New tests could nearly halve the rate of late-stage cancers, some scientists say — is that true?
What if a single blood test could determine if you have one of 14 types of cancer?
This is the question posed by a study published in November in the journal Cancer. Led by researchers at cancer detection testing company Exact Sciences, the paper models how cancer care for five million American adults could be changed by easy access to blood tests designed to detect many cancers – known as multicancer early detection (MCED) liquid biopsy tests.
But for now, liquid biopsies that test for multiple cancers still have unacceptably high false-positive rates. And even when they don’t, there are no clear guidelines on how to incorporate them into standards of care. This means they won’t visit the clinic in the short term, experts told Live Science.
Before the transformative effect predicted by the cancer paper can be confirmed, doctors will need to figure out how best to use these tests in the clinic.
The liquid biopsy pitch
The idea behind liquid biopsy tests is that they allow clinicians to look for cancer without getting close to the tumor itself, Dr Caroline Reduzzioncologist and director of the liquid biopsy platform at Weill Cornell Medicine, told Live Science.
“It’s like translating a tissue biopsy into blood,” said Reduzzi, who was not involved in the cancer report. These tests can detect various signs of cancerincluding individual circulating tumor cells (CTCs), pieces of tumor genetic material floating in the bloodstream, and even tiny fragments of tumor cells.
Because they do not direct tumor sampling, liquid biopsy tests are comparatively simpler and less invasive. Additionally, it is hoped that if clinicians repeat liquid biopsies regularly, they can get an idea of how a tumor is changing in response to treatment.
If a patient’s tumors contain many genetically distinct cells, tissue biopsies that take only part of the tissue can give a biased view of their disease, Reduzzi said. Liquid biopsy, on the other hand, should provide a broader picture of a patient’s cancer by facilitating the analysis of cells from multiple tumor sites.
What tests are currently used?
To date, the The United States Food and Drug Administration (FDA) has approved five liquid biopsy diagnostic tests, each for a single type of cancer. These tests have been validated by tests comparing their ability to detect signs of cancer to tests using tumor tissue samples.
No MCED tests are currently approved or available as part of routine clinical care, although some, such as Exact’s Cancerguard and GRAIL’s Galleri, are available in the United States as “laboratory developed tests” (LDTs). LDT exist in a regulatory gray area in which they are not formally approved by the FDA but are available to patients through their clinicians or independent telemedicine providers.
Dr Iseult Brownea clinical oncologist based at the Royal Marsden Hospital in London and the British Institute of Cancer Research, said progress in Europe is more uneven. The UK’s National Health Service is currently running a trial of Galleri, called PATHFINDER 2, based on data from 140,000 participants. This data will be published next year.
Browne and Reduzzi noted that inertia in the oncology field could delay further deployment of liquid biopsies. Oncologists have been developing diagnostic and treatment plans based on data from tissue biopsy analyzes for decades. It is difficult to shake these entrenched practices, even with data showing the usefulness of liquid biopsies.
Even for single-cancer tests, Browne says standardization remains a problem. “Everyone uses a different test,” so making direct comparisons to decide which test is best can be confusing. Different trials analyzed different cancer markers, at different times during disease progression, she said.
“Less optimistic” predictions
Ruth Etzionibiostatistician at the Fred Hutch Cancer Center in Seattle, is leading a multi-institute effort to examine emerging cancer treatments and diagnostics. Similar to the cancer report, Etzioni’s team modeled the impact of MCEDs and predicted that they would detect cancers at early stages.
However, she added, “our numbers are a little less optimistic.”
The usefulness of the tests varies by cancer type because it depends on how long different cancers persist at each stage of progression. If a cancer persists longer in stages I and II, then MCED testing would be well placed to diagnose it early. But if a cancer progresses quickly to stage IV, then the test will be less useful, Etzoni said.
How long different cancers stay in each stage is still a matter of debate. The “dwell times” used in the recent cancer report were more optimistic, assuming that cancers would progress slowly enough that an annual MDEC test would make a difference.
Another reason MCED tests are not ready to replace existing diagnostics is that some tests will still require a tissue biopsy, and current medical guidelines advise doctors to make certain clinical decisions based on tumor tissue samples.
I don’t think we have a test there. But I think we will. With time.
Dr. Carolina Reduzzi, Weill Cornell Medicine
“Immunotherapy is given in some cases based on the number of white blood cells in your tumor. [immune cells] infiltrating the tumor,” Reduzzi said. “You can’t get it in the blood.” All researchers interviewed for this article agreed that a positive result on a liquid biopsy test should be followed by additional testing before starting any cancer treatment.
So multi-cancer tests can diagnose cancer earlier, but whether this early diagnosis will lead to lower mortality rates will depend on how quickly these confirmatory tests are done, Etzioni said. And these follow-up tests must also be up to the task of identifying cancer at an early stage, she noted.
Fixing false positives
Emerging MCEDs also have problems with false positives, Browne said. Early non-peer-reviewed data from the PATHFINDER 2 trial shows that Galleri was extremely effective at identifying people without cancer – correctly identifying people without disease 99.6% of the time. But in the meantime, about 40 percent of the patients who were diagnosed with cancer by the test actually had no cancer at all.
A false positive rate of this magnitude unnecessarily worries the patient, Browne said, and each false positive could trigger follow-up tests that people would not otherwise have had. If expanded to the millions of people at high risk of cancer, it would represent a significant burden on any health system that adopts these tests.
To reduce false positive rates, future studies will need to find more reliable cancer signals to detect. Detect information from other cell types, like immune cellshas been shown to improve test specificity. Improvements in laboratory standardization could also help reduce the rate of false positives.
Browne hopes that liquid biopsy could one day help patients avoid the harmful side effects that were once inevitable in cancer treatment. For example, an ongoing trial at the Royal Marsden Hospital is evaluating whether a test could identify breast cancer patients who do not need post-operative chemotherapy. The test allows doctors to assess a patient’s risk even after their tumor is removed because it looks for tumor DNA in the blood.
Reduzzi believes that optimized multi-cancer tests – which would identify a large proportion of people with cancer while having a low false positive rate – will transform cancer diagnosis, and that such tests are on the horizon.
“I don’t think we have a test,” she said. “But I think we will. In time.”
This article is for informational purposes only and is not intended to offer medical advice.
