Should We Abandon PSA Testing Or Make it More Targeted?
Widespread contamination of the Prostate, Lung, Colorectal, and Ovary Cancer Screening Trial has reignited the debate around prostate-specific antigen testing.
The landmark Prostate, Lung, Colorectal, and Ovary (PLCO) Cancer Screening Trial found no survival benefit from prostate-specific antigen (PSA) testing, leading the United States Preventive Services Task Force (USPSTF) to recommend in 2012 against PSA testing for healthy men.1
The European Randomized Study for Screening of Prostate Cancer (ERSPC), however, found that PSA testing did reduce prostate-specific mortality.2 The efficacy of PSA testing has since been the subject of intense debate.
A recent evaluation of the PLCO trial found that it was deeply flawed, as more than 80% of men in the unscreened control arm received a PSA test at least once during the study.
The degree of contamination was revealed by an analysis presented in May 2016 by Jonathan Shoag, MD, of Weill Cornell Medical College in New York, New York, at the annual meeting of the American Urological Association, and published in the New England Journal of Medicine.3 The findings added to the debate over PSA testing, and effectively invalidated the landmark status of the PLCO trial.
Writing in the Journal of Clinical Oncology, Shoag and colleagues argued that the only remaining evidence from a randomized controlled trial–the ERSPC study–shows that PSA testing saves lives and should be continued “as an evidence-based recommendation.” They recommended that all men undergo PSA screening in their 40s or early 50s. 4
In an accompanying editorial, David Penson, MD, MPH, of Vanderbilt University Medical Center in Nashville, Tennessee, contended that the ERSPC trial may not alone provide enough evidence to support changing the guidelines against PSA testing.5 Dr Penson recommended that while screening should not be abandoned altogether, it should be done in a “smarter” and more personalized manner.
Dr Shoag's coauthor, Jim Hu, MD, director of the LeFrak Center for Robotic Surgery at New York Presbyterian and Weill Cornell Medicine in New York, New York, defended their recommendations in an email to Cancer Therapy Advisor.
“Dr Penson's editorial largely agrees with our findings that the PLCO is no longer a landmark study, given our discovery of significant limitations,” he said. “He also agrees that there should be continued screening, but that it should be smarter, or personalized. This is another way of saying: ‘conduct baseline screening and adjust future intensity accordingly.'”
“Dr Hu's suggestion is a potential option, but it is based on opinion and a single study showing that a PSA in a man's 40s predicts lethal prostate cancer later in life,” said Dr Penson in an email to Cancer Therapy Advisor. “Until we generate better evidence to figure out the best way to screen, I feel that the guideline recommendations of the NCCN, AUA, ACS, and ACP are still the best: engage in shared decision-making with men regarding the pros and cons of prostate cancer screening, and let each patient make his own choice.”
Dr Hu disagreed that his suggestion was based on a single study. “Several studies demonstrate a benefit of assessing a baseline PSA test in the 40s,” he said. “A high PSA indicates a greater lifetime risk of developing a lethal or metastatic cancer. Therefore the intensity of subsequent screening may be determined by the magnitude of the first PSA.”
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“The evidence for baseline screening is observational,” he admitted. “As we see with the PLCO study, however, there is too much background use of PSA testing in the U.S. to conduct a randomized controlled trial on the efficacy of baseline screening to reduce prostate cancer mortality.”