Prostate-specific antigen (PSA) blood testing is likely to reduce the risk of death from prostate cancer, found a new review published on Thursday by an influential international science research organization — a shift in medical evidence that could encourage wider use.
The Cochrane review’s first author, Juan Franco from Heinrich Heine University Düsseldorf in Germany, said at a press conference that they have “moderate certainty” that the screening test, which identifies high levels of PSA as a potential marker of prostate cancer, leads to a reduction in disease-specific deaths. The benefits are marginal: The review analyzed results from six trials involving 800,000 participants conducted in Europe and North America, and found about two fewer prostate cancer deaths for every 1,000 men screened.
The authors were careful to say that their findings aren’t a blanket endorsement of PSA screening and that men should consult with their doctors about the advisability of the test. Still, to find that PSA screening does reduce deaths constitutes a significant change compared with the last Cochrane review, published in 2013, which didn’t find similar benefits and contributed to PSA screening falling out of favor.
After being widely adopted as a screening tool in the 1990s and used for about 20 years, leading medical organizations discouraged its use, and the U.S. Preventive Services Task Force (USPSTF) changed its guidelines to discourage it, first in men 75 or older in 2008, and then for all men in 2012.
At the time, research was unable to show that screening saved lives, though it identified its harms: Widespread PSA testing led to overdiagnosis and overtreatment, and men with low-grade, slow-growing cancer — who would have otherwise lived long and comfortable lives and died of some unrelated cause — found themselves dealing with the physical and emotional toll of cancer diagnosis and treatment.
Prostate biopsies carry high risk of infection, and surgeries to remove tumors can lead to erectile dysfunction, while radiotherapy and other aggressive treatments have life-altering side effects. Considering half the prostate cancers diagnosed in the U.S. wouldn’t warrant aggressive treatment, and are rather conditions to monitor, the risk of worsening patients’ health while trying to treat them is high.
Compared with the 2013 version, the new review contains more long-term data, in particular from the ERSPC (European Randomized Study of Screening for Prostate Cancer) study, which had a follow-up time of up to 23 years. It confirms that PSA screening has a place, though it needs to be handled wisely. “This study is timely because I think it provides sufficient evidence to support that screening could be beneficial if it is offered appropriately to those who are most likely to benefit, and it could actually save lives,” said Simpa Salami, a professor of urology at the University of Michigan.
Though PSA screening needs to be administered wisely, he said, it is also less likely to lead to a cascade of interventions. “We are doing better now in selecting patients for biopsy,” Salami said. “In the past we would biopsy anyone with just an elevated PSA, but now we have other tools to further refine who should get a biopsy: We have biomarkers in urine, we have biomarkers in blood, we have MRI imaging to facilitate biopsies,” he said, “such that we are actually maximizing the detection of high-grade prostate cancer and minimizing the detection of low-grade prostate cancer.”
The review in itself doesn’t include guidelines or treatment recommendations, and it doesn’t immediately change how screening is implemented. Though as the results are understood, it is important to put them in the context they were collected, said Otis Brawley, a professor of oncology and epidemiology at Johns Hopkins University’s Sidney Kimmel Comprehensive Cancer Center, said it is important to put the results in the context of how they were collected, and understand what it means that disease-specific mortality is reduced through PSA testing.
“In the United States, there are a whole bunch of people who think that means, ‘Oh, if I get a PSA [test], I am doing something to save my life,’” he said, but the participants in the studies who experienced benefits didn’t just get their levels tested once, they did so on a regular basis, and worked with their physicians over time to interpret the results and decide further action.
“It is not what is commonly done in the United States, which is getting your PSA drawn from a van parked at a state fair, a van in the parking lot of a church, or at a football party where it’s, ‘Come on in, see the game, and get your PSA drawn,’” Brawley said. Consistent medical care, as well as accurate follow-ups and treatments, are a challenge in the American health care system, and without them PSA screening alone would fail to deliver its benefits, he said.
“I think the appropriate thing within the doctor-patient relationship is that a doctor ought to offer the test to the patient,” added Brawley, highlighting that there is evidence of the benefits, yet being clear about the risks of overdiagnosis and overtreatment. Doctors who have an ongoing relationship with their patients and can monitor their PSA results over time are well placed to reduce the risk of overtreatment, he said, because they have more data points to decide which patients need biopsies, for instance, and which don’t.
Brawley emphasized that there needs to be clarity on the size of the benefit of screening, and its capacity to prevent deaths. “If you have 15 men who are going to die from prostate cancer, screening them in a program of high-quality screening over a period of 20 years will prevent 1 of the 15 men from dying,” he said. “In the U.S., every man who dies from prostate cancer is viewed as a failure of that man to get screened, or the failure of the doctors to interpret the screening,” he said. “People cannot understand that the majority of people who were going to die from prostate cancer will still die from prostate cancer whether they are screened or not.”
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