Draft Guidelines Recommend Against PSA Screening: USPSTF Review

Clinical Context

Few topics in the field of preventive medicine are contentious as prostate cancer screening. Widespread screening for prostate cancer has had a remarkable effect on the epidemiology of this tumor, as demonstrated in a study by Welch and Albertsen published in the October 7, 2009, issue of the Journal of the National Cancer Institute. Their study found that the introduction of routine prostate cancer screening led to approximately 1.3 million more men being diagnosed with prostate cancer in the United States alone. Men younger than 60 years accounted for most of this surge in cases. The authors estimated that more than 20 additional men would have to be diagnosed with prostate cancer through screening to result in a single case of reduced mortality risk from prostate cancer.

These findings are fairly pessimistic regarding the value of prostate cancer screening. The current study commissioned by the US Agency for Healthcare Research and Quality provides a more complete review of important issues in screening for prostate cancer.

Study Synopsis and Perspective

The US Preventive Services Task Force issue draft recommendations against routine screening for prostate cancer using the prostate-specific antigen (PSA) test in the United States, where it is currently used more than in any other country in the world. As a result, prostate cancer is the most commonly diagnosed cancer in American men.

The USPSTF draft recommendation against routine screening with the PSA test was to have been published October 11 in the Annals of Internal Medicine, but the entire draft paper was leaked and posted October 6 on the Cancer Letter Web site, in “an egregious breach of our embargo and media policies,” according to the journal. The news has since been widely disseminated on the Internet; as a result, the journal published the paper early.

The USPSTF already recommends against routine PSA screening in men older than 75 years. In the new draft recommendation, it extends this to all men. It now recommends against routine screening in men younger than 75 years, giving this 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 news is likely to spark a furor in medical circles, not unlike the outcry that followed the USPSTF’s recommendation in 2009 against routine mammography screening for breast cancer in women younger than 50 years. This provoked outrage from some breast cancer experts, patient advocates, and professional societies, with accusations that this was a move toward the “rationing” of healthcare.

Angry reactions to the latest news have already begun. The “decision of no confidence on the PSA test by the US government condemns tens of thousands of men to die,” said Skip Lockwood, CEO of ZERO, the Project to End Prostate Cancer. ZERO is sponsored by many organizations with a stake in prostate cancer, such as Abbott, Beckman Coulter, Accuray, CyberKnife, Dendreon, and the American Urological Association (AUA).

Based on Reviews of Trials

The recommended change is based on a review of 5 randomized trials of screening and 3 trials and 23 cohort studies of treatments. Included in the review were the 2 largest trials of PSA screening, which reported conflicting results, the USPSTF notes. The European study found a reduction in mortality after 9 years of screening, but the American trial, which had high crossover and contamination rates, found no reduction in mortality after 10 years of screening, as previously reported by Medscape Medical News.

The review also noted that treatment for prostate cancer, such as prostatectomy and radiation, is associated with risks for problems such as erectile dysfunction, urinary incontinence, and bowel dysfunction.

The USPTSF concludes that “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 evaluation and treatments, some of which may be unnecessary.”

Delay in Announcement

This recommendation has been a long time coming, according to reports in the October 7 issue of the Cancer Letter and in the New York Times magazine. They assert that the timing of the release of this recommendation was influenced by political considerations. According to these reports, the task force first voted to recommend against routine PSA screening back in November 2009, but this “caused a violent political firestorm,” and subsequent follow-up meetings were cancelled. The final vote was taken in March. After this, a paper summarizing the recommendation was submitted to the Annals of Internal Medicine, where is it expected to appear next week.

PSA Test is Not Specific

The main problems with the PSA test are that it is not specific for prostate cancer and it cannot differentiate between aggressive and indolent forms of the disease.

“It cannot distinguish cancer that will never make a difference in a man’s lifetime from cancers that will make a difference,” so might prompt men to undergo aggressive treatment unnecessarily, Virginia Moyer, MD, MPH, chair of the USPTSF panel that made the recommendation, stated in an interview yesterday with Bloomberg News. “So you go from being a guy who feels fine and who is potentially one of the majority who would never have known they had this disease, to being a guy who wears adult diapers,” she said. Dr. Moyer is a professor of pediatrics at Baylor College of Medicine in Houston, Texas.

The PSA test is “hardly more effective than a coin toss,” said Richard Ablin, PhD, research professor of pathology at the University of Arizona College of Medicine in Tucson. Dr. Ablin discovered PSA in 1970. Using this test to screen for prostate cancer in the general population has been a “hugely expensive public health disaster,” he wrote in an opinion piece in the New York Times last year.

