Early detection of clinically significant prostate cancer: protocol summary and statistical analysis plan for the ProScreen randomised trial

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, and
complications from biopsies and overtreatment. However,
diagnostic accuracy studies have shown that detection of
clinically insignificant prostate cancer can be reduced by
MRI combined with targeted biopsies.
The aim of the paper is to describe the analysis of the
ProScreen randomised 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 intentionto-screen analysis of randomised 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 (2910/2017). Results will be
disseminated through publications in international peerreviewed journals and at scientific meetings.