PSA Screening: Don't Throw the Baby Out With the Bathwater

Roxanne Nelson, BSN, RN

July 21, 2016

Population-based prostate cancer screening remains decidedly controversial, especially after the US Preventive Services Task Force (USPSTF) recommended against routine prostate-specific antigen (PSA)-based prostate cancer screening for healthy men in 2012, regardless of age.

But prostate cancer experts have maintained that PSA testing is useful and that it reduces the risk for death — and this argument is made forcefully in a Comments paper published online July 18 in the Journal of Clinical Oncology (JCO).

Jonathan E. Shoag, MD, from New York Presbyterian Hospital, New York City, and colleagues, argue that the evidence shows that PSA testing does reduce prostate cancer mortality, and they call for a return to screening, albeit not a population-wide annual PSA testing.

Instead, they proposed that all men should undergo at least baseline PSA testing in their 40s or early 50s (except for individuals with a limited life expectancy). Subsequent screening after that would be tailored to individualized risk according "to schedules put forth in newer screening guidelines."

"The rapid uptake of PSA screening followed by its equally rapid decline in the United States has been analogized to a pendulum swinging back and forth," they comment. They warn that "reversion back to the pre-PSA era in recent years will translate into more prostate cancer deaths in the United States."

Some studies have already suggested that more advanced disease is being diagnosed since PSA testing has fallen.

Dr Shoag and colleagues also highlight a big problem with one of the two major randomized trials of PSA screening on which the USPSTF based its decision.

The two trials were the American Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, which found no survival benefit from PSA testing, and the European Randomised study of Screening for Prostate Cancer, which showed a substantial reduction in prostate cancer mortality attributable to PSA screening.

But the PLCO trial was deeply flawed, as has been reported previously, because the control arm of that trial was contaminated — many of the men who were in the unscreened arm of the trial did in fact have a PSA test. However, it is only recently that the huge scale of this contamination was revealed. Dr Shoag and colleagues reexamined the data and found that 90% of men in the unscreened arm of the trial had undergone a PSA test.

Dr Shoag presented this finding in May 2016 at the American Urological Association annual meeting, as reported by Medscape Medical News, and the data were also published in the New England Journal of Medicine (2016;374:1795-1796).

"We hope our analysis will cause policy makers to revise their recommendations on PSA [prostate-specific antigen] screening and encourage the use of smarter screening and diagnostics strategies," Dr Shoag told Medscape Medical News at that time.

Now, Dr Shoag and colleagues write in the JCO paper: "Given the previously unrecognized degree of contamination in the PLCO trial control arm, the results of this trial should no longer guide policy."

Given the previously unrecognized degree of contamination in the PLCO trial control arm, the results of this trial should no longer guide policy. Dr Jonathan E. Shoag

The only randomized evidence regarding PSA testing now comes from the European study, which showed that PSA screening resulted in a 21% relative reduction in prostate cancer mortality, they add.

In the absence of additional data, the evidence does appear to support PSA screening as a means of preventing prostate cancer deaths, they continue. This mortality benefit is also likely reflected in the US epidemiologic data, which have shown "dramatic and sustained decreases" in prostate cancer mortality since PSA screening was first introduced.

Dr Shoag and colleagues write that the "widespread misperception that PSA screening is proven to be ineffective likely can only be reversed by clear guidance regarding whether the benefits of screening outweigh the risks."

Testing Yes, but How?

In a related editorial, David F. Penson, MD, and Matthew J. Resnick, MD, from Vanderbilt University and the VA Tennessee Valley Geriatric Research, Education, and Clinical Center, Nashville, agree that PSA testing should not be completely abandoned.

They also agree that the approach needs to be more nuanced and individualized, but they exercise more caution as to exactly how to implement that.

The USPSTF is updating the guidance about prostate cancer screening that sparked so much controversy. "Given the data presented by Shoag et al, the panel will have to seriously reconsider the validity of the PLCO trial in their deliberations," Drs Penson and Resnick note.

However, they feel more evidence is needed before deciding on a screening strategy, such as the one proposed by Dr Shoag and colleagues, of baseline PSA testing for all men in their 40s and early 50s, followed by individualized screening.

"Although this may ultimately be a reasonable approach, it is primarily based on limited observational data and expert opinion," Dr Penson and Dr Resnick comment.

Instead, there is still much work to be done to "advance our understanding" of the best method of screening.

Data from the PLCO, they point out, will not help, and new markers shown to be useful in screening for and detecting high-grade cancers will further alter the current screening debate.

"All parties involved in this debate must accept that prostate cancer screening is not an 'all-or-none' proposition," Dr Penson and Dr Resnick comment.

All parties involved in this debate must accept that prostate cancer screening is not an 'all-or-none' proposition. Dr David F. Penson and Dr Matthew J. Resnick

"As a scientific community, we must acknowledge that the search for the holy grail of a single population-based prostate cancer screening strategy satisfying the needs of a heterogeneous population may prove fruitless," they add.

So while they cannot "emphatically endorse population-wide annual PSA screening on the basis of available evidence," they also cannot "dismiss the fact that, when done properly, screening confers a survival benefit."

Going forward, undoubtedly new evidence will be identified that will lead to more personalized screening strategies that maximize the benefits and minimize harms. "In the meantime, let us not throw the baby out with the bathwater," they conclude.

Dr Shoag has disclosed no relevant financial relationships; other authors report consulting or advisory role with Theralogix and Intuitive Surgical and serving on the speakers' bureau for Genomic Health. Dr Penson reports consulting or advisory role for Astellas Pharma, Medivation, and Dendreon and research funding for Medivation (institutional) and Astellas Pharma (institutional). Dr Resnick reports consulting or advisory role for MDxHealth and research funding for Genomic Health and Photocure (institutional).

J Clin Oncol. Published online July 18, 2016. Comment Editorial

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