Waiting on PSA

For years, doctors have recommended that men over 40 get tested for PSA, a marker for prostate cancer. But a debate rages in the medical community over whether PSA screening saves lives--or subjects thousands of men to invasive biopsies that might or might not improve their survival.

To screen or not to screen: That is the question posed by a growing number of middle-aged males worried about the health of their prostates. Just as women grapple with deciding whether to get routine mammographies to catch the earliest hints of breast cancer, men in their 40s and 50s now face their own dilemma: whether to add a blood test for prostate specific antigen (PSA) to their yearly physical.

An elevated PSA concentration can flag the existence of prostate cancer--and some physicians even support lowering the currently accepted PSA threshold in hope of identifying more men with cancer. Unfortunately, the test doesn't necessarily reveal whether these cancers might prove deadly. Many men live--and die--with cancerous cells residing innocuously in their prostates. As a result, PSA testing could send gents who have cancers that are not life-threatening for procedures that could ultimately do more harm than good. As medical professionals continue to debate the test, two ongoing clinical trials are addressing whether PSA screening reduces mortality in men with prostate cancer. Until these studies produce some answers, men will need to decide for themselves whether the benefits of screening outweigh the risks of unnecessary treatment.

When PSA testing was first introduced more than 15 years ago, "nobody knew what it meant," says radiation oncologist Anthony D'Amico at Brigham and Women's Hospital in Boston. Cells in the prostate gland squeeze PSA into semen, and the protein then leaks into blood. Cancer boosts the amount of PSA coursing through the body, perhaps by making blood vessels in the prostate leakier.

Physicians use the amount of PSA in a blood sample as a marker for cancer. When the amount of PSA tops 4 nanograms per milliliter (ng/ml), doctors recommend a biopsy, because initial studies indicated that 95% of men who had prostate cancer had PSA concentrations higher than that. Recently, however, doctors have found that some men with cancer have PSA concentrations as low as 2.5 ng/ml. As a result, some physicians are calling for lowering the PSA threshold to 2.5 to catch and treat more cases of prostate cancer.

But 70% to 75% of men who come in over 4 ng/ml don't have cancer. Many men experience expansion of the prostate as they age--a benign condition that also enhances the production of PSA. Because the screening has such a high rate of false positives, internist Gilbert Welch of the Department of Veterans Affairs Medical Center in White River Junction, Vermont, and others predict that lowering the PSA threshold for biopsies would substantially increase the number of men undergoing an unnecessary medical procedure.

Even when the screen does pick up cancer, in many cases the condition would not have proved lethal. Prostate cancer kills about 3% to 4% of the men diagnosed with it every year, amounting to about 25,000 to 30,000 deaths. But autopsy studies show that up to 80% of men over the age of 70 carry cancerous cells in their prostates, says public health researcher Ned Calonge of the Colorado State Department of Public Health and Environment in Denver. These cancer cells grow slowly and don't spread through the body--the event that makes them lethal. "The great majority of prostate cancer is the kind you die with and not the kind you die from," he says.

The problem with using the PSA test to ferret out cancers, says epidemiologist Russell Harris of University of North Carolina, Chapel Hill, is, "we can't tell the difference between the cancers that will give you problems and the ones that won't." As a result, doctors end up treating more men than necessary, including some who suffer serious side effects. Possible treatments for prostate cancer include radiation therapy, hormone treatments, chemotherapy, and, most aggressive of all, surgical removal of the prostate gland itself. "It's called a radical prostatectomy," says Harris. "The word 'radical' is there for a reason." Researchers estimate that between 15% and 60% men undergoing gland removal become impotent, and nearly 10% have problems with incontinence. "This is not a benign procedure," Welch says.

In addition, older men might not benefit from getting rid of their cancer at all. A small 2005 study in The New England Journal of Medicine found that men over the age of 65 with prostate cancer who'd undergone a radical prostatectomy did not live any longer than men whose cancers were not surgically removed, although the procedure did reduce cancer mortality for men between 59 and 65.

That study highlights the question of how effectively PSA screening--and follow-up treatment-- lowers the mortality rates in men who have prostate cancer. Oddly, clinical trials to answer that question have never been done, says Harris. For mammography, in contrast, researchers have conducted 8 different trials to assess whether the screen saves lives. This dearth of data on PSA and mortality prompted the U.S. Preventive Services Task Force--an organization mandated by Congress to advise private physicians based on clinical data--to make a nonrecommendation. "There is insufficient evidence to recommend for or against routine screening for prostate cancer using the PSA test," says Calonge, who heads the group.

But two large-scale studies are currently attempting to bridge the gap. The National Cancer Institute's Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial is following 38,350 men who started with no indication of illness to see if PSA screening reduces mortality. Researchers in the United Kingdom are conducting a parallel investigation.

The studies will also examine whether survival depends on the type of cancer one has--or when it gets detected. "It could be if you get the aggressive kind, it doesn't matter when you pick it up: You're not going to change mortality," says Calonge. "And if you get the slow kind, it doesn't matter what you do: You're going to outlive it." In other words, you’re going to die of other causes before the cancer can hurt you.

Still, most physicians agree that PSA testing should not be abandoned. For example, researchers have found that men whose PSA values rose most dramatically in the year prior to treatment were the ones for whom prostate cancer proved deadly. The observation suggests that following PSA concentrations over time could offer doctors a way to identify men who have dangerous disease--as opposed to a swollen prostate or nonthreatening cancer--and treat them most aggressively. "I think the way the story is evolving is that PSA is useful," says D'Amico, "We just haven't been using it properly."

Until the value of PSA screening is determined, experts agree that men and their doctors should discuss the test's potential risks and benefits. "If you look at all the recommendations from health organizations," says Harris, "you will find that all of them talk about informing the patients of the pros and cons." And if men want help in dealing with the uncertainty, then they can ask their sisters how their mammographies went.

Mary Beckman is a writer in southeast Idaho who is happy not to have a prostate.