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
- Conditions
- Prostate Cancer
- Interventions
- Diagnostic Test: PSA testDevice: multiparametric prostate Magnetic Resonance Imaging (mpMRI)Procedure: targeted MRI/US fusion-guided biopsyProcedure: combined prostate biopsy (systematic biopsy plus targeted MRI/US fusion-guided biopsy)Procedure: MRI inbore biopsy
- 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 (\>= 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).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Male
- Target Recruitment
- 1705
- Men aged from 50 to 75 years
- elevated PSA ≥ 4 ng/ml and/or cancer suspicious DRE
- 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
- Arm && Interventions
Group Intervention Description Arm A PSA test 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 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, 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. Arm A MRI inbore biopsy 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 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, 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. Arm A targeted MRI/US fusion-guided biopsy 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 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, 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. Arm C multiparametric prostate Magnetic Resonance Imaging (mpMRI) Men with PI-RADS 3 in conjunction with PSAD \< 0.15 will not be biopsied, but followed-up with MRI annually and PSA every 6 months for 3 years. Arm D PSA test Men with PI-RADS 1 or 2 will not be biopsied, but followed-up 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). Arm D multiparametric prostate Magnetic Resonance Imaging (mpMRI) Men with PI-RADS 1 or 2 will not be biopsied, but followed-up 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). Arm A multiparametric prostate Magnetic Resonance Imaging (mpMRI) 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 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, 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. Arm B PSA test 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 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, 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. Arm B multiparametric prostate Magnetic Resonance Imaging (mpMRI) 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 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, 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. Arm B combined prostate biopsy (systematic biopsy plus targeted MRI/US fusion-guided biopsy) 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 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, 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. Arm B MRI inbore biopsy 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 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, 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. Arm C PSA test Men with PI-RADS 3 in conjunction with PSAD \< 0.15 will not be biopsied, but followed-up with MRI annually and PSA every 6 months for 3 years.
- Primary Outcome Measures
Name Time Method detection rate of clinically significant and insignificant prostate cancers 84 months The composite primary endpoint comprises the detection rate of clinically significant prostate cancers (ISUP grade group \>= 2) and the detection rate of clinically insignificant prostate cancers (ISUP grade group 1) of TB (arm A) compared to TB + SB (arm B)
- Secondary Outcome Measures
Name Time Method detection rate of MRI inbore biopsy 84 months Detection rate of MRI inbore biopsy after negative TB
Patient Reported Outcomes (PROs) - operation/intervention time up to 84 months operation/intervention time 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
Pain score (Visual Analogue Scale [VAS]) 84 months Patient Reported Outcomes (PROs) - diagnostic burden in arm A and B
Patient Reported Outcomes (PROs) - quality of life according to EORTC-QLQ-C30 84 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 84 months quality of life according to EPIC-26 (Expanded prostate cancer index composite; Scoring according to manual) in all different study arms
Patient Reported Outcomes (PROs) - fatigue 84 months fatigue according to fatigue module EORTC-QLQ-FA12 (Scoring according to manual) in all different study arms
Patient Reported Outcomes (PROs) - sleep quality 84 months sleep quality according to PSIQ (Pittsburgh Sleep Quality Index; a global score is calculated from several component score whereat a lower score represents healthier sleep quality; Scoring according to manual) in all different study arms
detection rate of biparametric MRI 84 months Detection rate of biparametric MRI (no perfusion imaging)
Patient Reported Outcomes (PROs) - cognitive function 84 months cognitive function according to FACT-cog (Functional Assesment of Cancer Therapy - Cognitive Function; 5-point-Likert Scale; Scoring according to manual) in all different study arms
Patient Reported Outcomes (PROs) - anxiety and depression 84 months anxiety and depression according to PHQ-4 (Patient Health Questionaire; 4-point-Likert-Scale; Scoring according to manual) in all different study arms
number of biopsies avoided 84 months Number of biopsies avoided with pre-biopsy mpMRI
Number of up- and downgrading of PI-RADS score 84 months Number of up- and downgradings of PI-RADS (Prostate Imaging - Reporting and Data System) score in follow-up mpMRIs