Prostate Screening 'Wrongfully Convicted': PLCO Reanalysis

Kate Johnson

May 11, 2016

SAN DIEGO, California — As the US Preventive Services Task Force (USPSTF) ponders updating its controversial prostate screening recommendations, new evidence gives further support to the idea that the recommendations were ill-advised in the first place.

A reanalysis of the study that strongly influenced the USPSTF recommendations ― the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial ( N Engl J Med. 2009;360:1310-9) ― has raised more doubt about the trial and its fundamental conclusions.

Prostate screening was "wrongfully convicted" on the basis of results of the PLCO trial, investigator Jonathan E. Shoag, MD, from New York Presbyterian Hospital, New York City, told Medscape Medical News.

He hopes his findings, reported in a late-breaking session at the American Urological Association (AUA) 2016 Annual Meeting and published May 5 in the New England Journal of Medicine, will influence the fate of prostate screening in the United States.

"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," he said.

Initial results from the PLCO trial showed no mortality benefit for men who received PSA screening in comparison with those who did not (N Engl J Med. 2009 Mar 26;360:1310-9). The trial strongly influenced the USPSTF's current recommendation against PSA screening for prostate cancer.

Subsequent reanalyses of the data have revealed that many men in the control arm of the PLCO trial had received PSA testing, which might explain why their mortality rates were the same as the "screened group."

Now, data from Dr Shoag's group reveal that the rate of PSA testing was higher in the control arm than in the screened arm.

The new findings come from a follow-up survey, the Health Status Questionnaire (HSQ), that was administered to a subgroup of men in the PLCO study 10 times between 1997 and 2010.

In total, 4239 control patients were surveyed with the HSQ. They were asked whether they had ever undergone PSA screening and, if so, when and why. The original study report only counted control patients as having been previously screened if they had received a PSA test in the past year, but the HSQ asked about screening in the previous 2 or 3 years and earlier.

"Overall...the proportion of control participants who reported having undergone at least one PSA test before or during the trial was close to 90%," Dr Shoag reported.

Furthermore, when participants from the intervention arm were surveyed with the same HSQ, "men in the control group reported having had more cumulative PSA testing than men in the intervention group.

"These clarifications should be considered by policymakers and payers debating reimbursement and meaningful use of PSA testing, particularly given the mounting evidence that intermittent PSA testing decreases the costs and harms of screening while preserving the benefits of annual testing," noted Dr Shoag.

"The USPSTF recommendation against PSA screening has resulted in rapid declines in PSA screening nationally," he added. "As a result, we're diagnosing fewer prostate cancers, and perhaps most concerning, physicians may be under the mistaken impression that there is no value to prostate cancer screening. The remaining data, including the large, randomized ERSPC trial [ N Engl J Med. 2009 Mar 26;360:1320-8], demonstrate that PSA screening prevents men from dying of prostate cancer," he added.

"This helps to put the negative results of the PLCO study in perspective," Stacy Loeb, MD, from New York University, in New York City, told Medscape Medical News. "If virtually all men in the control group got screened, it is no surprise that the rates of prostate cancer death were similar to the screening arm."

But Gerald L. Andriole, MD, the lead author of the PLCO trial, told Medscape Medical News that Dr Shoag's data "are not new or substantially different" from what has been reported by others, including the PLCO statisticians themselves ( Clin Trials. 2010 Aug;7:303-11).

"Notwithstanding the PLCO results, it seems that, based on ERSPC results alone, the USPSTF task force seemed to believe that the relatively modest mortality benefit was not enough to justify the human costs of screening," said Dr Andriole, chief of urologic surgery, Washington University School of Medicine, St. Louis, Missouri.

"New data regarding screening are due out soon ― the PROTECT trial from the UK. Those are the data that should matter much more."

Dr Andriole "is correct that some of the HSQ data were included in a prior low-visibility paper but in a complex manner in the body of the manuscript and not in the abstract," responded Dr Shoag. "We therefore believed that even though a portion of these data was in theory available, given the widespread misunderstanding of this information and the immediate policy implications, it was imperative that these data be clarified promptly and prominently."

Indeed, clinicians' lack of awareness of this information was clearly evident at the meeting, added Dr Shoag's coauthor Jim C. Hu, MD, MPH, from Weill Cornell Medical College, New York City.

"Twitter responses by urologists in terms of their surprise show clearly that this knowledge was not widely known," he told Medscape Medical News.

Dr Shoag has disclosed no relevant financial relationships. Dr Hu is on the speakers bureaus for Intuitive Surgical and Genomic Health. Dr Andriole's trial was funded by the National Cancer Institute.

American Urological Association (AUA) 2016 Annual Meeting: LBA-02, abstract 1140, presented May 9, 2016.


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