PSA Screening Lowers Mortality, Analysis of Clinical Trials Concludes

Prostate cancer screening using prostate-specific antigen (PSA) does reduce mortality in prostate cancer, according to a review that used a new approach to analyze data from large clinical trials.

The findings suggest that current recommendations, which advise against PSA-based screening, might need to be revised, researchers write in their report, which was published in the journal Annals of Internal Medicine.

Interestingly, the study, “Reconciling the Effects of Screening on Prostate Cancer Mortality in the ERSPC and PLCO Trials,” used the same source data that the U.S. Preventive Services Task Force (USPSTF) had employed to issue recommendations against screening.

The studies were the European Randomized Study of Screening for Prostate Cancer (ERSPC; ISRCTN49127736) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; NCT00002540).

The ERSPC reported a 21 percent drop in prostate cancer mortality with screening, while the PLCO found no difference.

But researchers from the Fred Hutchinson Cancer Research Center in Seattle and the University of Michigan, among many others, noted that the studies differed in key factors, including study design and adherence.

For instance, the PLCO screened annually, while the ERSPC screened participants every two to four years. The PLCO also had a higher PSA threshold for referring patients for a biopsy and stopped screening after six rounds, researchers said.

These and other factors made researchers conclude that the PLCO “compared the effects of an organized screening program versus opportunistic screening rather than screening versus no screening.”

To overcome these differences, the research team built a mathematical model that took these differences in “screening intensity” into account.

Using the analysis they discovered that the PLCO control group had been exposed to more intensive screening than controls used in the ERSPC study.

Their analysis further showed that when differences were taken into account there was no difference in the outcome of screening between the trials, which, in fact, showed that screening was beneficial.

Screening was linked to a 7 percent to 9 percent decrease in risk of prostate cancer death for each year of the standardized screening measure.

This translated into estimates ranging between a 25 percent and 31 percent lower risk of death in screened patients in the ERSPC study, and between 27 percent and 32 percent in the PLCO intervention group, when compared with no screening.

Researchers argued that their study overcame the limitations of traditional statistical analyses, and might act to complement study results from the trial when the benefits and harms of screening are considered.