New study once again casts doubt on PSA screening

To screen or not to screen for prostate cancer? This remains an important question. Screening relies on a highly imperfect measure, the prostate-specific antigen (PSA) blood test, which is prone to false-positive results. And with mounting evidence that survival benefits from screening pale in comparison with the harms from overtreatment — particularly incontinence and impotence — the pendulum has steadily swung away from it. Still, screening research continues, in the hopes that some lifesaving benefits may be found.

Now the latest study once again casts doubt on PSA screening as an effective public health tool.

British scientists divided more than 400,000 men between the ages of 50 and 69 into two groups: one was screened for prostate cancer with a single PSA test, and the other wasn’t tested for the disease at all. After an average of 10 years of follow-up, prostate cancer death rates in both groups were nearly identical. Cancer was detected more often in the screened group, but mostly it was low-grade, with a questionable need of treatment.

"This was the largest study of PSA screening to date, and the results don’t support it," said Dr. Michael J. Barry, a professor of medicine at Harvard Medical School, and author of an editorial accompanying the published study.

Called the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), the study’s approach of giving men a single PSA test differs from the more traditional strategy of testing men repeatedly every few years. However, prior studies investigating repeated PSA tests have reached similar conclusions. One European study with 162,000 men, for instance, concluded that for every life saved by screening, 27 men would be diagnosed and treated for prostate cancer that wouldn’t have been lethal if left undetected.

During the CAP study, 189,386 men were assigned to screening and 219,439 men were assigned to a non-screening control group. After 10 years on average, 549 of the screened men had died from prostate cancer, compared to 647 men in the control group who hadn’t gotten a PSA test. The number of prostate cancer deaths among the controls was higher, but so was the number of men in that group to begin with. So the researchers adjusted for the different sample sizes with a statistical tweak: they compared death rates in terms of person-years, or the total number of years that men in either group had participated to the study. Analyzed that way, the study revealed 0.30 prostate cancer deaths per 1,000 person-years in the screened group, and 0.31 deaths from prostate cancer per 1,000 person-years in the controls, which amounts to a negligible difference.

Dr. Barry, who was recently a member of the US Preventative Services Task Force, an influential group of independent experts who publicly discourage PSA screening, emphasized that most men who opt for the test get it more than once. And with each additional PSA test, he said, the odds of being diagnosed with prostate cancer grow higher. "But is repeat screening worth the risk of a low-grade cancer diagnosis and all the treatment complications that come with it?" he asked. "It’s hard for us as clinicians to make those decisions for our patients. We need to make them with our patients to determine if they feel those risks are worth taking on."

Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org, agreed. "This study adds to the discouraging screening literature, and again, simply does not support screening of asymptomatic individuals," he said.

Fortunately, Garnick added, men diagnosed with prostate cancer following a PSA test may not have to be treated either in the short or long term. Depending on tumor characteristics, some can opt to have their cancer monitored with active surveillance, which relies on periodic prostate biopsies or MRI to look for new signs that treatment may be necessary. "Hopefully, current research that uses sophisticated genetic testing or biomarkers of prostate cancer may help provide more precise information about those who are likely to most benefit from screening and treatment," Garnick said. "But we are not there yet."

--  Charlie Schmidt