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

Not Applicable

Not yet recruiting

• Conditions: Prostate Cancer

• Registration Number: NCT04993508
• Lead Sponsor: Heinrich-Heine University, Duesseldorf

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.

Detailed Description

Men at the age of 50 to 75 years with an elevated PSA (≥ 3 ng/ml) and/or suspicious DRE receive a multiparametric MRI (mpMRI) and will be stratified based on MRI results. Only men with suspicious MRI, PI-RADS 4/5, and PI-RADS 3 in conjunction with high PSA density (PSAD \> 0.15) are biopsied.

These will be randomized into arms A nd B. While patients in arm A undergo only targeted MRI/US fusion-guided biopsies (TB), patients in the "combined" arm B receive systematic biopsies (SB) and TB.

Statistical analysis for the detection rate of clinically significant and insignificant prostate cancers is composed of testing the non-inferiority and superiority of TB vs. TB+SB, respectively, using a global significance level of α = 0.05.

Interventions that are conducted within the PRIMA trial include PSA testing, digital rectal examination of the prostate (DRE), multiparametric prostate MRI, systematic and MRI/US fusion-guided biopsies as well as MRI inbore biopsies.

Arms A + B: Men with PI-RADS 4/5 and PI-RADS 3 in conjunction with PSAD \> 0.15 will be randomized into arm A or arm B and biopsied as explained above. 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 in men with PI-RADS 4/5, men will be followed-up with MRI after 12 months. In the case of persistent PI-RADS 4/5, men will be re-biopsied.

Study Timeline

• Study First Submitted: 2021-06-08
• Study First Submitted QC: 2021-08-05
• Study First Posted: 2021-08-06
• Status Verified: 2024-09
• Last Update Submitted: 2025-09-23
• Last Update Posted: 2025-09-26
• Study Start: 2026-04-01
• Primary Completion: 2030-03-31
• Study Completion: 2030-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Male
• Target Recruitment: 1908

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
detection rate of clinically significant and insignificant prostate cancers	48 months	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)

Secondary Outcome Measures

Name	Time	Method
Pain score (Visual Analogue Scale [VAS])	48 months	Patient Reported Outcomes (PROs) - diagnostic burden in arm A and B
Patient Reported Outcomes (PROs) - complications after biopsy	30-day	30-day complication-rate after biopsy in arm A and B
Patient Reported Outcomes (PROs) - quality of life according to EORTC-QLQ-C30	48 months	quality of life according to EORTC-QLQ-C30 (European Organisation for Research and Treatment of Cancer - Quality of Life of Cancer Patientes; Scoring according to manual) in all different study arms
Patient Reported Outcomes (PROs) - quality of life according to EPIC-26	48 months	quality of life according to EPIC-26 (Expanded prostate cancer index composite; Scoring according to manual) in all different study arms
number of biopsies avoided	48 months	Number of biopsies avoided with pre-biopsy mpMRI
detection rate of MRI inbore biopsy	48 months	Detection rate of MRI inbore biopsy after negative TB
detection rate of biparametric MRI	48 months	Detection rate of biparametric MRI (no perfusion imaging)
Number of up- and downgrading of PI-RADS score	48 months	Number of up- and downgradings of PI-RADS (Prostate Imaging - Reporting and Data System) score in follow-up mpMRIs
IPSS	48 months	International Prostate Symptom Score
IIEF-6	48 months	International Index of Erectile Function