Genetic Testing Gains Increasingly Significant Role in Prostate Cancer

Leonard G. Gomella, MD

The role of genetic testing is becoming increasingly relevant in prostate cancer, as investigators begin to identify genes associated with heritable risk of disease, according to Leonard G. Gomella, MD.

"There is no question that genetic testing is expanding in all areas of medicine, and in particular in prostate cancer," said Gomella. "The challenge we have is that, unlike breast cancer where we have 15 to 20 years of really solid experience on these genes, we don't have long-term experience with the prostate cancer genes yet."

Inherited mutations such as BRCA1/2 and HOXB13 appear to inform prostate cancer risk. Genetic counseling and genetic testing may shed light on those alterations to direct treatment strategies for individual patients, Gomella continued.

Though hereditary prostate cancer appears to account for about 15% to 20% of all prostate cancer, targeted therapy could become invaluable for that patient subgroup, he added.

In an interview with OncLive^® during the 2019 Prostate Cancer Consensus Conference, Gomella, professor, chair, Department of Urology, director, Sidney Kimmel Cancer Center Network, Thomas Jefferson University Hospital, discussed the growth of genetic testing in prostate cancer, how to determine who should undergo testing, and what the future holds in this space.

OncLive: Could you discuss the rationale behind the 2019 Prostate Cancer Consensus Conference? What are the main goals you hoped to accomplish?

Gomella: This was our 2019 Philadelphia Prostate Cancer Consensus Meeting. We did this meeting for the first time in 2017 with the goal of trying to get content experts together to talk about how we are doing and what the unmet needs in genetic testing for prostate cancer are. That first conference focused on some of the very early issues about testing, such as what tests should be used and in what settings.

This conference is focusing more on the actual “nuts and bolts” of testing in the office, in the hospital, and in the clinic. [The goal is to] help guide providers to the best way to utilize genetic testing and genetic counseling. [Genetic counseling] is a very important component that you have to put with genetic testing.

What are the main areas speakers focused on at this conference?

We tried to bring in stakeholders from a variety of organizations to try to get some alignment in how we approach these problems. We have representatives from the National Comprehensive Cancer Network (NCCN), the American Cancer Society, and the Prostate Cancer Education Council. Different stakeholders such as the Society of Urologic Oncology, and the American Urologic Association are also involved. We get everyone's perspectives beyond just the providers.

There is also a heavy component of the genetic counselors here because they are the “boots on the ground” when it comes to these decisions about genetic testing.

As genetic testing is becoming more widely used in prostate cancer, what challenges still remain?

Many of the experts who were here are researchers who study the specific actions and the inheritance of these genes. We need to focus on what we don't know about genetic testing for prostate cancer.

There is growth, but the reality is that many providers are not yet aware of who needs to have genetic testing done, and who may be monitored without formal genetic testing.

What factors determine whether somebody should have genetic testing done?

We have some reasonably good guidelines right now. For example, NCCN guidelines state that if you have multiple family members who are under the age of 55 with prostate cancer, you should probably consider genetic testing.

Also, if you have prostate cancer and your family has a heavy burden of related cancers or hereditary cancer syndromes, such as breast cancer, ovarian cancer, melanoma, or pancreatic cancer, it may be wise to consider genetic testing.

Lastly, one of the least controversial areas right now in genetic testing is for men who present with metastatic prostate cancer. The reason is not only about inherited prostate cancer, but any day now we are going to introduce PARP inhibitors that will be driven by genetic testing.

In terms of exactly who to screen, who not to screen, and what family members have genetic testing, we are still finding our way. Over 80% of men who have prostate cancer have sporadic prostate cancer and you can't point a finger to any inherited or familial clustering of the cancer.

However, if you are in that 15% to 20% of men where there is a genetic connection, it is important to consider genetic testing.

In your opinion, what does the future of prostate cancer look like with regard to genetic testing?

The future of prostate cancer is what we have done in the past. It used to be that if somebody discovered a drug in colon cancer or lung cancer, you started treating all sorts of patients with prostate cancer [with the same drug] to see if it worked.

However, we have moved beyond that over the last 10 to 15 years, and we are focusing on precision medicine now. One significant component of precision medicine is identifying unique, genetic alterations in a given patient to help direct their treatment.

Right now, we are looking at mismatch repair for immunotherapy. It is not specific for prostate cancer, but it is an area we are using genetic testing for. That will clearly expand in the future.

In the next few years, the expansion of genetic testing coupled with pharmacogenomics in urology will become very prominent. We are going to identify very specific alterations in specific patients to choose what drug they should be treated with.

What specific trials are coming out in relation to genetic testing of prostate cancer?

There are literally dozens of trials that are ongoing. They are focusing on two general areas right now: PARP inhibitors and immunotherapy.

PARP inhibitors are already used extensively in other diseases, such as ovarian cancer. Many of the trials are looking for the genetic pharmacogenomics approval in a patient who has a germline [mutation].

In the immunotherapy world, we are looking at specific mismatch repair genes and other aspects of immunotherapy. Again, the good thing is it all based on precision medicine and trying to identify the best treatment for the patient at the point of time their disease is developing.