PSA Testing Continues to Polarize Medical Community

Roxanne Nelson

March 15, 2012

March 15, 2012 — Prostate cancer screening has become increasingly polarized, with experts weighing in on both sides of the equation. The draft recommendation issued by the US Preventive Services Task Force (USPSTF) in October 2011 ignited the controversy — like pouring gasoline into the fire.

Now 2 experts with opposing views on the USPTF recommendation offer evidence for and against routine screening with the prostate-specific antigen (PSA) test. The point–counterpoint appears in the March issue of Cancer Epidemiology, Biomarkers and Prevention.

The USPTF draft recommendation advised against routine screening with the PSA test, as reported at the time by Medscape Medical News. The USPTF had previously recommended against routine PSA screening in men older than 75 years, but the draft extends that to all men. It gives routine screening in men younger than 75 years a "D" rating, which means "there is moderate or high certainty that the service has no benefit or that the harms outweigh the benefits."

"The draft recommendation to downgrade PSA testing to level 'D' is unfounded and irresponsible," says William J. Catalona, MD, professor of urology at Northwestern University Feinberg School of Medicine in Chicago, Illinois, in his counterpoint.

Richard J. Ablin, PhD, DSc, professor of pathology at the University of Arizona, Tucson, in his defense of the draft recommendation, notes that, from his perspective as the discoverer of PSA in the human prostate during the 1970s, the "controversy and debate of PSA screening were predictable from the onset and should have never in all actuality occurred, nor should have the tragedy of the resulting overdiagnosis and overtreatment in excess of a million men in the United States."

Some Conflicting Evidence

The USPTF evaluated data from randomized controlled trials of the benefits of prostate cancer screening, along with cohort and cross-sectional studies of the psychological harms of false-positive PSA results. Included in the review were the 2 largest trials of PSA screening, which reported conflicting results.

The US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, funded by the National Cancer Institute, found that PSA screening did not reduce disease-specific mortality.

In contrast, the European Randomized Trial of Screening for Prostate Cancer (ERSPC) reported a relative risk reduction in prostate cancer mortality of 21%. A recently published updated analysis confirms the previous results.

Point

Dr. Ablin, who supports the recommendation, believes that the "outcome of the studies on which the USPSTF evidence-based review and recommendation have been made will become quite understandable and acceptable by looking back at the 'science' on which PSA screening for prostate cancer has been based."

He notes that the enthusiasm over the prospect of a blood test for the presence or absence of prostate cancer, even though the test was not cancer-specific, led to wide use of PSA testing even before approval by the US Food and Drug Administration (FDA).

This enthusiasm was significantly buoyed by the results of an early landmark study, followed by "clever marketing of PSA test manufacturers," along with the media, "through high-profile political, entertainment, and professional sports figures, and well intended but ill-informed urologists," writes Dr. Ablin. The proliferation of screening reached a "fervor which would not disgrace a medieval inquisition."

The FDA approved the PSA test in 1994. Dr. Ablin points out that this move was "particularly puzzling" because the test is not cancer-specific and could not be diagnostic of cancer. "Their evaluation was not based on a rigorous study of the specificity and sensitivity of the test," he writes, adding that the FDA never evaluated the benefits and risks of the test.

Dr. Ablin identifies what he refers to as the 4 fundamental "cruxes": PSA is not cancer-specific, prostate cancer is an age-related disease, the PSA test cannot distinguish an indolent from an aggressive cancer, and there is no level of PSA diagnostic for prostate cancer. These explain why the PSA test cannot do what it has been purported to do and the abject failure of recent clinical trials.

Decreases in prostate cancer mortality can be attributed to factors aside from PSA screening, he writes. These include improvements in surgical techniques and paradigms of treatment modalities, healthier patients being diagnosed with longer life expectancies, increased awareness of prostate cancer (which has resulted in more symptomatic men seeking medical care), and a general decline in mortality across the board in most cancers.

"The Task Force recommendation will hopefully lead us to look at more fruitful endeavors toward identifying men who will benefit from early diagnosis and treatment for prostate cancer, wherein multiple groups, including myself, are actively pursuing new biomarkers," concludes Dr. Ablin.

Counterpoint

In his counterpoint, Dr. Catalona notes that the USPSTF highlighted 3 randomized clinical trials but gave little weight to the 2 trials that showed a substantial decrease in prostate cancer mortality. "The panel gave more weight to PLCO than to ERSPC, despite the fact that PLCO is more flawed, and they conclude that the mortality benefit from screening is 'small to none'," he writes.

The panel also appears to have largely disregarded epidemiologic data on prostate cancer stage migration and mortality during the PSA era, Dr. Catalona points out. There has been a 75% reduction in the rate of advanced prostate cancer at diagnosis, and a 40% reduction in age-adjusted prostate cancer mortality in the United States since the beginning of routine PSA testing. Similar patterns have emerged in other countries when PSA screening has been widely implemented.

Screening has also not been adequately studied in high-risk populations, such as men with a strong family history of prostate cancer, he writes, but high-risk men are included in the draft recommendation against PSA screening. Also important is the fact that the panel did not include any urologists, radiation oncologists, or medical oncologists.

"This make-up may explain why many currently used prostate cancer risk assessment tools for decision making are absent from the rationale for the draft recommendation," he notes, adding that PSA screening in randomized controlled trials is not representative of how it is conducted in clinical practice today.

Dr. Catalona concludes that the draft recommendation polarizes the medical community and confuses patients. "Nearly all urologists and most internists support PSA screening," he adds, but because of extensive media coverage, "a change in clinical practice is likely and fewer patients will opt to be tested."

"PSA is the best screening test we have for the early diagnosis of prostate cancer," he says. "For now, no other way to identify prostate cancer in its curable stages exists."

Denying men the opportunity for informed decision making "needlessly places many patients with prostate cancer in positions of being denied a cure," Dr. Catalona adds. "To implement that denial based upon flawed science would be unconscionable."

Dr. Catalona reports receiving research support from Beckman-Coulter, OHMX, Nanosphere, deCODE genetics, the Urological Research Foundation, and the National Cancer Institute at the National Institutes of Health. Dr. Ablin reports being a consultant for various law firms for medical malpractice cases.

Cancer Epidemiol Biomarkers Prev. 2012;21:391-394, 395-397. Point abstract, Counterpoint abstract

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