Two large, long-awaited studies have failed to produce convincing evidence that routine prostate cancer screening significantly reduces the chances of dying from the disease without putting men at risk for potentially dangerous and unnecessary treatment. Does this information surprise you as much as it seems to be surprising the news media and some doctors? It shouldn’t.
According to a story, from the Washington Post: the PSA blood test, which millions of men undergo each year, did not cut the death toll from the disease in the first decade of a U.S. government-funded study involving more than 76,000 men, researchers reported today.
A second study, a European trial involving more than 162,000 men that was released simultaneously, did find fewer deaths among those tested. But the reduction was relatively modest and the study showed that the screening resulted in a large number of men undergoing needless, often harmful treatment.
Together, the two studies, one from the U.S. and the other from Europe, along with an accompanying editorial — released early by the New England Journal of Medicine to coincide with presentations at a scientific meeting in Stockholm — cast new doubt on the utility of one of the most widely used tests for one of the most common cancers.
“Americans have been getting screened for prostate cancer because there is this religious faith that finding it early and cutting it out saves lives,” said Otis W. Brawley of the American Cancer Society. “We’ve been doing faith-based screening instead of evidence-based screening. These findings should make people realize that it’s a legitimate question about whether we should be screening for prostate cancer.”
Other experts were more circumspect, arguing that the European study did indicate at least some benefit for some men, and the U.S. trial could eventually confirm those findings as it follows the men for longer periods. But they agreed that the new findings should prompt patients and their doctors to discuss the potential risks and benefits so they can make more individual decisions about whether to undergo the testing.
“It shouldn’t be a knee-jerk response to get tested,” said Christine D. Berg of the National Cancer Institute, which sponsored the U.S. study. “We should be telling these guys to go talk to their physician and say, ‘In light of the current evidence and what you know about me and my health, what should I do?’ ”
Some researchers, however, remained supportive of widespread testing, saying the U.S. study has flaws that could have undermined its ability to detect a reduction in deaths.
“I don’t think that screening should be summarily dismissed based on these trials,” said E. David Crawford, a professor of urology at the University of Colorado who helped conduct the U.S. study and heads the Prostate Conditions Education Council, which promotes testing. “I think they say we should be more smart when we screen.”
Focusing on the controversy surrounding PSA testing, the Los Angeles Times story reports, “Whether to screen or not has been a controversial topic for at least 20 years. Many clinicians have believed that finding a tumor early and cutting it out is the best possible way to treat prostate cancer, just as it is for most other tumors.”
Critics argue, however, “that many prostate tumors grow so slowly that the patient is likely to die of some other cause before the tumor becomes a threat.” They say “that treatment can cause more damage than leaving the tumor alone.”
USA Today coverage was even more blunt, reporting that the studies suggested “prostate cancer screening saves few, if any, lives, but may harm countless men by leading them to undergo therapies that can cause impotence, incontinence, and even death.”
The findings address perhaps the most important and contentious issue in men’s health — how best to detect and treat prostate cancer. More than 218,000 U.S. men are diagnosed each year and about 28,000 die of it, making it the most common cancer after skin cancer and second-leading cancer killer among men.
The PSA test, which measures a protein produced by prostate tissue called the prostate-specific antigen, has significantly increased the number of prostate cancer cases being caught at very early stages. But it has been far from clear whether that translates into a reduction in deaths from the disease. Prostate cancer often grows so slowly that many men die from something else without ever knowing they had it.
Because it is not clear precisely what PSA level signals the presence of cancer, many men experience stressful false alarms that lead to surgical biopsies to make a definitive diagnosis, which can be painful and in rare cases can cause serious complications.
Even when the test picks up a real cancer, doctors are uncertain what, if anything, men should do about it. Many are simply monitored closely. Many others, however, undergo surgery, radiation and hormone treatments, which often leave them incontinent, impotent and experiencing other sometimes debilitating or even possibly life-threatening complications.
“I know guys who are morbidly depressed because of the complications of their prostate cancer treatment,” Brawley said. “I know three people who attempted suicide. I know widows of guys who died from their treatment. There are significant harms associated with over-treatment of prostate cancer.”
Because of the uncertainty, many major medical groups have stopped recommending routine PSA testing. For example, the U.S. Preventive Services Task Force, which sets federal policy on preventive health care, last summer recommended that doctors stop testing elderly men and concluded it was unclear whether the screening was worthwhile for younger men. Nevertheless, PSA testing remains widespread, and many experts were hoping the two large trials would help settle the issue.
In the U.S. study, researchers randomly assigned 76,693 men ages 55 to 74 at 10 centers, including Georgetown University, to receive either six annual screenings consisting of PSA testing and physical examinations or whatever their doctors recommended on their own, which could include screening.
After seven years, 22 percent more prostate cancers were diagnosed in the PSA group, and 17 percent more were diagnosed after 10 years. But there was no significant difference in deaths from prostate cancer between the two groups.
Although the men will continue to be followed for at least 13 years, and a benefit might emerge with more time, an independent panel monitoring the study decided the researchers had a duty to inform the participants of the interim findings and make the results public.
The researchers noted there were actually more deaths overall in the screened group — 312 versus 225 — and they could not rule out the excess may have been the result of over-treatment.
In the European study, 162,243 men ages 55 to 69 in seven countries were randomly assigned to undergo PSA screening every four years, or no screening. After a median follow-up of nine years, there were 20 percent fewer prostate cancer deaths among those screened. Because of the study’s design, however, several experts said that reduction was hard to interpret. At best, it means about 10,000 men would have to be screened for about 10 years to prevent seven deaths. Put another way, 1,410 men would need to be screened and 48 would have to be treated to prevent one death.
“It’s very disturbing,” said Fritz H. Schroder of the Erasmus Medical Center in the Netherlands, who led the study. “That means in order to save one life you treat a very large number of men.”
By comparison, it takes treating just five or six women for breast cancer to save one life, Brawley said.
Experts cautioned that the decision to undergo screening remains individual. For men whose family members have died from prostate cancer, are relatively young and know they are at risk, the downside of potentially undergoing unnecessary treatment may be worthwhile. For others, especially older men with shorter life spans, it may not.
“Men who have a limited life expectancy on the order of seven to 10 years probably do not need to undergo PSA testing. I think that’s pretty clear,” said Gerald L. Andriole of Washington University School of Medicine, who led the U.S. study. “For younger men, for men with longer life expectancy, for men who are at higher risk for prostate cancer. . . . I think it’s still going to be worthwhile to get information from a PSA test.”
Dr. Otis Brawley, of the American Cancer Society, said, “The question we should now be asking is, do the harms of screening justify the benefits of screening?
The bottom line is that the answer to that question is still not known. Both studies have flaws that make it difficult to determine which answer is more apt to be correct.
Two things are pretty clear:
- screening leads to over diagnosis and over treatment of prostate cancer, and
- if there is a mortality reduction from PSA screening, it’s likely a small one.
“Some men would say, ‘If I can reduce my chance of dying from cancer, I’ll take that risk and face the music.’ Other men would say, ‘Gee, if you have to diagnose 50 to save one life, my chances are high I’ll be part of the 49. I’ll take my chances without it.’” said Michael J. Barry of Harvard Medical School, who wrote an editorial accompanying the study.
I think Dr. Barry’s “there are two sides to this coin” proposition is reasonable.
And, if there is one thing these two studies (along with others) clearly demonstrate is that there is NOT a one-size-fits-all recommendation when it comes to prostate cancer screening.