Utility in practice?
Although PRS has been billed as a predictive test, Dr. Catalona believes PRS could have a range of uses both before and after diagnosis.
PRS may, for instance, guide treatment choices for men diagnosed with prostate cancer, Dr. Catalona noted. For men with a PRS that signals a higher risk for aggressive disease, a positive prostate biopsy result could help them decide whether to seek active treatment with surgery or radiation or go on active surveillance.
PRS could also help inform cancer screening. If a PRS test found a patient’s risk for prostate cancer was high, that person could decide to seek PSA screening before age 50 – the recommended age for average-risk men.
However, Aroon Hingorani, MD, a professor of genetic epidemiology at the University College London, expressed concern over using PRS to inform cancer screenings.
Part of the issue, Dr. Hingorani and colleagues explained in a recent article in the BMJ, is that “risk is notoriously difficult to communicate.”
PRS estimates a person’s relative risk for a disease but does not factor in the underlying population risk. Risk prediction should include both, Dr. Hingorani said.
People with high-risk scores may, for instance, discuss earlier screening with their clinician, even if their absolute risk for the disease – which accounts for both relative risk and underlying population disease risk – is still small, Dr. Hingorani and colleagues said. “Conversely, people who do not have ‘high risk’ polygenic scores might be less likely to seek medical attention for concerning symptoms, or their clinicians might be less inclined to investigate.”
Given this, Dr. Hingorani and colleagues believe polygenic scores “will always be limited in their ability to predict disease” and “will always remain one of many risk factors,” such as environmental influences.
Another caveat is that PRS generally is based on data collected from European populations, said Eric Klein, MD, chairman emeritus of urology at the Cleveland Clinic and now a scientist at the biotechnology company Grail, which developed the Galleri blood test that screens for 50 types of cancer. While a valid concern, “that’s easy to fix ultimately,” he said, as the diversity of inputs from various ethnicities increases over time.
Although several companies offer PRS products, moving PRS into the clinic would require an infrastructure for testing which does not yet exist in the U.S., said Dr. Catalona.
Giordano Botta, PhD, CEO of New York–based PRS software start-up Alleica, which bills itself as the Polygenic Risk Score Company, said “test demand is growing rapidly.” His company offers PRS scores that integrate up to 700,000 markers for prostate cancer depending on ancestry and charges patients $250 out of pocket for testing.
Dr. Botta noted that thousands of American patients have undergone PRS testing through his company. Several health systems, including Penn Medicine, Brigham and Women’s Hospital, and the University of Alabama at Birmingham, have been using the test to help “see beyond what traditional risk factors allow,” he said.
However, this and other PRS tests are not yet widely used in the primary care setting.
A major barrier to wider adoption is that experts remain divided on its clinical utility. “People either say it’s ready, and it should be implemented, or they say it’s never going to work,” said Sowmiya Moorthie, PhD, a senior policy analyst with the PHG Foundation, a Cambridge University–associated think tank.
Dr. Klein sits in the optimistic camp. He envisions a day soon when patients will undergo whole-genome testing to collect data on risk scores and incorporate the full genome into the electronic record. At a certain age, primary care physicians would then query the data to determine the patient’s germline risk for a variety of diseases.
“At age 45, if I were a primary care physician seeing a male, I would query the PRS for prostate cancer, and if the risks were low, I would say, ‘You don’t need your first PSA probably until you’re 50,’ ” Dr. Klein said. “If your risk is high, I’d say, ‘Let’s do a baseline PSA now.’ ”
We would then have the data to watch these patients a little more closely, he said.
Dr. Moorthie, however, remains more reserved about the future of PRS. “I take the middle ground and say, I think there is some value because it’s an additional data point,” Dr. Moorthie said. “And I can see it having value in certain scenarios, but we still don’t have a clear picture of what these are and how best to use and communicate this information.”
A version of this article first appeared on Medscape.com.