A Randomized Trial of Early Detection of Clinically Significant Prostate Cancer (ProScreen)

Study Overview
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Brief Summary
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A population-based randomised trial of prostate cancer screening will be carried out. A total of approximately 117,200 men aged 50-63 in Helsinki and Tampere are randomised to intervention (screening) or control arm. A reduction in harms of screening in the form of overdiagnosis is sought, while retaining as much as possible of the mortality benefit (reduction in prostate cancer mortality). Novel methods that have been shown to increase specificity for clinically relevant prostate cancer but never tested in a randomised setting will be employed in screening and diagnostics. The main end-point is prostate cancer mortality at 10 and 15 years of follow-up.

Detailed Description
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Frequent adverse effects have so far tipped the balance of benefits and harms against prostate cancer screening, and therefore the investigators will focus on employing the best possible means for reducing them. The project introduces a novel concept for PC screening that minimises overdiagnosis and overtreatment, while retaining the mortality benefit to shift the balance of screening benefits and harms to a favourable net effect. The strategy for implementation as a randomised screening trial utilises three levels of risk assessment (PSA, kallikrein panel and MRI) before the diagnostic procedure (prostate biopsy), each aimed at eliminating detection of indolent disease. The study hypothesis is that by virtue of the novel three-tiered screening algorithm, the beneficial screening effect (prostate cancer mortality reduction) can be retained, while the overdiagnosis can be largely eliminated. The impact of an integrative approach has never been evaluated - each of the methods has only been assessed in isolation. The breakthrough potential of the proposal lies in combining the three novel approaches and taking them to the forefront of applied research through a randomised trial. The key impact of the study is in defining whether the overall balance of benefits and harms of prostate cancer screening can be reversed by applying the best possible methods to detect only clinically important disease. If the study hypothesis is affirmed, it opens the way to introduction of prostate cancer screening. If the balance of harms and benefits is still unfavourable, the problem of overdiagnosis in prostate cancer may be intractable.

Official Title
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Prostate Cancer Screening Trial

Conditions
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Prostate Cancer

Intervention / Treatment
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* Diagnostic Test: Prostate cancer screening


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50-63-year-old men (age in 2018) residing in Tampere or Helsinki Exclusion Criteria: Prevalent prostate cancer

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 63 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Of the approximately 117,200 men aged 50-63 years resident in Helsinki and Tampere regions, a fourth will be randomised to screening and the rest to control arm (after exclusion of prevalent cases).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Screening arm<br>Invitation to prostate cancer screening and questionnaires. | Diagnostic Test: Prostate cancer screening<br>* Depending on each diagnostic test result the participants in the screening arm will undergo PSA-testing, 4Kscore determination, MRI, and MRI/US fusion biopsy only.<br>|
| No Intervention: Control arm<br>Registry-based follow-up and a questionnaire. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate cancer (PrCa) mortality | An intention to screen analysis will be performed, with all men in the groups defined by random allocation, regardless of compliance. Follow-up starts at randomisation, and ends at death. Cox regression will be used with prostate cancer death as the outcome. | At 10 years of follow-up. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate cancer (PrCa) mortality - secondary analysis | A secondary analysis of prostate cancer mortality will be performed using the Cuzick method with correction for contamination and selection bias due to non-compliance. | At 10 years of follow-up. | 
| Cumulative incidence of advanced (T3-T4 or M1) prostate cancer | Intermediate outcomes include cumulative incidence of advanced (T3-T4 or M1) prostate cancer (number of cases relative to population size, not using incidence density to avoid the lead-time bias due to early detection by screening). | At approximately 5 years of follow-up. | 
| Cumulative incidence of low-risk cancer (Gleason<7) | Intermediate outcomes include cumulative incidence of low-risk cancer (Gleason<7) as an indicator of overdiagnosis. | At approximately 5 years of follow-up. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate cancer, Screening, Randomised trial, Kallikrein, Magnetic resonance imaging, Prostate-specific antigen