Prostate Cancer Detection Using the Stockholm3 Test and MR/Fusion Biopsies

Study Overview
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Brief Summary
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The STHLM3-MRI trial is a study comparing traditional prostate cancer detection using PSA and systematic biopsies with the improved pipeline for prostate cancer detection using the STHLM3 test and targeted biopsies in a screening context. The study includes individualised repeat invitations for re-screening to participants not diagnosed with prostate cancer.

Detailed Description
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The overarching strategy of the STHLM3-MR/Fusion projects are to study an improved diagnostic pipeline including an improved blood-based test for identification of men with increased risk of prostate cancer and use of MRI to select men for diagnostic workup with targeted prostate biopsies. The aim is to increase the specificity in early detection of prostate cancer without decreasing the sensitivity of aggressive prostate cancers. The primary endpoints are the number of performed biopsies, the number of performed MRI and the number of detected high-risk prostate cancers. Secondary endpoints include the number of low risk prostate cancers diagnosed and the proportion of patients with up-or downgraded disease after assessment of prostatectomy specimen. Additional aims include to assess the health economic consequences and development of automated image-analysis. The STHLM3-MR project is performed in two separate phases, analyzed separately. STHLM3-MR Phase 1 closed inclusion 2017-06-01. All participants underwent target and systematic biopsies together with STHLM3 test analysis. The study is constitutes a current practice cohort and levels of the STHLM3 test were not used for selecting participants. STHLM3-MR Phase 2 is a study comparing traditional prostate cancer detection using PSA and systematic biopsies with the improved pipeline for prostate cancer detection using the STHLM3 test and targeted biopsies in a screening context. STHLM3-MR Phase 2 reported outcomes from the first screening round 2023. Repeated screening with individualised screening intervals will be offered to participants without prostate cancer detected.

Official Title
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STHLM3 MR Phase 2: A New Diagnostic Chain for Prostate Cancer Detection Using the Stockholm3 Test and MR/Fusion Biopsies

Conditions
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Prostate Cancer

Intervention / Treatment
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* Procedure: MRI/Fusion biopsies
* Procedure: Systematic biopsies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Permanent postal address in Stockholm Exclusion Criteria: • Severe illnesses such as metastatic cancers, severe cardio-vascular disease or dementia Contraindications for magnetic resonance imaging (MRI) eg pacemaker, magnetic cerebral clips, cochlear implants or severe claustrophobia.

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 74 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two-step design with a first step using paired design for blood-analysis and a second step using randomisation between prostate biopsy strategy. Repeated screening using individualised screen intervals for participants randomised to the experimental (MRI) arm and without prostate cancer diagnosed.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Standard arm (One testing with PSA and standard biopsy)<br>The traditional/control arm consists of PSA testing and if PSA>3ng/ml a systematic biopsy of the prostate is performed. Only one screening is offered for participants. | Procedure: Systematic biopsies<br>* The intervention in the control arm is traditional systematic biopsies of the prostate.<br>|
| Experimental: STHLM3+MRI/Fusion including repeat screening.<br>The experimental arm consists of a Stockholm3 bloodiest and if elevated, an MRI is recommended with targeted biopsies to prostate lesions. Participants with PSA<1.5ng/ml are reinvented for prescreen after 6 years. Remaining participants with no prostate cancer detected are reinvited for re-screen at 2-3 years. | Procedure: MRI/Fusion biopsies<br>* The intervention in the experimental arm is an MRI with targeted biopsies using fusion technique to prostate lesions. Repeat screening is offered after 2-6 years on an individualised basis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of detected cancers characterized as Gleason Score ≥7 on evaluation of biopsy specimen | Cancers detected by pathological evaluation of biopsy specimen collected from the respective study arm | At 2 months after completing first screening round (included biopsy procedure). At two months after completing repeat screening rounds ( year 3, 6, 9, 12 and 15). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of detected cancer with Gleason Score 6 | Cancers detected by pathological evaluation of biopsy specimen collected from the respective study arm | At 2 months after completing first screening round (last included biopsy procedure). At two months after completing repeat screening rounds ( year 3, 6, 9, 12 and 15). | 
| Number of performed biopsy procedures in the study arms | Number of performed prostate biopsy procedures counted per study arm | At 2 months after completing first screening round (last included biopsy procedure). At two months after completing repeat screening rounds ( year 3, 6, 9, 12 and 15). | 
| Number of performed MRI in the study arms | Number of performed prostate MRI procedures counted per study arm | At 2 months after completing first screening round (last included biopsy procedure). At two months after completing repeat screening rounds ( year 3, 6, 9, 12 and 15). | 
| Number of infectious complications | As assessed by questionnaire within 2 month after biopsy procedure | Questionnaire collection finalised within 2months after last biopsy procedure in study | 
| Distribution of MRI findings in men positive for Stockholm3 and/or PSA | Distribution of PI-RADS (Prostate Imaging-Reporting and Data System; 1-5; 5=clinically significant cancer is highly likely to be present) scores among men undergoing an MRI | At 2 months after completing first screening round (last included biopsy procedure). At two months after completing repeat screening rounds ( year 3, 6, 9, 12 and 15). |