A randomized trial of early detection of clinically significant prostate cancer (ProScreen): study design and rationale.

The current evidence of PSA-based prostate cancer screening shows a reduction in cause-specific mortality, but with substantial overdiagnosis. Recently, new developments in detection of clinically relevant prostate cancer include multiple kallikreins as biomarkers besides PSA, and multiparametric magnetic resonance imaging (mpMRI) for biopsy decision. They offer opportunities for improving the outcomes in screening, particularly reduction in overdiagnosis and higher specificity for potentially lethal cancer. A population-based randomized screening trial will be started, with 67,000 men aged 55-67 years at entry. A quarter of the men will be allocated to the intervention arm, and invited to screening. The control arm will receive no intervention. All men in the screening arm will be offered a serum PSA determination. Those with PSA of 3 ng/ml or higher will have an additional multi-kallikrein panel and those with indications of increased risk of clinically relevant prostate cancer will undergo mpMRI. Men with a malignancy-suspect finding in MRI are referred to targeted biopsies. Screening interval is 6 years for men with baseline PSA < 1.5 ng/ml, 4 years with PSA 1.5-3.0 and 2 years if initial PSA > 3. The main outcome of the trial is prostate cancer mortality, with analysis at 10 and 15 years. The statistical power is sufficient for detecting a 28% reduction at 10 years and 22% at 15 years. The proposed study has the potential to provide the evidence to justify screening as a public health policy if mortality benefit can be sustained with substantially reduced overdiagnosis.