Debate About Recommendation Against PSA Test for Prostate Cancer to Continue
The recommendation by U.S. Preventive Services Task Force against PSA screening for men of any age for prostate cancer stirs
swirl of controversy: says special report in NCI Cancer Bulletin
By Carmen Phillips, National Cancer Institute
June 5, 2012 - A long-awaited update from the U.S. Preventive Services Task Force (USPSTF) recommends against screening
prostate cancer with the
prostate-specific antigen (PSA) test. The task force's 2008 recommendation
advised only against screening men aged 75 and older; the update has extended that guidance to include all men.
recommendation - published May 21 in the Annals of Internal Medicine and
USPSTF website - does not apply to PSA testing to monitor prostate cancer
progression after diagnosis or treatment.
"All men deserve to know what the science tells us about PSA screening: There is a very small potential benefit and
significant potential harms," the task force's co-chair, Dr. Michael LeFevre, explained in a statement on the new recommendation.
Based on some of the responses to the recommendation, however, the debate about the value and appropriate use of PSA screening is likely to
continue for some time.
Dr. Sushil Lacy, the current president of the American Urological Association, said the organization was unhappy that the
task force had failed to revise its recommendation to "more adequately [reflect] the benefits of the PSA test in the diagnosis of prostate
And in an accompanying
editorial in Annals, Dr. William Catalona, director of the Clinical Prostate
Cancer Program at the Robert H. Lurie Comprehensive Cancer Center in Chicago, and his colleagues from several other institutions argued that
the task force had "underestimated the benefits and overestimated the harms of prostate cancer screening."
Although task force Chair Dr. Virginia Moyer of the Baylor College of Medicine said that the USPSTF recommendation
essentially advises physicians not to suggest PSA screening for their patients, she added that there is no disagreement about the need for
shared decision-making among patients and physicians.
"We're not saying, 'Don't respond to your patients who ask about screening,'" she said. "Physicians need to have the
right information available, so when patients do ask they can give them accurate information and help them make the best decision."
In January, the
most recent update from the PLCO trial, based on 13 years of
follow-up in nearly 60 percent of the trial participants, showed that regular PSA
screening did not lead to fewer prostate cancer deaths. On the other hand, in the ERSPC trial, men who were screened had an approximately 20
percent lower risk of dying of prostate cancer after 9 years of follow-up.
The PLCO and ERSPC trials differed in design, however, and both had shortcomings that may have influenced the findings,
the task force acknowledged.
The PLCO trial, for example, had a substantial amount of "contamination." That is, about half of the men assigned to
usual care (the control arm) had at least one PSA test during the trial.
A Failing Grade
The USPSTF makes
its recommendations based on a
grading system. The task force gave PSA screening for prostate cancer a
grade of D, which means the evidence indicates "moderate or high certainty that the service has no net benefit or that the harms
outweigh the benefits."
previous recommendation, issued in 2008, PSA screening for men younger than 75 was given an I grade, meaning the task force concluded
that the available evidence was insufficient to judge whether screening had a net benefit or harm.
The task force
issued a draft of the updated recommendation last fall for public
comment, and some who commented suggested that PSA screening be given a C grade, meaning physicians may advise individual patients to
have a screening test or treatment because the evidence suggests there may be a small benefit.
But under the
task force's rules, "We really didn't have any choice about this recommendation," Dr. Moyer explained. "When we put all of the
evidence together, under the most optimistic view, the potential benefit of screening was very small. And the potential harm was
substantial. So the net [impact of PSA screening] comes out negative."
Although there was a lower contamination rate in the ERSPC trial, the reduced mortality risk in the screening arm was
driven almost entirely by participants from just two of the seven countries involved in the trial: Sweden and the Netherlands.
And, Dr. Moyer
noted, the vast majority of patients in the screening arms were treated at academic medical centers, while nearly all of those in the control
arm were treated in community health facilities. This could have biased the results in favor of the screening arm of the study.
Based on an analysis of these and other studies, the USPSTF concluded that no more than 1 death would be avoided for
every 1,000 men aged 55 to 69 years screened every 1 to 4 years for a decade.
In addition to what they called the "methodological flaws" of the two large screening trials, Dr. Catalona and his
colleagues argued that it is still too soon to draw firm conclusions on mortality reduction from either trial because the benefits of
screening for a slow-growing disease like prostate cancer may take years to become evident.
And the task force "gave little weight," wrote the editorialists, to
a PSA screening trial conducted in Göteborg, Sweden, which had longer follow-up
than the PLCO and ERSPC trials, but far fewer participants. That trial - which was part of the larger ERSPC trial - showed a 40 percent
relative reduction in mortality in men aged 50 to 64 who underwent regular PSA screening.
PSA screening likely played a substantial role in the 40 percent reduction in prostate cancer mortality in the United
States since the early 1990s, around the time when PSA screening began to proliferate, said Dr. H. Ballantine Carter, who directs the
active surveillance program for men with prostate cancer at the Johns Hopkins
University Brady Urological Institute.
"I don't think you can ignore those benefits," Dr. Carter said.
Dr. Moyer noted, however, that there would have been a substantial lag period, as long as 10 years, before any impact on
mortality would have been seen from PSA screening. Nevertheless, a 2008
modeling study funded through NCI's
Cancer Surveillance and Intervention Modeling Network, suggested that PSA
screening could account for anywhere from 45 to 70 percent of the observed drop in prostate cancer mortality.
Despite the disagreement the recommendations have caused, Dr. Carter believes the end result may be beneficial. "I think
this starts a conversation that we needed to have about harms and overtreatment, because for a long time those conversations haven't
happened," he said. "I think it will move the field toward more targeted screening."
Carmen Phillips has been writing about science and medicine for nearly 15 years. During that time, he’s written about a wide array of
topics, including infectious disease, cardiology, oncology, and health care policy. Prior to coming to NCI, Carmen wrote for the American Red
Cross, WebMD, and the American College of Cardiology; he has a master’s degree in science-medical writing from Johns Hopkins University.
Carmen’s writing interests include cancer prevention, late-stage clinical trials, and translating innovative research into the clinic. During
work hours, you can find him on Twitter @CarmenBPhillips and @NCIBulletin
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