Imaging and Genomic Biomarkers to Predict Response in Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Radiation: External beam radiation therapyRadiation: Prostate brachytherapy boostDrug: Androgen deprivation therapyDiagnostic Test: Positron emission tomography (PET)/magnetic resonance imaging (MRI)
- Registration Number
- NCT05477823
- Lead Sponsor
- University of Wisconsin, Madison
- Brief Summary
The purpose of this study is to evaluate the imaging and gene expression biomarkers in prostate cancer. Participants have high-risk prostate cancer and have indicated they will undergo external beam radiation therapy, brachytherapy, and androgen deprivation therapy (EBRT+BTX+ADT). Participants can expect to be in this study for up to 5 years.
- Detailed 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. PET/CT (computerized tomography) may be used instead if PET/MRI is not technically possible. 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
- 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 6-36 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 ≤20 with or without medical management; prostate ≤60 cc as measured by MRI or ultrasound; no prior trans-urethral resection of prostate (TURP); and, median lobe extending into the bladder <1 cm
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description EBRT + BTX + ADT, PET and MRI External beam radiation therapy Standard of care EBRT + BTX + ADT, with mid-treatment PET and MRI (or PET and CT) scans for research. EBRT + BTX + ADT, PET and MRI Androgen deprivation therapy Standard of care EBRT + BTX + ADT, with mid-treatment PET and MRI (or PET and CT) scans for research. EBRT + BTX + ADT, PET and MRI Prostate brachytherapy boost Standard of care EBRT + BTX + ADT, with mid-treatment PET and MRI (or PET and CT) scans for research. EBRT + BTX + ADT, PET and MRI Positron emission tomography (PET)/magnetic resonance imaging (MRI) Standard of care EBRT + BTX + ADT, with mid-treatment PET and MRI (or PET and CT) scans for research.
- Primary Outcome Measures
Name Time Method Imaging markers for mid-treatment response Mid-treatment (approximately 3 months into treatment) Evaluate prostate specific membrane antigen (PSMA) PET/MRI for imaging biomarkers that predict mid-treatment response to ADT and EBRT to identify participants at risk for poor response to radiation therapy and ADT.
- Secondary Outcome Measures
Name Time Method Genomic signatures correlated with imaging response Baseline and mid-treatment (approximately 3 months into treatment) Determine if the Decipher and PORTOS genomic scores (high vs low) and basal/luminal genomic subtypes are correlated with change in PSMA standardized uptake value (SUV) pre-to-mid-treatment.
Evaluate blood-based biomarkers for treatment response. Baseline and mid-treatment (approximately 3 months into treatment) Messenger RNA from circulating tumor cells (CTCs) will be extracted to determine if presence of androgen receptor variants and a neuroendocrine prostate cancer signature (a score based upon the expression of a set of genes) is correlated with pathologic response (determined as outlined in Outcome 3).
Establish a correlation between PET imaging response and pathologic response Baseline and mid-treatment (approximately 3 months into treatment) PET images will be assessed for response using change in SUV in order to establish a correlation between imaging response and pathologic response to ADT and EBRT on a lesion-by-lesion basis. Pathologic response will be evaluated considering change in percent core involvement, prostate cancer epithelial/stromal (E/S) ratio, PSMA, CC3 and Ki67 expression. Concordance will be assessed using the Kappa statistic.
Establish a correlation between MRI imaging response and pathologic response Baseline and mid-treatment (approximately 3 months into treatment) MR images will be assessed for response using change in apparent diffusion coefficient (ADC) in order to establish a correlation between imaging response and pathologic response to ADT and EBRT on a lesion-by-lesion basis. Pathologic response will be evaluated as described in Outcome 3. Concordance will be assessed using the Kappa statistic.
Imaging and genomic markers for prostate specific antigen (PSA) recurrence. Baseline, 3 months post therapy, every 6 months for 5 years Determine if imaging and genomic markers that predict for mid-treatment pathologic response also predict PSA recurrence.
Trial Locations
- Locations (1)
University of Wisconsin
🇺🇸Madison, Wisconsin, United States