“Drug companies continue peddling the tests, and advocacy groups push ‘prostate cancer awareness’ by encouraging men to get screened,” he wrote. “The medical community must confront reality and stop the inappropriate use of PSA screening,” he stated. “Doing so would save billions of dollars and rescue millions of men from unnecessary, debilitating treatment.”

Although PSA testing is recognized as being imperfect, it is the only test for prostate cancer that is widely available, and it does provide information that can be useful, proponents point out. One of the professional bodies that has long supported the use of the test, the AUA, emphasizes that it should not be used on its own, but needs to be combined with other information (such as family history).

The AUA issued a statement in reaction to the new USPSTF recommendations: “We are concerned that the Task Force’s recommendation 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.”

“The AUA’s current clinical recommendations support use of the PSA test, and it is our feeling that, when interpreted appropriately, the PSA test provides important information in the diagnosis, pretreatment staging or risk assessment, and posttreatment monitoring of prostate cancer patients,” according to the statement.

“Not all prostate cancers require active treatment and not all prostate cancers are life-threatening,” the statement points out, and the decision of whether to proceed to active treatment or whether surveillance is an option needs to be discussed in detail with the patient.

The Agency for Healthcare Research and Quality supported this study. Author disclosure information is available on the Annals of Internal Medicine Web site.

Ann Intern Med. Published online October 7, 2011.

Related Link
The American Urological Association offers a downloadable pocket guide to the interpretation and use of Prostate Specific Antigen that includes diagnostic and management algorithms.

Study Highlights

 

  • Researchers used common medical databases to address the following 4 questions:
    • Does PSA-based screening decrease prostate cancer €“specific or all-cause mortality risk?
    • What are the harms of PSA-based screening for prostate cancer?
    • What are the benefits of treatment of early-stage or screening-detected prostate cancer?
    • What are the harms of treatment of early-stage or screening-detected prostate cancer?
  • Specifically, researchers sought randomized trials of screening for prostate cancer among asymptomatic or minimally symptomatic men. They also included randomized trials and cohort studies that examined radical prostatectomy or radiation therapy for the treatment of prostate cancer.
  • They identified 2 fair-quality and 3 poor-quality randomized trials of PSA-based screening as well as 2 randomized controlled studies describing the benefits and harms of prostate cancer treatments. 9 cohort studies provided data regarding the benefits of prostate cancer treatment, and 14 cohort studies reported harms of treatment.
  • The most important studies contributing to the study conclusions regarding prostate cancer screening were the US Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC).
  • After 7 years of follow-up in the PLCO trial, screening was associated with an increased incidence of prostate cancer but no significant effect on prostate cancer €“specific or overall mortality. The PLCO trial was limited by contamination of the study cohort, with up to 52% of the men assigned to usual care receiving a PSA test at some point.
  • The ERSPC also demonstrated a higher incidence of prostate cancer associated with screening and no significant overall effect of screening on the risk for prostate cancer €“specific mortality. However, screening was effective in reducing the risk for prostate cancer €“specific mortality in a prespecified analysis of men between the ages of 55 and 69 years.
  • 3 poor-quality trials failed to find a difference between prostate cancer screening and control groups in the risk for prostate cancer €“specific mortality.
  • The risk for a false-positive test for cancer based on the PSA result was between 12% and 13%.
  • Serious infections or urinary retention occurred after 0.5% to 1.0% of prostate biopsies. No studies addressed possible psychological harms associated with prostate cancer screening.
  • One good-quality trial with 13 years of follow-up demonstrated that prostatectomy for localized prostate cancer reduced the risk for prostate cancer €“specific mortality compared with watchful waiting. However, this benefit appeared limited to men younger than 65 years.
  • Cohort studies demonstrated that both prostatectomy and radiation therapy reduced the risks for prostate cancer €“specific mortality and overall mortality.
  • Treating 5 men with prostatectomy resulted in 1 additional case of urinary incontinence. The number needed to harm for erectile dysfunction associated with prostatectomy is 3.
  • Radiation therapy is less associated with urinary incontinence, but it still has a number needed to harm of 7 to cause erectile dysfunction. Radiation therapy also appears to increase the risk for bowel injury, particularly in the short term.
  • Prostatectomy was associated with rates of perioperative death of approximately 0.5% and perioperative cardiovascular events of 0.6% to 3.0%.
  • On the basis of these data, draft recommendations from the USPSTF counsel against PSA-based screening for prostate cancer. This is a grade D recommendation, meaning that there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.

Clinical Implications

 

  • The 2 main studies examining screening for prostate cancer, the PLCO trial and ERSPC, failed to demonstrate any dramatic effect on mortality outcomes.
  • Draft recommendations from the USPSTF counsel against PSA-based screening for prostate cancer. This is a grade D recommendation.

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