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Wednesday, November 9, 2011

Should Doctors Stop Using PSA to Screen for Prostate Cancer?

The United States Preventive Services Task Force (USPSTF) says yes. 

Recently the influential Task Force gave the PSA (prostate specific antigen) screening test a “D” level rating, meaning that doctors should recommend against using the test for the purpose of early detection.  Prostate cancer is the second leading cause of cancer death in men after lung cancer.  Early detection of prostate cancer through screening with PSA  was introduced into clinical practice in 1986.  Over the past several decades prostate cancer mortality has fallen by approximately 30%. Statistical modeling suggests that this might correlate with the advent of screening with PSA.  In addition, over the past several decades there has been an increase in prostate cancer incidence and a shift toward the detection of earlier stage cancers—likely also a result of PSA screening.

The purpose of health screening is to detect disease in an earlier stage so that preventive measures can be initiated to improve health outcomes related to that condition.  However, in order to justify population level screening, the benefit associated with early detection must outweigh the harm that it potentially causes.  Healthy Americans and their physicians have embraced the practice of early detection, particularly with respect to cancer, which along with Alzheimer’s disease, is the most feared illness in our population.  The USPSTF analyzed available data on prostate cancer screening and treatment, including the results of the two largest clinical trials—one done in the United States and the other in Europe.  The American study (PLCO found no mortality benefit with PSA screening after a 7 to 10 year period of follow up.  Its results have been criticized with the possibility that findings were “contaminated” with too many men in the control group who received screening before and during the study, reducing the apparent efficacy of PSA screening.   In contrast, the European ERSPC study showed a statistically significant, but small reduction in prostate cancer mortality (20%), in men who were screened every 4 years over 9 years. Researchers found that 1,410 men would have to be screened and 48 additional cancers would have to be detected to prevent one death from prostate cancer.  This efficacy is similar in magnitude (slightly greater) to the effectiveness of using mammography to screen women in their forties for breast cancer.  A potential shortcoming of these studies is that the study time could have been too short to detect benefit given that prostate cancer may be very indolent. 

Needless to say urologists as a professional group object to the USPSTF’s recommendation, stating on the American Urologic Association website: 
The Task Force is doing men a great disservice by disparaging what is now the only widely available test for prostate cancer, a potentially devastating disease. We hold true to our current position as supported by the AUA's Prostate-Specific Antigen Best Practice Statement that, when interpreted appropriately, the PSA test provides important information in the diagnosis, pre-treatment staging or risk assessment and monitoring of prostate cancer patients. But not all prostate cancers are life-threatening. The decision to proceed to active treatment or use surveillance for a patient's prostate cancer is one that men should discuss in detail with their urologists.
The argument against using PSA to screen, itself an inexpensive blood test, is that it leads to over-diagnosis of clinically insignificant prostate cancer.  Postmortem data indicate that approximately one third of men between the ages of 50 and 65 have microscopic evidence of prostate cancer. This percentage increases to over 50 percent for men in their 70s and 80s. Analysis of data suggests that early detection leads to over-zealous treatment—including radiation and radical prostatectomy.  Over-treatment puts men in harm’s way with side effects related to treatment --loss of continence (ability to control urination) and erectile dysfunction.  I recently read a nice discussion the magnitude of risk associated with screening by Dr. Albert Fuchs. Both physicians and patients are participants in opting for aggressive interventions for early stage cancer.

Active surveillance or “watchful waiting” is an acceptable strategy for managing elevated PSA or even biopsy proven prostate cancer.  In practical terms this means that once cancer is detected it may be reasonable to do nothing aside from monitoring for evidence of prostate cancer progression. In some, this might entail monitoring the PSA velocity (or rate of increase) to help determine an appropriate time to treat.  Or, in others, it might include waiting to treat until the cancer becomes symptomatic with urinary symptoms or symptoms related to prostate cancer that has spread to the bone.  However it’s very difficult for patients and their doctors to sit tight with the knowledge that they might be living with cancer.  I’ve discussed the difficulty with watchful waiting with respect to breast cancer in the blog: “Is Watchful Waiting too Difficult?” 

As for me, I tend to find the USPSTF’s PSA screening recommendation a little too reactionary.  As stated in a recent New England Journal of Medicine editorial a “C” level rating for this test might have been more appropriate.   I am not completely ready to jump onto the anti-PSA bandwagon that many of my fellow internists seem to be espousing and go back to the 1970s.  However, I do see that a more cautionary approach to prostate cancer detection and treatment is warranted.  This will require discussion, courage, and culture change on the part of primary care physicians, urologists, and their patients alike as we try to effectively convey and accept the message that early detection of cancer is good, but that not all early cancer, or “pre-cancer,” needs early and aggressive intervention.

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