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September 8, 2017

PSA screening saves lives, new study says—but the controversy shows no signs of stopping

Daily Briefing

A new study published in the Annals of Internal Medicine states that the prostate-specific antigen (PSA) test "can significantly reduce the risk for prostate cancer death"—but the study has many critics who say the screening could lead to overdiagnosis and unnecessary treatments.

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'The controversy that refuses to die'

According to the New York Times, prostate cancer screenings typically involve a blood test that measures a patient's levels of PSA, a protein released by the prostate gland. Elevated levels of PSA could signify the presence of cancer, the Times reports, but it can also be caused by other, less serious factors, such as inflammation.

Overall, around 80 percent of positive PSA tests are believed to be false-positives, the Los Angeles Times' "Science Now" reports, which can result in patients undergoing unnecessary treatment with potentially serious side-effects, such as difficulties with urination and sexual function. Moreover, according to "Science Now," even among men who do have prostate cancer, the cancer is often so slow-growing that treatment is unnecessary.

As a result, the medical community has been long divided about the value of PSA tests, the Times reports. For instance, in 2009, two studies in the New England Journal of Medicine (NEJM) reached contradictory conclusions about the test: The first, called the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), found that the PSA screening did not reduce deaths among men with prostate cancer, while the second study, conducted in Europe, found that the screening reduced deaths by 21 percent. As one editorial, published alongside the studies, put it, the debate over the value of the PSA test is "the controversy that refuses to die."

Meanwhile, the U.S. Preventative Services Task Force (USPSTF) in 2012 recommended against routine screenings. In a proposal earlier this year, however, the panel revised its recommendations, urging men ages 55 to 74 to consult with their physicians about whether they would benefit from a test—although it still advises against routine screening for younger and older men.

Details on the newest study

For the latest study, researchers—including several involved in the 2009 NEJM studies—used three mathematical models to assess the data used in the NEJM studies. After comparing mortality rates between men who had undergone screening and those who hadn't, the researchers concluded that the PSA test, when administered to men who fit the criteria for screening, reduced prostate cancer deaths by 25 to 32 percent over the course of 11 years, primarily because the cancer was detected early.

Ruth Etzioni, a biostatistician at the Fred Hutchinson Cancer Research Center and lead author on the latest study, explained that the PLCO study was flawed because at the time it was conducted, "a lot of the population was already being screened for prostate cancer"—and that muddied the comparison between the screening and non-screening groups. According to Etzioni, around 46 percent of the men in the non-screened group underwent yearly PSA tests as part of their routine medical care, while some of the men in the screening groups were not actually screened. "Comparing the groups to one another wasn't answering the question everyone really wanted answered," she said. "What our analysis amounts to is the comparison that people really wanted: screening versus not screening."

That said, Etzioni acknowledged that for every life saved by the screening, about five men would be told they have cancer—even if that cancer would not spread, grow, or harm them during the course of their lives.

No easy answer, experts say

Despite the new study, many in the medical community said they remain divided over the test, STAT News reports.

For instance, Kenneth Lin of Georgetown University Medical Center said claiming PSA tests can reduce prostate cancer deaths by about 30 percent is likely an overstatement. "Models are models," he said. "No matter how sophisticated, they shouldn't trump data from real people who participated in the randomized trials."

Separately, Ted Karrison, a biostatistician at the University of Chicago, pointed out that men in the PLCO study's non-screening group who got screened could have differed from those who opted to not get screened—such as being more health conscious or conscientious. If so, those traits could be better aligned with lower prostate cancer mortality rates than the screening itself.

Meanwhile, in an accompanying editorial, Andrew Vickers, an attending research methodologist at Memorial Sloan Kettering Cancer Center, argued that the PSA test clearly saves lives—and that the debate needs to be reframed.

"It's not a take-it-or-leave-it," Vickers said. "A PSA test cannot really harm you or save your life. What can harm you is if the test leads you to get treatment you don't need, and what can save your life is the PSA test that finds the cancer that could kill you." As a result, the "controversy about PSA-based screening should no longer be whether it can do good but whether we can change our behavior so that it does more good than harm," he concluded (Healy, "Science Now," Los Angeles Times, 9/4; Rabin, "Well," New York Times, 9/4; Begley, STAT News, 9/4).

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