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Expert Urges Revisiting PSA Screening After Pivotal Trial Update

Gina Columbus @ginacolumbusonc
Published: Tuesday, Sep 13, 2016

Jim C. Hu

Jim C. Hu, MD

After updated findings from the landmark Prostate, Lung, Colorectal, and Ovary (PLCO) screening trial were presented earlier this year, members of the oncology community strongly suggested that the United States Preventative Services Task Force (USPSTF) revise its views on prostate-specific antigen (PSA) screening for patients with prostate cancer.

Originally launched in 1993, the PLCO trial involved 77,000 men with an average risk of prostate cancer who were randomized to annual PSA screening for 6 years and digital rectal exam for 4 years or no screening for prostate cancer. At a follow-up of 7 years, it was determined that there was no difference in prostate cancer detection or mortality between the screening and control groups.1

These data were instrumental in the recommendation made by the USPSTF against PSA screening.

However, an updated analysis of the study showed that 80% of the control group reported at least 1 PSA test during the trial.2 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. These results demonstrate that the original comparisons cannot be interpreted—and that PSA does indeed have a role—the authors noted.

“We shouldn’t bury PSA yet; this is kind of a ‘smoking gun’ for the demise of PSA,” says study author Jim C. Hu, MD. “We did more investigative work to really look at the study design and found that there was more contamination than there originally was, which, unfortunately, makes the PLCO study uninterpretable. Therefore, any conclusions drawn from that, any policy made as of results to that study, should really be rethought.”

In an interview with OncLive, Hu, the Ronald P. Lynch Professor of Urologic Oncology at Weill Cornell Medicine and NewYork-Presbyterian Hospital, sheds light on the updated PLCO findings and what this means for the role of PSA in the field of prostate cancer.

OncLive: What are some of the challenges associated with PSA screening?

Hu: PSA testing was introduced in the early 1990s, and it certainly led to an increased incidence. We found more prostate cancers, and we found that the prostate cancer–specific mortality went down—roughly by 50% compared with pre-PSA.

We also saw a decrease in the likelihood of metastatic disease at surgery. For instance, before PSA testing, about 30% of men who went to surgery had cancers that had gone to the lymph nodes—that has now decreased to about 2% to 3% after adoption of PSA testing.

PSA, on average, has shown that it may detect prostate cancers about 7 to 12 years before they were detected previously. This means that the lead-time bias for detecting cancers is much earlier. This then leads to catching what we already know could be indolent or slow-growing prostate cancers.

Although it leads to earlier detection of prostate cancer, it also detects a lot of indolent tumors that leads to an overdiagnosis and overtreatment issue, as some men may not understand the tumor biology, and the risks associated with watching it versus getting a biopsy. This is why it has been controversial.

What happened with the original PLCO trial, and why does it need to be revaluated?

The original study randomized men to PSA testing annually for 6 years versus no testing whatsoever. At the end of the trial follow-up—after about 9 to 10 years—they did not see a difference in prostate cancer-specific mortality. The conclusion of the trial was that PSA testing does not lessen prostate cancer¬–specific mortality.

However, in the same issue of The New England Journal of Medicine, the results of a European study were published.3 It was about twice as large in study design; PSA testing wasn’t conducted annually, but every 4 years. In that study, there was a 21% decrease in prostate cancer mortality.

Why was the European trial showing 1 thing, and nothing in the American study? As the investigators reported in 2009, there was 52% contamination in the control arm—which was comprised of the men who were randomized to not have PSA testing. Many of us felt that this study was really a comparison of annual testing versus occasional testing because of that 52% contamination.

The USPSTF, which reviews a lot of screening guidelines for other issues, looked at all the evidence originally in 2011 and finalized the recommendation in 2012, giving PSA testing a grade D recommendation. This means that there was fairly good evidence that PSA testing didn’t do much good.

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