The U.S. Preventive Services Task Force's (USPSTF) recent recommendation against prostate-specific antigen (PSA) testing for men of any age has been met with opposition, with many calling it a detriment to men's health. The Southern Medical Association spoke with Peter N. Schlegel, MD, FACS, the James J. Colt Professor and Chairman of Urology at The Weill Medical College of Cornell University and a Trustee of the American Board of Urology, asking his opinion on the decision and the studies that played a key part in the final recommendation.
SMA: Do you view PSA screening as beneficial?
PS: Before the PSA blood test was introduced in the mid-1980s, we projected that there would be more than 60,000 deaths per year from prostate cancer at this point in time. We have less than half of that and that is not because there has been any decrease in cardiovascular deaths overall; it has not gone up and it is not replacing prostate cancer. We have done better in decreasing the risk of prostate cancer death and that is through PSA testing and treatment.
SMA: What are your initial thoughts on the USPSTF's recommendation?
PS: I believe the USPSTF recommendation is not well supported by the information that we have from the studies that have been done on PSA screening and its role in decreasing prostate cancer deaths. More information will progressively come out about the value of PSA screening and subsequent treatment of prostate cancer. My interpretation of the information is that treatment for prostate cancer clearly provides benefits for men.
SMA: In issuing its grade "D" recommendation, which is defined as moderate or high certainty that the service has no benefit or that the harms outweigh the benefits, the USPSTF cited two studies, the U.S. PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial and the European Randomized Study of the Screening for Prostate Cancer (ERSPC). Could you provide an explanation of these studies and their limitations?
PS: These studies were done to examine PSA screening and its effects on deaths from prostate cancer. The U.S. study compared screening (having regular PSAs) to "usual care" in the United States and "usual care" in the United States is actually to screen. This means the comparison was essentially screening versus screening, and not surprisingly, no benefit to PSA screening was shown in that study. The contamination of the control group by screening was so great that it really invalidates anything that you could take out as a conclusion from that study, in most experts' views. The European study actually had a lower rate of contamination about 20% of the men did still have some form of screening or PSA blood test in the control arm, but it was a much lower rate than in the screening arm. Not surprisingly, they showed a benefit of approximately 30% overall decreased death rate from prostate cancer, even with the relatively short nine-year follow-up.
SMA: Were there additional limiting factors?
PS: Another difficulty with the studies as they have been done and reported to this point is that death from prostate cancer usually takes at least 10 to 15 years; maybe 20 or more years from the time of diagnosis. That is why any time people are recommended screening, it is only for those with a life expectancy of more than 10 years. Therefore, if you want to determine what benefit you receive from screening, having the study that lasts only seven years, as in the U.S. study or nine years as in the European study, is clearly not long enough.
SMA: In its recommendation, the USPSTF states the risks of PSA testing outweigh the benefits and task force member Virginia Moyer, MD, MPH, cited that only one out of 1,000 men screened would benefit from the testing. Do you believe this to be an accurate assessment?
PS: That is based on the results of the American study and that is inadequate. Even the results of the European study are too premature to actually measure the full benefits of screening. More appropriately, if you look at the high-risk groups in follow-up studies, it appears that the number needed to treat to save a life (the number of men who need to have surgery to be cured) is approximately four or five; and in cancer, that is a very good number. The original European study showed a benefit to screening but found that the NNT (number needed to treat to save one life) was 48. This is a relatively low benefit of treatment. However, if you look at the high-risk groups, meaning people who are younger and therefore who are going to live longer, and look at longer (more appropriate follow-up for prostate cancer), the number needed to treat to is likely to be closer to four or five in that subgroup based on extended analysis and additional follow-up beyond the original study. The more recently published follow-up studies have already suggested that the number needed to treat has dropped from 48 to 12. Furthermore, if you then look at the patients who are at higher risk, those who are younger (in this case, less than 65 years of age), or those who have a higher risk of prostate cancer, like men with a family history of prostate cancer or African-American men, then the benefit that you will get from treatment is much higher than what has been published to date.
SMA: The American Cancer Society supports the USPSTF recommendation. As such, there are those who will question the necessity of having a PSA screening when there may be a medical need. How do you address this?
PS: Testing doesn't commit you to having a biopsy and a biopsy doesn't commit you to having treatment. Each of these steps needs to be carefully discussed and this is a level "C" recommendation where there is a discussion between the physician and the patient about the risks and benefits of treatment.
SMA: Could you discuss how risks of treatment relate to the USPSTF's recommendation?
PS: There is always a concern about risks from any treatment and particularly when death or major health risks from prostate cancer will not occur for many years after detection of localized disease and the treatment can bring on early complications. But to reiterate, it is a decision for patients to make individually with their physicians to potentially allow detection of disease that is curable; advanced or metastatic prostate cancer is incurable. Although there are small risks to performing a biopsy (if the PSA is abnormal, a biopsy is performed to diagnose cancer), there are more substantial risks of treatment if the biopsy shows cancer, and those primarily are incontinence and impotence. Unfortunately, although there is much being made about the potential risks of those treatments, these risks are very difficult to quantify.
SMA: Do you believe the USPSTF recommendation will lead to changes in the way physicians approach PSA screening?
PS: A couple of recent studies tried to measure the impact of the USPSTF's 2008 recommendation that men over the age of 75 not be screened with PSAs. If you look at the frequency of testing men over the age of 75 before that recommendation and the frequency after the recommendation, it is essentially identical levels of PSA screening. Therefore, it is quite possible that physicians are not going to change practice or behavior based on the recommendation the USPSTF has issued now. Even the president had a PSA after the most recent lack of screening recommendation came out, so it is somewhat difficult, I think, for the government to limit that.
SMA: Do you have any final thoughts regarding the USPSTF recommendation and the studies on which it is largely based?
PS: I think we need to consider the course of this disease and consider the studies that have been done and what they are really measuring. If you have inadequate or severely flawed studies and you accept them as they are, you may devise an inaccurate interpretation of the benefits of PSA screening. Most experts in the field of prostate cancer do not believe these studies should be accepted at face value and that there are clearly benefits if you interpolate and extrapolate from the European study. As more follow-up occurs with subset studies from the European analysis, we are seeing greater and greater measurable benefits to PSA screening.
1. Moyer VA; on behalf of the U.S. Preventive Services Task Force. Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement; Ann Intern Med 2012; May 21: [Epub ahead of print].