Radiogenomic Characterization of Prostate Cancer: Distinguishing Aggressive From Indolent Disease
Abstract
The emergence of multi-parametric magnetic resonance imaging (mpMRI) has led to significant improvement in the detection of aggressive prostate cancer (PCa), i.e., PCa with the potential of causing harm if untreated. Although mpMRI misses close to 20 % of aggressive PCa, this imaging modality has been rapidly adopted to make treatment decisions, e.g., for selecting patients for active surveillance (AS) and for delineating areas for focal therapy. Commercially available tissue-based assays, such as Oncotype DX™, Prolaris™, and Decipher™, which are designed to provide global cancer prognostic information based upon the assessment of a single biopsy or cancer focus, do not take into account PCa multifocality and molecular heterogeneity. Hence, the biological and clinical significance of aggressive cancer areas missed by mpMRI or biopsy are currently unknown. The overall goal of this project is to improve the detection of aggressive PCa. We have developed a novel, PCa-specific, urine-based assay as an alternative way of making a global assessment of the prostate and believe that this approach provides a whole gland assessment. We hypothesize that a novel PCa-specific urine-based assay will outperform both mpMRI and commercially available, tissue-based, genomic tests performed to detect aggressive PCa. The successful completion of this project will provide an optimal paradigm for detecting aggressive PCa using mpMRI and tissue/urine biomarkers in patients with newly diagnosed PCa. In the first Specific Aim, we will assess the accuracy of a novel urine-based assay for the detection of aggressive PCa at first biopsy and in the setting of negative versus positive mpMRI. The results from this aim may provide a new paradigm for assessing patients with negative initial biopsy, negative mpMRI, and negative mpMRI targeted biopsy, i.e., men with low-grade PCa considering AS. In the second Specific Aim, we will comprehensively assess DNA and RNA changes associated with low- and high-grade cancers that are visible on mpMRI. Understanding the molecular basis of PCa visibility on mpMRI can help guide treatment decisions based on mpMRI and may lead to the rapid development of new biomarkers, imaging, and therapeutic modalities for aggressive disease. In the third Specific Aim, we will determine and compare tissue- versus urine-based prognostic assays to predict the simultaneous presence of aggressive disease that may have been missed by mpMRI or biopsy. The successful completion of this aim has the potential to significantly alter how urine- and tissue-based biomarkers are used clinically to identify men with aggressive PCa. Overall, the proposed project will have a near-term patient impact by elucidating the optimal approach to using mpMRI and urine- and tissue-based biomarkers to detect aggressive PCa. The Principal Investigator’s (PI’s) goal is to become a world expert and leader in translational PCa research and patient care. The proposed project will hone the PI’s translational research skills. It will allow the PI to consolidate both his clinical and scientific training and facilitate his transition into a successful career as an independently funded urologic surgeon-scientist. During the period supported by this grant, the PI will seek to further the development of his research skills and establish himself as a productive surgeon-scientist by participating in basic science and cancer biology seminars/journal clubs organized at the University of Michigan (UM) and major national/international conferences. The UM offers an excellent environment for career development, including providing numerous training workshops (e.g., grant writing and graduate-level courses for junior faculty members), emphasizing collaboration across multiple disciplines, and facilitating strong mentorship. Both mentors, Drs. Ganesh S. Palapattu and Scott A. Tomlins, are seasoned experts in PCa biology, biomarkers, genomics, transcriptomics, a
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810219
Entities
People
- Simpa Salami
Organizations
- United States Army
- University of Michigan