Neoplasms

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Prostatic Neoplasms

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Genital Neoplasms, Male

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Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Systematic biopsies (SB) and targeted biopsies (TB) are performed in the same patients by two independent operators. In patients without abnormalities on mp-MRI, no targeted biopsies will be carried out and the detection of "clinically significant cancer" will be considered as negative for the TB strategy.

Prostate biopsy

Background: Prostate cancer is difficult to detect using ultrasound. As a result, in case of suspicion of prostate cancer based on digital rectal examination (DRE) or Prostate Specific Antigen (PSA) level, it is currently recommended to perform "blinded" systematically distributed biopsies with 10-18 samples obtained from predefined locations in the gland.

These so-called systematic biopsies (SB) may lead to improper patient management by (i) missing clinically significant cancer, especially in the anterior half of the gland that tends to be undersampled, (ii) inducing chance detection of clinically insignificant cancer foci that may result in overtreatments, (iii) undersampling the tumor foci and thus underestimating their volume and aggressiveness.

Multiparametric Magnetic Resonance Imaging (mp-MRI) has yielded promising results in detecting aggressive (Gleason ≥7) prostate cancers. Several monocenter studies showed that targeted biopsies (TB) based on mp-MRI findings could detect significantly more aggressive cancers, reduce the diagnosis of clinically insignificant cancers, and better evaluate the aggressiveness of detected cancers than SB. However, these monocenter studies only provide low-level evidence and three recent independent reviews of literature concluded that there was a need for a robust multicenter trial evaluating the diagnostic yield of TB as compared to SB. This is particularly important since many academic and private centers in France already perform mp-MRI before prostate biopsy in daily routine. Therefore the risk is that this approach becomes the norm without being properly evaluated and it is crucial and urgent to perform a controlled multicentric study to provide high-level evidence as to whether mp-MRI should or should not be obtained before prostate biopsy.

One controlled multicentric study has been published recently in which SB and TB had been obtained by two different operators in 95 patients. TB yielded a significantly higher detection rate for all prostate cancers (69% vs 59%, p=0.033) and for clinically significant cancers (67% vs 52%, p=0.0011). However, this study was limited by the fact that patients with negative mp-MRI were not included.

Research hypotheses: There is currently no robust multicenter trial comparing prostate TB based on mp-MRI findings versus the current standard of care (SB). We propose a multicentre prospective trial comparing the results of SB and TB performed in the same patients by two independent operators. Our hypothesis is that TB detects aggressive (Gleason ≥7) cancers in a significantly higher percentage of patients than SB.

Main objective: To compare the percentage of patients with "clinically significant cancer" (using definition A, i.e. cancer with Gleason score ≥7) detected by SB versus TB.

Assessment of Prostate MRI Before Prostate Biopsies

Improvement in the Detection of Aggressive Prostate Cancer by Targeted Biopsies Using Multiparametric MRI Findings

The different subgroups are :

* Patients with clinical stage T1c (i.e. normal DRE) versus T2a-T2c,
* Patients with a PSA level \<10 ng/mL versus 10-20 ng/mL,
* Patients with a prostate volume ≤50 cc versus \>50 cc,
* Patients in whom TB have been performed with ultrasound/MRI fusion versus cognitive guidance

Hospices Civils de Lyon

This is a cohort study where participating men will be asked to donate blood, urine, tissue in addition to access to standard of care tissue and medical data (including imaging files). Men will also consent to longer term healthcare data linkage.

Biopsies will be performed as part of standard of care, additional cores will be performed for research. Access to standard of care prostate biopsy tissue will also be requested after standard of care reporting is complete.

Tissue donation

Phlebotomy will be performed prior to tissue collection following trust standard operating procedures or drawn when cannula already in situ in preparation for the prostate biopsy.

Blood Donation

Urine will be collected prior to prostate biopsy

Urine Donation

Men will consent to healthcare data linkage via national databases.

Healthcare data linkage

Hashim U Ahmed, FRCS

ReIMAGINE Prostate Cancer Risk is a multi-centre, prospective, observational, longitudinal cohort study of men referred to secondary care with a suspicion of prostate cancer. The aim of the study is to develop a robust baseline risk stratification system for men at risk of prostate cancer.

Men whose serum Prostate Specific Antigen (PSA) level is 20ng/ml or less, whose multi-parametric magnetic resonance imaging (mpMRI) scan has been scored as Prostate Imaging Reporting and Data System (PIRADS)/LIKERT score 3, 4 or 5, and who have been advised and accepted the need for a targeted and systematic prostate biopsy will be invited to take part in the study and be asked to donate blood, urine, imaging files and prostate biopsy for biomarker analysis.

ReIMAGINE Prostate Cancer Risk is a multi-centre, prospective, observational, longitudinal cohort study of men referred to secondary care with a suspicion of prostate cancer or men who are undergoing further tests for prostate cancer staging assessment. Men with a serum PSA level of 20ng/ml or less, whose mpMRI scan has been scored as PIRADS/LIKERT score 3, 4 or 5, and who have been advised and accepted the need for a targeted and systematic prostate biopsy will be invited to enrol.

Men will be recruited across a number of high-volume National Health Service (NHS) centres which already have an mpMRI based diagnostic pathway. All eligible patients referred to secondary care with a suspicion on prostate cancer will be considered for screening. Potential participants will be identified at the point of referral or routine urology cancer clinics. Patients will be approached by the ReIMAGINE study team and consented. The initial discussion may be over the telephone Once the consent form is signed, patients will be asked to donate blood, urine and three additional samples of prostate tissue (taken at the time of their biopsy) for biomarker and Deoxyribonucleic acid (DNA) analysis.

Imaging files from the MRI scan will also be collected and stored on the study data warehouse. Small sections of tissue will be cut from the standard of care blocks (post NHS reporting) and then returned back to the hospital.

After collection of the cross-sectional biological samples within ReIMAGINE, men will revert to NHS standard of care, attending a routine outpatient appointment to obtain the results from their biopsy. We will collect healthcare information on study participants during the study and three years after their prostate biopsy. Further funding will be explored for life-long collection of this data.

The ReIMAGINE team aim to recruit 1,000 men with a PIRADs/LIKERT score 3, 4 or 5 who are undergoing an MRI-directed prostate biopsy. Of these 1,000 biopsies, we anticipate that 60% will have any cancer detected on histology (3+3 or greater) giving approximately 400 cases of clinically significant cancer (Gleason 7 or more).

ReIMAGINE Prostate Cancer Risk

A Prospective Cohort Study in Men With a Suspicion of Prostate Cancer Who Are Referred Onto an MRI-based Diagnostic Pathway With Donation of Tissue, Blood and Urine for Biomarker Analyses (ReIMAGINE Prostate Cancer Risk)

Proportion of men with significant prostate cancer categorised as gleason pattern 7 or greater

Development of secondary cancers or cancer recurrence

Time to prostate cancer related death in men diagnosed with prostate cancer

Presence of newly diagnosed prostate cancer in men who were cancer free at baseline

Time to cancer progression in men identified with prostate cancer at baseline

Time to prostate cancer specific death in all men

Medical Research Council

Cancer Research UK

Imperial College London

King's College London

University College, London

Men being evaluated for prostate cancer based upon standard of care clinical parameters (e.g. elevated PSA levels, abnormal DRE, mpMRI) will be considered for enrollment. Men who have undergone prostate mpMRI that has revealed an area(s) of suspicion for prostate cancer are eligible for enrollment. All men enrolled in the study undergo fusion targeted biopsy, visual estimation biopsy, and systematic biopsy. As a result the study includes a single arm with direct comparison of biopsy techniques.

Targeted Biopsy

Samr S Taneja, MD

This is a prospective single center trial to examine the rates of cancer diagnosis when using computerized software to target suspicious lesions within the prostate identified on mpMRI. The primary evaluation involves comparing the rate of cancer diagnosis when using software-based MRI-Ultrasound image fusion guided biopsy to sample mpMRI findings to the use of visual guided biopsy (cognitive or mental targeting) of the same target. The hypothesis being tested is that fusion guided biopsy will increase detection prostate cancer within mpMRI findings as compared to visual guided biopsy of these areas

Use of Multi-Parametric MRI With Prostate Biopsy for Cancer Diagnosis.

Comparative Analysis of Software-based MRI-Ultrasound Image Fusion Against Cognitive Targeting of Multi-Parametric MRI Findings With Prostate Biopsy

The primary endpoint of the study is the evaluation of the rates of prostate cancer diagnosis using software based MRI-TRUS imaging fusion targeting of mpMRI lesions as compared to cognitive co-registration and targeting of mpMRI lesions.

The secondary endpoint of the study is the evaluation of the rate of cancer diagnosis using targeted biopsy (software or cognitive targeting) as compared to standard of care prostate biopsy.

NYU Langone Health

Co-Director, Smilow Comprehensive Prostate Cancer Center

conventional/systematic biopsy, targeted fusion biopsy and cognitive biopsy

Targeted biopsy

This is a pilot study to determine cancer detection rate of conventional/systematic versus targeted biopsy methods in diagnosis of potentially lethal prostate cancer. This is a diagnostic trial using each patient as his own control.

Each biopsy session would be preceded by mpMRI, which would be delineated and assigned a degree of suspicion by a radiologist (see above).The PI-RADS scoring system will be used to assign a degree of suspicion to regions of interest within the prostate. A second reader will independently score the RSI on a Likert scale, blinded to the other MRI data. The regions of interest will be delineated using software developed by Eigen in collaboration with a study co-author (D.M.), now commercially available and in use by the UCLA team for the past 2 years (ProFuse, Eigen).The RSI data will be integrated with the standard mpMRI data and any change in scoring or presence of additional lesions, determined by RSI, will be quantified. For men with a MR-visible target of PI-RADS score 3 or more, irrespective of RSI score, the biopsy session would then proceed in an ordered routine, as follows:

1. Conventional ultrasound-guided 12-core systematic biopsy would be performed first. This portion will be performed without operator knowledge of the MRI report, i.e., the urologist will be blinded to possible tumor location and use the method in standard practice throughout the U.S. for many years.
2. Next a targeted biopsy would be performed using visual guidance (cognitive fusion), under the supervision of a radiologist specializing in prostate MRI. The radiologist will be in the biopsy suite and help the urologist direct needle at location of region of interest in the prostate seen on MRI. Three directed biopsy cores will be obtained.
3. Third, a targeted biopsy using Artemis device fusion of MRI and ultrasound images would be performed. The prostate will be scanned and the MRI region of interest (target) brought into the 3D model via device fusion. Targeted biopsy will be performed by taking three cores of tissue from the target area, visualized as a 3D region in the fusion device.

Biopsy sites to be dictated by geometric guides (12 point pattern vs visual direction of radiologist vs fusion target), not chosen arbitrarily.

The above biopsy schema will not require any more procedure time or samples taken than fusion biopsy as performed under IRB approval at our institution for the last five years. Additional cores will be required for the visual biopsy method, but no biopsy cores will be obtained from secondary targets. Most patients exhibit secondary targets. An analysis of data from past 2 years demonstrated that the chance of a secondary target showing significant cancer, not present in a primary target, is less than 1%. Therefore, secondary targets will not be sampled, as cores are instead taken from primary targets using the two methods. In 200 men undergoing initial biopsy, an average of 17 +/- 3 S.D. cores/patient has been obtained. In the present proposal, 18 cores will be taken. Thus, the number of cores/patient in this trial will not substantially exceed the number that has been routinely taken in our practice in the past.

A sampling method of three directed cores per target was chosen as a compromise between what is clinically feasible and a statistical ideal of taking additional cores for significant cancer detection in lower grade targets.

The cognitive biopsy will require approximately 90 seconds of additional time, but this added time will be more than compensated by the reduced time obtained from excluding secondary targets. The overall biopsy schema should require no more (and probably less) than the 15-20 minutes/procedure as in the past. Biopsies will be performed by an experienced team, which has been working together since 2009.

Prospective Assessment of Image Registration for the Diagnosis of Prostate Cancer

Paired CAP: Prospective Assessment of Image Registration for the Diagnosis of Prostate Cancer

Patient participation is only confined to the biopsy visit.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Assessment of Prostate MRI Before Prostate Biopsies	NCT02485379	Prostate Cancer	Prostate biopsy	18 Years - 75 Years	Hospices Civils de Lyon
ReIMAGINE Prostate Cancer Risk	NCT04060589	Prostate Cancer	Tissue donation Blood Donation Urine Donation Healthcare data...	18 Years - 90 Years	University College, London
Use of Multi-Parametric MRI With Prostate Biopsy for Cancer Diagnosis.	NCT01964638	Prostate Cancer	Targeted Biopsy	40 Years - 75 Years	NYU Langone Health
Prospective Assessment of Image Registration for the Diagnosis of Prostate Cancer	NCT02425228	Elevated PSA Prostate Cancer	Targeted biopsy	-	Jonsson Comprehensive Cancer Center
Use of Multi-Parametric MRI With Prostate Biopsy for Cancer Diagnosis.	NCT01964638	Prostate Cancer	Targeted Biopsy	40 Years - 75 Years	NYU Langone Health
Use of Multi-Parametric MRI With Prostate Biopsy for Cancer Diagnosis.	NCT01964638	Prostate Cancer	Targeted Biopsy	40 Years - 75 Years	NYU Langone Health
ReIMAGINE Prostate Cancer Risk	NCT04060589	Prostate Cancer	Tissue donation Blood Donation Urine Donation Healthcare data...	18 Years - 90 Years	University College, London
Prospective Assessment of Image Registration for the Diagnosis of Prostate Cancer	NCT02425228	Elevated PSA Prostate Cancer	Targeted biopsy	-	Jonsson Comprehensive Cancer Center
ReIMAGINE Prostate Cancer Risk	NCT04060589	Prostate Cancer	Tissue donation Blood Donation Urine Donation Healthcare data...	18 Years - 90 Years	University College, London

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