February 17, 2023 – In January 2022, Anthony Arenz, a 51-year-old from Mesa, Arizona, breathed a sigh of relief.
The blood Test that checks for 50 types of cancer – generally known as the gallery test – had not detected any positive signs.
That can be welcome news for anyone, but especially for a firefighter whose job carries a 9% higher risk of cancer and 14% higher risk The risk of dying from it is larger than for the typical person. The unit in Mesa had already lost two soldiers, Cancer within the last 3 years. Both were greater than a decade younger than Arenz.
But when town of Mesa offered additional free tests – including a full-body MRI for firefighters over 50 – Arenz initially dismissed them. With a negative Galleri test in hand, he didn't wish to hassle with it any further.
Still, he felt a pang of guilt for skipping a test that lots of his deceased colleagues had not been offered. He tried to ease his fears by doing research. But a take a look at the corporate's website didn’t put his mind comfy. According to Grail Bio, the maker of the Galleri test, a results of “No cancer signal detected” doesn’t rule out cancer.
Arenz has booked his free MRI.
The result was serious: stage I kidney cancer. The Galleri test had missed it.
Arenz received his free Galleri test through a Cancer prevention The program is funded by the City of Mesa on the Vincere Cancer Center in Scottsdale. Led by radiation oncologist and Vincere co-owner Dr. Vershalee Shukla, this system screens first responders without spending a dime in greater than 10 Arizona cities.
Vincere began using Galleri shortly after the test launched to consumers in June 2021. Since then, the primary responder program has change into an avid user of the test.
But Galleri's ability to detect cancer and, perhaps more importantly, the implications of false results have been under scrutiny because the test was introduced to the market. Galleri is just not yet FDA-approved and remains to be so recent that few know what false results appear like in practice and the way common they might be.
“Good”, but “not finished yet”
After conducting the test on about 2,000 first responders, Shukla can provide some insight into the test's true utility in a high-risk population.
“Cancer prevention is a very complicated issue,” she says. And “to be honest, the tests are good, but not yet fully developed [for wider use].”
Arenz was not the one firefighter who experienced a surprise after a Galleri test.
In nearby Phoenix, 51-year-old Mike Curtis knew his risk for cancer was high, but he wasn't too apprehensive. Curtis had been running into fires since he was 17, and his father, also a firefighter, had died of cancer at age 58.
He had taken advantage of each free screening offered by Vincere Cancer Center because the program began in late 2018 — long before Shukla began using Galleri in 2021. His most up-to-date lung scan was normal. But he took the Galleri test just to remain alert.
The results were a shock. The test had found signs of cancer.
Curtis decided not to inform anyone, not even his wife. Until he was sure, he desired to bear the bad news alone.
Shukla, nevertheless, immediately doubted the outcomes of the blood test. She immediately ordered several follow-up tests. Per week later and after scans of Curtis' abdomen and pelvis, her suspicions were confirmed. The Galleri test was unsuitable, Curtis didn’t have cancer.
The price for his peace of mind: a comprehensive examination price $4,000. Fortunately, the bill was covered by the screening program.
Overall, within the just over 18 months that Shukla has been using the blood test, he has only seen one other false positive result out of about 2,000 Galleri results.
With Galleri, she also discovered two positive cancer signals that were confirmed in follow-up tests. One was a chordoma, a rare style of bone cancer, and the opposite was a squamous cell carcinoma of the top and neck. Galleri discovered each of those remarkably early, in time for treatment.
But for Shukla, the false negatives were particularly “terrifying.” Arenz was just one in every of 28 cancers the blood test missed. And since 500 negative tests haven’t yet been confirmed, the 28 false negatives could also be an underestimate.
In her experience, the binary test result – an easy positive or negative cancer signal – is a simplification of risk, she says. It “gives the false impression that you either have cancer or you don't” when the test itself is inconclusive.
Whitney Jones, chief medical officer at Grail, agrees that the test is just not intended as a standalone cancer screen. Galleri's goal is to “complement other screenings, not replace them,” he says.
According to an evaluation of Galleri data and Shukla's experience, the test's specificity was over 99%, meaning the test successfully minimizes the variety of false positives.
