By Sharon Begley
NEW YORK (Reuters) - A task force advising the U.S. government on Monday recommended against routine use of the prostate-cancer screening test called PSA, or prostate specific antigen, for lack of a discernible health benefit.
Like a draft proposal last October, the U.S. Preventive Services Task Force gave PSA screening a D, for "don't recommend" in healthy men.
The reaction was fast and furious. Screening advocates warned that the recommendation will cost lives, but critics of PSA testing said thousands of men will be spared impotence and incontinence as a result of needless cancer treatment.
A D means there is "moderate or high certainty" that a procedure has no net benefit or that harms outweigh benefits. It is a downgrade from the panel's last PSA recommendation, in 2008, which said the evidence was insufficient to assess the procedure's risks and benefits, although PSA screening for men 75 and older was not recommended.
Now, however, "there is convincing evidence that the number of men who avoid dying of prostate cancer because of screening after 10 to 14 years is, at best, very small," the task force said in the May 22 issue of the Annals of Internal Medicine. Doctors, therefore, should discourage it.
The recommendation does not preclude men from asking for PSA screening, or doctors from offering it. But it could affect whether insurers, including the government's Medicare program, cover the test's $60 to $80 cost.
The only other screening method is the old-fashioned digital rectal exam, which cannot detect small, early cancers. Neither the exam nor PSA can distinguish slow-growing from aggressive cancers.
About one in six American men will be diagnosed with prostate cancer during his life; 2.8 percent, or a projected 28,000 this year, will die of it. Many cases pose no risk even without treatment. Research has shown that between one-quarter and one-third of 60-something men have prostate cancer, often without knowing it. Three-quarters of men older than 85 years have prostate cancer but few die of it.
PSA, a blood test, is a poor screening tool because PSA levels can rise for reasons unrelated to cancer, including age and prostate enlargement. Yet an elevated PSA level can trigger a biopsy to check for cancer.
Most biopsies show no cancer, which means the PSA was a false positive. But prostate biopsies that detect cancer do so based on research from the 1840s, explained Dr. Otis Brawley, chief medical officer of the American Cancer Society.
"As many as 70 percent of these lesions are cancer only by this antiquated definition and not in behavior," he said. That is, they are indolent or inert and will not threaten a man's health or life.
Radiation oncologist Anthony D'Amico of Dana-Farber Cancer Institute in Boston acknowledges that PSA screening causes overdiagnosis, "but if you get rid of the PSA test, men will suffer and die of prostate cancer," he said.
"I'm shocked that they would let people die in order to avoid incontinence and erectile dysfunction, which can be corrected."
The task force analyzed 64 studies, but focused on two, both published in 2009 and updated this year.
The U.S. study compared 76,685 men aged 55 to 74. About half were assigned to receive annual PSA screening and half to "usual care," which sometimes included a PSA test. The study found no evidence that PSA screening saved lives after 13 years.
The European study was similar, with about half of 162,243 men aged 55 to 69 getting regular PSA tests and half not. But for every 1,055 men who were screened every one to four years, there was one fewer death from prostate cancer after 11 years compared to men in the unscreened group. That is the basis for the task force's conclusion that PSA screening for a decade will prevent at most one man in 1,000 from dying of prostate cancer.
The trials themselves were imperfect, polarizing the debate even further.
The American trial was marred by the fact that some men in the "unscreened, usual care" group did receive PSA tests. Such so-called crossovers can weaken a trial's conclusions.
"With the rate of screening in the ‘unscreened arm' matching that in the ‘screened' arm, you can never measure a difference" in the death rates "even if one exists," said D'Amico.
The trial scientists disagreed, saying the crossovers were statistically equivalent to having fewer people in the trial, said biostatistician Paul Pinsky of the National Cancer Institute, a member of the study team. "But there was twice as much screening in the intervention arm, and we did not find a mortality benefit."
The European study is actually seven studies, each from one country. In five, the results mimicked the American findings: no statistically significant reduction in deaths from prostate cancer among screened men. But studies from Sweden and the Netherlands showed benefits.
The European scientists and their supporters argued that the Swedish trial in particular was strong enough to stand on its own as evidence that PSA screening saves lives.
Perhaps the greatest problem with the European study is that the screened men diagnosed with prostate cancer generally received top-of-the-line care from academic physicians. If the unscreened men developed prostate cancer, they received less specialized, less aggressive care. "That means this was a trial not only of PSA screening but also of aggressive vs. non-aggressive treatment," said Brawley.
Against the tiny benefit of PSA testing, the task force weighed its harms. At least 15 percent of PSA tests will trigger a biopsy, after which up to one-third of men experience pain, fever, bleeding, infection, difficulty urinating, or other problems requiring medical attention, studies show.
If a biopsy finds seemingly malignant cells, as happens to 120 in 1,000 screened men, about 90 percent of men opt for surgery, radiation or hormone-deprivation therapy. Up to five men in 1,000 opting for surgery will die within a month of the operation; 10 to 70 more will have serious cardiovascular complications such as a stroke or heart attack.
After radiotherapy and surgery, 200 to 300 of 1,000 men suffer incontinence, impotence or both. Hormone-deprivation therapy causes erectile dysfunction in about 400 of 1,000 men.
"When you stack up those harms, the tiny or zero benefits do not outweigh the risk," said task force co-chair Dr. Michael LeFevre of the University of Missouri Medical School. Because PSA tests cannot distinguish between aggressive and indolent cancer, said ACS's Brawley, "men are rendered impotent and put in diapers, and for what?" he asked. "They never really had cancer in the first place."
The task force is not saying no man of any age under any circumstances should undergo PSA screening. "A D recommendation does not preclude discussions between clinicians and patients to promote informed decision making that supports personal values and preferences," it said. The recommendation is against routine screening.
"Our recommendation should not preclude a physician offering a PSA test or a man requesting it," said co-chair LeFevre. He would be glad to provide the test for his patients, he said, if the decision were based on a clear understanding of the possible benefits and harms. ACS's Brawley agrees that "a fully-informed man who wants to be screened in his doctor's office should be screened." Only if physicians are prepared to explain all this, including that PSA screening misses just as many cancers as it finds, said the task force, can men make an informed choice.
Experts on both sides do agree that mass free screenings offered by hundreds of urology clinics and hospitals should end. "There is minimal discussion of risks and benefits; a pamphlet isn't going to do it," said D'Amico. "But a lot of fear gets invoked."
(Reporting By Sharon Begley; Editing by Michele Gershberg and Cynthia Osterman)