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

Not Applicable

• Conditions: Prostate Cancer
• Interventions: Diagnostic Test: Prostate cancer screening

• Registration Number: NCT03423303
• Lead Sponsor: Tampere University

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2018-01-15
• Study First Submitted QC: 2018-01-30
• Study First Posted: 2018-02-06
• Study Start: 2018-04-23
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-06
• Last Update Posted: 2022-12-09
• Primary Completion: 2032-12-31
• Study Completion: 2032-12-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: Male
• Target Recruitment: 17400

Inclusion Criteria

• 50-63-year-old men (age in 2018) residing in Tampere or Helsinki

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Exclusion Criteria

• Prevalent prostate cancer

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Screening arm	Prostate cancer screening	Invitation to prostate cancer screening and questionnaires.

Primary Outcome Measures

Name	Time	Method
Prostate cancer (PrCa) mortality	At 10 years of follow-up.	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.

Secondary Outcome Measures

Name	Time	Method
Prostate cancer (PrCa) mortality - secondary analysis	At 10 years of follow-up.	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.
Cumulative incidence of advanced (T3-T4 or M1) prostate cancer	At approximately 5 years of follow-up.	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).
Cumulative incidence of low-risk cancer (Gleason<7)	At approximately 5 years of follow-up.	Intermediate outcomes include cumulative incidence of low-risk cancer (Gleason\<7) as an indicator of overdiagnosis.

Trial Locations

Locations (2)

University of Tampere; 🇫🇮 Tampere, Finland

Helsinki University and Helsinki University Hospital; 🇫🇮 Helsinki, Finland