Title
Pilot Study to Identify Radiogenomic Biomarkers to Predict Early Treatment Response to Androgen Deprivation Therapy and Radiation Therapy in High Risk Prostate Cancer

Description
This is a pilot study to prospectively investigate potential predictive imaging and genomic biomarkers for patients with high-risk prostate cancer treated with standard of care EBRT + BTX + ADT. The primary imaging modalities that will be evaluated will be PSMA positron emission tomography (PET) and multi-parametric magnetic resonance imaging (MRI). Pre-treatment PET/MRI scans will also be obtained as part of standard of care prior to study enrollment. Response will be assessed on a mid-treatment PET/MRI scan obtained for research purposes after completion of EBRT but prior to brachytherapy boost. Imaging response will be compared to pathology from image-directed prostate biopsies taken at the time of the brachytherapy boost. The primary genomic marker that will be evaluated is a clinically available gene-expression array, Decipher, that will be obtained as part of standard of care prior to study enrollment.

Objective
Primary
Determine the imaging and pathologic response rates in the primary tumor from patients with newly diagnosed high risk prostate cancer treated with standard of care androgen deprivation therapy (ADT) and external beam radiation therapy (RT) followed by a brachytherapy boost.

Secondary
Prospectively evaluate a clinically available pre-treatment gene-expression biomarker (Decipher) as a tool for predicting imaging and pathologic response to ADT and RT in high-risk prostate cancer.
Develop a pre-treatment imaging biomarker to predict which patients will respond poorly to ADT and external beam RT.
Establish a relationship between imaging response and pathologic response to ADT and external beam RT on a lesion-by-lesion basis.
Determine if the genomic and imaging markers that predict for mid-treatment imaging and pathologic response also predict PSA recurrence.

Exploratory
Prospectively evaluate additional pre-treatment gene-expression biomarkers, namely PORTOS and basal/luminal subtyping, as tools for predicting imaging and pathologic response to ADT and RT in high-risk prostate cancer.
Evaluate changes in gene expression from pre- to mid-treatment, and their association with response to therapy.
Evaluate higher order radiomic metrics (e.g. measures of lesion heterogeneity) as potential predictive markers for response to ADT and RT.
Evaluate changes in imaging markers (e.g. lesion intensity or volume) from pre- to mid-treatment, and their association with treatment response.

Treatment Experimental: EBRT + BTX + ADT, PET and MRI
Standard of care EBRT + BTX + ADT, with mid-treatment PET and MRI scans for research.
Radiation: External beam radiation therapy
Standard of care EBRT
Radiation: Prostate brachytherapy boost
Standard of care BTX
Drug: Androgen deprivation therapy
Standard of care ADT
Diagnostic Test: Positron emission tomography (PET)/magnetic resonance imaging (MRI)
Pelvic PET scanning with tracer will take approximately 45 minutes. This will be followed by the injection of a contrast agent followed by whole body PET/MRI scanning which will take approximately 30 minutes.

Key Eligibility Inclusion Criteria:

Age >/= 18

Histologically confirmed adenocarcinoma of the prostate

Cancer classified as high-risk or very high-risk by National Comprehensive Cancer Network (NCCN) criteria: Grade group >/=4, PSA >20, or primary tumor stage >/=T3a

ECOG performance status 0-1

Agreed to undergo EBRT, high dose rate (HDR) brachytherapy boost, and 18 months of ADT as part of standard of care therapy prior to study enrollment

Able to undergo a HDR brachytherapy implant: Pre-radiation IPSS score
No prior or concurrent malignancy unless disease-free for at least 5 years

Evidence of regional or distant metastatic disease on pre-treatment bone scan, pelvic MRI, and/or CT of the abdomen/pelvis

Prior pelvic radiation therapy

Applicable Disease Sites
Prostate

Participating Institutions
UW Health University Hospital