Blood tests designed to screen for many common types of cancer are showing high reliability and may become a reality sooner than expected, according to data from two studies presented April 28 at the American Association for Cancer Research (AACR) Virtual Annual Meeting.
In one study, of a multi-cancer early detection test made by Grail Inc., of Menlo Park, California, researchers found that cancer was detected with a high degree of accuracy — along with information on where the tumor originated — in people suspected of having cancer. The test produced a false-positive rate — the rate at which a test comes up positive for cancer when it is not there — of less than 1 percent.
Another study showed that a blood test made by Thrive Earlier Detection Corp., of Baltimore, could identify cancers in people with no history of the disease and more than doubled the number of cancers that were detected by screening.
“I think this is one of the areas of cancer research that is most rapidly becoming a reality,” said Antoni Ribas, MD, PhD, AARC's program chair and a professor of medicine at the University of California in Los Angeles.
Neither Dr. Mardis nor Dr. Ribas were involved in the two studies.
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Dectecting Fragments of Cancer DNA in the Bloodstream
Tests like mammograms, Pap smears, and colonoscopies are available to screen healthy populations for breast cancer, cervical cancer, and colon cancer, respectively, but those tests sometimes miss cancer. In addition, there are no screening methods to detect many other types of cancers, says David D. Thiel, MD, the chair of the Mayo Clinic Florida department of urology, who presented the Grail test data.
“Many cancers are detected too late,” he says. “There is a huge survival difference between [detecting] local or advanced cancer. Our thought is a simple and noninvasive multi-cancer test could decrease cancer-related mortality.”
Both of the blood tests reported on at the conference rely on detecting circulating tumor DNA (ctDNA), tiny fragments from cancerous tumors that are shed into the bloodstream.
These ctDNA tests — which are sometimes referred to as “liquid biopsies” — are already sometimes used to monitor cancer patients for early signs of recurrence or to identify the tumor’s genetic information.
But the technology to reliably find new cases of cancer in a large population of seemingly healthy, asymptomatic people using a small blood sample has proved to be the greatest challenge.
The studies presented at AACR show the technology is no longer theoretical, says David G. Huntsman, MD, an oncologist with BC Cancer in Vancouver, British Columbia.
Dr. Huntsman was not involved in either study. “Screening is the biggest challenge,” he says of the various uses of ctDNA technology. “When we consider the number of people who could benefit from ctDNA testing, screening is the peak.”
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Closing In On Detecting Tumors With ctDNA Technology
In the Grail Inc. study, Dr. Thiel and his colleagues explored a subgroup from the 15,000-person Circulating Cell-free Genome Atlas (CCGA) trial. People being evaluated for cancer were classified into those who had confirmed cancer (through clinical tests) and those who were confirmed as having no cancer. The blood test correctly identified all the patients who did not have cancer. Among those people with confirmed cancer, detection across all cancer stages was 46.7 percent.
When renal (kidney) cancers were excluded from the analysis — early kidney cancer produces very little detectable circulating tumor DNA — detection across all stages of cancer improved to 59.3 percent. More advanced cancers had higher detection rates, Thiel said.
Among the blood test results where a cancer signal was detected, the organ in which the tumor had started was correctly predicted in almost all samples.
The study “shows the potential to detect cancer and predict tumor origin in individuals with high suspicion of cancer and ahead of confirmed pathological diagnosis,” Thiel says.
The other ctDNA cancer screening study presented at AACR involved nearly 10,000 women with no history of cancer to see if the Thrive Earlier Detection blood test could detect malignancies, especially early-stage tumors.
The results of the study, dubbed the DETECT-A study, showed that among a subset of 96 women ages 65 to 75 who developed cancer, 26 were first identified by the blood test. (In the remainder of the women, 24 cancers were first identified by standard-of-care screening methods and 46 were first identified by symptoms or other means.) Overall, the blood test more than doubled the number of cancers that were first detected by screening.
The test detected cancers in 10 different organs, seven of which currently have no screening test (such as ovarian cancer, kidney cancer, and thyroid cancer). About 65 percent of the cancers identified in the blood test were local or regional — meaning they were not advanced cancers or cancers that had spread to distant parts of the body.
The Thrive Earlier Detection blood test had a 1 percent rate of false-positive results.
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Liquid Screening Tests: When Will They Be Available?
The idea of a ctDNA blood test is to shift “symptom-detected” cancers to more “screen detected” cancers, the authors say.
But many questions remain before either test is approved for use and becomes widely available, experts say. Two large-scale studies are underway on the Grail test, and more work is needed to better detect early-stage cancer, Thiel says.
The cost of the tests will also be a factor in how widely adopted they become, experts note. Neither company has suggested a potential price for their tests. Health insurers will require information on whether the tests ultimately produce a savings, experts say.
“For population health, we need to show improved survival and cost-effectiveness,” says Nickolas Papadopoulos, PhD, a professor of oncology at Johns Hopkins University in Baltimore, who presented the DETECT-A study data.
In order to be widely used, the tests cannot generate an excess of false-positive results (called the specificity rate), because false-positive results lead to unnecessary medical tests, such as biopsies and imaging tests, on healthy people and cause patients undue anxiety, Huntsman says.
“Specificity has to be close to perfect,” says Dr. Papadopoulos. Moreover, he adds: “The proof of improved overall survival will take large prospective studies of long duration. We are moving in the right direction, but we are not there yet. … These two large studies both move the field forward.”