Prostate Specific Antigen testing (2004-05-31)

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A recent report in the New England Journal of Medicine [incomplete] highlights the continuing controversy over Prostate-Specific Antigen (PSA) testing. This controversy is interesting to me because it highlights the uncertain nature of medical research. Keep in mind that I am not a doctor (read my disclaimer) and if you are confronting this issue with regard to your own health, please discuss this with your doctor.

PSA is a test commonly used to detect prostate cancer, and any value larger than 4.0 ng per milliliter is considered by some as cause for additional testing. The article examines prevalence of prostate cancer among men in the control arm of a large randomized prevention trial. Of the 9,459 men in the trial, 2,950 had measured PSA that never exceeded  4.0, and yet 15% of these men had prostate cancer confirmed by biopsy.

This is a reversal perhaps, from recent suggestions that the PSA test is overused and has led to too great a degree of intervention in patients who may not have a serious problem with prostate cancer. On the other hand, you could interpret this as yet another reason not to use the PSA test; not only does it leads to overly aggressive treatment when it is positive, and a negative result doesn't provide you with much comfort either.

As a general rule, when you are trying to decide how to apply the results of a diagnostic test you need to take into account

In the case of PSA testing, the next step after a positive test would actually be just another test, such as a needle biopsy. so the costs of a false positive would actually be the costs of an unnecessary second test.

You need to put the costs of false positives and negatives in perspective. For example, you shouldn't discount the cost of  a temporary surge in stress and anxiety while waiting for the results of a more definitive test. Also, a false negative finding for a test administered yearly may not be so serious. What's the harm if the disease is slow to develop as long as the disease is unlikely to cause serious damage in the year or two that it stays undiagnosed?

Indeed, there are suggestions that perhaps the best approach for prostate cancer may be watchful waiting. For example, a report in the December 1994 FDA Consumer suggests:

For older men with early-stage prostate cancer, a number of physicians are dispensing a different kind of advice: Wait and see. Doctors clearly are divided on its merits, but this "watchful waiting" philosophy got a boost by a 1994 report in the New England Journal of Medicine. The study analyzed case records of 828 prostate cancer patients treated conservatively (watchful waiting or hormone treatments but no surgery or radiation therapy). It found that 10 years after diagnosis, 87 percent of those with slow-growing, localized prostate tumors still were alive. Of those diagnosed with more aggressive cancer, 34 percent remained alive at the 10-year mark. Supporters say watchful waiting is a practical alternative for men in their late 60s or older, whose lifespans may be limited by advanced age and serious ailments such as heart disease. If treated, these men could suffer the trauma and adverse effects of cancer therapy with little or no benefit.

If such an intervention is appropriate for certain confirmed cases of prostate cancer, then perhaps leaving the condition undiagnosed isn't all that bad either.

It seems somewhat paradoxical, but too much screening can actual cause more problems than it solves. In an interview with Newsweek, Dr. Ian Thompson points out that greater levels of screening are not necessarily going to lead to better outcomes:

We know PSA screening finds cancer early. But does screening find cancers that are destined to cause death? One of the possibilities—and we don’t know for sure—is that screening may find slower growing cancers that may pose no risk and may miss faster growing cancers that do pose risk. For example between 50 and 75 percent of men in the United States have had a PSA test in the past five years, but prostate cancer death rates [have fallen only marginally]. So screening by itself probably can’t prevent all prostate cancer deaths. There is a real problem in screening if you find a cancer that is not going to cause a man a problem in his lifetime and then treat that man for that cancer and he ends up having side effects from the treatments. That means all those side effects and all of the costs associated with treatment were unnecessary. This study says that a man should look at our data and say, “I should look at my risk based on my PSA and other risk factors, think about my own priorities and perhaps consider investigating whether I have prostate cancer before my PSA [level] gets to 4.0.”

The controversy over PSA testing is too complex to summarize here. Perhaps a sign that we need to particularize this test to reflect the needs and the values of the individual patient. Many of the comments made above are value laden, and values do change from patient to patient. The best example of the importance of individual values involves a treatment whose side effects included diminished fertility. For some people, this side effect might be serious enough to dismiss any consideration of the treatment. Others might be totally indifferent to this side effect, and still others might actually view this side effect as a benefit. David Sackett discusses the role of particularizing and individualizing treatments to specific patients; I need to write a web page about this when I get a chance.

Additional links on the PSA test