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

• ClinicalTrials.gov Identifier: NCT03423303
• Recruitment Status: Enrolling by invitation
• First Posted: February 6, 2018
• Last Update Posted: December 9, 2022
• Sponsor: Tampere University
• Collaborators: Helsinki University Hospital, Finland; Tampere University Hospital, Finland; Finnish Cancer Registry, Finland; University of Turku, Finland; Lund University; Fimlab Laboratories, Finland; Laboratory HUSLAB, Finland; University of Helsinki; Hospital District of Helsinki and Uusimaa; Clinical Research Institute HUCH Ltd, Finland
• Information provided by (Responsible Party): Anssi Auvinen, Tampere University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Diagnostic Test: Prostate cancer screening	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 17400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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)
• Primary Purpose: Screening
• Official Title: Prostate Cancer Screening Trial
• Actual Study Start Date: April 23, 2018
• Estimated Primary Completion Date: December 31, 2032
• Estimated Study Completion Date: December 31, 2032

Arms and Interventions

Arm	Intervention/treatment
Experimental: Screening arm; Invitation to prostate cancer screening and questionnaires.	Diagnostic Test: Prostate cancer screening; 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.
No Intervention: Control arm; Registry-based follow-up and a questionnaire.

Outcome Measures

Primary Outcome Measures :

1. Prostate cancer (PrCa) mortality [ Time Frame: 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 :

1. Prostate cancer (PrCa) mortality - secondary analysis [ Time Frame: 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.
2. Cumulative incidence of advanced (T3-T4 or M1) prostate cancer [ Time Frame: 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).
3. Cumulative incidence of low-risk cancer (Gleason<7) [ Time Frame: At approximately 5 years of follow-up. ]
   Intermediate outcomes include cumulative incidence of low-risk cancer (Gleason<7) as an indicator of overdiagnosis.

Other Outcome Measures:

1. Analysis of screening test performance - 4Kscore [ Time Frame: At 2, 4, and 6 years. ]
   Diagnostic performance of 4Kscore among men with PSA>3 in terms of predictive values, sensitivity, and specificity for clinically significant PrCa (defined as Gleason 7+ cancers - including those diagnosed within the next four years for test-negative non-biopsied men i.e. false negatives).
2. Analysis of screening test performance - MRI [ Time Frame: At 2, 4, and 6 years. ]
   Diagnostic performance of MRI based on PI-RADS v2 scores among men with PSA>3 and positive 4Kscore in terms of predictive values, sensitivity, and specificity for clinically significant PrCa (defined as Gleason 7+ cancers - including those diagnosed within the next four years for test-negative non-biopsied men i.e. false negatives).
3. Assessment of health-related quality of life in men with prostate cancer [ Time Frame: At 4 years. ]
   Health-related quality of life among men diagnosed with prostate cancer will be assessed using the EPIC 26 instrument enrolling screen-detected and interval cases, as well as those diagnosed among non-participants and in the control arm.
4. Assessment of short-term prostate cancer (PrCa)-specific anxiety [ Time Frame: At 4 years. ]
   Anxiety among men diagnosed with prostate cancer will be assessed using the Memorial Anxiety Scale for Prostate Cancer (MAX-PC), enrolling screen-detected and interval cases, as well as those diagnosed among non-participants and in the control arm.
5. Adverse effects of prostate biopsy immediately after the biopsy [ Time Frame: During the first year. ]
   Adverse effects of biopsy are evaluated using a questionnaire on complications including assessment of bleeding, lower urinary tract symptoms (LUTS), erectile dysfunction (ED), pain, and antibiotic treatment immediately after the biopsy.
6. Adverse effects of prostate biopsy 30 days after the biopsy [ Time Frame: During the first year. ]
   Adverse effects of biopsy are evaluated with a questionnaire on complications, including assessment of bleeding, lower urinary tract symptoms (LUTS), erectile dysfunction (ED), pain, and antibiotic treatment 30 days after the biopsy.
7. Cost analysis (incremental cost effectiveness ratio) [ Time Frame: At 5 (cost analysis) and 10-15 (final analysis) years of follow-up. ]
   Economic evaluation will commence with cost analysis, and the final analysis of incremental cost effectiveness ratio (with a decision analysis) will be conducted once data on both long-term cost and real outcome data on both utilities (quality-adjusted life-years) and mortality are available.

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 63 Years (Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Trial participants will be identified by the Finnish Population Register Centre.
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

• Prevalent prostate cancer

Contacts and Locations

Locations

Finland

Helsinki University and Helsinki University Hospital

Helsinki, Finland

University of Tampere

Tampere, Finland

Sponsors and Collaborators

Tampere University

Helsinki University Hospital, Finland

Tampere University Hospital, Finland

Finnish Cancer Registry, Finland

University of Turku, Finland

Lund University

Fimlab Laboratories, Finland

Laboratory HUSLAB, Finland

University of Helsinki

Hospital District of Helsinki and Uusimaa

Clinical Research Institute HUCH Ltd, Finland

Investigators

• Principal Investigator: Anssi Auvinen, MD, PhD; Tampere University

  Study Documents (Full-Text)

Documents provided by Anssi Auvinen, Tampere University:

Study Protocol and Statistical Analysis Plan  [PDF] September 5, 2017

More Information

Additional Information:

Website of the study. 

• Responsible Party: Anssi Auvinen, Professor, Tampere University
• ClinicalTrials.gov Identifier: NCT03423303
• Other Study ID Numbers: 2910/2017
• First Posted: February 6, 2018
• Last Update Posted: December 9, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The data will be managed and made openly available with Finnish Social Science Data Archive (FSD) and publisher websites. The type of data includes numerical data, mainly counts, and continuous variables classified as categorical. The data will be uploaded in tabular form (as a data matrix). The data will be deidentified and supplied only as frequencies. The released data will be available under CC license for research purposes (accessible for registered users of FSD database). Citation of the original research is needed whenever used by third parties.
• Supporting Materials: Study Protocol; Informed Consent Form (ICF)
• Time Frame: The data wil be released after publication of the results (approximately 2032-).
• Access Criteria: CC license, FSD database registered users

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Anssi Auvinen, Tampere University:

Prostate cancer; Screening; Randomised trial; Kallikrein; Magnetic resonance imaging; Prostate-specific antigen

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases