Clinical trial NCT03423303: A Randomized Trial of Early Detection of Clinically Significant Prostate Cancer (ProScreen)
Official title: Randomized Population-Based Pragmatic Prostate Cancer Screening Trial Based on PSA, Kallikrein Panel, and MRI
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Prostate Cancer
Keywords: Prostate cancer
Screening
Randomised trial
Kallikrein
Magnetic resonance imaging
Prostate-specific antigen
Lead sponsor: Tampere University
Sponsor class: OTHER
Collaborators: name: Helsinki University Central Hospital
name: Tampere University Hospital
name: Finnish Cancer Registry, Finland
name: University of Turku
name: Lund University
name: Fimlab Laboratories, Finland
name: Laboratory HUSLAB, Finland
name: University of Helsinki
name: Hospital District of Helsinki and Uusimaa
name: Clinical Research Institute HUCH Ltd
First posted: 2018-02-06
Enrollment: 17400
Sex: MALE
Minimum age (years): 50
Maximum age (years): 63
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Of the 112,347 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).
Primary purpose: SCREENING

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* Prevalent prostate cancer

Primary outcomes:
measure: Prostate cancer (PrCa) mortality
timeFrame: At 10 years of follow-up.
Secondary outcomes:
measure: Prostate cancer (PrCa) mortality - secondary analysis
timeFrame: At 10 years of follow-up.
measure: Cumulative incidence of advanced (T3-T4 or M1) prostate cancer
timeFrame: At approximately 5 years of follow-up.
measure: Cumulative incidence of low-risk cancer (Gleason<7)
timeFrame: At approximately 5 years of follow-up.
Other outcomes:
measure: Analysis of screening test performance - 4Kscore
timeFrame: At 2, 4, and 6 years.
measure: Analysis of screening test performance - MRI
timeFrame: At 2, 4, and 6 years.
measure: Assessment of health-related quality of life in men with prostate cancer
timeFrame: At 4 years.
measure: Assessment of short-term prostate cancer (PrCa)-specific anxiety
timeFrame: At 4 years.
measure: Adverse effects of prostate biopsy immediately after the biopsy
timeFrame: During the first year.
measure: Adverse effects of prostate biopsy 30 days after the biopsy
timeFrame: During the first year.
measure: Cost analysis (incremental cost effectiveness ratio)
timeFrame: At 5 (cost analysis) and 10-15 (final analysis) years of follow-up.
Locations:
city: Helsinki
country: Finland
facility: Helsinki University and Helsinki University Hospital
city: Tampere
country: Finland
facility: University of Tampere
Study officials:
affiliation: Tampere University
name: Anssi Auvinen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Auvinen A, Tammela TLJ, Mirtti T, Lilja H, Tolonen T, Kenttamies A, Rinta-Kiikka I, Lehtimaki T, Natunen K, Nevalainen J, Raitanen J, Ronkainen J, van der Kwast T, Riikonen J, Petas A, Matikainen M, Taari K, Kilpelainen T, Rannikko AS; ProScreen Trial Investigators. Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial. JAMA. 2024 May 7;331(17):1452-1459. doi: 10.1001/jama.2024.3841.