Protocol summary and statistical analysis plan for the randomized trial of early detection of clinically significant prostate cancer (ProScreen)

Abstract

ABSTRACTIntroductionEvidence on the effectiveness of prostate cancer screening based on prostate-specific antigen is inconclusive and suggests a questionable balance between benefits and harms due to overdiagnosis. However, diagnostic accuracy studies have shown that detection of clinically insignificant prostate cancer can be reduced by magnetic resonance imaging combined with targeted biopsies.The aim of the paper is to describe the analysis of the ProScreen randomized trial to assess the performance of the novel screening algorithm in terms of the primary outcome, prostate cancer mortality, and secondary outcomes as intermediate indicators of screening benefits and harms of screening.MethodsThe trial aims to recruit at least 111,000 men to achieve sufficient statistical power for the primary outcome. Men will be allocated in a 1:3 ratio to the screening and control arms. Interim analysis is planned at 10 years of follow-up, and the final analysis at 15 years. Difference between the trial arms in prostate cancer mortality will be assessed by Gray’s test using intention to screen analysis of randomized men. Secondary outcomes will be the incidence of prostate cancer by disease aggressiveness, progression to advanced prostate cancer, death due to any cause and cost-effectiveness of screening.Ethics and disseminationThe trial protocol was reviewed by the ethical committee of the Helsinki University Hospital (HUS 2910/2017). Results will be disseminated in an international peer-reviewed journal(s) and at scientific meetings.Trial RegistrationNCT03423303STRENGTHS AND LIMITATIONSThis population-based, randomized multicenter trial targeting at recruiting 111,000 men will provide high quality evidence on the effectiveness of a novel screening strategy for prostate cancer mortalityBroad eligibility criteria and pragmatic approach embedded in normal clinical practice enhances the external validity of the trial and provide evidence applicable to decision making in public health and health careChallenges for the trial include the maintenance of high compliance to screening and the extent of opportunistic PSA testing in the population