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

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.

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.

Eligibility Criteria:
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.