bpMRI and Risk Based Shared Clinical Decision Making in Prostate Cancer Diagnosis (multiIMPROD2)

Prebiopsy Magnetic Resonance Imaging in Men With Suspicion of Prostate Cancer - A Multi-centre Trial on Clinical Utility of IMPROD bpMRI in a Shared Decision Making Setting

The shortcoming of the pre-biopsy prostate MRI approach is the recommendation to biopsy all men post-MRI even if there is no lesion seen in MRI, ie. risk of PCa is very low. Therefore, the primary objective of this trial is to compare if there is a difference between significant cancer detection rate in men undergoing prostate biopsies after MRI scan compared to men undergoing post-MRI prostate biopsies only after a shared decision-making based on prostate cancer risk estimation.

The trial will enrol 600 patients. The primary outcome measure is the the proportion of men with CSPCa (Gleason 4+3 prostate cancer or higher) between the control and intervention arms at baseline. Eligible men are randomised 1:1 in two groups. In control arm in all men prostate biopsies are performed after MRI whereas in intervention arm prostate biopsies are performed only after a shared decision-making between urologist and the patient and the discussion is based on risk estimation.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Diagnostic test: A shared decision making

Detailed Description

Although most of the prostate cancers (PCas) are currently being diagnosed at early stage, at present, 30% of men are diagnosed with primarily metastatic disease. The need for better diagnostic methods is, therefore, warranted. Recent studies have shown that an alternative pathway using multiparametric (mpMRI) or biparametric (bpMRI) magnetic resonance imaging as a triage test reduces unnecessary biopsies, decreases the detection of clinically non-significant PCa (non-SPCa), and improves the detection of clinically significant PCa (CSPCa). In addition, based on these trials, also EAU guideline was updated to recommend that all men should undergo pre-biopsy mpMRI. However, shortcoming of the approach is the recommendation to biopsy all men post-MRI even if there is no lesion seen in MRI, ie. risk of PCa is very low. Therefore, the primary objective of this randomised controlled trial is to compare if there is a difference between significant cancer detection rate in men undergoing prostate biopsies after MRI scan compared to men undergoing post-MRI prostate biopsies only after a shared decision-making based on prostate cancer risk estimation.

The trial will enrol 600 patients from four hospital districts: Varsinais-Suomi, Satakunta, Pirkanmaa and Keski-Suomi. Key inclusion criteria are suspicion of prostate cancer based on elevated PSA and/or abnormal digital rectal examination. Men with previous PCa diagnosis and contraindications for MRI are excluded. The primary outcome measure is the comparison of the proportion of men with CSPCa (Gleason 4+3 prostate cancer or higher) between the control and intervention arms at baseline.

Using PSA as strata, eligible men are randomised 1:1 in two groups. After randomisation MRI examination is performed and interpreted by one experienced uro-radiologist using Likert and PI-RADS2.1 classifications. In control arm in all men prostate biopsies are performed after MRI whereas in intervention arm prostate biopsies are performed only after a shared decision-making between urologist and the patient and the discussion is based on risk estimation. Men with negative biopsies or with no biopsies performed are all assigned for five-year follow-up with semi-annual PSA. Long-term follow-up based on health records and national registries is performed for additional 15 years for all patients.

• Study Type: Interventional
• Enrollment (Anticipated): 600
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Boström, MD; Phone Number: 358 023130000; Email: peter.bostrom@tyks.fi
• Study Contact Backup: Name: Otto Ettala, MD; Phone Number: 358 023130000; Email: otto.ettala@tyks.fi

Study Locations

• Finland
  • Jyväskylä, Finland, 40620
    • Recruiting
    • Central Finland Central Hospital
    • Contact: Heikki Seikkula, MD; Phone Number: 358 142691811; Email: heikki.seikkula@ksshp.fi
  • Pori, Finland, 28500
    • Recruiting
    • Satakunta Central Hospital
    • Contact: Marjo Seppänen, MD; Phone Number: 358 262771; Email: marjo.seppanen@satshp.fi
  • Tampere, Finland, 33520
    • Recruiting
    • Tampere University Hospital
    • Contact: Antti Kaipia, MD; Phone Number: 358 3311611; Email: antti.kaipia@pshp.fi
  • Turku, Finland, 20521
    • Recruiting
    • Turku University Hospital
    • Contact: Otto Ettala, MD; Phone Number: 358 23130000; Email: otto.ettala@tyks.fi
    • Contact: Peter Boström, MD; Email: peter.bostrom@tyks.fi
    • Sub-Investigator: Kari Syvänen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Age: 18 years or older
• Language spoken: Finnish
• Clinical suspicion of prostate cancer, based on: serum level of PSA from 2,5 ng/ml to 20 ng/ml and/or abnormal digital rectal examination according to the referral physician
• Mental status: Patients must be able to understand the meaning of the study
• Informed consent: The patient must sign the appropriate Ethics Committee (EC) approved informed consent documents in the presence of the designated staff

