Are cancer-screening blood tests close to prime time?

The vision of a single blood test capable of detecting dozens of different cancers has appealed to oncologists for more than a decade.

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Science has advanced at a rapid pace: what started with analyzing protein levels in the blood has progressed to examining tiny amounts of DNA and feeding the data into algorithms that can highlight changes suggestive of cancer.

This has led to a number of eye-catching developments. In one study, a blood test called Mercury correctly identified 13 cancers with an average accuracy of 87%, including 77% stage 1 cancers.

“It’s amazing that we can do this,” says Dr. Aadel Chaudhuri, a radiation oncologist at the Mayo Clinic in Rochester, Minnesota, who himself researches multi-cancer blood tests. “If you had asked me 10 years ago, my answer would have been: ‘It’s not feasible.’ If we think about DNA extracted from a small tumor, it’s like being on the Washington DC beltway and looking for a Volkswagen.

The ultimate hope lies in a test that can accurately detect a range of cancers early enough that they are still curable. This would translate into lives saved.

But in February, disappointing news arrived: The largest-ever trial of blood tests for cancer failed to meet its main goal. The trial was conducted by Grail, a biotechnology company that makes a test called Galleri that it says can detect more than 50 different types of cancer by measuring fragments of DNA in the blood.

But the trial results, released by the company, found no significant reduction in advanced cancer diagnoses among people who had the Galleri test compared to those who did not.

“It’s hard to argue that this isn’t a setback,” said Chaudhuri, who was not involved in the trial. However, it is premature to consider the trial a total failure, he said. Full results have not yet been published and it appears that in some types of cancer the test has been able to detect more cancers at the earliest stages, while the number of stage 4 diagnoses – cancers that have spread to distant organs and are considered incurable – has declined. “Clinically, what really matters to me is a decrease in stage 4 cancers,” Chaudhuri said.

Survival data

Dr. Deb Schrag, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York, said that for multi-cancer blood tests like Galleri to be considered a paradigm shift by the medical profession, they will need to demonstrate that they can help save lives. Grail will continue to follow patients in its trial for up to eight years after they have their first test to see if there has been a reduction in deaths.

Schrag said this data will be crucial because one reason some cancers might release detectable amounts of DNA into the bloodstream is because they are very aggressive. This could mean that even if a test could detect these tumors earlier, it is not necessarily guaranteed that they will be more treatable.

“If it can’t be cured or there’s nothing that can be done, then it’s not clear that you helped,” Schrag said.

The challenge for Grail and other developers is that as people with advanced cancer live longer than ever before thanks to improved treatments, it may take many years to truly know whether their tests can actually make a difference in patient survival.

“So we are, in a sense, victims of our own success,” Schrag said. “As patients live longer, these trials become increasingly difficult to perform. »

There is another reason why survival data is important. It could prove crucial that multi-cancer blood tests get broader reimbursement from insurers.

So far, none of these tests have been approved by the Food and Drug Administration, although Grail may have used a regulatory loophole to market and sell the Galleri test without review. But because very few insurers are willing to cover it, it’s mostly sold through high-end clinics and medical concierge services to people willing to pay for it out of pocket.

Cancers without screening methods

Even without survival data, there may be other ways in which the tests can demonstrate their short-term value. Nickolas Papadopoulos, a professor of oncology at Johns Hopkins School of Medicine, said he wants to see if the trials show they are able to detect cancers for which there are currently no approved screening methods.

While screenings for breast, lung, colon, prostate, and cervical cancers effectively detect early cases and reduce cancer deaths, these five cancers account for less than a third of all annual cancer diagnoses in the United States.

“Current screening misses many important cancer types,” Schrag said. “This includes one of the deadliest cancers, pancreatic cancer, but many other important cancers.”

Papadopoulos said he was waiting for the full breakdown of data from the Galleri trial before judging whether it was a success.

“I would love to know what they found,” said Papadopoulos, who led a session Tuesday on blood tests for cancer at the American Association of Cancer Research annual conference in San Diego. “Did they find cancers that are not part of standard screening?

Oncologists also want to evaluate how the accuracy of the Galleri test varied across the cancer types participating in the trial. One of the major limitations of multi-cancer blood tests so far is that their performance tends to vary widely across different forms of cancer. A study of a test called CancerSEEK, for example, found that it detected 98% of ovarian cancers but only 33% of breast cancers.

According to Chaudhuri, this is because tumor types vary in the amount of DNA they release into the blood, with kidney, thyroid and early-stage prostate and breast cancers being “low shedding”, while head, neck and pancreatic tumors tend to be more detectable.

But over time, there may be other ways to detect even the smallest excretions. Chaudhuri said there is considerable optimism that new tests can be developed that are even more effective at detecting signs of early-stage cancers by integrating multiple sources of data collected from a person’s blood, from protein levels to the size of DNA fragments and using AI to look for abnormalities.

Although it may take several years to gather the evidence that blood tests can make a difference in patients’ lives, Schrag said she is still incredibly excited about the potential of the technology and believes we are on the verge of a “breakthrough.”

However, she added, it might be too optimistic to have a single test that can detect several dozen cancers. Instead, she said, the likely future is that there could eventually be a set of blood tests to screen for different families of cancers.

“The dream is that you go to the doctor and get a blood test that will identify 75 different types of cancer, from the most common to the rarest of the rarest,” she said. “We may not get there. There may be one blood test for lung cancers, another for blood cancers, another for digestive cancers, etc.”