Randomized Prospective Multi Center Cohort Study for Primary Diagnosis of Clinically Significant Prostate Cancer With Combination of PSA/DRE and Multi Parametric Magnetic Resonance Imaging

NCT04993508 | Not Yet Recruiting

• 1 other identifier: 2021-1389
• Study Type: interventional
• Target: 1,908
• Locations: 0 countries
• Sites: N/A

Brief Summary

This randomized prospective multi center study is designed to confirm a new diagnostic pathway in primary diagnosis of clinically significant prostate cancer by combination of serum levels of prostate specific antigen (PSA), digitorectal examination (DRE), and multiparametric magnetic resonance imaging (mpMRI). Men at the age of 50 to 75 with an elevated PSA (\>= 3 ng/ml) and /or suspicious DRE receive an upfront multi parametric MRI. Only men with MRI results suspicious of clinically significant prostate cancer will be biopsied. Those will be randomized into arm A and arm B. Arm A undergoes only targeted MRI/US fusion-guided biopsies (= TB with a maximum of 3 targets and 4 cores per target). Arm B receives systematic biopsies (= SB with 12 biopsy cores) and TB. Men with unsuspicious mpMRI will be receive follow-up according to current clinical standards. PRIMA will prospectively evaluate if stand-alone targeted MRI/US fusion-guided biopsy alone is sufficient to detect clinically significant prostate cancer (csPC with (ISUP grade group ≥ 2) and to avoid unnecessary detection of low-grade PC (ISUP 1) in biopsy-naïve men compared to a combined biopsy (systematic plus targeted) approach. The results of this study will directly influence clinical practice, will have a positive impact on patients' lives, and will lower the financial burden due to reduced overdiagnosis and over treatment.

Conditions

Prostate Cancer

Keywords

prostate cancer; prostate cancer diagnosis; multiparametric Magnetic Resonance Imaging (mpMRI); detection of clinically significant prostate cancer; avoidance of over diagnosis; PSA

Outcome Measures

Primary Outcomes (1)

• detection rate of clinically significant and insignificant prostate cancers

  The composite primary endpoint comprises non-inferiority in detecting clinically significant prostate cancer (ISUP grade group ≥ 2) and superiority in avoiding detection of clinically insignificant prostate cancer (ISUP grade group 1) of TB (arm A) compared to TB+SB (arm B)

  48 months

Secondary Outcomes (10)

• Pain score (Visual Analogue Scale [VAS])

  48 months

• Patient Reported Outcomes (PROs) - complications after biopsy

  30-day

• Patient Reported Outcomes (PROs) - quality of life according to EORTC-QLQ-C30

  48 months

• Patient Reported Outcomes (PROs) - quality of life according to EPIC-26

  48 months

• number of biopsies avoided

  48 months

Study Arms (2)

Arm A

EXPERIMENTAL

Men with PI-RADS 4/5 or PI-RADS 3 in conjunction with PSAD ≥ 0.15 that are randomized into arm A will undergo only targeted MRI/US fusion-guided biopsies. Men with PI-RADS 3 and PSAD \> 0.15 with negative biopsy results will receive a follow-up MRI after 12 months. In case of upgrade to PI-RADS 4/5, men will be re-biopsied. Men with PI-RADS 4/5 without cancer diagnosis or with clinically insignificant cancer in the subsequent biopsy will be offered an additional MRI inbore biopsy. If MRI inbore biopsy is negative or with clinically insignificant cancer, men will be followed-up with MRI after 12 months. In the case of persistent PI-RADS 4/5, men will be re-biopsied.

Diagnostic Test: PSA test; Device: multiparametric prostate Magnetic Resonance Imaging (mpMRI); Procedure: targeted MRI/US fusion-guided biopsy; Procedure: MRI inbore biopsy

Arm B

ACTIVE COMPARATOR

Men with PI-RADS 4/5 or PI-RADS 3 in conjunction with PSAD ≥ 0.15 that are randomized into arm B will undergo targeted MRI/US fusion-guided biopsies and systematic biopsies (standard of care). Men with PI-RADS 3 and PSAD \> 0.15 with negative biopsy results will receive a follow-up MRI after 12 months. In case of upgrade to PI-RADS 4/5, men will be re-biopsied. Men with PI-RADS 4/5 without cancer diagnosis or with clinically insignificant cancer in the subsequent biopsy will be offered an additional MRI inbore biopsy. If MRI inbore biopsy is negative or with clinically insignificant cancer, men will be followed-up with MRI after 12 months. In the case of persistent PI-RADS 4/5, men will be re-biopsied.

