Germline Genomics of Active Surveillance Failure
The Urological Research Foundation supports Dr. Catalona’s trailblazing research in prostate cancer. This includes the SPORE Project he co-leads, which is the largest study to date of men on active surveillance. This research is doing important work identifying genetic variants that can hopefully help guide treatment decisions in the future.
A crucial factor in the management of prostate cancer is determining which patients are good candidates for active surveillance, defined as careful “watchful waiting” that will be switched to active treatment if there is evidence that the tumor is more aggressive than initially suspected.
Prostate cancer is one of the most heritable of common cancers, with germline factors (genetic factors inherited from parents that are present in all cells in the body) for more than 40% of the variation in individuals’ likelihood to develop prostate cancer. Prostate cancer also is more frequent and more aggressive in African- American men.
Focus on germline genetic variants
Most of the currently available genetic tests for prostate cancer aggressiveness are performed on biopsy samples taken from the prostate gland. However, testing only the biopsy samples risks missing other regions of the cancer in the prostate gland that were missed by the biopsy procedure.
Recent studies have shown that some germline genetic variants that can be tested in blood samples are found more frequently in patients with aggressive prostate cancer. In this regard, ongoing work by Dr. Catalona’s research group and others has identified nearly 200 germline genetic variants associated with prostate cancer susceptibility, as well as some that are associated with its aggressiveness. These variants may provide critical information regarding which men with low-risk prostate cancer are most likely to have disease progression if they are managed with active surveillance rather than early active treatment.
Therefore, the goal of this project is to further develop, apply, and validate a novel germline genetics-based panel of blood tests that, along with other information, will help distinguish which men diagnosed with prostate cancer could safely be selected for active surveillance.
Dr. Catalona’s current SPORE project is a study spanning genetic variants across the entire genome searching for germline genetic variants in men with early, low-risk prostate cancer that are associated with active surveillance failure. They currently have enrolled more than 6,500 patients from around the world. Based upon data from several other active surveillance patient groups, they anticipate that 20% to 30% of patients will withdraw from active surveillance within two years, and an additional 20% to 30% within five years. By increasing the sample size and additionally oversampling African- American men, their approach has a high likelihood of identifying novel variants associated with active surveillance failure, including some less common and more powerful variants than have been identified to date.
The project has a strong leadership team. The project co-leaders are William J. Catalona, M.D. of Northwestern University, John S. Witte, Ph.D of University of California San Francisco, and Brian T. Helfand, Ph.D, M.D. of NorthShore University HealthSystem and University of Chicago. Project co-investigators include Denise M. Scholtens, Ph.D, of Northwestern University and Jianfeng Xu, Ph.D, of NorthShore University HealthSystem and the University of Chicago.
The SPORE Project is supported by a grant through the National Institutes of Health. The Urological Research Foundation provides additional funding for the project.