PSMA PET/CT vs. mpMRI in Patients With a High Suspicion of Prostate Cancer: a Head to Head, Parallel, Prospective Trial

Study Overview
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Brief Summary
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This is prospective single-arm case-control study designed to compare in parallel PSMA PET/TRUS (trans-rectal or trans-perineal) fusion biopsy (experimental test) with mpMRI/TRUS fusion prostate biopsy (standard test) in men with a high suspicion of PCa after at least one negative biopsy.

Detailed Description
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All patients fulfilling inclusion criteria and providing informed consent to the study will undergo mpMRI and PSMA PET followed by software assisted fusion biopsy, performed in day-hospital setting. The inclusion criteria are: blood PSA level >4.0ng/ml; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy (min 12 cores); ASAP and/or high-grade PIN; negative digital rectal examination. The exclusion criteria are: antiandrogen therapy; prostate needle biopsy <21 days before PET and/or mpMRI; known active secondary cancer; endorectal coil/probe not applicable; active prostatitis; anaphylaxis against gadolinium-DOTA. The total duration of the project is 36 months. We expect to enroll the first patient within 1 month after study activation, and complete recruitment within 30 months. Completion of all study analyses on biological materials and experimental imaging is expected within 32 months. The last period is planned for data analysis, biostatistics and manuscript preparation. All patients eligible according to inclusion criteria and having signed the informed consent will undergo 68Ga-PSMA PET/CT and mpMRI scans within one month distance from each. Dedicated software for image visualization will be used to interpret and quantify 68Ga-PSMA PET/CT SUVmax and SUVratio. Images will be analyzed by an expert nuclear physician; who will proceed to the definition of the suspicious areas candidate to biopsy. mpMRI will be evaluated by an expert radiologist using the following phases: morphological, diffusion-weighted imaging (DWI) and spectroscopy. Reading criteria for mpMRI will be determined based on PI-RADS ver.2 [29]. Target delineation on PSMA PET and mpMRI will be performed as previously described [References]. Biopsy session will be completed within one month from 68Ga-PSMA PET/CT and mpMRI scans. Targeted TRUS-fusion needle biopsy will be performed for all lesions detected with PET and mpMRI. A subsequent randomized biopsy sampling consisting of 12 samples will be performed from the peripheral region of the prostate. The biopsy frustules will then be evaluated by an expert pathologist on PCa detection.

Official Title
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Diagnostic Performance and Clinical Impact of PSMA PET/CT vs. mpMRI in Patients With a High Suspicion of Prostate Cancer and Previously Negative Biopsy: a Head to Head, Parallel, Prospective Trial (PROSPET-BX).

Conditions
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Prostate Cancer

Intervention / Treatment
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* Diagnostic Test: PSMA PET/TRUS (trans-rectal or trans-perineal) fusion biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years blood PSA level >4.0ng/ml; free-to-total PSA ratio <20%; progressive rise of PSA levels in two consecutive blood samples despite antibiotics; serum blood tests suspicious for PCa; at least one previous negative biopsy (min 12 cores); ASAP and/or high-grade PIN; negative digital rectal examination. Exclusion Criteria: antiandrogen therapy; prostate needle biopsy <21 days before PET and/or mpMRI; known active secondary cancer; endorectal coil/probe not applicable; active prostatitis; anaphylaxis against gadolinium-DOTA.
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PSMA PET/TRUS (trans-rectal or trans-perineal) fusion biopsy<br>Single-arm case-control imaging trial designed to compare in parallel PSMA PET/TRUS (trans-rectal or trans-perineal) fusion biopsy (experimental test) with mpMRI/TRUS fusion prostate biopsy (standard test) in men suspected for PCa after at least one negative biopsy. | Diagnostic Test: PSMA PET/TRUS (trans-rectal or trans-perineal) fusion biopsy<br>* The prostate profile and ROIs will be drawn on PSMA PET and mpMRI and fused in real time with the TRUS image stack during biopsy. Biopsies, transrectal or transperineal according to lesion site, will be performed with patients in the dorsal lithotomy position, under antibiotic prophylaxis and local anesthesia, using 3D triplane transrectal ultrasound system (BK Medical, Analogic Ultrasound Group, Pro Focus, Transducer 8818, 6/9 MHz). Biopsy cores will be numbered according to ROI number and topography. Specimens will be processed and evaluated by a genitourinary pathologist. Tumor foci will be quantified and graded according to the ISUP consensus conference on Gleason grading.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity, Specificity, NPV, PPV, Accuracy | To evaluate the diagnostic performance of PSMA PET-TRUS fusion prostate biopsy in determining the presence of PCa in comparison to mpMRI-TRUS fusion prostate biopsy analyzed in parallel in the same subset of patients. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized uptake value and Gleason Score | To determine the correlations between the index test standardized uptake values (i.e. SUVmax, SUVratio; SUVmean) and the histopathological characteristics of the specimen (Gleason Score) in order to validate optimal cut-off points able to detect intraprostatic malignancy and differentiate clinically relevant PCa lesions. | 36 months | 
| Number of spared biopsies | To determine the clinical utility of the index test compared to the standard test in terms of number of spared biopsies compared to mpMRI. | 36 months | 
| Cost-effectiveness | To determine the clinical utility of the index test compared to the standard test in terms of cost-effectiveness. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSMA PET/CT, Primary Diagnosis, multiparametric MRI