Dr. Deb Schrag, Chair of the Department of Medicine, says: “This is the brave new world of testing. And although lots more work must be done before this approach becomes standard, it could eventually transform cancer diagnosis and treatment.”
A blood test that could detect multiple cancers at their earliest stages has long been a dream of the medical community. Now results from a pilot study, published in The Lancet, suggest that a single blood test might identify the presence of more than 50 cancer types.
The experimental test analyzes DNA shed from cancer cells into the bloodstream, looking for telltale genetic “cancer signals.” The goal is to detect these early signs of cancer well before symptoms occur or results are obtained from other diagnostic methods. This kind of test is often called a liquid biopsy.
The study is preliminary but included two important findings:
- Nearly half of the newly diagnosed cancers were identified at an early stage.
- The test detected many cancer types for which there are no current screening tests endorsed by the U.S. Preventive Services Task Force, the regulatory authority that influences health insurance coverage.
“This work is still preliminary, but it is provocative and could represent a future approach to cancer diagnosis and screening,” says Deb Schrag, MD, MPH, Chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSK) and first author of the manuscript published in The Lancet. “We need further research to confirm this approach to screening will translate into meaningful clinical benefits.
Early Cancer Detection Results
In the study, called PATHFINDER, more than 6,600 patients who did not have signs of cancer agreed to submit a blood sample for testing. If a cancer signal was detected, the test also indicated where the cancer likely started to focus further diagnostic tests that could give a more definitive answer.
Overall, a cancer signal was detected in 92 patients — about 1.5% of those screened. In about a third of those patients, cancer was confirmed. The other two-thirds of patients with initial positive results did not turn out to have cancer.
“The blood test is not definitive that someone has cancer,” Dr. Schrag says. “The test identifies people for further diagnostic evaluation. About 1 in 3 whose screening test was positive were ultimately confirmed to have a cancer.”
Many cancer screening tests, such as mammograms for breast cancer or low-dose computed tomography (CT) scans for lung cancer, can produce false positive results. In that regard, this test was no different, says Dr. Schrag. Like all screening tests, this test generated “false positives,” which then required time, effort, and expense to resolve. However, the percentage of false positives was relatively low when considering the overall number of people being screened, Dr. Schrag notes.
Lethal Cancer Types Might Be Caught Early
Importantly, the test resulted in early detection for cancer types that are considered rare, including cancers of the bile duct, small intestine, and pancreas, which are not likely to be found during routine physical examination or current screening.
The results were based on analyzing DNA circulating in the bloodstream — known as cell-free DNA, or cfDNA. The test is made by the biotech company GRAIL, which sponsored this study.
Researchers looked for cancer signals derived from methylation patterns. Methylation, a chemical modification of DNA, is one of the factors that influences gene expression and can be significantly altered in cancer cells.
The participants in the PATHFINDER trial were from outpatient clinics across seven U.S. healthcare systems. Patients were recruited from December 2019 to December 2020, when Dr. Schrag, who joined MSK in 2021, worked at the Dana-Farber Cancer Institute. The study included adults over 50, with and without elevated cancer risk. Elevated risk was based on having one or more of the following:
- A personal history of cancer at least three years earlier
- A history of tobacco use
- Genetic risk
- A strong family history of cancer
Dr. Schrag explains that including patients who already survived one type of cancer was strategic for multiple reasons:
- These people face increased risk of developing a new cancer type as well as recurrence of the initial cancer. Recruiting high-risk patients decreases the total number of participants required to answer a research question.
- Cancer survivors are likely to have a deep understanding of what blood testing and imaging studies entail, and they are well-informed to make decisions about participation in this type of research.
- Cancer survivors are motivated to participate in research if it has even a small chance of helping others avoid the ordeal of cancer treatment.
Dr. Schrag cautions that the results from this study are preliminary. Validating the clinical usefulness of liquid biopsy testing to screen for multiple cancers simultaneously will require a randomized trial that recruits a diverse group of patients. New studies are already underway — including one called PATHFINDER2 — to evaluate the test in a larger and more diverse U.S. population.
There is also an important randomized trial evaluating cancer detection in people who had the liquid biopsy test compared with those who did not in patients from the U.K.’s National Health Service. Results from this study are expected in a few years.
The PATHFINDER results are early but significant: They show the feasibility of a new means of early cancer detection.
“This is the brave new world of testing. And although lots more work must be done before this approach becomes standard, it could eventually transform cancer diagnosis and treatment,” Dr. Schrag says.
