Epidemiologic studies have demonstrated significant declines in prostate cancer motality rates coincident with the introduction of widespread PSA-based screening. For example, Jemal et al. reported an annual 4.1% reduction in U.S. prostate cancer mortality from 1994 to 2005.20
Mathematical models have suggested that PSA screening has accounted or approximately 80% of the reduction in advanced stage prostate cancer, and 40 to 75% of the decline in prostate cancer-specific mortality.21, 22
In European countries where screening is practiced, reductions in prostate cancer mortality have similarly been reported compared to other regions where screening is not routinely performed.23, 24
To date, the most definitive evidence that screening saves lives was reported by Schroder et al. in the ERSPC.18
In the intent-to-treat analysis, the authors reported a rate ratio of 0.80 for prostate cancer mortality (i.e. a 20% reduction) in the screening arm compared to the control arm. That notwithstanding, some men randomized to screening did not receive screening (noncompliance) and some men randomized to the control arm underwent opportunistic screening (contamination). Factoring in the approximate frequency of noncompliance and contamination, Roobol et al. estimated a risk reduction of up to 33%.25
Furthermore, van Leeuwen et al. reported a relative risk of 0.63 for prostate cancer-specific mortality in the Rotterdam ERSPC group compared to similarly aged men from Northern Ireland.19
It is possible that the mortality reduction in the ERSPC will increase with additional follow-up.
It is noteworthy that a second randomized trial- the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO)- did not demonstrate a survival difference between the screening and control arms. 26
There are many underlying reasons to explain these divergent results. In contrast to the European population, PSA screening had already become common in the United States at the time PLCO was initiated. As such, much of the “prevalent pool” of prostate cancer had already been diagnosed with prostate cancer. Beyond this issue of “prescreening,” contamination of the control arm was a much greater issue in the PLCO. Because more than 50% of controls underwent screening during the study period, Cooperberg and Carroll suggested that it be more aptly considered a trial of more versus less screening.27
In addition, compliance with prompt prostate biopsy was poor among those with abnormal screening results.28
Clearly, greater similarity in the screening practices between the two arms of the trial would reduce the mortality risk difference between groups.
A final issue related to prostate cancer screening is the possibility for the diagnosis and treatment of some tumors that would not cause harm. This can be reduced through the use of more judicious screening practices (ex: performing baseline PSA measurements in the 40s for risk stratification, use of PSA velocity, discontinuing screening for elderly men with limited life expectancy), by reserving definitive treatment for patients who are most likely to benefit, and by further reducing treatment-related morbidity.