The United States Preventive Services Task Force (USPSTF) issued draft recommendations in October 2011 counseling against prostate-specific antigen (PSA) based screening for prostate cancer. In its overall conclusion, the Task Force stated “the mortality benefits of PSA based prostate cancer screening through 10 years are small to none, while the harms are moderate to substantial. Therefore, the USPSTF concludes with moderate certainty that PSA based screening for prostate cancer, as currently utilized and studied in randomized, controlled trials, has no net benefit.”

This is a striking recommendation in light of the fact that millions of men are being screened every year and going on to obtain biopsies and treatments with non-trivial side effects. This point has been made by the discoverer of the test Richard Ablin, who described it last year in the New York Times as “a profit-driven public health disaster.”

Controversy

The draft recommendation immediately caused a controversy as members of the task force defended their conclusion while patients and clinicians involved in treating patients voiced strong disagreement. In some cases, the disagreements could not have been starker.

Virginia Moyer, the chairwoman of the Task Force, told the NY Times “Unfortunately, the evidence now shows that this test does not save men’s lives.” Also, she told the Times, “the Task Force’s recommendation against PSA testing theoretically is a no-brainer. It’s obvious.”

Contrast this conclusion with that of Dr Eric Klein of the Cleveland Clinic who told the same newspaper “I think there’s a substantial amount of evidence from randomized clinical trials that show that among younger men, under 65, screening saves lives.” According to the Times, thousands of men believe a PSA test saved their lives.

The Evidence

 The Task Force relied on several streams of evidence including two meta-analyses which found no statistically significant reduction in prostate cancer deaths or in overall mortality. When considering that screening leads many men to choose treatments with significant harms in terms of incontinence and impotence, the Task Force concluded “…that the harms of PSA based screening for prostate cancer outweigh the benefits.”

Mammography

 This is reminiscent of the controversy surrounding the Task Force’s recommendation on mammography screening for women in the 40-49 age group. However, in that scenario, even though the Task Force acknowledged that screening would save lives, it judged on balance that the benefit did not outweigh the harm. It refrained from recommending routine screening on a population basis and advised women to consult with their physicians. Women who believed they were among those whose lives were saved disagreed on the importance of routine screening.

With these prostate cancer screening guidelines, there is no recognized benefit in terms of lives saved. The thousands of men who believe their lives have been saved cannot find support for their belief in the guidelines.
 

Grade D Recommendation

The USPSTF gave its prostate recommendation a grade D, meaning there is a moderate or high certainty that the service has no real net benefit or that the harms outweigh the benefits. It discourages the use of this service. This contrasts with the grade C recommendation it gave mammography screening last year because there was at least moderate certainty that the net benefit is small.

It recommended the use of the service only if other considerations support offering or providing the service in an individual patient.  For prostate cancer no such other considerations were seriously mentioned.

The review of the evidence commissioned by the USPSTF found small to no reduction in prostate cancer specific mortality after about 10 years in randomized trials of treatment either with surgery or radiation. However, all the cohort studies of treatment consistently found that surgery and radiation decreased all cause and prostate specific mortality compared to watchful waiting. These results do not appear to have influenced the USPSTF because, as stated in the review, the “estimates are susceptible to residual confounding, even after statistical adjustment.”

Paradox

The failure to find a clear benefit from screening is surprising and even seems paradoxical. If treatment for prostate cancer saves the lives of some men with the disease, as found in one trial for men younger than 65 and in the cohort studies, and if screening uncovers more men with such curable disease, then it should follow that screening contributes to saving lives.

One possible explanation is that there are only two kinds of prostate cancer - the kind that will not kill you before the end of your natural lifetime, and the kind that will kill you irrespective of treatment. If these are the only two kinds of disease, screening could not save lives but  treatment could only harm them.

Curable Disease

On the other hand, if there is a third type of disease, a form curable with proper treatment, then any procedure which detects this curable disease should theoretically benefit the men who are treated, and their increased survivability should be reflected in the overall death rates or especially in the prostate-specific death rates reported in the studies. Failure to find this increased survivability could be explained if the number of men with curable disease is too small to produce a detectable difference in the studies carried out, or if the treatments received were not effective ones.

If so, men with PSA detected cancer after screening face a difficult dilemma as they are left to wonder whether or not they are in that small subset who can stand to benefit or if they are in the larger subset unlikely to experience a survival benefit. From a public health perspective, the harms outweigh the benefits as the Task Force concluded, however, from an individual perspective, the chance of being in a group with a cancer that can be helped might be enough to choose treatment.

Individual Perspectives

The Task Force recognized that from an individual perspective, a man might place a higher value on the small possibility of benefit than on the harms that studies have documented are likely to occur. It said, “An individual man may choose to be screened because he places a higher value on the possibility of benefit, however small, than the known harms that accompany screening and treatment of screen-detected cancer, particularly the harms of overdiagnosis and overtreatment.” Perhaps is not surprising that controversy erupts because the large group which experiences the harms is different from the small group which could experience the benefits.

American Cancer Society

Wrestling with the same issues as the USPSTF, the American Cancer Society has emphasized the importance of providing men with information and allowing them to decide based on what is most important to them. They labeled as “uncertain” the benefit of screening for an individual.

According to Otis Brawley, chief medical officer of the American Cancer Society, “We all need to keep an open mind regarding screening and support the basic and clinical research which might ultimately allow us to predict the localized prostate cancers that are destined to progress versus those localized cancers that are destined to remain dormant. If we find and validate such a test we can actually determine just how good our current treatments are.”

Readers who wish to read the draft recommendation from the USPSTF can visit:

http://tinyurl.com/3wuyzdm

To access a copy of the latest review of the evidence published on October 7, visit the annals of medicine at :

http://tinyurl.com/3chm8be

For a recent interesting account of the controversy, read the article in the NY Times magazine entitled “Can Cancer Ever Be Ignored?” by Sharon Brownlee and Jeanne Lenzer at www.nytimes.com