Leonard G. Gomella, MD
An increased understanding of the genetic makeup of prostate cancer could allow for the introduction of more effective therapies for patients who develop advanced disease, said Leonard G. Gomella, MD. However, how to best use genetic testing to screen potentially at-risk patients early on remains unclear.
The role of genetic testing is finding its way right now. We know much more about using these tests in women with breast cancer,” said Gomella, a professor and chair of the Department of Urology and director of the Sidney Kimmel Cancer Center Network and Thomas Jefferson University Hospital. “We are still trying to figure out how to best use these methods in prostate cancer.”
Over the years, investigators have identified which traditional genes play a key role in the development of aggressive disease. For instance, BRCA1/2
mutations are particularly important in prostate cancer, as they are known to increase the likelihood of metastases and have been associated with poor prognosis.
“What's happening with BRCA
mutations—in particular, the DNA repair gene pathways—is that identifying men with these abnormalities allows us to use more effective drugs when they develop advanced disease,” said Gomella. “For example, PARP inhibitors may work better in men who have these alterations in their DNA.”
In an interview with OncLive
, Gomella underscored the need for genetic testing in prostate cancer, shed light on important biomarkers in the space, and explained how these tests are helping oncologists facilitate a precision medicine approach.
OncLive: Could you speak to the importance of genetic testing in prostate cancer?
: The area of testing men for inherited risk of developing prostate cancer is rapidly evolving. We are learning more about the best way to test the traditional genes that we think about in breast and ovarian cancers, which are proving to also be important in men with prostate cancer. These are the BRCA1/2
genes. It is very important for us to understand that these genes themselves do not cause prostate cancer, but if a man does develop prostate cancer, having these mutated genes appears to cause the cancer to take a very drastic course, becoming more aggressive and increasing the likelihood that the patient will develop metastases.
Unfortunately, men who do develop prostate cancer and have these genes live 10 years less on average than men who do not have them. Understanding these mechanisms and bringing that knowledge into patient care is what we would like everyone to know.
What other biomarkers do you think have promise in prostate cancer?
There are many biomarkers out there; there are a lot to keep track of. These biomarkers help us make the decision on whether or not a man with a rising prostate specific antigen (PSA) needs a prostate biopsy. Our traditional PSA elevation that used to be the trigger for a prostate biopsy now gives us intermediate decision points to look at, such as PI-RADS score or the SelectMDx in the urine. There is a new exosome study test that is available in the urine. Again, if PSA is elevated, instead of going right to a biopsy we can look at some of these biomarkers and see if they suggest whether a man has an aggressive form of prostate cancer or not.
What is the prevalence of genetic testing in prostate cancer today?
Clearly, all men with metastatic prostate cancer should undergo this genetic testing to look for these abnormalities, because it may direct treatment for advanced disease. Where we need a lot more information is in earlier-stage disease, and how to best use these tests to screen patients who may be at risk for developing aggressive prostate cancer.
If you look across the board, almost everything that's happening in all areas of medicine apply precision medicine, whether that's using tissue staining to identify certain factors under the microscope or through the use of molecular genetic testing. We are moving in this direction in all areas of medicine, particularly prostate cancer, in order to develop more focused approaches. [We’re] moving away from a one-size-fits-all approach to using more specific therapy. We don’t want to waste our time using therapy that may not work.
Looking back to the 2019 Genitourinary Cancers Symposium, were there any studies in prostate cancer that you felt were particularly important?
The ARAMIS study received a lot of attention. It looks like darolutamide is going to be a third agent available for men who have M0, rising PSA, castration-resistant prostate cancer without evidence of metastasis. Having 3 different drugs available with slightly different mechanisms of action is a good thing for patients. However, the question of exactly which drugs to use and how to use them will need to be figured out.
How has the outlook improved for patients in recent years?
What's really happening in prostate cancer, if you consider all of the dramatic advances we've had, is that we are really turning it into a chronic disease. We have so many medications right now that if one therapy fails, we have a back-up options. We might not be able to cure all men with prostate cancer, but if they can live a long time with a good quality of life, we're making good progress in that area.