Ongoing Study May Answer Genetic Testing Questions in Prostate Cancer

Heather H. Cheng, MD, PhD

In the era of precision medicine, the role of genetic testing is becoming increasingly relevant in prostate cancer. However, challenges have emerged regarding when to introduce genetic testing for patients and how to best relay genomic testing results to family members, said Heather H. Cheng, MD, PhD.

The ongoing, prospective GENTleMEN trial (NCT03503097) is attempting to answer these questions through an online study where consenting men with prostate cancer are determined to be eligible for genetic testing based on their family history.

“[GENTleMEN] is an attempt to try to deliver genetic testing in a new way when we know that there are some limitations with our existing framework,” said Cheng.

In the trial, the participant’s saliva is tested for genomic alterations. If relevant mutations are found, the information is relayed to the participant via phone by a genetic counselor. The goal is to identify high-risk mutations prior to the presentation of metastatic disease. GENTleMEN also aims to increase awareness for a patient’s family members who may be at high risk of developing prostate cancer.

"Inherited cancer risk mutations that give rise to more aggressive prostate cancer features, which is increasingly more important because now we have treatment opportunities for those men who have metastatic disease,” explained Cheng. “There is a relatively new intersection between inherited cancer risk and treatment of [patients with] prostate cancer in the advanced disease setting."

In an interview with OncLive during the 2019 Philadelphia Prostate Cancer Consensus Conference, Cheng, an associate professor of medical oncology at the University of Washington School of Medicine, and director of the Seattle Cancer Care Alliance Prostate Cancer Genetics Clinic, discussed the GENTleMEN trial and the widening role of genetic testing for patients with prostate cancer.

OncLive: How is the role of genetic testing changing in prostate cancer?

Cheng: We now have PARP inhibitors and platinum-based chemotherapies that are available for men who otherwise wouldn't have those options. It is an exciting time, but it presents new challenges. How do we deliver that care, and to which patients, and at what stage of prostate cancer? [We need to] figure out some of those nuances and how we address them as a field.

What factors are being investigated to attempt to answer those questions?

It really is critical to think about who the [individual] patient is and where he is in the disease path. I am a medical oncologist, so I typically meet people who have metastatic prostate cancer. Usually, those patients are thinking about two factors: what their treatment options are, and what information we can provide to their family members that may help them take action to empower their own health.

Those two questions are options for all of our patients, but are not of similar importance to all of them. Some may care more about treatment, while others may care more about family.

Then, there are different areas. For example, in localized disease where men are first getting diagnosed, treatment implications are less prominent because of the early stage.

Patients with certain inherited mutations, such as BRCA2, are more likely to have aggressive disease, so we want to pay attention to those patients, think about enrolling them in clinical trials, and design new opportunities to figure out how we can improve their chances of cure.

Then, there is a third group of men who do not yet have cancer but have these mutations. What do we do for those men? At least for BRCA2 mutations, the risk of developing prostate cancer and more aggressive disease is higher.

[Ongoing clinical trials] are trying to identify cancer early so that we can then intervene in a more definitive fashion and hopefully, not lead to metastatic disease. It's the whole spectrum: patients who have not been diagnosed, patients who are diagnosed early, and those who have metastatic disease.

There is a lot of discussion about implementation. We are all quite aware that there are limited genetic counselors. Their skill set is so valuable, especially in making sure that family members also get the appropriate information and have opportunities for testing. How do we maximize efficiency in terms of delivering care and doing it in a timely fashion?

It’s a new challenge, but it also forces new creativity because of some of the limitations of the resources that are available. It also depends on what individual institutions have.

Could you discuss the GENTleMEN study?

GENTleMEN has been open since 2007; we are trying to address some of these disparities. It is a web-based study where men go to the website, read about the study, provide informed consent online, and answer some questions about their family history, their knowledge, and distress. It takes approximately 40 minutes for most patients, and if they meet qualifications, they are mailed a saliva kit. Then, they receive the results by phone with a genetic counselor if they have a [relevant] mutation identified. They are also invited to come in person or to follow-up by phone with a counselor as well.

Have any data been reported from the GENTleMEN trial yet?

In 2016, there was a seminal paper in the New England Journal of Medicine, which showed that the prevalence of inherited cancer risk mutations in DNA repair genes was almost 12% in the metastatic prostate cancer setting.

That led to changes with the National Comprehensive Cancer Network guidelines, that all men with metastatic prostate cancer should be considered for genetic testing. Now, those guidelines have been updated to recommend genetic testing.

Thus far, GENTleMEN suggests that the prevalence for this population [for genetic testing] looks to be approximately 10%.

Moreover, what are the distress measures? How do patients feel upon receiving their results? Is this an acceptable method of delivering genetics care? Can we improve upon it? Those are some other ancillary questions to figure out how to implement this outside of a clinical trial.

As GENTleMEN is ongoing, what are your hopes for the future regarding the role of genetic testing for prostate cancer?

I hope that we will learn that this method is very effective for some patients and it is a way to deliver this service to them.

Also, I hope those patients who do have mutations will have future research opportunities, such as learning about clinical trials or treatments available to them because of an identified mutation. If they have a BRCA2 mutation, they may have opportunities for PARP inhibitors.

Then, the other important thing is finding out if their family members can have opportunities for cascade testing, which is identification of people who are at risk for cancer earlier.

What is your take-home message for genetic testing in prostate cancer?

It is clear that genetic testing, genetic counseling, and issues around genetics is taking a larger place at the table in prostate cancer care across the spectrum. That includes primary care, urology, internal medicine, and oncology. There are new opportunities and demand for creativity for because of the constraints of the existing system. I would encourage people to talk with genetic counselors, who still play a critical role. We may need to shift that role to maximize their expertise and improve access what they uniquely provide. As the medical field, we need to work together to make sure that happens in a thoughtful way.