Clinical trial NCT04993508: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
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
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
Collaborators: name: University Hospital, Aachen
name: University Hospital, Bonn
name: University Hospital of Cologne
name: University Hospital, Essen
name: University Hospital Muenster
name: German Cancer Research Center
First posted: 2021-08-06
Enrollment: 1705
Sex: MALE
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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 (\>= 4 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 2 cores per target). Arm B receives systematic biopsies (= SB with 12 biopsy cores) and TB. Men with normal mpMRI will be observed in a structured manner but will not be biopsied (arms C and D). The primary objective comprises the demonstration of non-inferiority of the detection clinically significant prostate cancer (ISUP grade group 1) of TB (arm A) compared to TB+SB (arm B). Overall, our study aims to improve patient care by reducing the number of patients biopsied, by reducing the number of biopsy cores per patient, and by lowering the risk of overdiagnosis of indolent prostate cancer. 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 (≥ 4ng/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.

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

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 annually and PSA every 6 months for 3 years. 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 annually and PSA every 6 months for 3 years. In the case of persistent PI-RADS 4/5, men will be re-biopsied. Men with an upgrade to PI-RADS 4/5 or an increase in PSAD will be randomized for biopsy into arms A or B.

Arm C: Men with PI-RADS 3 and PSAD \<= 0.15 will be classified as arm C with MRI annually and PSA every 6 months for 3 years.

Arm D: Men with unsuspicious findings on MRI (PI-RADS 1 or 2) will be assigned to arm D with PSA every 6 months for 3 years. A control MRI will be performed after 3 years. At any time, a follow-up can be performed in case of clinical suspicion of PCa or a relevant PSA increase (\> 1.0 ng/ml/a).

Eligibility criteria: Inclusion Criteria:

* Men aged from 50 to 75 years
* elevated PSA ≥ 4 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

Primary outcomes:
measure: detection rate of clinically significant and insignificant prostate cancers
timeFrame: 84 months
Secondary outcomes:
measure: Pain score (Visual Analogue Scale [VAS])
timeFrame: 84 months
measure: Patient Reported Outcomes (PROs) - operation/intervention time
timeFrame: up to 84 months
measure: Patient Reported Outcomes (PROs) - complications after biopsy
timeFrame: 30-day
measure: Patient Reported Outcomes (PROs) - quality of life according to EORTC-QLQ-C30
timeFrame: 84 months
measure: Patient Reported Outcomes (PROs) - quality of life according to EPIC-26
timeFrame: 84 months
measure: Patient Reported Outcomes (PROs) - fatigue
timeFrame: 84 months
measure: Patient Reported Outcomes (PROs) - sleep quality
timeFrame: 84 months
measure: Patient Reported Outcomes (PROs) - cognitive function
timeFrame: 84 months
measure: Patient Reported Outcomes (PROs) - anxiety and depression
timeFrame: 84 months
measure: number of biopsies avoided
timeFrame: 84 months
measure: detection rate of MRI inbore biopsy
timeFrame: 84 months
measure: detection rate of biparametric MRI
timeFrame: 84 months
measure: Number of up- and downgrading of PI-RADS score
timeFrame: 84 months
Other outcomes:
Locations:
Study officials:
affiliation: Heinrich Heine University Düsseldorf / Urology
name: Rouvier Al-Monajjed, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heinrich Heine University Düsseldorf / Radiology
name: Lars Schimmöller, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Heinrich Heine University Düsseldorf / Urology
name: Peter Albers, MD
role: STUDY_CHAIR
affiliation: Heinrich Heine University / Radiology
name: Gerald Antoch, MD
role: STUDY_CHAIR
affiliation: University Hospital Bonn / Pathology
name: Glen Kristiansen, MD
role: STUDY_CHAIR
affiliation: University Hospital Essen / Urology
name: Boris Hadaschik, MD
role: STUDY_CHAIR
affiliation: University Hospital Essen / Urology
name: Jan Philipp Radtke, MD
role: STUDY_CHAIR
affiliation: German Cancer Research Center / Epidemiology
name: Rudolf Kaaks, PhD
role: STUDY_CHAIR
References: