PSA Test Is Imperfect Tool: What to Do?

From Medscape Medical News
Nick Mulcahy

Authors and Disclosures

October 1, 2009 — The controversies surrounding population-based screening for prostate cancer — and the problems that plague the use of the prostate-specific antigen (PSA) test — will not go away anytime soon, suggest the authors of a new essay published online September 24 in the British Medical Journal.

There are a host of unanswered questions about PSA screening, including whether or not the test reduces mortality over the long term, assert the essayists.

New data from ongoing trials will provide some answers in the next 5 years or so, lead essayist Jennifer Stark, ScD, an epidemiologist from the Harvard School of Public Health in Boston, Massachusetts, told Medscape Oncology.

However, even with more data on the benefits and risks of the PSA test, it is an imperfect tool for screening men for prostate cancer, Dr. Stark and colleagues say.


"PSA screening cannot differentiate between indolent and lethal prostate cancer," they write.

The test sends many men down a path of diagnostic biopsies and treatment with no certainty of mortality benefit but with much anxiety and overtreatment, she said.

In the United States, the PSA test has triggered the mass overtreatment of men. An estimated 1 million men have been overtreated for prostate cancer since the advent of the widespread screening in the mid-1980s, as recently reported by Medscape Oncology.

What to Do?
Change is clearly in order, suggested a spokesperson for the American Urological Association (AUA). "A complete cultural overhaul is needed to change the perception that all prostate cancer needs to be treated," J. Brantley Thrasher, MD, from the University of Kansas in Lawrence, told Medscape Oncology. The change in perception needs to include clinicians and patients, said Dr. Thrasher.

The change will require physician "re-education" and the consideration of active surveillance as an alternative to treatment, he said.

However, the AUA remains in favor of PSA screening, unlike many other organizations that do not recommend population-based screening because of insufficient data on its benefits and harms. They include the European Urological Association, the US Preventive Services Task Force, Cancer Council Australia, the National Health Committee (New Zealand), the Japanese Urological Association, and the Swedish Board of Health and Welfare, note Dr. Stark and her colleagues.

Recently, at their annual meeting, the AUA issued a revision of their prostate cancer screening guidelines and dropped the age at which men should start to consider baseline PSA testing to 40 years, as reported by Medscape Urology.

"The AUA believes that, when offered and interpreted appropriately,the PSA test may provide essential information for the diagnosis, pretreatment staging or risk assessment, and post-treatment monitoring of prostate cancer," the AUA stated.

At the time, Otis Brawley, MD, chief medical officer of the American Cancer Society, told WebMD that the call for a baseline PSA at age 40 will likely lead to more screening and more overtreatment of men who will not benefit.

Patients Must Be Well Informed About Initial PSA — But How?

In their essay, Dr. Stark and colleagues agree that the PSA test needs to be offered appropriately, and describe that change as "urgently needed." Echoing the AUA, they recommend that men be well informed about the test before having the blood work done.

"You wouldn't just decide on the spot to do a mammogram," said Dr. Stark, explaining that such quick decisions are common with PSA testing.

"Somehow, we have to approach screening for prostate cancer with the same prudence we would have in screening for breast cancer or colon cancer," she added.

However, as recently reported by Medscape Oncology, the primary care setting, where most PSA testing is done initially, is currently ill-suited for discussing the complexities of prostate cancer screening.

"Today's practice environment presents few incentives or support tools for those clinicians and patients who prefer a discussion rather than simply marking a checkbox for PSA on a laboratory requisition form," Steven H. Woolf, MD, MPH, and Alex Krist, MD, MPH, from Virginia Commonwealth University in Richmond, write in an editorial published in the September 28 issue of Archives of Internal Medicine (2009;169:1557-1559).

That editorial accompanied a paper detailing results from a survey, which showed that nearly one third of men receiving a PSA test did not have any discussion with their doctor about the test (Arch Intern Med. 2009;169:1611-1618).

Interpretation of PSA Test

Another point highlighted by Dr. Thrasher in the interview with Medscape Oncology was that PSA test results should not be considered on their own, but need to be interpreted along with other information.

"PSA does not work well by itself in predicting prostate cancer," Dr. Thrasher said.

The interpretation of PSA tests by a urologist should always be done in conjunction with other factors that contribute to prostate cancer risk, such as overall health, family history, age, comorbidities, the rate of change in PSA value over time (PSA velocity), and physical examination, Dr. Thrasher explained, referring to the AUA's Prostate-Specific Antigen Best Practice Statement.

"I don't want people to walk away from PSA and say it's useless," he remarked. "We believe we are still saving lives with the test."

More Unanswered Questions

New data from ongoing trials will provide answers to some of the questions that remain about PSA testing, including the crucial question of whether it reduces mortality, Dr. Stark told Medscape Oncology.

Two major trials are evaluating the effectiveness of PSA screening — the European Randomized Study of Screening for Prostate Cancer (ERSPC) and, in the United States, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).

Recent published data from these trials involved a median follow-up of 7 years in the United States and 9 years in Europe (N Engl J Med. 2009;360:1310-1319 and 1320-1328). Those results showed no affect on mortality from prostate cancer in the American trial, and a small reduction in mortality in the European trial, as reported by Medscape Oncology.

Lead time, or the interval of time by which screening advances a diagnosis, is necessary to reduce morbidity and mortality associated with disease, write the Dr. Stark and her coauthors. It has been estimated that mean lead times for PSA testing were 11 to 13 years among men aged 50 to 69 years, which is "much longer" than for other cancer screening, they write. This time frame explains Dr. Stark's contention that, in another 5 years, ERSPC and PLCO will provide answers to some currently unanswered questions about PSA screening.

With continued follow-up in these major trials, there should be answers to questions about the predictive value of a negative PSA result (what percentage of men go on to have prostate cancer despite the negative result?), and solid information on the percentage of men who are overdiagnosed, Dr. Stark said. The screening trials will also be able to firmly determine how many men need to be treated to avert 1 death; the ERSPC estimate is currently 48, she added.

With regard to the question of what percentage of men are overtreated, although the trials will be helpful, the answer might require more extended follow-up, said Dr. Stark.

"Because of the long life expectancy of many men diagnosed with prostate cancer, combined with the long lead time for PSA screening, it is going to take considerably longer to determine who ultimately benefits from treatment of a screen-detected cancer and how this benefit compares with the side effects and mortality associated with treatment," she said.

The essay authors have disclosed no relevant financial relationships.

BMJ. 2009;339:b3601. Abstract