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PSA Test Cuts Prostate-Cancer Deaths -- At a Cost

European PSA Study: Screen 936 Men, Save 1 Cancer Death

By Daniel J. DeNoon
WebMD Health News

Reviewed by Louise Chang, MD

March 14, 2012 -- The odds of dying from prostate cancer are 21% lower 11 years after men are offered routine screening with the controversial PSA blood test, European researchers find.

Those odds go down 29% if you only count men who actually got screened in the huge European Randomized Study of Screening for Prostate Cancer, or ERSPC. The study enrolled 182,160 men ages 50 to 74 in eight European countries.

The findings strengthen confidence in earlier results reported in 2009, says study leader Fritz H. Schroder, MD, PhD, professor of urology at the Netherlands' Erasmus University.

"While we don't understand the downside completely, the upside of screening has improved with this report," Schroder tells WebMD. "We more definitively show there is an advantage in screening for prostate cancer, and that the reduction in prostate cancer mortality for those men who are screened amounts to 29%."

Despite this benefit, Schroder says the findings do not mean that all men should get regular PSA tests.

"The difficulty is we still haven't made any progress in avoiding the overdiagnosis and overtreatment [of PSA-screened men], which is the main factor impacting their quality of life," he says. "There is no way at this moment to come to a population-based screening policy anywhere in the world. Men must still be confronted with the need to make their own decisions."

Overdiagnosis is the detection and treatment of a latent or slow-growing cancer that would never kill. Schroder and colleagues estimate that half of screening-detected prostate cancers are overdiagnosed. They calculate that 936 men must be screened for 11 years, and 33 cancers detected, to avert a single cancer death.

The cost of overdiagnosis is high, says University of Toronto researcher Anthony B. Miller, MD.

"We know the complications of screening," he says. "One of the major ones is that you find latent prostate cancers -- ones that are not likely to progress, will never kill an individual, would not cause that individual symptoms -- yet if you find them you have to treat them. The consequences of treatment can be quite severe. Men become impotent and incontinent. Both in the U.S. and European trials, deaths have occurred as a result of treatment for prostate cancer."

European PSA Study vs. U.S. PSA Study

The European findings are in contrast to those from the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) study. Miller says the U.S. study "shows absolutely no indication of a benefit" even after 13 years of routine PSA screening.

Miller, one of the PLCO investigators, is critical of the European study. In an editorial accompanying the Schroder report, he suggests that PSA-screened men were more likely to be treated for prostate cancer at academic centers, where they got more state-of-the-art treatment.

And even though the screened men were less likely to die of prostate cancer, death from any cause was just as likely in screened as in unscreened men.

Schroder says the PLCO study has its own flaws -- not least of which is that about half the men in the group that was supposed to be unscreened actually had a PSA test before the study began. This, he says, means that many men with hidden, aggressive cancers were never enrolled in that group.

Indeed, in the European study, three-fourths of the screened men who died of prostate cancer had their disease detected on first screening.

Both Schroder and Miller agree that while they complement each other in some ways, the two large PSA studies have many differences. These include:

  • European men were screened only once every four years (every two years in Sweden); U.S. men were screened every year.
  • In Europe, screened men got prostate biopsies when their PSA level was 3 ng/mL. In the U.S., the PSA cutoff was 4 ng/mL.
  • In the European study, 13% of screening tests were false positives (no cancer detected on biopsy). The false-positive rate in the U.S. study was 7%.
  • The European PSA study enrolled about twice as many men as the U.S. study.
  • Overdiagnosis rates were about 50% in the European trial, but 17% to 30% in the U.S. trial.

The PSA Test: Advice to Men

Despite their very different takes on the two PSA studies, Schroder and Miller are in remarkable agreement about the lessons men should take from them.

Both agree that the U.S. Preventive Services Task Force is correct to say that men should not routinely be given PSA tests.

But Schroder argues for a more nuanced approach -- the one advocated by the American Cancer Society. That advice is for doctors to sit down with each individual patient to give him a thorough explanation of both the risks and benefits of regular PSA tests.

Unfortunately, Schroder says, doctors are more or less on their own. What they need is research that will tell them the most effective way to help men make this important decision.

"The time has come to develop and validate balanced information on the advantages and disadvantages of PSA screening for the man on the street," he suggests.

The Schroder report, and Miller's editorial, appear in the March 15 issue of the New England Journal of Medicine.

SOURCES: Schroder, F.H. New England Journal of Medicine, March 15, 2012.Miller, A.B. New England Journal of Medicine, March 15, 2012. Fritz H. Schroder, MD, PhD, professor of urology, Erasmus MC University Medical Center, Rotterdam, Netherlands, and principal investigator, European Randomized Study of Screening for Prostate Cancer. Anthony B. Miller, PhD, professor of epidemiology and social/behavioral health sciences, Dalla Lana School of Public Health, University of Toronto, Canada. Andriole, G.L. Journal of the National Cancer Institute, published online Jan. 6, 2012.

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