by Piri Welcsh, PhD
A new blood test is being promoted by the company that developed it and the media as a simple test that can detect 50 different cancers at the earliest stages.
For years, researchers have tried to develop a “liquid biopsy”—a simple blood test that could detect cancer earlier than current methods of screening. Ideally, a liquid biopsy would reduce the need for other types of biopsies and invasive screening procedures to identify the type of cancer and indicate how best to treat it. This type of test would be particularly helpful for small or hard-to-reach and inaccessible tumors, where surgery may be risky, painful or unable to collect enough cancer cells. Many laboratories are actively researching ways to develop these tests.
Not ready for prime time
The test currently making headlines is Galleri, which was developed by the ambitiously named company Grail. Galleri is being marketed as a way to detect over 50 types of cancer in the earliest stages when they are more treatable. While promising, the test is not yet proven to live up to its media headlines and hype. While “Grail” aptly describes the hope and need for a single accurate test for multiple cancers, the media appears to be fixated more on the company’s name than the lack of scientific basis for its claims.
- One study showed that Galleri detected 39% of stage I, 69% of stage II, 83% of stage III and 92% of stage IV cancers. While the test more accurately detected cancers of increasing stage, it failed to detect almost 60% of stage I cancers.
- In another study published by GRAIL to validate Galleri, the test detected 51.5% of cancers. Again, the sensitivity of the test increased with the stage of cancer. Galleri identified about 77% of stage III and 90% of stage IV cancers. Once again, however, the test failed to dependably detect early-stage cancers, finding only about 17% of stage I cancers and 40% of stage II cancers.
- Early results of yet another study have also been reported by GRAIL. The PATHFINDER study looked at people older than 50 who had an elevated risk for cancer because they were smokers, previously had cancer or had an inherited mutation that significantly increased their cancer risk. In this study, the frequency of false-positive results produced by Galleri was an issue; almost 30% of the positive tests were false positives (the tests were positive for cancer when the individuals had no cancer). False-positive results can lead to additional tests, anxiety and potentially surgical biopsies.
Although the science is promising, many experts caution that liquid biopsies remain unproven, and it is unclear how well these tests perform in people who are at high risk for cancer. During the closing panel of our Annual Joining FORCEs Virtual Conference (you can watch it here), Dr. Susan Domchek of the Basser Center for BRCA at the University of Pennsylvania said of these liquid biopsy screening tests:
“We all want them to work...these tests are going to get better, but from what I've seen so far, these tests are not ready yet...Believe me, the minute we think these tests are good enough, we will roll them out to you!"
For this reason, most experts aren’t ordering these tests for patients. Nor have expert panels that set national guidelines added these tests to their recommendations.
Other issues to consider
Finding cancer early is the key to improved treatments and extended survival. While it seems odd, finding cancers early is not always better. Some tumors may never grow enough to need any treatment. In this case, early detection might result in overtreatment.
False-positive test results are another major concern because they indicate that a tumor may be present, but none can be found. False positives can lead to needless anxiety and unnecessary additional procedures.
Cost is also an important consideration. These tests may cost hundreds of dollars. The current cost for Galleri, for example, is $949. Since these tests are not yet included in screening guidelines most health insurance companies don’t cover them for early detection.
As Dr. Domchek said, “These tests will get better.” As they do improve, insurance companies may be more likely to cover them, and out-of-pocket costs may go down. Now, however, people need to compare the costs and benefits of these tests. In the meantime, you might consider participating in a research study looking at early detection for cancer. Some research studies do not provide participants with the results of their tests, so if you do enroll in a study and knowing your results is important to you, be sure to ask if you will be given your results.
Media coverage is a problem
Hyped headlines describe Galleri as “revolutionary,” “groundbreaking,” “innovative,” “a once in a generation breakthrough,” “a new paradigm for cancer screening,” and, not surprisingly, the “Holy Grail” of oncology.
Gary Schwitzer, the founder and publisher of HealthNewsReview, notes that “…incomplete, fawning news coverage of health screening tests is one of the most clearly established problems in health news coverage.” Underlying this issue is the idea that the benefits of cancer screening have been historically overstated while the harms have been largely ignored.
Much of the media reported that Galleri correctly identified when cancer was present in 51.5% of cases, across all stages of the disease, and wrongly detected cancer in only 0.5% of cases. But there was no analysis of what those numbers mean to patients. Most of the media skirted the entire sensitivity issue. And most did not explain that the 51.5% sensitivity of the test—its ability to find cancer—means that almost 50% of cancers were not detected.
What's more, the test's sensitivity varies based on the type and stage of a cancer, which isn't optimal. For instance, Galleri has been shown to detect just 18.2% of kidney cancers compared to 93.5% of lung cancers. While overall it picks up 90.1% of stage 4 cancers, it only detects an average of 16.8% of stage 1 cancers. Yet it is being touted as a test that can detect cancer early.
The future of liquid biopsies
More well-controlled studies are needed, as well as expert evaluation of results to validate screening tests like Galleri before anyone can confidently declare that these tests benefit patients and improve outcomes.
The next few years could provide valuable answers toward the accuracy and acceptability of tests like Galleri. The U.K.’s National Health Service is conducting an ambitious 140,000-person, randomized trial of Galleri that should be particularly helpful in understanding how well the test can detect early-stage cancer.
Notably, liquid biopsies are also being looked at across many areas of oncology, including finding biomarkers for targeted therapies, monitoring treatment response and looking for evidence of recurrence earlier. The research is still very early, but very promising! Stay tuned!
Read more about liquid biopsies in our XRAY review.