PSA screening: Risks, benefits explored

Edition: March 2012 - Vol 20 Number 03
Article#: 3939
Author: Repertoire

PSA screening remains a useful tool for detecting prostate cancer. However, what physicians and their patients decide to do based on the findings of the PSA test may be a different story.

“PSA screening is doing what it’s supposed to do – picking up tumors early,” says J. Brantley Thrasher, MD, William L. Valk Chair of Urology and professor in the department of urology, University of Kansas Medical Center. “Are patients being overtreated? Possibly, yes. Is there not enough surveillance? Possibly. Are we seeing complications? All of the answers are potentially ‘yes.’ But let’s not demonize PSA screening. It’s a good preventive tumor marker. It will pick up cancers early. But if you tie it to treatment, that’s a whole other argument.” Thrasher serves as an expert for the American Urological Association.

The debate about PSA screening was ignited in October, when the United States Preventive Services Task Force released its report, “Screening for Prostate Cancer: A Review of the Evidence for the U.S. Preventive Services Task Force.” Essentially, the Task Force referred to two major studies that appear to indicate that PSA screening and subsequent treatment (such as surgical removal of the prostate) has little to no effect on mortality.

The debate could find Repertoire readers facing some tough questions from customers. But reps selling PSA tests have some strong supporters in their corner, most notably, the American Urological Association.

“The AUA’s current clinical recommendations support the use of the PSA test, and it is our feeling that, when interpreted appropriately, the PSA test provides important information in the diagnosis, pre-treatment staging or risk assessment and monitoring of prostate cancer patients,” said the association in a statement released in response to the Task Force’s report.

Not the first time

Sponsored by the Agency for Healthcare Research and Quality, the U.S. Preventive Services Task Force is an independent panel of private-sector experts in prevention and primary care. It is charged with assessing the evidence for the effectiveness of a broad range of clinical preventive services, including screening, counseling and preventive medications; making recommendations about which preventive services should be incorporated routinely into primary medical care and for which populations; and identifying a research agenda for clinical preventive care.

Its report on PSA screening wasn’t the first time the Task Force has gotten itself into hot water. In November 2009, for example, it stirred controversy by suggesting that routine mammograms should begin at age 50 rather than 40; that women should receive the test every two years instead of annually; and that education on breast-self-examination should be eliminated.

Concerning mammography, the Task Force acknowledged that mammography does indeed detect cancers that otherwise would go undetected among women in their 40s. But more than 1,900 women would have to be screened for a decade to save a single life, it said. The risks presented by false-positive test results – over-diagnosis, unnecessary biopsies and surgical procedures, and anxiety – outweigh the benefits of screening for women in that age group, it concluded.

The Task Force’s discussion about PSA screening hit on similar themes. “Screening based on PSA identifies additional cases of prostate cancer, but most trials found no statistically significant effect on prostate cancer-specific mortality,” it said. What’s more, screening presents its own set of dangers.

Some forms of prostate cancer are slow-growing and may never impact a man’s life. In fact, a man can live for decades without having any symptoms or needing any treatment. Many men die with prostate cancer, rather than as a result of it. In these cases, active surveillance instead of aggressive treatment may be the best course of action.

The problem is, at this point in time, there’s no way to determine if a particular case of prostate cancer is slow-growing or aggressive. Hence the dilemma: Should a man have PSA screening or not?

The risks

“Screening is associated with potential harms, including serious infections or urine retention in about one of 200 men who undergo prostate biopsy as a result of an abnormal screening result,” said the Task Force. “False-positive screening results occurred in 12 percent to 13 percent of men randomly assigned to PSA-based screening, with one trial reporting no prostate cancers in three quarters of screening-triggered biopsies. Screening also is likely to result in overdiagnosis because of the detection of low-risk cancers that would not have caused morbidity or death during a man’s lifetime, and overtreatment of such cancers, which exposes men to unnecessary harms.”

