Prognostic Biomarkers in Active Surveillance: Parsing Risk in Early Stage Prostate Cancer
Abstract
Scientific Objective and Rationale: Prostate cancer is the most common non-skin cancer diagnosed in men and the second leading cause of death from cancer among men in the United States. However, while some prostate cancers may become aggressive and ultimately lethal, most will never become clinically significant. Active surveillance is a technique developed to spare men with early-stage prostate cancer from the side effects of surgery or radiation while monitoring them closely for development of more-aggressive disease that should be treated. Current guidelines for active surveillance rely on information from digital rectal exam, blood tests (prostate-specific antigen), and biopsies performed over time. Tumors that appear low-grade under the microscope are not predicted to become aggressive, whereas higher-grade tumors are considered more risky. However, not all tumors that appear low-grade may act the same. Recent evidence suggests that some of these seemingly low-grade tumors actually harbor genetic changes that predict transformation to more risky tumor types. Therefore, we aim to study these genetic changes in order to predict which men have truly indolent cancer and which men may develop more-aggressive cancer. Secondly, biopsies of the prostate carry significant side effects, and recent research has focused on ways to assess cancer with blood tests instead of biopsies. We aim to study whether these so-called "liquid biopsies" that look for tumor DNA that circulates in the bloodstream can provide evidence about the aggressiveness of the tumor. Applicability of the Research: This research targets men with early-stage prostate cancer and aims to provide them and their physicians with greater information and confidence in making decisions about active surveillance versus surgery or radiation. Based on our research, we foresee the use of genetic studies on prostate biopsies and blood tests for circulating tumor DNA to give a more accurate sense of risk of a patient s cancer. There would be no increase in risk for patients, since both blood and prostate biopsies are already standard of care. We foresee relevant clinical results within the next decade from this research. Principal Investigator s Career Goals: My overarching goal as a researcher and clinician is to understand which patients should be exposed to treatment-related morbidity and which patients should be spared in order to maximize outcomes -- both cancer-related and quality-of-life-related -- in both groups. This research will help me develop skills in genetic research and working with banks of patient tissue samples. I plan to remain active in clinical care, bringing the results of cutting-edge research to the patients in my office and to the community. Likely Contributions of This Study: This research has implications for patients, but it also will help researchers more broadly understand the behavior of prostate cancer. Studying genetic changes in tumors and circulating DNA from tumors could also help develop better tools for making decisions for men with more-advanced prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710350
Entities
People
- David E. Einstein
Organizations
- Beth Israel Deaconess Medical Center
- United States Army