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

• ClinicalTrials.gov Identifier: NCT04287088
• Recruitment Status: Recruiting
• First Posted: February 27, 2020
• Last Update Posted: November 23, 2021
• Sponsor: Turku University Hospital
• Collaborators: Tampere University Hospital; Satakunta Central Hospital; Central Finland Hospital District; Memorial Sloan Kettering Cancer Center; Mount Sinai Hospital, New York
• Information provided by (Responsible Party): Turku University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Diagnostic Test: A shared decision making	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: 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
• Actual Study Start Date: February 17, 2020
• Estimated Primary Completion Date: December 31, 2021
• Estimated Study Completion Date: December 31, 2041

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Gleason 4+3=7 prostate cancer, baseline [ Time Frame: 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

Secondary Outcome Measures :

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

Other Outcome Measures:

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Peter Boström, MD; 023130000 ext 358; peter.bostrom@tyks.fi

Contact: Otto Ettala, MD; 023130000 ext 358; otto.ettala@tyks.fi

Locations

Finland

Central Finland Central Hospital; Recruiting

Jyväskylä, Finland, 40620

Contact: Heikki Seikkula, MD 142691811 ext 358 heikki.seikkula@ksshp.fi

Satakunta Central Hospital; Recruiting

Pori, Finland, 28500

Contact: Marjo Seppänen, MD 262771 ext 358 marjo.seppanen@satshp.fi

Tampere University Hospital; Recruiting

Tampere, Finland, 33520

Contact: Antti Kaipia, MD 3311611 ext 358 antti.kaipia@pshp.fi

Turku University Hospital; Recruiting

Turku, Finland, 20521

Contact: Otto Ettala, MD 23130000 ext 358 otto.ettala@tyks.fi

Contact: Peter Boström, MD peter.bostrom@tyks.fi

Sub-Investigator: Kari Syvänen, MD

Sponsors and Collaborators

Turku University Hospital

Tampere University Hospital

Satakunta Central Hospital

Central Finland Hospital District

Memorial Sloan Kettering Cancer Center

Mount Sinai Hospital, New York

More Information

Additional Information:

multi-IMPROD trial 

IMPROD trial 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Turku University Hospital
• ClinicalTrials.gov Identifier: NCT04287088
• Other Study ID Numbers: T326/2019
• First Posted: February 27, 2020
• Last Update Posted: November 23, 2021
• Last Verified: November 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• 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.
• Access Criteria: Publicly available. Free access.

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

Keywords provided by Turku University Hospital:

bpMRI; shared decision making; IMPROD; risk calculation

Additional relevant MeSH terms:

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