What to Make of the Prostate Cancer Screening Studies

The latest studies on PSA screening for prostate cancer seem to conflict, but actually both make sense.

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By Bernadine Healy, M.D.

Two ongoing prostate screening studies, one in the United States and the other in Europe, provide an early peek at mortality information. The studies, discussed in the just released issue of The New England Journal of Medicine, have caused a storm of confusion, since they seem to conflict. Actually, the studies are complementary, both make a lot of sense, and they are certain to influence medical practice even before they are completed.

For background, U.S. health policymakers are concerned that too many people get screened with the prostate-specific antigen test, which can identify prostate cancer long before symptoms develop. For this slow-growing tumor, that can mean before it needs to be detected, leading to unnecessary treatment, side effects, and cost. Thus, many think PSAs should be reined in. In contrast, in Europe, where PSAs are not routinely available to screen healthy men for disease, prostate cancer mortality is higher, leading some to believe that the reins on the test should be loosened up.

The two major randomized, controlled trials, begun in the early 1990s, offer a peek after roughly 10 years of monitoring and seem to affirm both views: The European study shows a mortality benefit from screening, while the American study, in which half of those in the control group (supposed to be unscreened) were unwilling to give up their PSAs, showed no benefit.

Though some pundits might dismiss one or the other of these studies from both sides of the pond, the two together provide powerful insights. Inderbir Gill, chairman of the University of Southern California Institute of Urology, believes that the studies are a huge step forward in understanding PSA screening. And "they surely serve as a moment of pause and reflection for those who might be too aggressive in treatment," he adds.

The original plan for both studies was a head-to-head comparison of groups of healthy men who were or were not screened with PSAs. What has emerged are two very different trials highly influenced by the varied European and American medical practices. In Europe, PSA screening of healthy men is not recommended routinely, and the mortality rate for prostate cancer is generally higher than in the United States. The men in the control group in the European study did not have the ready option of getting PSA tests from their community doctor outside of the study. And in the screening group, the Europeans found almost twice as many cases of prostate cancers as compared with the control group.

The European results show that picking up cancers before they produce symptoms brings a 20 percent improvement in mortality, and if the analysis is done including only those people who actually got screened (some signed on but did not get tested), the benefit was 28 percent. Based on bone scans, the screened group was 40 percent less likely to have cancer that spread to bone, the favored site for prostate cancer metastasis.

However, the benefit came with a lot of overtreatment if one looks only at the first-decade mortality figures: To save one life, the European study tested more than 1,000 men and treated close to 50 of them. That's sobering, considering the cost and side effects of treatment—unless, of course, you're that one man.

In the American trial, the background of medical enthusiasm for routine, yearly PSA screening had great influence. The health-conscious men who usually sign up for a research study had trouble giving up their regular PSAs.

To start with, almost half of the men entering the trial had been getting PSAs before joining, and those who did had a 25 percent lower mortality rate at the 10-year mark than the other men who joined the trial without prior testing. Once in the trial, more than half of the men in the "control" group continued to get their PSAs as part of their routine medical care outside of the study. So what the American trial is really comparing is a more intensely screened group in which 85 percent of men get their PSAs (some men in the screening group never got tested) with a moderately screened group where only 52 percent do. No surprise that in the control group nearly as many cancers were detected as in the so-called screened group.

It is also not surprising that the American study shows, so far during the first decade, no mortality difference between groups. From this, one could conclude that leaving the choice of whether to be screened up to men comes at no peril to public health. There is no need to try to force mass screening when moderate screening may work as well, particularly since the treatment of the disease comes with harm that many men are unwilling to accept.

In the meantime, practice continues to change. PSA screening has improved since the trials began and will get better yet. Doctors have come to recognize that watchful waiting is a sound option when a prostate cancer is small and slow growing. And regardless of their views on early screening, most urologists in the United States today agree that the decision to detect and treat prostate cancer needs to be personalized, and ultimately made by the patient.