Clinical Trial 22098

• Overview

  Study Title:

  Non-Invasive Biomarkers in Prostate Cancer Disease Management

  Summary:

  Investigators will use multi-parametric magnetic resonance imaging (mpMRI) to globally characterize the perfusion and diffusion characteristics of the entire prostate gland, enabling them to identify tumor regions and generate surrogates for underling tumor pathology using quantitative metrics (radiomics, deep features).

  Objective:

  Aim 1. Cohort selection and Quantitative Imaging (radiomics) to assess cancer regions: The H. Lee. Moffitt Cancer Center, a National Cancer Institute only designated Comprehensive Cancer Center in the state of Florida has an active urology department that caters to the treatment of prostate cancer patients. It s located in the state and region with high density of patients with wide disease stage/grades, who could be potential candidates for the study. The study will prospectively enroll diverse racial patients, seen during the standard of care, who will be consented through the institutional protocol (Total Cancer Care, TCC) and accessed retrospectively with this study protocol. The study will capture wide disease grade/stages, both at early/low-intermediate risk (non-surgical) to late/high risk (surgery) of cancer progression. We will leverage retrospective collection of patients enrolled; samples bio-banked using the institutional (TCC) protocol. All the patients routinely receive diagnostic imaging with multi-parametric 3.0T (body coil) Magnetic Resonance Imaging (mpMRI) that includes diffusion weighted imaging (DWI), dynamic contrast enhancement (DCE) and T2 weighted (T2w) imaging, as part of standard of care (SOC). We will develop methodologies to semi-automatically identify regions (habitats) in the multi-modality fused mpMRI maps using the radiologist marker lesion boundary for most aggressive grade tumors to accurately localize the region. The regions of interest ('habitats') will be characterized using quantitative metrics (radiomics) to describe the morphology across the modalities. Aim 2. Develop fluid-based markers: There have been a number of bio-fluid based biomarkers that utilize molecular characteristics such as proteins, circulating cells (ctDNA, exosomes, etc) have shown promise to identify aggressive disease pathology. We will assess the potential of fluid (blood plasma, urine) based biomarkers along with conventional PSA and imaging features to enhance disease detection and assess disease progression. Aim 3. Develop Histology markers using Immunohistochemistry: We will obtain tissue sections from the aggressive cancer regions and stain for genetic markers that are known to be related to aggressive prostate cancer (up to 18 markers). We will use multiplex immunohistochemistry or immunofluorescence supported by Vectra®3 (or equivalent) Automated Quantitative Pathology Imaging System, tissue specimens obtained from the cohorts described in previous aim. The slides will be digitized, regions will be quantified at the regions that are enhanced for the targeted markers. Over laid to native H&E to obtain digital characterization of the sections. Aim 4. Patient level disease risk assessment: We will use multiscale data consisting of mpMR imaging, histology, biofluids (proteins, exosomal RNAs) to characterize the tumor and assess the disease condition. We will assess the disease condition for two wide disease grades, Intermediate risk (early stage, no-surgery): this group of patients will be those with localized disease, diagnosed with Gleason Score ≥ 4+3 and High risk (surgery patients): this group of patients who has prostatectomy as the standard of care treatment (Gleason Score ≥ 4+3). Although the multiscale risk assessment could be obtained by fusing information in different ways, the overlay of the following specific modalities will be investigated: a) MR habitats using co-registered biopsy level with histology, b) histology markers with fluid markers (proteins, exosomal RNAs), c) MR habitat, histology combined with clinical/radiological semantics, to assess aggressiveness, disease progression.

• Inclusion Criteria

  • Prostate cancer patients who had received primary diagnosis at Moffitt or outside the cancer center with available records (radiology, pathology, access to samples).
  • No-Surgery (Intermediate risk) group: patients diagnosed with pre-biopsy mpMRI, blood plasma: the biopsy must consist of a pathological diagnosis with a Gleason pattern score.
  • Surgery (High risk) group: patients who had radical prostatectomy (RP) with (or with-out) mpMR imaging, bio fluids available for research will be accrued for this group. We follow the NCCN recommendations for high-risk groups inclusion and follow-up criteria (58, 89, 90).
  • ≥ 4 ng/ml and /= 10 ng/ml (for late disease), within 3 months of study enrollment.
  • Age 35 through 85 years.
  • Zubrod/ECOG performance status > Ability to understand and willingness to sign a written informed consent document.
  • Patients who agree to have a multiparametric MRI with targeted/template biopsy.
  • Patients must agree to fill out the longitudinal psychosocial questionnaires assessing health related quality of life.
  • Availability of Bio-samples (blood plasma, urine) for exosomal, proteomic, genomic and pathology (H&E slides, IHC slides).
  • Quantity of bio-samples; Blood, Urine, tissue sections (including FFPE) for each region of interest.

• Exclusion Criteria

  • Subject is not a candidate for multiparametric MRI with contrast. Some reasons may include (but are not limited to): renal insufficiency, foreign body or pacemakers.
  • No prior pelvic radiotherapy
  • No prior surgery to the prostate, other than transurethral procedures for benign prostatic hyperplasia (e.g., transurethral resection, green light laser treatment)
  • No concurrent, active malignancy, other than non-metastatic skin cancer of any type, superficial bladder cancer, or early-stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma) or > Bilateral hip replacement.

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