As screening falls, will more men die from prostate cancer?

Physicians, scientists, and public health experts who long warned that PSA screening for prostate cancer is more harmful than helpful have finally gotten what they wanted: significantly fewer men are having the blood test today than in 2005, two studies reported on Tuesday.

Now begins the crucial experiment: with fewer PSA tests, will more men die of prostate cancer?

An editorial accompanying the papers published in the Journal of the American Medical Association argues yes. The 33,519 fewer detected cases of prostate cancer in 2012 compared to 2011, as one study reported, mean that prostate cancer will eventually kill 1,241 more men because their disease was not detected early, calculated urological surgeon Dr. David Penson of Vanderbilt University.

Other experts disagree.

The claim that fewer PSA tests will cause more prostate cancer deaths “is based on putting all your faith” in a European study that found a mortality benefit from the screening, said Dr. Kenneth Lin, a family medicine physician at Georgetown University School of Medicine. “It’s not right to ignore the other trials,” which did not show the blood test saves men’s lives.

The debate over PSA testing has been roiling medicine for years. About 10 years ago, evidence began growing that the test, which detects levels of an enzyme (prostate specific antigen) released by prostate cells, had led to an epidemic of overdiagnosis and overtreatment. Elevated levels of PSA, it turned out, might indeed detect prostate cancer. But many and perhaps most of those cancers are so slow-growing they pose no threat to a man’s health or life.

Men could die with prostate cancer, not of it.

“The problem is, PSA tests find a whole lot of prostate cancers that will never kill people,” said urological surgeon Dr. Peter Albertsen of the University of Connecticut Health Center. As a result, the test “saves as little as one life out of every 1,000 men screened.”

Yet the dread that a diagnosis of cancer inspires, to say nothing of physicians’ fears of malpractice suits, means that many men with elevated PSAs receive biopsies. And if malignant cells are found that further results in surgery, radiation, and chemotherapy. In some men, the treatments cause incontinence and impotence. While that’s better than dying, it’s a high price to pay if the cancer is never destined to cause problems.

That calculation led the US Preventive Services Task Force, a group of medical experts assembled by the federal government, to recommend against PSA screening for men 75 and older in 2008. The task force recommended against it for all men in May 2012, though a draft of that advice came out seven months before and received extensive media coverage.

The two JAMA studies analyze what happened next.

One paper, by researchers at the American Cancer Society (which also funded it), found that the incidence of diagnosed prostate cancer in men 50 and older, as reported in national registries, fell from 541 per 100,000 men in 2008 to 416 per 100,000 in 2012. Those rates began falling in 2008, after the task force’s first recommendation. The largest decrease came between 2011 and 2012.

In absolute terms, 213,562 men 50 years and older were diagnosed with prostate cancer in 2011, vs. 180,043 in 2012, a decline of 33,519.

That decline in cancer detection coincided with changes in the PSA screening rate for men 50 and older, as reported by a national interview survey of thousands of men. In 2005, 37 percent of men 50 and older said they’d had a PSA screening in the previous 12 months. That rose to 41 percent in 2008 but fell to 38 percent in 2010 and 31 percent in 2013.

The second JAMA study found slightly different PSA rates — 34 percent in 2005, 36 percent in 2010, and 31 percent in 2013 — but the decrease occurred only in men younger than 75, for unknown reasons.

Experts didn’t expect a decline at all. “I’m a little surprised,” said Georgetown’s Lin, a former staff member of the preventive services task force. After that panel recommended that women get fewer mammograms and start at a later age, “the rate of mammography barely budged.”

Lin suspects that many physicians have first-hand experience with patients who have been harmed by PSA screening, and are, therefore, following the American Cancer Society’s recommendation to clearly explain the test’s potential risks and benefits rather than reflexively order it as part of a routine physical.

What the decline in screening and the accompanying drop in prostate cancer diagnoses mean for men’s health may not be known for years.

One hopeful sign is that the fewer PSA screenings have not been accompanied by an overall change in the stage at which prostate cancer is detected (by symptoms or physical exam), the cancer society found. Incidence of later-stage cancer was unchanged, except for an increase in non-Hispanic white men 75 and older.

Penson’s calculation of 1,241 additional prostate cancer deaths from a single year’s decline in PSA screenings is based on a 2014 study in eight European countries. In six, the tests did not save lives, but in Sweden and the Netherlands it did, enough for the overall study to find a small benefit in lives saved.

“But of 11 trials, all say there are harms from the test and only [those] two say it works,” said Dr. Otis Brawley, chief medical officer of the cancer society and co-author of its JAMA paper.

In contrast, a long-running American study has not found that PSA screening saves lives. It did not have clean comparison groups, however: many men randomly assigned to the non-PSA group had the test anyway, raising concerns that the study didn’t really compare PSA screening to no PSA.

One way to move past the PSA debate, said Albertsen of the University of Connecticut, might be to offer the tests only to men at high risk for prostate cancer (the task force recommendation against PSA screening applies to all men). Men with a family history of the disease or who have relatively high PSA levels at age 45 or so, for instance, have a greater chance of developing it.