NO SURVIVAL BENEFIT OF PSA SCREENING

NEW YORK (Reuters Health) - A novel new analysis supports results of a major U.S. prostate cancer screening trial that found prostate-specific antigen (PSA) screening does not reduce deaths from the disease at a cutoff point of 4 ng/mL for doing a biopsy.

"We should not use the PSA screening cutoff of 4.0 ng/mL blindly, but look at all of the data available to us and determine whether or not to biopsy a patient," Dr. Jonathan Shoag, of the Department of Urology at New York Presbyterian Hospital, who worked on the analysis, told Reuters Health by email.

PSA screening is highly controversial, he noted, and a major reason for this controversy is debate about the applicability of the PLCO prostate cancer screening trial, which did not identify a benefit to PSA screening.

"There are multiple critiques of this trial, one of which is the high rate of screening in the control arm of the study. As such the trial has been dismissed as comparing 'screening versus screening.' However, despite its limitations, the PLCO trial is likely to remain the only large scale randomized trial of PSA screening in the U.S.," Dr. Shoag explained.

He and colleagues applied a technique used by economists called regression discontinuity (RD) to the screening arm of the PLCO dataset. "This technique is pretty intuitive, and is really underutilized in medicine," Dr. Shoag said. "By applying this technique to the screening arm of PLCO, we could understand the impact of prostate cancer screening without worrying about screening contamination of the control arm."

With RD, the researchers could introduce a "pseudo-randomization into the screening arm of the PLCO study," Dr. Shoag explained. "This is because men who had a PSA just below 4.0 ng/mL were unlikely to be biopsied and men whose PSA was just above 4.0 ng/mL were much more likely to be biopsied."

"By utilizing this cutoff we found that biopsy based on screening increased the detection of low-risk, but not more aggressive prostate cancer. That doesn't mean the PSA level is not associated with aggressive cancer (it is), but just that biopsying every patient screened for prostate cancer at a PSA cutoff of 4.0 ng/mL is probably not beneficial," Dr. Shoag told Reuters Health.

"This is in line with more recent thinking on how to use PSA in conjunction with other tests and the patient's medical history and preferences," the researcher said. "The idea of a cutoff is something that many clinicians follow not because they think it is good medicine, but because of fear of litigation and the pressure to practice defensive medicine."

Summing up, Dr. Shoag said this RD analysis shows that in the population screened in PLCO, "there was no benefit to biopsy based on screening at a PSA of 4.0 ng/mL even when the control group is excluded. There are many other issues with the PLCO trial, but this does provide an argument in support of the initial trial results being applicable in the U.S."

"We need better ways to analyze the increasing amounts of large data we are collecting so that the data can appropriately inform our decisions. Regression discontinuity is a readily applicable way to do this in a wide range of fields and could supplement data from randomized controlled trials to guide decision making," he noted.

The study had no funding. One author works as a consultant for Percys, Boston Scientific, Olympus, Cook, and Radius Pharmaceuticals and is an owner of Ravine Group.

SOURCE: http://bit.ly/1NJKMsl

JAMA Oncol 2015.