To PSA or Not To PSA-
The Great Prostate Screening Debate
By: David A Fein, MD
It’s the second leading cause of cancer death and the most common cancer in non-smoking men. Prostate cancer claims more than 28,000 men each year. It used to be an even more common cause of death until the 1994 introduction of a blood test, Prostate Specific Antigen (PSA), which was followed by a 40% decline inprostate cancer mortality. Then, in May, 2012, the US Preventive Services Task Force ignited a controversey when it released a recommendation advising against routine screening for prostate cancer, including PSA tests. As the debate about the Task Force’s recommendation rages in the medical community patients are left confused about the pros and cons of prostate cancer screening. So, what should you do?.
Let’s start with the downside of screening.
It has been known for many years that if a man lives long enough he is almost certain to get prostate cancer. Autopsy studies have shown that by age 85 almost 100% of men have cancer in the prostate. But only a very small percentage of those tumors spread beyond the prostate and become clinically apparent. Unfortunately, medicine does not yet have a reliable way of telling in advance which tumors are likely to spread and cause illness or death and which ones are so indolent that they are likely to remain limited to the prostate.
The prostate makes PSA and prostate cancers make the level of this marker in the blood climb even higher. But the PSA test is prone to false positives. There are reasons other than prostate cancer for the PSA to rise such as common mild infections or the enlargement of the prostate that often comes with aging. When the PSA is elevated doctors often recommend a series of biopsies of the prostate, in itself a pretty unpleasant procedure, to look for the presence of cancer cells. Since the prevalence of prostate cancer increases with age, biopsies are very likely to spot at least a few cancer cells in older men. But many, possibly most, of those cancers would not have progressed to a dangerous stage had they never been found.
Two recent studies found that there was little or no improvement in survival in men who had screening tests for prostate cancer. The first trial took place in the US and found there was no benefit at all to the men who were screened. A second trial in Europe found a small improvement in survival among the men who were screened but also found that many more were treated without benefit. Overall, in the European study only 1 out of every 49 men who underwent treatment (surgery, radiation or hormonal therapy) for prostate cancer appeared to have any improvement in longevity.
Treating prostate cancer often results in incontinence, impotence, rectal bleeding and surgical complications that can seriously impact quality of life. Put all this together and you appear to have a test that frequently turns out not to indicate the presence of cancer when mildly elevated, often leads to unneeded,uncomfortable biopsies and can result in treatment that may be worse than the disease.
But it turns out not to be that simple.
It helps to first understand that the problem is not with the PSA test itself. It does a pretty good job of identifying who needs further evaluation. Even though up to 80% of the men with elevated PSA levels turn out to be fine, that is not at all unusual in medicine. Many common tests, including mammography, have comparable false-positive rates. Just as important is the Negative Predictive Value. This means that if your PSA is very low, it is very unlikely that you have clinically significant prostate cancer at that point. That is useful information.
It also turns out that the data on which the Task Force based their decisions may have been premature and potentially flawed. Nearly 40% of the patients enrolled in the US study had a PSA level done prior to the start of the study. This could result in “selection bias” where many of the men with early prostate cancer would have already been treated and thereby excluded from the study. Additionally, about 50% of the PSA tests done did not follow the recommended protocol.
Just as important, it takes many years for the survival benefit to show up in these types of studies. The average follow up of the data published last year in the European study was only 9 years. As the study participants continued to be followed It has since become apparent, according to data presented by the researchers at a recent urology meeting, that a significant survival benefit has started to appear in the men who had PSA screening. The relative risk of dying of prostate cancer is now 29% lower in the group of men who had PSA testing compared with those who were not screened.
So, maybe the PSA test is not so useless after all.
Meanwhile, doctors have been exploring new options for those who are found to have an elevated PSA or a biopsy that shows cancer. Mildly elevated PSA levels can be monitored to see if there is a significant increase over time. Levels that are stable may not require aggressive therapy. If we can be more selective about who gets treated it is likely the benefits of treatment will become more apparent.
It is also important to consider the age and underlying health of someone who is a candidate for screening. It often takes 15 years or more for a prostate tumor to develop, spread and cause death. For an 80 year old man with poor overall health it very likely does not make sense to do a PSA test. It is almost certain that if his PSA is elevated and enough biopsies are done a cancer will be found. But that cancer is unlikely to be a cause of his demise before his other medical problems.
At the other end of the spectrum, a healthy 45 year old man with a rapidly rising PSA who turns out to have prostate cancer is very likely to find that tumor shortening his life without treatment. It is very difficult to argue that we should not be screening that man for such a common and treatable causes of cancer death.
The FDA has recently approved a new screening strategy for prostate cancer called the Prostate Health Index. This test combines 3 tests: the PSA, the Free PSA (which specifically measures PSA that is not bound to proteins in the blood) and a new marker called the -2 Pro PSA. It appears to be more accurate at detecting prostate cancer and may reduce the need for biopsies in men with elevated PSA levels but without cancer. This test is currently available in Europe but is not yet in use here.
New genetic tests are in development that may help us to better differentiate the cancers that are more aggressive from the ones that can be left alone. Researchers recently claimed to have found genetic markers that may identify the more dangerous forms of the disease. This is likely to be the true key to improving treatment for prostate cancer. If we can reliably identify the cancers that will spread and cause death we can limit the treatment to those who will benefit most.
For now, Princeton Longevity’s recommendations are that men under the age of 70 should continue to have an annual digital rectal exam and PSA level coupled with a discussion of the current data on screening. In men over 70, the decision should be guided by an assessment of overall health. When life expectancy is less than 10-15 years, the benefits of detection and treatment using currently available technology may be limited.