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

Introduction: Evidence 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. Methods: The 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 dissemination: The 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 Registration: [NCT03423303][1] ### Competing Interest Statement Antti Rannikko declares consultant and lecture fees from Janssen and Orion, and board memberships in the Ida Montin Foundation and Orion Research Foundation. ### Clinical Trial NCT03423303 ### Funding Statement This work was supported by the Academy of Finland (grant number 311336) the Finnish Cancer Foundation, the Jane and Aatos Erkko foundation, Competitive State Research Funding administered by Tampere University Hospital (grant number 9V02), and Paivikki and Sakari Sohlberg Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical committee of the Helsinki University Hospital (HUS 2910/2017) gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03423303&atom=%2Fmedrxiv%2Fearly%2F2023%2F05%2F10%2F2023.05.09.23289669.atom