More than three-quarters of men with localized prostate cancer (about 90 percent of screening-detected cancers are localized, that is, confined to the prostate gland) undergo prostatectomy or radiation therapy, reported the Task Force. Data from one study suggests that the rate of overdiagnosis with screening was estimated to be as high as 50 percent, and that 48 men received treatment for every prostate-cancer–specific death prevented. “Treating approximately three men with prostatectomy or seven with radiation therapy instead of watchful waiting would each result in one additional case of erectile dysfunction, and treating approximately five men with prostatectomy instead of watchful waiting would result in one additional case of urinary incontinence.” Prostatectomy was also associated with perioperative (30-day) mortality (about 0.5 percent) and cardiovascular events (0.6 percent to 3 percent), and radiation therapy was associated with bowel dysfunction.

“In summary, PSA-based screening is associated with detection of more prostate cancers; small to no reduction in prostate cancer–specific mortality after about 10 years; and harms related to false-positive test results, subsequent evaluation, and therapy, including overdiagnosis and overtreatment,” said the Task Force report.

The benefits

Despite the Task Force’s report, the American Urological Association remains a strong proponent of PSA screening.

“The American Urological Association applauds the U.S. Preventive Services Task Force for its interest in reviewing the use of the prostate-specific antigen (PSA) test,” said the association in its statement. “However, we are concerned that the Task Force’s recommendations will ultimately do more harm than good to the many men at risk for prostate cancer both here in the United States and around the world.

“Not all prostate cancers require active treatment and not all prostate cancers are life threatening. The decision to proceed to active treatment is one that men should discuss in detail with their urologists to determine whether active treatment is necessary, or whether surveillance may be an option for their prostate cancer.”

The AUA is currently preparing a new clinical guideline on this topic, and has convened a panel of experts to review not only the use of the PSA test, but also early detection of prostate cancer overall, taking into account the new tests and diagnostics that are becoming available, the association said. “Until there is a better widespread test for this potentially devastating disease, the USPSTF – by disparaging the test – is doing a great disservice to the men worldwide who may benefit from the PSA test.”

Says Thrasher, “You can say we’re overtreating, but you can’t overlook the fact that since 1991, we’ve seen an approximately 40 percent decline in mortality rates in prostate cancer, and that’s about the time that PSA screening was implemented in this country.”

One of the studies cited by the Task Force – the European Randomized Study of Screening for Prostate Cancer, or ERSPC – did show a difference in mortality rates following detection and treatment of prostate cancer, Thrasher points out. And the second study – the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, or PLCO – was flawed in its methodology. What’s more, the Task Force cited information that is outdated, he adds.

Indeed, the Task Force concedes shortcomings in the research it cited. “The evidence on treatment-related harms reviewed for this report seemed to be most applicable to open retropubic radical prostatectomy and EBRT [electron beam radiation therapy], although details of specific surgical techniques or radiation therapy techniques and dosing regimens were frequently lacking. We found little evidence with which to evaluate newer techniques for prostatectomy (including nerve-sparing approaches that use laparoscopy, either robotic-assisted or freehand) compared with watchful waiting, but found no pattern suggesting that more recent studies reported different risk estimates than older studies. Limited data suggest that low-dose brachytherapy may be associated with fewer harms than high-dose brachytherapy or EBRT.”

Individual decision

At bottom, the decision to be tested and then treated is the individual’s decision, made in conjunction with his doctor, says Thrasher. And it is one that needs to be taken one step at a time.

Following screening, the first “decision fork” is whether to proceed with a biopsy or not, Thrasher points out. “That needs to be predicated on the health of the patient, concurrent medical problems, patient’s race, PSA rate of change – so many things go into that decision.” A biopsy indicating cancer presents another decision fork. “There, we need to make a decision based on age, grade of tumor, stage of cancer.” In some cases, treatment may be called for; in others, watchful waiting may be in order.

The public comment period on the US Preventive Services Task Force’s review of evidence ended Dec. 13. At press time, the Task Force was reviewing those comments, according to a spokesperson. The Task Force will issue a final recommendation concerning PSA screening, but no firm date has been set.