Genetic Testing Gaining Larger Role in Prostate Cancer

Leonard G. Gomella, MD

Genetic testing to identify men with prostate cancer who have BRCA1/2 mutations and other abnormalities could provide insight as to whether they may develop aggressive disease and early metastasis, said Leonard G. Gomella, MD, FACS.

This advancement in the field, as well as other assays to determine disease characteristics, is changing the space of prostate cancer for the better, continued Gomella.

"If you look at all the dramatic advances in prostate cancer, we are converting it to chronic disease," said Gomella. "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 are making good progress."

In an interview with OncLive, Gomella, professor, chair, Department of Urology, director, Sidney Kimmel Cancer Center Network, Thomas Jefferson University Hospital, discussed the role of genetic testing and emerging biomarkers in prostate cancer.

OncLive: What is the rationale for genetic testing in prostate cancer?

Gomella: The area of testing men for inherited risk for developing prostate cancer is very rapidly evolving. We are learning more about the best way to test men for the traditional BRCA1/2 genes we think about in breast and ovarian cancer. Those genes are proving to be important in men with prostate cancer.

These genes themselves do not cause prostate cancer, but if a man does develop prostate cancer, these mutated genes appear to cause the cancer to take a drastic course, becoming more aggressive, and more likely to develop high-grade Gleason score of 8 and early metastasis.

Unfortunately, men who have this abnormality and develop prostate cancer live 10 years less than men [with prostate cancer] who do not have these genetic abnormalities.

Are we beginning to see therapies geared toward patients with this specific BRCA mutation?

We are seeing that in identifying men who have these BRCA mutation abnormalities, certain drugs may be more effective to treat them when they develop advanced disease. For example, PARP inhibitors may work better in men who have these DNA alterations.

What other emerging biomarkers are showing some promise?

There are a lot of biomarkers out there — in fact, there are a lot to keep track of. However, we use them to help us make the decision of whether or not a man with elevated prostate-specific antigen (PSA) needs a biopsy. Traditionally, elevated PSA used to be the trigger for a prostate biopsy; however, now, it gives us an intermediate decision point to look at factors like the PIRADS score, 4Kscore Test results, and SelectMDx urine analysis results. There is also a new exosome study test that [tests the] urine.

Therefore, if an elevated PSA is present, instead of going right to a biopsy, we can look at some of these biomarkers to see if they give us a suggestion that a man has an aggressive form of prostate cancer.

Is genetic testing in prostate cancer becoming more standardized?

The role of genetic testing in prostate cancer is finding its way right now. We know much more about using these tests in women with breast cancer. Right now, we are trying to determine the best way to use these tests in men with prostate cancer.

Clearly, all men with metastatic prostate cancer should undergo 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 to determine exactly how to use these genetic tests to screen men who may be at risk for developing aggressive prostate cancer in a logical fashion.

Are we getting to the point where we could say, “We have a precision medicine approach in prostate cancer?”

Across the board, all areas of medicine imply precision medicine, whether that's tissue staining to identify certain factors under the microscope or using molecular genetic testing. In prostate cancer, the goal is to develop very focused approaches. Everything is going in the direction of identifying a specific abnormality in a man through precision medicine, which will allow us to give a focused, specific therapy so we do not waste our time on other therapies that might not work.