Patients in cohort 1 continued for prolonged periods given the difficulties encountered in the COVID period and to date in this setting evidence has already developed that reduces the the innovativeness of the project.

BIOPSTAGE is a prospective, non-randomized, diagnostic, multi-cohort investigational study to evaluate the impact of pelvic Multi-parametric 3-Tesla magnetic resonance imaging (mp-3TMRI) and whole-body 68Ga-PSMA PET/CT for diagnosis of clinically-significant prostate cancer and pre-surgical staging.

The aim of this study is to characterize the diagnostic accuracy of both multi-parametric pelvic Magnetic Resonance Imaging (MRI) (T2-weighted, Diffusion Weighted Imaging (DWI), Dynamic Contrast Enhancement (DCE) and 68Ga-chelated Prostate Specific Membrane Antigen ligand (68Ga-PSMA) Positron Emission Tomography/Computed Tomography (PET /CT) in three cohorts of patients:

• COHORT 1 Guiding prostate biopsies in men with clinical suspicion and/or unconfirmed clinically-significant prostate cancer (CS-PCa) on initial prostate biopsy;
• COHORT 2 Targeting repeat prostate biopsy in patients on Active Surveillance (PRIAS Study), scheduled for PRIAS repeat biopsy;
• COHORT 3

Providing pelvic / whole-body pre-surgical staging in:

• 3a: men with high-risk PCa (HR-PCa);
• 3b: men candidates for nerve sparing surgery (NSS);

Inclusion Criteria:

Cohort 1 - Biopsy guidance in clinically-suspected PCa

1. Men aged 45 to 75 years old with clinically-suspected PCa candidated for either initial or repeat TRUS-guided prostate biopsy, meeting any of the following criteria:

a) Abnormal PSA metrics, defined as follows:

A rising and/or persistently elevated serum PSA (i.e PSA > 2.5ng/ml for men in the age group comprising 60 to 75 years old; PSA > 3.0ng/ml for men in the age group comprising 45 to 60 years old) and at least one of the following PSA-based metrics:

i. Percent free PSA (%fPSA) < 25% with PSA range 4-10ng/ml (NCCN); ii. PSA velocity (PSAvel) >0.35 ng/mL/y; iii. PSA density (PSAden) > 0.25ng/mL/cc iv. PSA > 10ng/ml, 50% risk of PCa (EAU) b) Suspicious digital rectal examination (DRE), 5-30% risk of PCa; c) Prostate Cancer Gene 3 (PCA3) > 35; d) Suspicious findings on first-round biopsy: i. A few Atypical Glands immediately adjacent to HG-PIN, 50% risk of PCa; ii. Atypical Small Acinar Proliferation, 40% of PCa; iii. Multifocal High-Grade Prostatic intraepithelial neoplasia (HG-PIN), 30% ; iv. Intraductal carcinoma as solitary finding, 90% of PCa;

Cohort 2 - Biopsy guidance on Active Surveillance

Men consenting to enter the PRIAS MRI side-study as per currently inclusion criteria in Version Number 1.0 dated August 20, 2013. These are:

1. Histologically-proven adenocarcinoma of the prostate;

2. Age ≥ 18

3. Men should be fit for curative treatment;

4. Clinical stage T1c or T2;

5. Gleason score 3+3=6;

6. One or two biopsy cores invaded with prostate cancer:

   1. If an MRI, including targeted biopsies on positive lesions, is done at inclusion, there is no limit in the number of positive cores (that is, more than two, and no limit in the % of cancer present in the cores);
   2. If saturation biopsies (either trans-perineal or trans-rectal) are done 15% of the cores can be positive with a maximum of 4 (i.e. 26 cores 4 cores can be positive) (all other inclusion criteria still apply);

7. PSA density (PSA D) less than 0.2;

8. PSA-level at diagnosis ≤ 10 ng/mL;

Cohort 3a - Pre-surgical TNM staging in high-risk prostate cancer

1. Male, aged 18 years or older;

2. Cyto / histological confirmation of PCa (i.e. TRUS-guided biopsies; TURP);

3. Any of the PCa high risk features for Organ-Confined Disease (OCD):

   • Clinical T stage ≥ T2c;
   • Gleason Score ≥ 8;
   • Serum PSA > 20 ng/mL;

4. Any of the PCa high-risk features for Locally-Advanced Disease (LAD):

   • Clinical T stage ≥ T3b-T4 OR any T and clinical N1 disease;
   • Gleason Score ≥ 8;
   • Serum PSA > 20 ng/mL;

5. Routine clinical staging (CTscan ± Bone scan) performed within 12 weeks enrolment returning negative or equivocal results for distant metastatic disease;

Cohort 3b - pelvic TNM staging of prostate cancer prior to nerve-sparing radical prostatectomy

1. Male, aged 18 years or older;

2. Cyto / histological confirmation of PCa (i.e. TRUS-guided biopsies; TURP);

3. All of the following PCa-related features must be met for nerve-sparing (either mono- or bi-lateral):

   • Clinical T stage ≤ T2b;
   • Gleason Score ≤ 7 (3+4) and maximum one biopsy with Gleason > 6 at the ipsilateral side;
   • Serum PSA < 10 ng/mL;

Exclusion Criteria:

The participant may not enter the study if ANY of the following apply:

1. Hormone androgen deprivation therapy of any type within 6 months prior to enrollment.
2. Prior pelvic radiotherapy;
3. Sickle cell disease;
4. Insufficient renal function (eGFR < 30 mL/min/1.73 m2);
5. Hip prosthesis, vascular grafting or other conditions affecting imaging;
6. Contraindication to MRI, including but not restricted to: pacemaker or other electronic im-plants, known metal in the orbit, MR incompatible surgical or cerebral aneurysm clips, shrapnel, tattoos, non-removable body piercings (relative contraindications);
7. History of allergic reactions attributed to compounds of similar chemical or biologic com-position to 68Ga-PSMA or Gadolinium-based contrast agents used in the study.