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 (PRIMA)

Heinrich-Heine University, Duesseldorf

Status: Begins enrollment in 1 month

Conditions: Prostate Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04993508

2021-1389

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,908 estimated patients

Sex: Male

Ages: 50 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,908 participants in 2 patient groups

Arm A

Experimental group

Description:

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.

Treatment:

Diagnostic Test: PSA test

Procedure: MRI inbore biopsy

Device: multiparametric prostate Magnetic Resonance Imaging (mpMRI)

Procedure: targeted MRI/US fusion-guided biopsy

Arm B

Active Comparator group

Description:

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.

Treatment:

Diagnostic Test: PSA test

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

Procedure: MRI inbore biopsy

Device: multiparametric prostate Magnetic Resonance Imaging (mpMRI)