Analysis of the Genetic Landscape in the Evolution of Oligometastatic Prostate Cancer Through Peripheral Bioanalytes
Abstract
The FY20 PCRP overarching challenges that will be addressed in this proposal are: 1. Develop treatments that improve outcomes for men with lethal prostate cancer 2. Define the biology of lethal prostate cancer to reduce death Prostate cancer is the most common cancer affecting men in the United States. Although many cases are detected at early stages, some of those cases will go on to develop metastatic disease, which at this time is not curable. At particular risk are aging Veterans, whose duties can result in exposure to chemicals such as Agent Orange that increase their risk. African American men are also at greater risk of developing advanced forms of the disease; that is, when the cancer spreads from the prostate to invade lymph nodes or bones. Treatment for disease that has reached that metastatic stage is drug therapy, which slows disease progression and can prolong life, but does not cure the disease. However, with recent advances in imaging, radiation delivery, and drug therapy, we may be able to cure some men with metastatic disease. The term “oligometastatic” prostate cancer refers to disease that has spread beyond the prostate but to only a few isolated spots (usually less than five). Our group was the first to show that treating these spots with radiation, instead of just giving drug therapy, resulted in these patients living longer. That study was done with patients who had metastases from lung cancer. Building on that experience, we are now testing this approach of delivering radiation to isolated metastases that come from prostate cancer. That trial is called EXTEND (for External Beam Radiation to Eliminate Nominal Metastatic Disease). Part of that trial involves testing blood samples and tumor tissue samples from patients participating in the trial so that we can study the biology of disease at this oligometastatic stage and develop markers that will allow us to identify which patients have disease at that stage. An analogy we use in the clinic is that metastatic prostate cancer is like an iceberg. With our current imaging techniques, we can see the part of the iceberg that is above the water, but we cannot see what is under the water—is there a lot of disease or just a little? In the EXTEND trial, we are trying to develop ways of telling which people have a small amount of disease “under the water,” so that we can give those patients radiation therapy and hopefully extend their survival. In contrast, people with a lot of metastatic disease “under the water” would be spared the unnecessary side effects, time away from family, and financial costs of radiation that probably would not help control the disease. To do this, we propose to develop a panel of tests to be used on blood samples from men in the EXTEND trial. These tests will measure changes in the genetic material that the prostate tumor releases into the blood. The tests will take advantage of new, highly sensitive technologies to measure specific mutations in genes, changes in the ways the genes are expressed (known as RNA expression), and modifications in the chemical markers that surround and control the genes (known as methylation). We will develop these tests in parallel and investigate combining information from multiple tests. Our goal in this proposal is to improve our understanding of oligometastatic prostate cancer so that we can choose the best therapy for men with this kind of cancer. Better knowledge of this new, relatively unstudied disease state will help us to understand how prostate cancer progresses—and how to treat it at each stage of the progression. By using samples that we have already collected through the EXTEND trial, we hope to be able to develop a useable test in 3 years.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110474
Entities
People
- Chad Tang
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army