Clinical trial NCT05819606: Positron Emission Radiomics With PSMA Radioligands on Newly Diagnosed Prostate Cancer Patients
Official title: PERsonalized Positron Emission Radiomics With Prostate Cancer Specific Membrane Antigen Radioligands on Newly Diagnosed Prostate Cancer Patients.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Prostate Cancer
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2023-04-19
Enrollment: 160
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with newly diagnosed biopsy confirmed intermediate/high risk PCa will be consecutively enrolled.

All patients will undergo a multiparametric MRI (mpMRI) examination at Radiology Department and a PET/CT with PSMA radioligands for staging in the PET/CT Center, both in the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). After PET scan all patients will be eligible for radical prostatectomy.

Brief summary: The primary aim of this large prospective study consists of exploring the correlation among Volumetric and Radiomic parameters extracted from staging PSMA PET/CT Imaging versus conventional baseline clinical biochemical data, conventional imaging and the aggressiveness of the tumor based on the post-surgical-Gleason Score (GS) in patients with intermediate/high risk prostate cancer (PCa).

Secondarily, Volumetric and Radiomic features extracted from the same PET images will be compared with the amount of the Circulating Tumor Cells (CTCs), with the expression of specific receptors on CTCs surface,

Possible mutations encoding androgen receptors (AR) on CTCs surface, and with PSMA density on primary tumor cells provided by the Immunohistochemistry method (IHC) applied on post-surgical histological samples.

According to PET images, Volumes of interest (VOI) encompassing the whole prostate with foci of PSMA uptake suspected for PCa will be drawn to extract semiquantitative and radiomic PET features.

The association between PSMA PET radiomics and CTCs molecular and genomic panel at staging could potentially lead to a more personalized and more effective therapeutic chances.

Detailed description: Background and rationale:

Besides PET semiquantitative assessment, new radiomic parameters could be extracted from baseline PET/CT images. Radiomics is a high-through put approach that translates medical images into minable data by extracting many quantitative features describing the intensity, shape, and heterogeneity of targeted lesions. Radiomic models could indirectly be an expression of tumor biology behavior and could be considered an additional support, together with clinical and histological data, to help the clinicians in the diagnostic iter. Recently PSMA PET metrics were suggested to predict high-risk pathological tumor features in primary PC patients. As far we know, no large studies have been published about the integration of PSMA PET/CT radiomic and CTCs amount and their molecular characteristics. This project aims to gap this knowledge, studying a large dataset of patients in our referral university hospital by an experienced multidisciplinary team.

OBJECTIVES Primary objective consists of exploring any correlation among volumetric and radiomic parameters extracted from volume of Interest (VOIs) within the whole prostate from staging PSMA, PET/CT imaging with baseline conventional clinical, biochemical, radiologic and histological data in a large prospective consecutive cohort of patients with intermediate/high risk prostate cancer before radical prostatectomy.

Secondary Objectives: Volumetric and radiomic features extracted from same VOIs will be compared with the amount of CTCs and with the expression of specific receptors and their potential mutations on CTCs surface.

METHODS Study design: This is an observational, prospective and monocentric study. Population: Patients with newly diagnosed biopsy confirmed intermediate/high risk PCa will be consecutively enrolled.

All patients will undergo a multiparametric MRI (mpMRI) examination at Radiology Department and a PET/CT with PSMA radioligands for staging in the PET/CT Center, both in the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy). After PET scan all patients will be eligible for radical prostatectomy.

Study duration: 12 months

Patients Inclusion criteria:

* Age ≥ 18 years old
* Able to sign informed consent
* Biopsy-confirmed intermediate/high risk prostate cancer
* Good compliance to undergo mpMRI scan and PET/CT scan
* Eligible for radical prostatectomy

Patients Exclusion criteria:

* Contraindication to mpMRI (such. Metal implants and/or pacemaker)
* Poor compliance to undergo PET/CT (i.e.claustrophobia)

Variables and procedures

The following clinical conventional parameters will be collected:

age, results of DRE, Prostate-Specific Antigen (PSA) levels, results from mpMRI (PIRADS categories from 1 to 5 according to v2.1 and biopsy-based Gleason Score (GS).

Furthermore, the amount of circulating tumor cells by the bloodstream peripheral samples (CTCs), as well as the overexpression of specific receptors on the CTCs surface, such as the epidermal grow factor receptor (EGFR), PSMA receptor will be assessed.

Genomic data, in terms of possible presence of AR mutation on CTCs will be collected.

ENDPOINTS Primary endpoint

* Association among conventional PET parameters and first-order radiomic features (tSUVmax, tSUVmean, tMTV, tTLA, tSkewness, tKurtosis) and advances ones, extracted from VOIs within the whole prostate gland) with PSA, bioptical and post-surgical GS and positive/negative mpMRI and DRE Secondary endpoints
* Association among above-mentioned PET parameters with the amount of CTCs and with the expression of specific receptors and their potential mutations on CTCs surface.

Sample size calculation A prospective cohort of 160 patients will be enrolled to develop a baseline radio-genomic model which is compared to the conventional clinical and histological parameters at staging, according to the medium per-year number of available PET scans and current data available on literature.

In depth, Sample size is determined on an AUC measure equal to 0.93 (Zamboglu et al., 2019), by considering the dichotomized Gleason Score (\>=8) as primary outcome, a significance level (alpha) equal to 0.05, an expected power of the test (1- probability of type II error) equal to 0.95, and a K=controls/cases ratio equal to 4. Accounting for this, the sample size is equal to 160.

Randomization: Not any randomization is considered in this protocol

Expected results and impact. Staging PSMA PET/CT metric applied on prostate with suspected neoplastic involvement would have the potential to predict the extent (in terms of lymph node involvement or distant metastases) and the aggressiveness of disease based on histological post-surgical specimen GS, as well as on the PSMA overexpression in percentage on tumor cell surface assessed by IHC. PSMA PET/CT metric could be associated to consistent amount of CTCs at diagnosis, as well as increased PSMA OR EGFR expressed on CTCs surface, so paving the way for a radiogenomic panel, which would lead to a more personalized and more effective therapeutic chances.

Eligibility criteria: Inclusion Criteria:

* Able to sign informed consent
* Biopsy-confirmed intermediate/high risk prostate cancer
* Good compliance to undergo mpMRI scan and PET/CT scan
* Eligible for radical prostatectomy

Exclusion Criteria:

* Contraindication to mpMRI (such. Metal implants and/or pacemaker)
* Poor compliance to undergo PET/CT (i.e.claustrophobia)

Primary outcomes:
measure: Evaluation of aggressiveness of prostate cancer.
timeFrame: 9 months
Secondary outcomes:
measure: Radiogenomic panel of prostate cancer.
timeFrame: 9 months
Other outcomes:
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Study officials:
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