PRostate Evaluation for Clinically Important Disease: Sampling Using Image-guidance Or Not?

Study Overview
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Brief Summary
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This evaluates the detection rates of prostate cancer by MRI-targeted prostate biopsy compared to standard 12-core trans-rectal ultrasound guided (TRUS) prostate biopsy. Each participant will be randomly allocated to one of the biopsy tests. We hypothesise that MRI-targeted biopsy will detect no fewer clinically significant cancers than TRUS biopsy but will detect fewer clinically insignificant prostate cancers than TRUS biopsy.

Detailed Description
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The classical pathway for the diagnosis of prostate cancer is trans-rectal ultrasound guided (TRUS) biopsy of the prostate following a raised PSA. This is currently the mainstay for prostate cancer diagnosis in the majority of centres. It has many advantages and can be performed routinely under local anaesthetic in an outpatient setting. However it does have some limitations, including the over-diagnosis of insignificant cancer and the under-diagnosis of significant cancer. An alternative pathway for the diagnosis of prostate cancer in men with raised prostate specific antigen (PSA) is to perform a multi-parametric MRI to localize cancer and to use this information to influence conduct of a subsequent biopsy, known as an MRI-targeted biopsy. MRI-targeted biopsy has been shown in preliminary studies to detect a similar amount of clinically significant cancer to TRUS-biopsy but may have several advantages, for example in reducing the number of men who require biopsy. This randomized controlled trial aims to assess the detection rate of clinically significant and clinically insignificant cancer of MRI-targeted biopsy compared to standard 12-core TRUS biopsy in men referred with clinical suspicion of prostate cancer who have had no prior prostate biopsy. A 'clinically insignificant cancer' is cancer which is unlikely to progress or affect a man's life expectancy and therefore does not warrant treatment. However when diagnosed with insignificant cancer a large proportion of patients request treatment in case a more significant cancer is present. A prostate cancer detection pathway that finds significant cancers while avoiding the diagnosis of insignificant cancer is a major unmet need. The potential implications of this trial include: A redefining of the prostate cancer diagnostic pathway A reduction in the number of patients undergoing prostate biopsy A reduction in the number of biopsy cores taken per patient A reduction in biopsy-related sepsis, pain and other side effects A reduction in the over-diagnosis of clinically insignificant prostate cancer A reduction of the economic burden of diagnosing and treating prostate cancer

Official Title
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A Randomized Control Trial of Magnetic Resonance Imaging-targeted Biopsy Compared to Standard Trans-rectal Ultrasound Guided Biopsy for the Diagnosis of Prostate Cancer in Men Without Prior Biopsy

Conditions
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Prostate Neoplasm

Intervention / Treatment
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* Device: MRI
* Procedure: MRI-targeted biopsy
* Procedure: TRUS-biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men at least 18 years of age referred with clinical suspicion of prostate cancer who have been advised to have a prostate biopsy Serum PSA ≤ 20ng/ml within the previous 3 months Suspected stage ≤ T2 on rectal examination (organ-confined prostate cancer) within the previous 3 months Fit to undergo all procedures listed in protocol Able to provide written informed consent Exclusion Criteria: Prior prostate biopsy Prior treatment for prostate cancer Contraindication to MRI (e.g. claustrophobia, pacemaker, estimated glomerular filtration rate ≤ 50mls/min) Contraindication to prostate biopsy Men in whom artifact would reduce the quality of the MRI Previous hip replacement surgery, metallic hip replacement or extensive pelvic orthopaedic metal work Unfit to undergo any procedures listed in protocol

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRI-arm<br>Men in this arm will undergo multi-parametric MRI. In the presence of a suspicious area, a man will undergo MRI-targeted biopsy with cores targeted to the suspicious lesion. In the absence of a suspicious area, no biopsy will be taken. | Device: MRI<br>* This will be a multi-parametric MRI of the prostate<br>Procedure: MRI-targeted biopsy<br>* This will be a biopsy targeted to suspicious areas on the MRI<br>|
| Active Comparator: TRUS-biopsy arm<br>Men in this arm undergo standard 12-core trans-rectal ultrasound guided prostate biopsy | Procedure: TRUS-biopsy<br>* This will be a standard 12 core trans-rectal prostate biopsy<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 detected |  | 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 in MRI arm who avoid biopsy |  | When MRI results available, at an expected average of 30 days post-MRI | 
| Proportion of men with MRI score 3, 4 or 5 who have no clinically significant cancer detected |  | When histology results available, at an expected average of 30 days post-biopsy | 
| Proportion of men who go on to definitive treatment for prostate cancer | Definitive treatment can be localised (e.g. radical prostatectomy, radiotherapy, brachytherapy) or systemic (hormone therapy, chemotherapy) | After treatment decision, at an expected average of 30 days post-biopsy | 
| Cancer core length of the most involved biopsy core (maximum cancer core length) | Cancer core length in mm | When histology results available, at an expected average of 30 days post-biopsy | 
| Proportion of men with post-biopsy adverse events |  | 30 days post biopsy | 
| EQ-5D-5L Quality of Life scores | EQ-5D gives a measure of health-related quality of life. The descriptive system gives a weighted index score from 0-1 where 1 is perfect health and 0 is the worst health possible. The visual analogue score is a measure of overall self-rated health status where 100 is the best imaginable health state and 0 is the worst imaginable health state. | Baseline, 24 hours post intervention and 30 days post intervention | 
| Proportion of men undergoing Radical prostatectomy who have Gleason grade upgrading |  | An expected average of 90 days post-biopsy | 
| Cost per diagnosis of cancer |  | 30 days post-biopy | 
| Proportion of men with clinically insignificant detected |  | When histology results available, at an expected average of 30 days post-biopsy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Detection, Prostate biopsy, transrectal