COMMENTARY

New Study Finds PSA Screening Reduces Prostate Cancer Deaths by Approximately 25% -- Is It Valid?

Kenneth W. Lin, MD, MPH

Disclosures

September 12, 2017

Editorial Collaboration

Medscape &

I'm Dr Kenny Lin, a family physician at Georgetown University Medical Center in Washington, DC, and I blog at Common Sense Family Doctor.

In a previous Medscape commentary on the draft prostate-specific antigen (PSA) screening recommendations from the US Preventive Services Task Force (USPSTF), I described the two major randomized trials that informed the Task Force's analysis: the US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)[1] and the European Randomized Study of Screening for Prostate Cancer (ERSPC).[2]

Ideally, to best estimate the benefits and harms of screening, only the group assigned to receive screening should have had PSA tests. Unfortunately, in the 1990s, many US physicians, who already thought that screening was effective, "contaminated" the PLCO trial by ordering PSA tests on men in the usual-care group. When the ERSPC concluded that PSA screening reduced prostate cancer mortality but the PLCO did not, some researchers suggested that contamination was the main reason for the discrepancy in the results.[3] And in their draft recommendations, the USPSTF appeared to discount the PLCO trial by estimating that 1 to 2 of every 1000 men age 55 to 69 years who are offered PSA screening will avoid death from prostate cancer over the next decade.[4]

A recent analysis by Dr Alex Tsodikov and colleagues in the Annals of Internal Medicine seems to support the hypothesis that PSA screening reduces prostate cancer mortality.[5] The authors, who included investigators from both trials, used three independent analytic models to simulate what would have happened in both trials in the absence of control group contamination. The models estimated a novel measure of screening intensity called "mean lead time," which they used to calculate a prostate cancer mortality reduction of 25% to 32% relative to no screening in both of the trials. This range is slightly higher than that observed in the actual ERSPC trial, which reported a 21% reduction after 13 years of follow-up.[2]

An Argument Against Selective Screening

Supporters of PSA screening will likely seize upon this analysis to petition the USPSTF to finalize its draft recommendations favoring selective PSA screening, a big—and in my view, ill-advised—change from its "don't do PSA screening" position in 2012. But we should be clear what the analysis is and what it is not. It represents the consensus projections of three mathematical models based on individual trial participant data; it does not illustrate what actually happened. I agree with four former USPSTF members who argued in 2013 that "projections from models which differ substantially from the results of large randomized trials cannot provide sufficient strength of evidence to contravene trial results."[6]

In the PLCO trial,[1] deaths from prostate cancer in the group assigned to screening have consistently exceeded those in the group assigned to usual care. After 15 years of follow-up, there were 255 deaths from prostate cancer in the screening group and 244 in the control group. Contamination might have obscured a potential mortality benefit, but it should not have led to more people dying from prostate cancer in the screening group than in the control group.

Finally, even if you choose to believe the slightly greater relative reduction in prostate cancer mortality calculated by Tsodikov and colleagues, the absolute benefit remains very small: about 1.7 fewer deaths from prostate cancer per 1000 men screened instead of 1.3. It barely affects the projected outcomes of PSA screening in real life, representing a small absolute benefit at best, and still outweighed by harms of unnecessary evaluation and treatment.

This has been Dr Kenny Lin for Medscape Family Medicine. Thank you for listening.

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