Exclusion Criteria:

• previous diagnosis of prostate cancer
• any contraindications for MRI
• any other conditions that might compromise patient's safety, based on the clinical judgment of the responsible urologist
• bilateral hip prosthesis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; After IMPROD bpMRI all men undergo prostate biopsies. In men with Likert scores of 1-2, TRUS guided systematic biopsies are performed. In men with Likert 3-5 score, in addition to systematic biopsies, two targeted biopsies are taken from each lesion (up to two lesions).
Experimental: Intervention; After IMPROD bpMRI prostate biopsies are performed according to shared decision-making by the treating urologist and the patient. If biopsies are to be performed, in men with IMPROD bpMRI likert scores of 1-2, 12-core systematic TRUS guided biopsies are performed and in men with Likert 3-5 score lesions systematic biopsies are performed and two targeted biopsies are taken from each lesion (up to two lesions). If biopsies are not performed, men are referred for a PSA follow-up.	Diagnostic test: A shared decision making; Based on prostate cancer risk calculation (age, usage of 5-ARI medication, baseline PSA, IMPROD bpMRI Likert, prostate volume) a shared decision making whether to perform prostate biopsies or not

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gleason 4+3=7 prostate cancer, baseline	The proportion of men with clinically significant prostate cancer (Gleason 4+3 [ISUP grade group, the GGG, 3]) prostate cancer or higher) in the control and intervention arms after primary diagnostic pathway	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gleason 3+4=7 or lower prostate cancer, baseline	The proportion of men with clinically non-significant prostate cancer and intermediate risk prostate cancer (Gleason 3+3 [GGG 1], and Gleason 3+4 [GGG 2]) and benign biopsies in the control and intervention arms after primary diagnostic pathway	baseline
Men undergoing biopsies	The proportion of men undergoing biopsies in the control and intervention arms	baseline
Biopsy related complications	The proportion of men having biopsy-related complications in the control and intervention arms	baseline
Gleason 4+3=7 prostate cancer, follow-up	The proportion of men with clinically significant prostate cancer (Gleason 4+3 [GGG 3], prostate cancer or higher) in the control and intervention arms during the five years of follow-up	during the five years of follow-up
the Memorial Anxiety Scale for Prostate Cancer -questionnaire (MAX-PC)	Total score in MAX-PC in the control and intervention arms. Score range: 0-54. Higher scores in MAX-PC denote higher anxiety.	baseline, 6months, 12months
Biopsy probability	The probability of performing biopsy in experimental arm	baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biopsy criteria outcome	The number of biopsies and the number of clinically significant prostate cancer detected for each biopsy criteria	baseline
Calibration of the model	Calibration of the model using both Likert and PI-RADS2.1 criteria	Baseline
Calibration of the model using biomarkers	Calibration of the model using biomarkers such as the four kallikrein panel	Baseline

Collaborators and Investigators

• Sponsor: Turku University Hospital
• Collaborators: Memorial Sloan Kettering Cancer Center; Tampere University Hospital; Mount Sinai Hospital, New York; Central Finland Hospital District; Satakunta Central Hospital

Publications and helpful links

General Publications

• Ettala O, Jambor I, Montoya Perez I, Seppanen M, Kaipia A, Seikkula H, Syvanen KT, Taimen P, Verho J, Steiner A, Saunavaara J, Saukko E, Loyttyniemi E, Sjoberg DD, Vickers A, Aronen H, Bostrom P. Individualised non-contrast MRI-based risk estimation and shared decision-making in men with a suspicion of prostate cancer: protocol for multicentre randomised controlled trial (multi-IMPROD V.2.0). BMJ Open. 2022 Apr 15;12(4):e053118. doi: 10.1136/bmjopen-2021-053118.

Helpful Links

• multi-IMPROD trial
• IMPROD trial

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2041

Study Registration Dates

• First Submitted: February 25, 2020
• First Submitted That Met QC Criteria: February 25, 2020
• First Posted (Actual): February 27, 2020

Study Record Updates

• Last Update Posted (Actual): November 23, 2021
• Last Update Submitted That Met QC Criteria: November 15, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: shared decision making; bpMRI; IMPROD; risk calculation
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: T326/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Study protocol and statistical analysis plan will be published in peer-reviewed journal. Also, all MRI scans (pseudoanonymised), MRI reports, calculator risk scores and relevant clinical data will be provided online and publicly available similarly to previous IMPROD studies, see Links below. Informed consent form and analytic code are shared upon request.
• IPD Sharing Time Frame: Study protocol and SAP will be published during spring 2020. MRI scans, MRI reports, calculator risk scores and clinical data will be published at the time of the actual publication.
• IPD Sharing Access Criteria: Publicly available. Free access.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No