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PSA screening reduces prostate cancer mortality

Two influential prostate cancer screening trials offer compatible evidence that PSA screening significantly reduces deaths from prostate cancer, according to research published in Annals of Internal Medicine.

“In 2012 the U.S. Preventive Services Task Force (USPSTF) determined that there was ‘very low probability of preventing a death from prostate cancer in the long term’ and recommended against routine use of [PSA screening],” Alex Tsodikov, PhD, from the University of Michigan, Ann Arbor, and colleagues wrote.

“The USPSTF recommendation relied heavily on results from the ERSPC (European Randomized Study of Screening for Prostate Cancer) and the PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial). However, the trials had apparently conflicting results, with the ERSPC reporting a 21% reduction in prostate cancer mortality and the PLCO finding no difference in mortality between the trial groups.”

Tsodikov and colleagues performed a re-analysis of the ERSPC and PLCO trials to determine whether the effects of screening on prostate cancer mortality differed between the two studies relative to no screening. They conducted Cox regression while adjusting for age and trial, as well as extended statistical analyses using mean lead times to account for increased occurrence due to screening and diagnostic work-up in each group. The ERSPC included 88,921 control participants and 72,473 screening participants aged 55 to 69 years, whereas the PLCO included 38,343 controls and 38,340 screening participants aged 55 to 74 years.

The researchers found that the mean lead times for the ERSPC and PLCO intervention groups were similar; however, the PLCO control group had significantly longer mean lead times than the ERSPC control group. According to the extended analyses, there was no difference between trials in the effects of screening. Longer mean lead times were associated with a lower prostate cancer mortality risk. In the ERSPC and PLCO, screening substantially reduced the risk for prostate cancer by 25% to 31% and 27% to 32%, respectively, compared with no screening.

“Taken together, the data from the ERSPC and PLCO do not provide evidence that screening efficacy (relative to no screening) differed between the trials after we accounted for differences in implementation and setting,” Tsodikov and colleagues concluded. “Our estimation of the common effect of screening suggests that it can significantly reduce the risk for prostate cancer death. However, as for all interventions, the benefit of screening must be weighed against its potential harms for informed clinical and shared decision making.”

In an accompanying editorial, Andrew J. Vickers, PhD, from the Memorial Sloan Kettering Cancer Center, hopes that this study will “finally put to rest” whether PSA screening decreases mortality from prostate cancer.

“PSA-based screening does reduce prostate cancer mortality, but whether this benefit outweighs the harms of overdiagnosis and overtreatment depends on how screening is implemented,” he concluded. “Unfortunately, the way screening has been implemented in the United States leaves much to be desired. The controversy about PSA-based screening should no longer be whether it can do good but whether we can change our behavior so that it does more good than harm.”

Recently, the USPSTF changed its recommendation on prostate cancer stating that the potential benefits and harms of PSA–based screening are closely balanced in men aged 55 to 69 years and therefore, clinicians should talk to these men about the potential benefits and harms of screening.

For men aged 70 years and older, the USPSTF maintained its 2012 recommendation, based on the position that the potential benefits of PSA–based screening do not outweigh the harms, and these men should not be screened for prostate cancer. – by Alaina Tedesco

Disclosures: Tsodikov reports no relevant financial disclosures. Please see full study for complete list of all other author’s relevant financial disclosures. Vickers reports personal fees from Genomic Health, Genome DX and GSK, as well as having a patent Arctic Partners and a patent Opko.