Diagnostic Test: PSA test; Device: multiparametric prostate Magnetic Resonance Imaging (mpMRI); Procedure: combined prostate biopsy (systematic biopsy plus targeted MRI/US fusion-guided biopsy); Procedure: MRI inbore biopsy

Interventions

PSA test DIAGNOSTIC_TEST

testing for blood levels of PSA

Arm A; Arm B

multiparametric prostate Magnetic Resonance Imaging (mpMRI) DEVICE

mpMRI acquisition and reporting will be performed according to the current version of the Prostate Imaging-Reporting and Data System (PI-RADS). MpMRI will be performed at the different study centers on a 3 Tesla MR scanner using multi-phased array surface coil. MpMRI includes T1-weighted and T2-weighted imaging (T1WI, T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCE-MRI). Hyoscine butyl bromide will be administered to optimize image quality. Prostate imaging quality will be assessed by the prostate imaging quality score (PI-QUAL). In case of contraindications to MRI contrast agents, DCE will be omitted. In case of contraindications to hyoscine butyl bromide, it will be omitted. Lesions with a PI-RADS score of ≥ 4 and 3 with PSAD \> 0.15 will considered suspicious for csPCa.

Arm A; Arm B

targeted MRI/US fusion-guided biopsy PROCEDURE

Targeted MRI/US fusion-guided biopsy (TB) are performed using transrectal ultrasound (max. 4 cores from 3 targets). MRI/US fusion-guided biopsies can be performed transrectally or transperineally. Ultrasound-guided biopsies will be performed with a 3-D probe and with local or general anesthesia. Coverage with antibiotics has to be provided as per local standard of care for all biopsies.

Arm A

combined prostate biopsy (systematic biopsy plus targeted MRI/US fusion-guided biopsy) PROCEDURE

The combined biopsy comprises systematic biopsy (SB) and targeted MRI/US fusion-guided biopsy (TB). They are performed using transrectal ultrasound (number of cores: SB 12 cores, TB max. 4 cores from 3 targets). MRI/US fusion-guided biopsies can be performed transrectally or transperineally. Ultrasound-guided biopsies will be performed with a 3-D probe and with local or general anesthesia. Coverage with antibiotics has to be provided as per local standard of care for all biopsies.

Arm B

MRI inbore biopsy PROCEDURE

MRI inbore biopsies will be offered after negative initial MRI/US fusion-guided biopsy or diagnosis of only clinically insignificant PCa in initial biopsy in arms A or B. Before performing MRI inbore biopsy the PI-RADS scoring will be re-confirmed. The number of cores will be 2 per target. In case of inaccurate needle position additional cores are allowed to ensure correct targeting. Needle position will be verified in 2 planes. Coverage with antibiotics has to be provided as per local standard of care.

Arm A; Arm B

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men aged from 50 to 75 years
• elevated PSA ≥ 3 ng/ml and/or cancer suspicious DRE

You may not qualify if:

• Men with known prostate cancer
• men with prior prostate biopsy
• men with non-MRI compatible devices
• men with acute prostatitis

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead
• University Hospital, Aachen: collaborator
• University Hospital, Bonn: collaborator
• University Hospital of Cologne: collaborator
• University Hospital, Essen: collaborator
• University Hospital Muenster: collaborator
• German Cancer Research Center: collaborator
• Marienhospital Herne: collaborator
• Städtische Kliniken Mönchengladbach: collaborator
• Evangelische Kliniken Essen-Mitte: collaborator
• Klinikum Dortmund: collaborator
• Stiftungsklinikum PROSELIS gGmbH Recklinghausen: collaborator

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Rouvier Al-Monajjed, MD

  Heinrich Heine University Düsseldorf / Urology

  PRINCIPAL INVESTIGATOR

• Lars Schimmöller, MD

  Heinrich Heine University Düsseldorf / Radiology

  PRINCIPAL INVESTIGATOR

• Peter Albers, MD

  Heinrich Heine University Düsseldorf / Urology

  STUDY CHAIR

• Gerald Antoch, MD

  Heinrich Heine University Düsseldorf / Radiology

  STUDY CHAIR

• Matthias Boschheidgen, MD

  Heinrich Heine University Düsseldorf / Radiology

  STUDY CHAIR

• Jan Philipp Radtke, MD

  Heinrich Heine University Düsseldorf / Urology

  STUDY CHAIR

• Axel Benner

  German Cancer Research Center / Biostatistics

  STUDY CHAIR

• Boris Hadaschik, MD

  University Hospital Essen / Urology

  STUDY CHAIR

Central Study Contacts

Johanna Droop, PhD

CONTACT

+49 0211 81 19414; johanna.droop@med.uni-duesseldorf.de

Rouvier Al-Monajjed, MD

CONTACT

+49 0211 81 18110; rouvier.al-monajjed@med.uni-duesseldorf.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: August 6, 2021
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: September 26, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share