“The medical community must confront reality and stop the inappropriate use of PSA screening. Doing so would save billions of dollars and rescue millions of men from unnecessary, debilitating treatments,” Richard J. Ablin wrote last year in The New York Times. The University of Arizona College of Medicine professor went on to label PSA testing as “a profit-driven public health disaster.”

Coming from just anyone, that opinion might appear extreme. But Richard Ablin isn’t just anyone. He is the scientist who, in 1970, discovered prostate-specific antigen (PSA)!

Do the facts support Dr. Ablin’s conclusions? In an attempt to answer that question, let us review the history of the PSA test.

Following Ablin’s discovery, it took many years of research before the FDA finally approved, in 1987, the clinical use of PSA as a screening test for prostate cancer. Subsequently, based on a 1991 study published in the New England Journal of Medicine by Northwestern University urologist, Dr. William Catalona, and his colleagues, a value of 4 nanograms per 100 ml blood became the accepted “cutoff” between a normal and high level of PSA.

Catalona’s almost single-handed advocacy that routine PSA screening could save countless lives by detecting prostate cancer at an early stage (in some cases, years before it might become clinically evident), soon resulted in its widespread adoption. The result?  An apparent epidemic of early prostate cancer: a 2.5-fold rise in new diagnoses was observed between 1990 and 1992. Somewhat tellingly, the greatest increase occurred in the year following Catalona’s 1991 publication.

Suddenly, thousands of otherwise healthy, asymptomatic men, among them celebrities and politicians, such as former New York mayor, Rudy Giuliani, were found to have prostate cancer and underwent radical prostate surgery and/or radiation treatments. Grateful for the chance to be “cured”, most accepted the risk of life-altering after-effects, including a high incidence of impotence and possible incontinence.

But even then, there were warning signals that PSA screening may not be making a difference to survival; despite the unprecedented increase in early diagnosis and treatment, there was, as yet, no significant change in the death rate. “It’s too soon to tell. Wait ten years,” countered the growing number of “PSA believers”, mainly urologists.

In response, the researchers  who identified the “epidemic” raised a red flag: “…publicity accompanying research published in the most influential medical and scientific journals, often cultivated to improve public awareness of important medical advances, may also amplify the impact of medical research whose interpretation is ambiguous…When the report is inconclusive and unaccompanied by editorial signals for cautious interpretation, its impact may be disproportionate and unexpected,” they warned .

Time would prove them right. The PSA test turned out to be far from infallible. Tens of thousands of biopsies later, it became evident that Dr. Catalona’s PSA algorithm was incorrect. A value above 4 does not accurately predict the presence of prostate cancer. Indeed, the National Cancer Institute now points out that only 25 to 35 percent of men who have a biopsy due to an elevated PSA level actually turn out to have cancer. In other words, for the majority, the test gives a false-positive result.

Why? As one example, the level of PSA also correlates with the size of the prostate gland. As men grow older, the prostate often enlarges, usually a benign condition that can result in slowing of the urinary stream and getting up more frequently at night to urinate. In such cases, the PSA is often elevated to levels between 5 and 8. Other causes of a false-positive PSA test include infection or inflammation of the prostate, as well as ejaculation or certain physical activities, such as bicycle riding, up to 24 hours prior to the test.

On the opposite side of the coin, one large study found that 15% of men diagnosed with prostate cancer on biopsy, had low or normal levels of PSA; the test missed their cancer (a false-negative result). Since some widely-prescribed medications (anti-inflammatories, certain diuretics, and cholesterol-lowering drugs) can push down the PSA, their use might contribute to false-negatives.

By the late 1990’s, as the specificity and sensitivity of the test became increasingly cloudy, it was evident that large, properly-designed clinical trials would be needed to determine whether PSA screening saved lives. The results of two such trials, one in the United States , the other in Europe , involving over 250,000 men, half screened with PSA tests and the other half not, were published in 2009. 

Their outcomes were best summarized by New York Times journalist, Gina Kolata: “The PSA blood test, used to screen for prostate cancer, saves few lives [none in the American trial; 7 per 10,000 screened in the European trial] and leads to risky and unnecessary treatments for large numbers of men, two large studies have found. The findings, the first based on rigorous, randomized studies, confirm some longstanding concerns about the wisdom of widespread prostate cancer screening,” she wrote.

However, the American Urological Association (AUA), the leading advocate for PSA screening, remained unconvinced. Although it issued revised guidelines in response to the studies’ results, the AUA continued to recommend that the PSA test be “offered” to “well-informed men 40 years of age or older who have a life expectancy of at least 10 years”.

Professor Ablin vigorously disagrees. “American men have a 16 percent lifetime chance of receiving a diagnosis of prostate cancer, but only a 3 percent chance of dying from it. That’s because the majority of prostate cancers grow slowly. In other words, men lucky enough to reach old age are much more likely to die with prostate cancer than to die of it.

“Even then, the test is hardly more effective than a coin toss. As I’ve been trying to make clear for many years now, PSA testing can’t detect prostate cancer and, more important, it can’t distinguish between the two types of prostate cancer — the one that will kill you and the one that won’t,” he argues .

Now, in a paper just published in the Annals of Internal Medicine, the U.S. Preventive Services Task Force (USPSTF), an arm of the Agency for Healthcare Research and Quality (AHRQ) of the United States government, has weighed in firmly on the side of Dr. Ablin.

As outlined in the October 7 issue of The Cancer Letter, the purpose of the USPSTF “is to use a set of highly structured, pre-specified procedures to separate the science of screening from the politics of screening and to safeguard the process from conflicts of interest.”

Previously, it recommended against PSA screening in men 75 and over. Now, on the basis of its analysis of 5 randomized trials of PSA-based screening, and 3 randomized trials and 23 cohort studies of prostatectomy or radiation therapy versus watchful waiting for localized prostate cancer, the USPSTF has extended its D (“Don’t do”) recommendation to all men, regardless of age.

“After about 10 years, PSA-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluations and treatments, some of which may be unnecessary,” its report concluded.

Elaborating on the potential harm from “subsequent evaluations and treatments” in men diagnosed with small localized tumours, many of which may be clinically irrelevant, the USPSTF panel’s chairperson, Dr. Virginia Moyer of Houston’s Baylor University College of Medicine, commented, “So you go from being a guy who feels fine and who potentially is one of the majority who never would have known they had this disease, to being a guy who wears adult diapers. This is not insignificant.”

Yet, many prostate cancer experts feel that, in rejecting PSA screening, the USPSTF is throwing out the baby with the bath water. Referring to the European PSA study, the Cleveland Clinic’s Dr. Eric Klein told The New York Times, “I think there’s a substantial amount of evidence from randomized clinical trials that show that among younger men, under 65, screening saves lives.”

My bottom line? We desperately need a good screening test that is specific for prostate cancer and can separate lethal from non-lethal tumours. Unfortunately, as Dr. Ablin and the USPSTF have correctly determined, PSA is not that test.