Major health policy implications follow findings from the landmark Prostate, Lung, Colorectal, and Ovary screening trial, after it was found that 80% of the control group reported at least one PSA test during the trial.
Jonathan Shoag, MD
Major health policy implications follow findings from the landmark Prostate, Lung, Colorectal, and Ovary (PLCO) screening trial, after it was found that 80% of the control group reported at least one PSA test during the trial. Additionally, more than half had PSA assessments within the year prior to enrollment, and 70% reported having a PSA test in the 2 years prior to joining the control group of the trial.
A high rate of PSA testing in the control arm demonstrates meaningful comparisons with the “intervention” group impossible, according to the new analysis of data, which was reported at the 2016 American Urological Association Annual Meeting.
Given that PLCO data played a major role in the US Preventive Services Task Force (USPSTF) recommendation against routine PSA screening, the findings have significant implications, Jonathan Shoag, MD, stated during the meeting.
“There was a very high rate of PSA testing in the control arm of PLCO,” said Shoag, a resident at New York Presbyterian Hospital and Weill Cornell Medical College in New York. “You cannot compare trial arms to evaluate the effect of screening. Policy based on the PLCO trial results needs to be reconsidered.”
The analysis was reported simultaneously as a research letter in the New England Journal of Medicine (NEJM).
Launched in 1993, the PLCO trial involved 77,000 men with an average risk of prostate cancer, randomized to annual PSA screening for 6 years and digital rectal exam for 4 years or to no screening for prostate cancer. After 7 years of follow-up, the data showed no difference in prostate cancer detection or mortality between the screening and control groups.1
Rates of PSA screening in the PLCO control arm have sparked controversy since the trial results were reported in 2009. Authors of the 2009 report said that about 50% of patients in the control arm had been screened at least once during the trial. A subsequent publication, based on 13 years of follow-up, referred to the 2009 report for PSA testing rates in the control arm, rather than updating this figure.2
In its 2012 recommendation against routine PSA screening, the USPSTF cited the 2009 publication in support of the recommendation. This version may have contained immature data, since the rates of PSA testing during the PLCO trial were determined by a follow-up survey administered to a subgroup of patients in the control group. The survey elicited information about the number and timing of PSA tests relative to enrollment in PLCO, as well as the reason for the test.
“This is an inaccurate interpretation of PSA testing in the control group during the trial,” Shoag and coauthors stated in their NEJM correspondence.
In the 2009 report, the definition of “contamination” was limited to men who reported having a PSA test within the past 12 months as part of a routine physical exam. Men who cited other screening frequencies and other reasons were not counted as having been tested, said Shoag.
Including other response categories increased the testing contamination rate in the control group to more than 80%, or more than 90% when added to the baseline contamination rate of 10%. Over the 13 years of follow-up in the PLCO trial, men in the control group had higher rates of PSA screening than did those in the intervention arm, when the screening definition included all of the categories on the questionnaire.
The Centers for Medicare and Medicaid Services had started work on a proposal that would effectively discourage PSA testing in all men, said Shoag. The agency temporarily suspended development of the proposal in March. In the meantime, the USPSTF has begun the process of updating its recommendations related to prostate cancer screening.
“The decisions made by these two organizations are likely to determine the fate of PSA screening in the United States,” the authors of the NEJM correspondence stated.