Evidence of Benefit
The following are several possible explanations for the lack of a reduction in mortality so far in this trial:
- Annual screening with the PSA test using the standard U.S. threshold of 4 ng per mL and DRE to trigger diagnostic evaluation may not be effective.
- The level of screening in the control group could have been substantial enough to dilute any modest effect of annual screening in the screening group.
- Approximately 44% of the men in each study group had undergone one or more PSA tests at baseline, which would have eliminated some cancers detectable on screening from the randomly assigned population; thus, the cumulative death rate from prostate cancer at 10 years in the two groups combined was 25% lower in those who had undergone two or more PSA tests at baseline than in those who had not been tested.
- Potentially, the most important explanation is that improvement in therapy for prostate cancer during the course of the trial probably resulted in fewer prostate-cancer deaths in the two study groups, which blunted any potential benefits of screening.
- The follow-up may not be long enough for benefit from the earlier detection of an increased number of prostate cancers in the screening group to emerge.
The European Randomized Study of Screening for Prostate Cancer (ERSPC) was initiated in the early 1990s to evaluate the effect of screening with PSA testing on death rates from prostate cancer. Through registries in seven European countries, investigators identified 182,000 men between the ages of 50 and 74 years for inclusion in the study. The men were randomly assigned to a group that was offered PSA screening at an average of once every 4 years or to a control group that did not receive such screening. The predefined core age group for this study included 162,243 men between the ages of 55 and 69 years. The primary outcome was the rate of death from prostate cancer. Mortality follow-up was identical for the two study groups and ended on December 31, 2006.
Recruitment and randomization procedures differed among countries and were developed in accordance with national regulations. In Finland, Sweden, and Italy, the trial subjects were identified from population registries and were randomly assigned to the trials before written informed consent was provided. In the Netherlands, Belgium, Switzerland, and Spain, the target population was also identified from population lists, but when the men were invited to participate in the trial, only those who provided consent were randomly assigned.
In the screening group, 82% of men accepted at least one offer of screening. With 14 years of data, and a median follow-up of 9 years, there were 5,990 prostate cancers diagnosed in the screening group and 4,307 in the control group, corresponding to a cumulative incidence of 8.2% and 4.8%, respectively. There were 214 prostate-cancer deaths in the screening group and 326 prostate cancer deaths in the control group in the core age group. The unadjusted rate ratio for death from prostate cancer in the screening group was 0.80 (95% CI, 0.67-0.95); after adjustment for sequential testing with alpha spending due to two previous interim analyses (based on Poisson regression analysis), the rate ratio was 0.80 (95% CI, 0.65-0.98). The rates of death in the two study groups began to diverge after 7 to 8 years and continued to diverge further over time.