Extended Systematic Versus Mri-Assisted pRostate Transperineal Biopsy

Study Overview
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Brief Summary
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This is a randomized controlled trial to evaluate the detection of clinically significant prostate cancer (csPCa) by MRI-targeted approach (MRI-arm) versus 24-core transperineal (TP) systematic biopsy (TP-arm). Clinically significant prostate cancer (csPCa) is defined as ISUP (International Society of Urogenital Pathology) Grade group ≥2 prostate cancer. Patients with elevated PSA 4-20 ng/mL with or without abnormal digital rectal examination (DRE) will be randomized in a 1:1 manner to MRI-arm or TP-arm. In the MRI-arm, multiparametric MRI prostate will be performed for each subject. MRI prostate is considered abnormal if PI-RADS (Prostate Imaging-Reporting and Data System, version 2.1) score is 3, 4 or 5. For subjects in MRI-arm with abnormal MRI, MRI-targeted biopsy will be performed, followed by 12-core systematic transperineal biopsy (sparing MRI-target). For subjects in MRI-arm with normal MRI, no biopsy is performed. For subjects in TP-arm, 24-core systematic transperineal biopsy will be performed without MRI guidance. The study flowchart is provided in Figure 1. The detection rates of csPCa will be compared between MRI-targeted biopsy plus 12-core systematic biopsy (in MRI-arm) versus TP-arm. The study hypothesis is MRI-guided prostate biopsy with 12-core systematic biopsy is superior to 24-core transperineal systematic biopsy in detection of csPCa.

Detailed Description
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The current study is a randomized controlled trial using a superiority design with the subjects randomized in 1:1 manner to either MRI-arm or TP-arm. In the MRI-arm, multiparametric MRI is performed for all subjects. If MRI is abnormal (PI-RADS score 3-5), 3-4 core targeted followed by 12-core systematic transperineal biopsies under local anaesthesia will be performed. If MRI is normal, no biopsy is performed. A 12-core systematic biopsy is also included in MRI-targeted biopsy as it has been shown in the Trio study that adding systematic biopsy increased the detection of csPCa. In the TP-arm, no MRI will be performed, and all subjects will receive 24-core transperineal prostate biopsy under local anaesthesia. Patient will be followed up in clinic about 30 days after biopsy to review pathology result and complication.

Official Title
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A Randomized Controlled Trial Comparing Magnetic Resonance Imaging (MRI)-Targeted Biopsy and Extended Transperineal Systematic Biopsy for Detection of Clinically Significant Prostate Cancer: the SMART Trial

Conditions
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Prostate Cancer

Intervention / Treatment
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* Diagnostic Test: MRI and MRI-guided prostate biopsy
* Diagnostic Test: TP-arm Systematic biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men ≥18 years of age Clinical suspicion of prostate cancer and indicated for prostate biopsy Serum Prostate-specific antigen (PSA) 4-20 ng/mL Digital rectal examination ≤ cT2 (organ confined cancer) Able to provide written informed consent Exclusion Criteria: Prior prostate biopsy Past or current history of prostate cancer MRI prostate performed within past 5 years Contraindicated to undergo MRI scan (e.g. pacemaker in-situ, claustrophobia, estimated glomerular filtration rate < 50ml/min in serum renal function test within 3 months) Contraindicated to transperineal prostate biopsy: active urinary tract infection, fail insertion of transrectal ultrasound probe into rectum (abdominal perineal resection, anal stenosis), fail to be placed in lithotomy position, uncorrectable coagulopathy, antiplatelet or anticoagulant which cannot be stopped (keep aspirin before and after biopsy is permitted)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized controlled trial, 1:1 allocation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRI arm<br>MRI prostate with contrast, followed by MRI-guided biopsy under local anaesthesia only if MRI show suspicious lesion. Men with non-suspicious MRI will not receive a biopsy. | Diagnostic Test: MRI and MRI-guided prostate biopsy<br>* Multiparametric MRI prostates in the MRI arm will be performed using 1.5 or 3.0 Tesla scanner with a pelvic phased array coil and contrast injection. T2-weighted, diffusion weighted and dynamic contrast enhanced scans will be included and the reporting of MRI finding will be done according to PI-RADS (Prostate Imaging-Reporting and Data Systems) v2.1 recommendations. MRI-guided targeted biopsy will be performed by Urologists experienced in MRI-guided biopsy for men with PI-RADS score 3-5.<br>|
| Active Comparator: TP-arm Systematic biopsy<br>24-core Systematic transperineal prostate biopsy under local anaesthesia | Diagnostic Test: TP-arm Systematic biopsy<br>* Transperineal 24-core biopsy using a free-hand technique under local anaesthesia will be performed under transrectal ultrasound guidance for men in this arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of men with clinically significant Prostate cancer(csPCa), diagnosis of ISUP Grade group 2 or above prostate cancer in at least 1 biopsy core in MRI-arm Vs TP-arm | ISUP Grade 2 or above prostate cancer diagnosed on biopsy | When histology results available, at an expected average of 30 days post-biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of men with diagnosis of clinically insignificant prostate cancer (ISUP Grade group 1) | ISUP Grade 1-5, the higher grade the higher risk. | When histology results available, at an expected average of 30 days post-biopsy | 
| Proportion of men in MRI arm with normal MRI who could avoid a biopsy | The number of patients in MRI arm with normal MRI | When MRI results available, at an expected average of 30 days post-MRI | 
| Proportion of men with post-biopsy adverse events within 30 days after biopsy | The severity of Adverse event is grade by Clavien-Dindo classification | 30 days post biopsy | 
| Proportion of men with csPCa in MRI-arm (Targeted biopsy only) Vs TP-arm (24-core Systematic biopsy) | ISUP Grade 2 or above prostate cancer diagnosed on biopsy | When histology results available, at an expected average of 30 days post-biopsy | 
| Cancer core length of the most involved biopsy core | maximum cancer core length in mm | When histology results available, at an expected average of 30 days post-biopsy | 
| Health-related Quality of life scores | EQ-5D-5L | At recruitment, and at 30 days after intervention | 
| Cost per diagnosis of cancer | Cost to diagnosis one cancer | 30 days post-biopsy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate biopsy, Prostate Cancer, MRI prostate, Transperineal biopsy