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

Overview

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.

Interventions

• Diagnostic test PSA test
  testing for blood levels of PSA
• Device multiparametric prostate Magnetic Resonance Imaging (mpMRI)
  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 qu
• Procedure targeted MRI/US fusion-guided biopsy
  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.
• Procedure combined prostate biopsy (systematic biopsy plus targeted MRI/US fusion-guided biopsy)
  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.
• Procedure MRI inbore biopsy
  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

Primary outcome measures

• detection rate of clinically significant and insignificant prostate cancers [Time frame: 48 months]

Secondary outcome measures (10)

• Pain score (Visual Analogue Scale [VAS]) [Time frame: 48 months]
• Patient Reported Outcomes (PROs) - complications after biopsy [Time frame: 30-day]
• Patient Reported Outcomes (PROs) - quality of life according to EORTC-QLQ-C30 [Time frame: 48 months]
• Patient Reported Outcomes (PROs) - quality of life according to EPIC-26 [Time frame: 48 months]
• number of biopsies avoided [Time frame: 48 months]
• detection rate of MRI inbore biopsy [Time frame: 48 months]
• detection rate of biparametric MRI [Time frame: 48 months]
• Number of up- and downgrading of PI-RADS score [Time frame: 48 months]
• IPSS [Time frame: 48 months]
• IIEF-6 [Time frame: 48 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Al-Monajjed R, Albers P, Boschheidgen M, Radtke JP, Droop J, Benner A, Hadaschik B, Antoch G, Schimmoller L; PRIMA Study Group. PRIMA: randomized prospective multicenter non-inferiority study for primary diagnosis of clinically significant PRostate cancer by PSA and MR IMAging-study protocol for a randomized diagnostic accuracy trial. Trials. 2026 Apr 25;27(1):320. doi: 10.1186/s13063-026-09750-z. PMID 42032761

Identifiers

NCT: NCT04993508 · 2021-1389

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