searching for fewer cancers and/or targeting testing to certain patient groups — such as those with multi-cancer familial syndromes.

“I would hope that these results do not dampen enthusiasm for what is potentially a paradigm-shifting approach to cancer screening,” Hoffman said. “These tests are continually evolving to improve their diagnostic accuracy and may find a better niche by limiting the number of tested cancers, targeting high-risk populations, and being used for cancer surveillance.”

Welch reported receiving royalties from three books including “Should I be tested for cancer?” Hoffman disclosed professional activities for Wolters Kluwe. Houlston reported having no disclosures.

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X: @SW_MedReporter.