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

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ClinicalTrials.gov Identifier: NCT03423303
Recruitment Status : Enrolling by invitation
First Posted : February 6, 2018
Last Update Posted : May 3, 2018
Sponsor:
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
Helsinki University
Hospital District of Helsinki and Uusimaa
Clinical Research Institute HUCH Ltd, Finland
Information provided by (Responsible Party):
Anssi Auvinen, Tampere University

Tracking Information
First Submitted Date  ICMJE January 15, 2018
First Posted Date  ICMJE February 6, 2018
Last Update Posted Date May 3, 2018
Actual Study Start Date  ICMJE April 23, 2018
Estimated Primary Completion Date December 31, 2028   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03423303 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2018)
  • 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.
  • 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).
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 30, 2018)
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Randomized Trial of Early Detection of Clinically Significant Prostate Cancer (ProScreen)
Official Title  ICMJE Prostate Cancer Screening Trial
Brief Summary A population-based randomised trial of prostate cancer screening will be carried out. A total of approximately 67,000 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 Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Of the approximately 67,000 men aged 50-63 years resident in Helsinki and Tampere, 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
Condition  ICMJE Prostate Cancer
Intervention  ICMJE 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.
Study Arms  ICMJE
  • Experimental: Screening arm
    Invitation to prostate cancer screening and questionnaires.
    Intervention: Diagnostic Test: Prostate cancer screening
  • No Intervention: Control arm
    Registry-based follow-up and a questionnaire.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Enrolling by invitation
Estimated Enrollment  ICMJE
 (submitted: January 30, 2018)
11056
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2028
Estimated Primary Completion Date December 31, 2028   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

Exclusion Criteria:

  • Prevalent prostate cancer
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Gender Based Eligibility: Yes
Gender Eligibility Description: Trial participants will be identified by the Finnish Population Register Centre.
Ages  ICMJE 50 Years to 63 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Finland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03423303
Other Study ID Numbers  ICMJE 2910/2017
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Informed Consent Form (ICF)
Time Frame: The data wil be released after publication of the results (approximately 2028-).
Access Criteria: CC license, FSD database registered users
Responsible Party Anssi Auvinen, Tampere University
Study Sponsor  ICMJE Tampere University
Collaborators  ICMJE
  • Helsinki University Hospital, Finland
  • Tampere University Hospital, Finland
  • Finnish Cancer Registry, Finland
  • University of Turku, Finland
  • Lund University
  • Fimlab Laboratories, Finland
  • Laboratory HUSLAB, Finland
  • Helsinki University
  • Hospital District of Helsinki and Uusimaa
  • Clinical Research Institute HUCH Ltd, Finland
Investigators  ICMJE
Principal Investigator: Anssi Auvinen, MD, PhD Tampere University
PRS Account Tampere University
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP