Abbreviated Name

P-MRI

Lead Investigator

Wei, John — University of Michigan Recruiting

Coordinating Investigator

Zheng, Yingye — Fred Hutchinson Cancer Center

Involved Investigators

• Chesnut, Gregory — Center for Prostate Disease Research Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center
• Watts, Kara — Montefiore Medical Center
• Liss, Michael — The University of Texas Heath Science Center, San Antonio
• Olumi, Aria — Beth Israel Deaconess Medical Center
• Crichton, Dan — NASA Jet Propulsion Laboratory
• Gaston, Sandra M. — University of Miami Miller School of Medicine
• Kibel, Adam — Brigham and Womens Hospital
• Sonn, Geoffrey — Stanford University Medical Center
• Wei, John — University of Michigan Recruiting
• Wei, John — University of Michigan Pathology
• Pow-Sang, Julio — H. Lee Moffitt Cancer Center and Research Institute, inc.
• Rais-Bahrami, Soroush — University of Alabama at Birmingham
• McClure, Tim — Cornell University
• Chan, Daniel — Johns Hopkins Medical Institutions
• Sanda, Martin — Emory University School of Medicine
• Barocas, Dan — Vanderbilt University
• Lotan, Yair — UT Southwestern Medical Center at Dallas
• Diaz-Mayoral, Norma — Frederick National Laboratory for Cancer Research
• Srivastava, Sudhir — National Cancer Institute
• Punnen, Sanoj — University of Miami
• Pavlovich, Christian — Johns Hopkins University
• Nyame, Yaw — University of Washington
• Liss, Michael — University of California, San Diego
• Zheng, Yingye — Fred Hutchinson Cancer Center

Abstract

The commercialization of MRI fusion biopsies has resulted in a dramatic increase in the use of MRI imaging for prostate cancer. How best to use MRI in the initial prostate biopsy setting given the availability of validated prostate cancer early detection markers is uncertain. The primary aim of this study is to see if the addition of prostate MRI to a panel consisting of PSA, PCA3, TMPRSS2:ERG will significantly improve specificity for high-grade prostate cancer by 10%. The subsequent exploratory aims will 1) create an optimal panel of urine, blood and tissue biomarkers that will select those cases most likely to benefit from an MRI targeted biopsy, 2) directly compare PSA and urinary biomarkers with MRI to determine which ones are value added in the setting of initial biopsy, 3) evaluate changes in these biomarkers and MRI to determine if longitudinal changes predict subsequent high-grade prostate cancer, and 4) optimize MRI imaging to improve test performance. Importantly, this study will create a unique, prospective, cohort that will become the foundational reference set for of a range of future biomarker studies. From a logistical perspective, this project will roll out in two phases. In phase 1, we will initiate the cohort, standardize MRI and biopsy techniques, enroll approximately 340 cases and refine the final sample size necessary to address the hypothesis in Aim 1. Phase 1 is projected to take 30 months. From there, Phase 2, will be completion of enrollment to the final target goal (current estimate is approximately 1500 cases), closure of study and report findings. This phase is projected to take an additional 30 months for an overall project timeline of 5 years.

Aims

Specific aim 1. To examine the incremental specificity for high grade prostate cancer (i.e. > Gleason sum 6) of prostate MRI above and beyond PSA, PCA3 and TMPRSS2:ERG with the sensitivity held constant at 90% in the initial biopsy setting. Specific aim 2. To evaluate the potential for novel laboratory biomarkers, including but not limited to urine RNA sequencing chip, tissue prints for biomarker field effect to predict findings on MRI 2a. To evaluate the relationships between laboratory biomarkers and MRI sequences. 2b. To develop an algorithm that optimizes laboratory biomarkers to predict high-grade prostate cancer from a prostate MRI fusion biopsy. Specific aim 3. To evaluate the role of radiomics to improve upon standard MRI protocols in the diagnosis of high-grade prostate cancer Specific aim 4. (Longitudinal) To evaluate how changes in laboratory biomarkers and prostate MRI over a two-year period predicts subsequent diagnosis of high-grade prostate cancer Specific aim 5. To expand the current EDRN’s unique pre-diagnostic reference set with RNA sequencing of pre-biopsy urine. We will apply the uMIPS RNA sequencing chip on banked urine samples from the PCA3 cohort. This will be evaluated on those who underwent initial and repeat prostate biopsies.    5a: To conduct a head-to-head comparison of urine biomarkers for the detection of HG Pca on needle biopsy. This may include commercial assays such as SelectMDx if they provide support to run their assays.    5b: To develop a novel algorithm based on 83 distinct RNA sequences on uMIPS_v1 for the detection of HG Pca. Specific aim 6. To evaluate the potential for precancerous lesions to progress to invasive over a two-year period. We will follow cases of isolated high-grade PIN and isolated PINatyp with a targeted biopsy at two years using the targeted biopsy software. Our primary endpoint will examine concordance of erg status between PIN and cancer when found in the same location upon repeat biopsy. A secondary endpoint will be finding of any cancer at the same location as prior PIN even if erg status differs. Only cases with PIN and without invasive cancer at initial biopsy will be included. If successful, we would have tested the value of MRI above and beyond PCA3 and TMPRSS2:erg fusion. If the null hypothesis is rejected, we would conclude that MRI in the setting of an initial prostate biopsy is value added and should be included in the evaluation of men in the initial biopsy setting when PCA3 and TMPRSS2:erg fusion are performed.

Analytic Method

see Protocol

Outcome

•The primary aim of this study is to see if the addition of prostate MRI to a panel including PSA, PCA3, TMPRSS2:ERG will significantly improve specificity for high-grade prostate cancer by 10% •To create an optimal panel of urine, blood and tissue biomarkers that will select those cases most likely to benefit from an MRI targeted biopsy •To directly compare blood, urine and MRI biomarkers in a head to head comparison to determine which ones are value added in the setting of initial biopsy •To evaluate changes in biomarkers and MRI to determine if longitudinal changes predict subsequent high-grade prostate cancer •To optimize MRI imaging to improve test performance •To create a robust, prospective reference set for of a range of future imaging and biomarker studies

Publications

• No publications available at this time for this protocol.

Biomarkers

• No biomarkers available at this time for this protocol.

Data Collections

There is one collection of data that has not yet been made public. Logging in may you give you access to the names of the non-public data collections.

Start Date

Oct 12 2017

Estimated Finish Date

Oct 11 2020

Protocol ID

430

Protocol Type

Validation

Fields of Research

• Other
• Proteomics

Collaborative Group

Prostate and Urologic Cancers Research Group

Cancer Types

• Malignant neoplasm of prostate

Phased Status

2