Detection of prostate cancer: the impact of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

The European Randomized Study of Screening for Prostate Cancer (ERSPC) is a large, randomized controlled trial of screening versus control, conducted in eight European countries (Belgium, Finland, France, Italy, the Netherlands, Spain, Sweden, and Switzerland). This article focuses on important aspects relating to recent findings from the ERSPC about two topics: first, leadtime and overdiagnosis, and second, prostate-specific antigen (PSA) as a test for repeated screening. The ERSPC together with the prostate cancer arm of the Prostate, Lung, Colon and Ovary (PLCO) screening trial of the National Cancer Institute in the United States are set to show or exclude an effect of screening on prostate cancer mortality. Both studies are progressing according to plan. Definitive endpoint-related data can be expected between 2005 and 2010 depending on the difference in prostate cancer mortality that may be shown between the screening and control arms. The ERSPC will allow a risk-to-benefit analysis including parameters of quality of life and cost. Overdiagnosis with present prostate cancer screening regimens is high. This amount of overdiagnosis is likely to be unacceptable for most healthcare policy makers and providers. Addressing overdiagnosis will be a major research task for urologists for the years to come. Present screening needs to be more "selective" for cases that have aggressive patterns and are likely to lead to clinical diagnosis of prostate cancer and/or death. The test characteristics of prostate-specific antigen (PSA) change after one use. The positive relation between PSA levels and positive predictive value (PPV) and detection rates in first screening rounds are lost. This may be compatible with the observation that tumor volumes in second round screening are smaller, and larger tumors are harvested. Tumor volume becomes a negative predictor in round 2, indicating that a large proportion of elevated PSA values are caused by benign prostatic hyperplasia (BPH) rather than by prostate cancer. While the outcome of the ongoing randomized studies is uncertain, screening tests cannot be refused to men who are well-informed and accept to take the risk of experiencing more harm than benefit as a result of a positive screening test result.