18F-PSMA-1007 PET to detect primary prostate cancer: a comparative study with mpMRI and correlation to histopathology

Rationale: Prostate cancer (PCa) is the second most common diagnosed malignancy
in males worldwide, with over 1.2 million new patients diagnosed every year.(1)
Since the introduction of prostate-specific antigen (PSA) the primary diagnosis
consisted of histologic confirmation by transrectal ultrasound (TRUS)
systematic biopsies.(2) However, in recent years this has changed into
performing multi-parametric MR imaging (mpMRI) prior to prostate biopsy.(3)
mpMRI has proven to be a valuable tool to avoid unnecessary prostate biopsies
and prevents over-treatment of low-grade PCa, while maintaining equal or higher
detection rates of high-grade PCa.(4-6) mpMRI comprises of anatomical (i.e.
T2-weighted images [T2-WI]) in combination with functional sequences, that is
diffusion weighted Images (DWI) representing cellular density, and dynamic
contrast-enhanced imaging (DCE-MRI) that depicts vascularity.(7) DWI emerged as
the most important functional modality since an inverse relationship between
the apparent diffusion coefficient (ADC) value (derived from the DWI), and PCa
aggressiveness was established.(8, 9) Prostate MRI is evaluated using the
Prostate Imaging-Reporting and Data System (PIRADS).(10) Lesions are given a
category score, from 1 (high-grade PCa is unlikely to be present) to 5
(presence of high-grade PCa is highly likely). A PIRADS 3 is an equivocal
scan.(10, 11) Nonetheless, mpMRI has room for improvement as its specificity
for high-grade tumors is only 37% and local staging is limited with mpMRI.(6,
12) Also, the mpMRI is frequently unclear as 4-39% of detected lesions are
classified as PIRADS 3.(13)
Prostate-specific membrane antigen receptor (PSMA) is highly overexpressed by
95% of the prostate cancer cells and seem to positively correlate to
aggressiveness of the tumor.(14, 15) PSMA-positron emission tomography (PET)
uses this feature by visualizing PSMA expressing prostate tumors.(14, 15)
Currently, the PSMA-PET is generally used to detect recurrences or
metastases.(16) However, there is an increasing interest for PSMA-PET scans in
patients with a primary diagnosis of PCa for staging purposes.(17-19) Yet,
there is no published data on the role of PSMA-PET on PCa prior to biopsy in
comparison to the detection rate of mpMRI and histopathology.

This explorative study aims to investigate the added value of a 18F-PSMA PET to
mpMRI in the detection of local prostate cancer lesions.

This is a prospective single arm explorative study in which 75 patients will
receive both mpMRI and PSMA-PET.

The study will require time and effort from participating patients. Even though
a large portion of these patients will undergo a 18F-PSMA PET scan as part of
standard of care, patients with PIRADS 1-2 lesions will undergo a PSMA PET scan
which they would normally not get. Moreover, an additional 18F-PSMA PET scan
can also be beneficial for patients as the mpMRI can miss PCa.
There is no reported risk for the injection with 18F-PSMA itself as this scan
is already performed for years in thousands of patients and no adverse events
have been reported to date. The injection however, contains Fluor-18 which is
radioactive (photons). Nevertheless, the radioactive exposure is in the lowest
range and comparable with a normal 18F-FDG PET scan, therefore delayed
stochastic effects are not expected. Also, a large portion of patients will
receive the scan in case of positive biopsy, as part of clinical routine in our
hospital. It will not be necessary to repeat the PET scan for these patients.