Systematic Germline Genetic Testing Is Feasible in Veterans With Metastatic Prostate Cancer

The implementation of systematic germline genetic testing in veterans with metastatic prostate cancer appeared to be feasible due to high consent rates, especially with direct oncologist involvement, according to results from a prospective trial. Additionally, data showed that the frequency of germline DNA damage-repair (DDR) alterations is similar to those with prostate cancer who are not veterans.

In the pilot study, investigators studied the feasibility of a systematic workflow that helped oncologists identify veterans with metastatic prostate cancer at VA Puget Sound Health Care System, which cares for veterans who require ongoing cancer therapy. After the patients were prescreened and identified by a research coordinator, an oncologist would discuss germline testing in great detail with both the patients and their families.

A total of 227 patients were approached in this trial. Out of these patients, 84% (n = 182) consented to genetic testing and 90% completed it. Results showed that 7% (n = 12) had a gDDR mutation: BRCA2 (n = 3), BRCA1 (n = 2), ATM (n = 4), and CHEK2 (n = 3).

“The main idea of the study was to identify patients systemically and have oncologists provide germline testing, without creating an extra infrastructure for genetic counseling. Genetic counseling is a different subunit, so patients don’t typically utilize the service,” said lead study author Alexandra Sokolova, MD. “Nowadays, germline testing is important for both patients and their family members because it can help with both the treatment process and the prognosis.”

In an interview with OncLive, Sokolova, a hematology-oncology fellow at Seattle Cancer Care Alliance, discusses the importance of germline testing in patients with metastatic prostate cancer, and the feasibility data observed through a systematic testing model.

OncLive: Could you discuss the rationale of this study?

Sokolova: In 2017, the National Comprehensive Cancer Network (NCCN) recommended germline testing for all men with metastatic prostate cancer. In 2019, this was updated to include all men with high-risk, localized prostate cancer or those [with a family history]. Since prostate cancer is the second most common cancer for men in the United States, this created a strong need to provide germline testing for a larger patient population.

Notably, a lot of men need to have germline testing. At the time, there was no streamlined infrastructure to deliver this service to men, thus, we had to figure out the best way to implement the idea. Ultimately, we decided to create a pilot study, which consisted of systematic delivery of germline testing for veterans with metastatic prostate cancer at the VA Puget Sound Health Care System.

What was the design of this pilot trial?

In this study, we tried to test the systematic identification of men with metastatic prostate cancer that would qualify for germline testing. A research coordinator was in charge of prescreening patients at each prostate cancer clinic and would flag patients with metastatic prostate cancer. This helped oncologists understand which patients qualified for germline testing and it reminded them to talk about it with their patients.

Notably, when talking to patients with metastatic prostate cancer, there is a lot of information that must be covered. Oncologist cover their symptoms, their quality of life, their treatment plan, their prognosis, etc.

We created a structure that allowed us to notify oncologists when we identified patients that qualified for germline testing. Oncologists then discussed it with patients during regular follow-up appointments, informing them of the pros and cons. If patients were interested, they would sign a consent form and would provide a saliva test the same day of the appointment. This made the process simple and convenient. We tried to streamline the collection of saliva samples, as well.

If the patients agreed, genetic counseling was provided by the Color Genomics panel. The main idea of the study was to identify patients systemically and have oncologists provide germline testing, without creating an extra infrastructure when it came to genetic counseling. Genetic counseling is a different subunit, so patients don’t typically utilize the service. Out of all the patients approached, 84% agreed to perform germline testing and 90% of them completed the process at the time of data collection. Out of the 190 patients that were approached, 182 completed germline testing.

Recently, we had an exciting PARP inhibitor approval for patients with DDR mutations. If we identify those mutations, we can inform patients who have DDR mutations, such as BRCA2, which puts them at risk of developing breast cancer, melanoma, or potentially pancreatic cancer. It’s important for them to understand that their family member could also be at risk. For example, their daughters or sisters could be at risk of developing breast cancer later on in life.

Therefore, by providing the service to our patients, not only can we help patients make the right decisions, but we can also help them inform their family members about the process and all that it entails. Encouraging more people to participate in germline testing could save lives.

What steps should be taken to help make germline genetic testing part of clinical practice?

There are several barriers of testing; some of them are on the patient’s side and others are on the providers side. One of the biggest barriers on the provider side is lack of infrastructure. In our old model, when a patient was sent to a genetic counselor, they first had pretest counseling, then testing, and then they had post-test counseling.

This is very time consuming, and, at this time, there aren’t enough resources to provide testing to all patients who qualify. We have to come up with alternative models that could help us streamline and use the resources available to provide this type of care to our patients.

In our study, genetic counseling was done through videos. The genetic counselor was initiated by a medical oncologist who was highly trusted by patients. However, another issue is insurance coverage. Currently, insurance companies don't cover cascade genetic testing. In cascade testing, when a patient has a mutation, family members are also recommended to undergo testing. Oftentimes, patients have a tough time getting coverage for this procedure. This being said, working on policy changes to ensure we have an infrastructure that could help take pressure off our patients is important. We want to provide patients and their families with everything that they need.

What other studies in this space would you like to highlight?

We have another method that helps us deliver germline testing to men with metastatic prostate, but it’s a much different mode. This model is web-based, and it is patient initiated. In this study, after oncologists provide the patients with all the information, patients then proceed to a website where they fill out their information and go through pre-test counseling. If they qualify, a saliva sample is sent to their home, and a genetic counselor later discusses the results over the phone. This model is great for some patients, although, it’s more challenging for others, especially for those who do not have good internet connection or are not savvy with technology.

Reference

Sokolova A, Miyamoto AN, Pouv DL, et al. Implementation of systematic germline genetic testing (GT) for metastatic prostate cancer (mPC) patients at the Puget Sound VA prostate oncology clinic. J Clin Oncol. 2020;38(suppl 15):1578. doi:10.1200/JCO.2020.38.15_suppl.1578