However, the sensitivity of the test was much lower. Shukla's data on first responders showed a sensitivity of 6.7%. This implies that the test misses about 93 out of 100 cancers. According to Grail's latest data In greater than 6,300 people over 50 years of age, the sensitivity of the test was 29%.
Specificity and sensitivity are metrics used to certify a test and ensure the reliability of its ability to detect the goal disease. A test with high specificity can appropriately discover patients without the disease in query, while a test with high sensitivity can appropriately discover patients with the disease. However, there are trade-offs between sensitivity and specificity. One is increased on the expense of the opposite.
It's normal for specificity to be a priority in a cancer screening test, says Dr. Aparna Parikh, an oncologist at Massachusetts General Hospital Cancer Center in Boston. With a test like Galleri, which is meant for use along side other screening tests, “we see at least good specificity, which is important because we don't want false positives that can cause significant distress to the patient.”
Overall, Jones said, Grail Bio's goal is to develop a test that’s sensitive enough to detect essentially the most dangerous cancers without flooding the health care system with false positives. Additionally, Jones said, sensitivity varies by cancer type and tends to be lower for cancers for which other screening tests exist already and for early-stage disease.
But the Galleri sensitivity values are “a little scary,” says Ji-Hyun Lee, a public health physician and director of the division of quantitative sciences on the University of Florida Health Cancer Center. Lee, who is just not affiliated with Grail, reviewed the corporate's publicly available data in addition to Shukla's data for WebMD.
Although there is no such thing as a definitive threshold for sensitivity, error rates of as much as 93% and 71% respectively “offer little confidence in the [accuracy of the] test,” says Lee.
However, positive and negative predictive values are more clinically relevant measures of a screening test. These numbers provide information about how likely a patient's results are to be accurate and therefore how concerned they should be about a positive result and how confident they should be about a negative one.
Among first responders, Shukla found that only half of the positive Galleri tests were confirmed cancer cases. And an analysis of Grail’s data showed only 38% of Galleri tests positive – 35 out of 92 people – had a confirmed cancer diagnosis.
If only 38 percent of positive Galleri results in the general population actually indicate cancer, the test is “not a real decision-making aid for either the patient or the medical staff,” says Lee.
Galleri can also be costly for patients, regardless of the result, says Dr. Electra Paskett, an epidemiologist and cancer screening expert at Ohio State University. A positive Galleri test requires a series of follow-up tests, with no coverage from payers. If the result is negative, Galleri recommends that the patient be retested in one year. This costs $950 annually, plus any follow-up tests if Galleri does indeed find anything.
“If a provider wants to offer the Galleri test, I think all of these things need to be made very clear,” says Paskett.
After a negative Galleri test, Arenz's cancer didn’t go unnoticed as he received further free imaging tests. However, whether all doctors go that far to substantiate Galleri results even in negative patients is unknown.
A negative result can provide patients “an enormous false sense of security,” Shukla says. And if a test is positive, the investigation isn't easy, she says. Searching for cancer, especially cancer that isn't there, can be nerve-wracking and expensive.
So the question is: why do Galleri testing at all if it requires so much validation?
Parikh says a high-risk group like firefighters would be an ideal use case for Galleri and other liquid biopsy tests. But, she says, if it were used more widely in the general population, she would be “skeptical that the system can handle this test in mass.”
Shukla says she's less concerned with the results she's getting today and more concerned with making the test even more effective for her patients in the future. First responders need a test like this one that can quickly identify multiple cancers, she says. But to improve it, Grail needs more data on this high-risk group. That's her goal.
Curtis doesn't regret having the Galleri test. He doesn't think the emotional burden of thinking he might have cancer for a few days was too high a price to pay. The test is part of cancer screening.
However, he says it would have been a far more stressful experience if he had been financially responsible for the investigation or if he had not had Shukla to manage his case from start to finish.
Since it was free, Arenz Galleri has no regrets. But he advises his colleagues to check the site, do some research and get themselves checked out more closely.
“You need to watch out in any medical center that only does this one test,” says Shukla. “It's not that straightforward.”