PSA Screening for Prostate Cancer -- Controversy Continues

A rekindled controversy over the use of PSA screening to help detect prostate cancer highlights the different perspectives physicians may take in framing issues, evaluating studies and deciding on best practices.

Kirsten Bibbins-Domingo, MD, PhD

Kirsten Bibbins-Domingo, MD, PhD

Differing perspectives at UCSF include those of a leading urologist, and of an epidemiologist and internist who is a member of the United States Preventive Services Task Force. In its new draft recommendations the task force now says healthy men should not undergo PSA testing.

The task force based its recommendations on a review of reseach studies published Oct. 7 in the Annals of Internal Medicine. The task force concluded that PSA screening saves few lives or none, while the harms are real and significant.

Many physicians may still feel stuck on the horns of a dilemma when it comes to recommending PSA testing, and all wish for a better way to diagnose prostate cancer – and to distinguish life-threatening tumors from slow-growing ones. The task force will consider public comment before finalizing its recommendations.

UCSF internist and epidemiologist Kirsten Bibbins-Domingo, MD, PhD, is a member of the task force and an author of the recommendation statement. "Unfortunately, the PSA does not distinguish the aggressive cancers that we all want to find and treat from the slow-growing ones that may never cause a problem,” she says.

“Treating most men who screen positive as is currently the practice means that many slow-growing cancers are treated, subjecting men to the harms of treatment.”

Because most men with prostate cancer detected as a result of PSA screening have slow-growing tumors that are unlikely to cause death, treatment would be unlikely to be life-saving for a majority.

“Nearly one-quarter to one-third of men who are treated have incontinence or impotence,” Bibbins-Domingo says. “Some have more serious complications, including death, without benefit from reduced deaths from cancer."

But deaths due to prostate cancer have declined in recent years, a trend many urologists credit largely to PSA screening and to early detection of life-threatening tumors.

The American Urological Association, which is reviewing its own guidelines, issued a statement disagreeing with the task force. “When interpreted appropriately, the PSA test provides important information in the diagnosis, pre-treatment staging or risk assessment and monitoring of prostate cancer patients,” according to the statement.

UCSF urologist and surgeon Peter Carroll, MD, MPH, director of clinical services for the Helen Diller Family Comprehensive Cancer Center, also values PSA tests, but says results must be evaluated in the context of a man’s age, family history of prostate cancer and ethnicity.

Because prostate cancers develop and grow very slowly in the majority of cases, younger men who are relatively healthy and have a long life expectancy benefit most from screening, Carroll says.

“The task force recommendations should be a catalyst for a better understanding of PSA, and of how to use and apply it,” he says. “Detection should not be linked automatically to treatment.”

Treatment outcomes vary, and at UCSF — an academic medical center in which many men are treated with prostatectomy or radiation therapy every year — outcomes are better than at community hospitals in terms of relapse-free survival, avoiding incontinence and preserving sexual function, Carroll says. Treatment-related deaths at UCSF occur in fewer than one-in-1,000 prostate cancer patients, he adds.

Carroll, although he is a leading surgeon, is committed to avoiding overtreatment and is studying a large group of men whose disease is being monitored by “active surveillance.”

With active surveillance men diagnosed with prostate cancer that appears to be low-grade are not treated immediately but instead are biopsied periodically to detect worsening cancer.

PSA Studies Yield Contradictory Findings

The research review upon which the recommendations are based found that the two best studies — which it regarded as only “fair,” and which had contradictory results — were the European Randomized Study of Screening for Prostate Cancer (ERSPC), and the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial.

In the ERSPC study, 182,000 men age 50 to 74 years were assigned to PSA testing every two to seven years, with PSA levels of from 2.5 micrograms per liter to 4.0 micrograms per liter triggering diagnostic evaluation.

Although prostate cancer specific mortality was not reduced overall, in the subgroup of men ages 55 to 69 that received this routine screening cancer deaths dropped by 20 percent.  Additional analysis pointed to considerable variability across study sites and suggested that the beneficial results may have been driven by a single site, according to the evidence review used by the task force.

In the PLCO study, 76,693 men ages 55 to 74 were randomly assigned to either “usual care” or to annual PSA in combination with digital rectal exams. Through 10 years of follow-up, screened men were found to be no less likely to die due to prostate cancer or from any cause.

The same studies aroused similar controversy when they were published two years ago and received media attention.Carroll regards the European study as the better of the two.

The US study was significantly flawed, according to Carroll, in ways that made detecting a significant life-saving benefit less likely.

A large percentage of men in the PLCO study control group already had undergone PSA testing and other screening in the year prior to the study, culling out some men whose cancers already were detected from the study.

In addition, at least fifty percent of men in the control group received PSA screening during the course of the study.

“This was a trial of planned screening versus ad hoc screening,” Carroll says. In addition, the PLCO relied on a single PSA “cut point” to trigger biopsy, he added.

“Nowadays we no longer recommend a single cut point,” Carroll says. “You look at PSA, age, family history and ethnicity to arrive at a decision of whether or not to undergo biopsy.

“That’s far better than looking at a single PSA. You’re more likely to detect those cancers that are a higher risk.”

All men who wish to be screened should begin early-detection efforts in their forties, Carroll says.

African American Men Are at High Risk for Prostate Cancer

Prostate cancer has a large impact on African Americans. Black men are 56 percent more likely to be diagnosed with prostate cancer than white men, according to National Cancer Institute estimates from 2010. They are more than twice as likely to die from the disease.

If there is in fact a benefit to early detection of prostate tumors, then black men -- because their risk for the disease is so much higher -- would be expected to benefit the most from PSA screening and follow-up.

However, possibly because relatively few African Americans have taken part in studies of PSA screening, no significant reduction in prostate cancer deaths as a result of screening them has been reported yet.

"More focused efforts to detect prostate cancer in the African American community are needed,” Carroll says.

“When we detect prostate cancer in an African American, as with any other man we need to assess the risk to the individual and treat appropriately."