Integration of Magnetic Resonance Imaging and Protein Biomarkers for Identification of Aggressive Prostate Cancer
Abstract
Although blood tests for PSA have made it easier to detect prostate cancer (PCa) earlier, most of the cancers detected are slow-growing and non-lethal. The big challenge is detecting highly aggressive, lethal prostate cancers early enough for treatment to be effective, while making sure we neither under-treat aggressive PCa nor over-treat indolent tumors. The usual way to do this is to take biopsies of the prostate gland and ask a trained pathologist to “grade” the tumor for likelihood of aggressive behavior. The problem is, PCa exists as little islands of malignant tissue in a complex 3D structure, and random biopsies can miss the crucial zones. Magnetic resonance imaging (MRI) can be used to guide biopsies and provide more information about the tumor, but current technologies are imperfect and often miss aggressive PCa. There is a need to improve upon current MRI technologies and integrate molecular biomarkers (small molecules from the tumor that predict aggressive cancer) to gain additional information about the biology of individual tumors and help determine who will need more aggressive or less aggressive treatment. We propose a unique imaging technique called “Shutter Speed” Magnetic Resonance Imaging (SSMRI) that will be evaluated to determine whether it improves upon current standard prostate MRI methods for early identification of aggressive prostate tumors. Another approach to improve detection of lethal PCa is to measure protein biomarkers associated aggressive behavior using mass spectrometry. We will integrate our MRI findings with candidate protein biomarkers associated with development of distant metastases (spread of cancer outside the prostate) over time. We will obtain MRI images in patients prior to routine surgical removal of their prostate cancer, then we will cut the removed prostate into sections and map the MRI images to tumors within the prostate that we identify under the microscope. We will conduct research on the tumor tissue that is matched to the MRI images to figure out what changes in the tissue and its proteins affect the ability of MRI to detect the cancer. We will also identify how much value the protein biomarkers add for predicting more aggressive disease, such as invasion of the tumor outside the prostate or into the lymph nodes. Similarly, for patients with initially lower risk cancers who are managed with active surveillance of their cancer (by periodic biopsies, blood tests, and prostate exams), if the tumor is visible on MRI, we will evaluate the ability of the protein biomarker to predict which cancers will become more aggressive on biopsies taken during active surveillance that are targeted to the MRI-identified tumors. This research will be highly applicable toward improving early detection of aggressive prostate cancer through imaging and protein biomarkers, with the goal of defining the biology of lethal prostate cancer to reduce death from prostate cancer in Veterans, African Americans, and other high-risk groups. Only a small percentage of prostate cancers are metastatic at initial diagnosis, while others might develop metastases years after treatment. Unlike other molecules from the cancer, such as DNA, proteins are downstream functional molecules that most accurately reflect the biology of the tumor. By revealing underlying biological changes, this research not only helps us design better early detection tests but also informs “precision oncology” treatments based on individual tumor biology. The MRI technology may also have immediate applicability prior to diagnostic prostate biopsy in men with suspicion of prostate cancer. Tissue-based biomarker tests may eventually be developed into less invasive urine or blood-based tests that could be performed prior to undergoing a tissue biopsy or for monitoring disease on surveillance. These new technologies being developed pose no increased immediate risks beyond standard MRI imaging and routine tumor analysis b
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010634
Entities
People
- Ryan Kopp
Organizations
- Oregon Health & Science University
- United States Army