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From the Winter 2014 Quest

William J. Catalona, M.D.

The 2013 American Urological Association (AUA) guidelines for the detection of prostate cancer are untenable for providing optimal care to men younger than 55 years or older than 69, or men at high risk for prostate cancer.

Flawed and Incomplete Data

The mandate of the guideline panel was to produce evidence-based guidelines. For the benefits of screening they did not go beyond the available poor quality, level-1 evidence from randomized trials. However, in their analysis they placed too much weight on these poor quality trails. Moreover, there was unevenness in their methods. While they considered only level-1 evidence for benefits, for harms they used non-level-1 evidence and cited older studies that clearly overestimated harms.

The mortality benefit takes many years to become apparent in clinical trials of prostate cancer screening. Thus, the short-term trial results underestimate the absolute benefits of screening during a man's lifetime. Early trial data also exaggerate over-diagnosis. Many excess cancer cases detected in the screening arm are truly early detected, life threatening prostate cancer counted as over-diagnosed cases.

Inaccurate Estimates of Harms and Benefits

The AUA panel linked the risk of PSA testing with the risk of treatment, wrongly assuming that every man with an abnormal PSA test undergoes a biopsy procedure and every patient with prostate cancer receives treatment. Active surveillance has increasingly become a standard of care.

In the Goteborg trial, 9 years after screening was stopped at the upper age limited of 69, the incidence of high risk and fatal prostate cancer increased in the screening arm until it equaled that of the unscreened arm.5 In this regard, the National Cancer Institute Surveillance Modeling Network has projected that if screening were phased out in 2012, the number of cases of distant stage and fatal disease would return to the pre-PSA screening era level by the year 2025, thus yielding back much of the 47% reduction in prostate cancer specific mortality that has occurred during the PSA era.

The AUA guidelines dictate that we tell our patients that 1,000 men must be screened to prevent 1 prostate cancer death. However, statistical modeling studies estimate that only 5 additional cancers need to be detected to prevent 1 prostate cancer death.1 The panel ignored the important fact that PSA testing reduces metastases, which substantially shifts the balance toward benefits and away from harms.2

Other organizations, such as the European Association of Urology and the National Comprehensive Cancer Network, have reviewed the same limited body of evidence and created more liberal screening guidelines.3 Many of these new guidelines recommend PSA testing for men in their 40s and early 50s.

High Risk Men

High risk men are all but lost in the AUA guidelines. A baseline PSA greater than 1.0 ng/mL in a man in his 40s is a strong risk factor for life threatening prostate cancer.4 One simply cannot identify most high risk men without measuring a baseline PSA in early midlife.

The AUA guidelines panel stated they do not recommend screening average risk men younger than 55 years or older than 70. Their language would have been more accurate if they had indicated that there are insufficient data to recommend for or against screening men in these age groups. Most other guidelines recommend screening for men with a 10-year life expectancy. In the U.S., life expectancy at age 70 is 15 years. Older men have a far greater risk of aggressive prostate cancer and some may benefit from early detection of an aggressive tumor.

“The AUA guidelines transmit a powerful message to the public about how urologists weigh the risks and benefits of prostate cancer screening. The message used to be men should get screened for prostate cancer. Now vulnerable groups of men are not being screened. The AUA guidelines panel should incorporate new panel members who have a different interpretation of the data on the benefits and harms of prostate cancer screening.”

The AUA guidelines suggest increasing the PSA biopsy threshold to greater than 10 ng/mL for men older than 70 based on the flawed Prostate Cancer Intervention Versus Observation Trial (PIVOT). However, because high grade cancers produce less PSA on a per cell basis, higher PSA thresholds may not result in the timely detection of aggressive cancers.

The AUA guidelines state that the preferred screening interval may be 2 years or more - but PSA can go from 2.4 to 24 ng/mL in 2 years. Longer screening intervals are more likely to detect aggressive cancers too late, and they would still detect the harmless, low risk cancers. Thus, longer screening intervals could do more harm than good.

Adapted from Dr. Catalona's presentation at the 2014 AUA meeting in Orlando, Florida.

  1. Etzioni R, Gulati R. Response: Reading between the lines of cancer screening trials: using modeling to understand the evidence. Med Care 2013; 51(4): 304-6.
  2. Schroder FH. et al: Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC). Eur Urol 2012; 62(5):745-52.
  3. Loeb S. Guideline of guidelines: prostate cancer screening. BJU Int. 2014; Epub ahead of print.
  4. Vickers AJ, et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study. BMJ. 2013; 346:f2023.
  5. Grenabo Berdahl A, et al. Incidence of prostate cancer after termination of screening in a population-based randomised screening trial. Eur Urol 2013; 64(5):703-9.
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