As the role of germline genetic testing becomes more widespread in prostate cancer, a recent trial aimed to identify how genetic counseling could impact an individuals decision to undergo genetic testing and ultimately, identify strategies to improve access to this service for men with potentially lethal prostate cancer, according to Huma Q. Rana, MD, MPH.

There is an increasing recognition of the importance of genetic testing for men with prostate cancer, said Rana. That being said, there are logistical challenges to having [these patients] undergo germline genetic testing, [including those that pertain to additional] appointments for patients who already have advanced cancer, limited expertise of germline genetic testing, and a limited genetics workforce.

During the 2020 ASCO Virtual Scientific Program, Rana presented findings from the randomized controlled ProGen trial (NCT03328091), which evaluated the role of video-education or in-person genetic counseling for men with potentially lethal prostate cancer.

Of 662 eligible patients with signed consent, 164 were randomized to undergo in-person genetic counseling and 498 were randomized to receive 8 minutes of video education. Patients then elected to undergo genetic testing via a 67-gene panel that identified common genetic alterations, such asBRCA1, BRCA2, ATM, CHEK2,and other DNA damage and repair genes. Participants also took part in various surveys, some of which are awaiting further analysis.

Of those patients who received in-person genetic counseling, 88% received the intervention and 98% consented to undergo genetic testing. In the video-education arm, 93% received the intervention and 99% consented to genetic testing.

Overall, 84 pathologic variants were identified in 13% of patients. Of these patients,BRCA1/2accounted for 32% of positive results.

In an interview withOncLive, Rana, an assistant professor of medicine at Harvard Medical School and clinical director of Cancer Genetics and Prevention at Dana-Farber Cancer Institute, discussed the rationale for conducting the ProGen trial, findings from the study, and the clinical implications the results may have on the genetic testing paradigm of men with potentially lethal prostate cancer.

OncLive:What was the rationale to conduct the ProGen trial?

Rana:Access to germline cancer genetic testing has been a long-standing issue. There are increasing indications for germline genetic testing. Through studies by our colleagues, we had recognized that there was a high prevalence of inherited mutations among men with advanced prostate cancers and that this could have significant implications on their treatment.

Men with advanced prostate cancer, and in particular, those who also had underlying mutations in genes likeBRCA2,are known to have poor outcomes. Therefore, it is important to identify these men to match them with targeted therapies that are available to them.

Prostate cancer is a very common disease. Recognizing that traditional germline genetic testing would be difficult and could potentially overwhelm the already strained systems for genetic testing, we decided to conduct this randomized controlled trial. We compared a short educational video, which focused on the educational components of a genetic counseling visit, with in-person genetic counseling for men with potentially lethal disease.

What is the role of genetic testing in men with prostate cancer currently, and how has it evolved in recent years?

Traditionally, cancer genetic testing has focused on women with a personal or family history of breast cancer. In many ways, we thought that the populations of men with advanced prostate cancer and men with potentially lethal prostate cancer were underserved. [We saw an] opportunity to reevaluate how we do germline genetic testing.

What genetic alterations are most prevalent among this patient population?

The main actionable findings among men with advanced prostate cancer are pathogenic or likely pathogenic variants in genes that are responsible for homologous recombination repair. That includes genes such asBRCA1/2, as well as other genes within the same homologous recombination, Fanconi anemia, DNA repair pathway likePALB2 andATM,among others.

In our study, we found that 13% of subjects had a pathogenic variant identified. Of those subjects, 32% had either aBRCA1orBRCA2pathogenic or likely pathogenic variant. This has implications potentially for their own treatment in terms of a matched targeted therapy, such as a PARP inhibitor. Additionally, this could also have significant implications for their relatives in terms of risk stratification for their sisters and daughters and risk of prostate cancer among men in their families.

What was the design of this study and what eligibility criteria were used to select patients?

Eligible subjects were those who had potentially lethal prostate cancer, including men with metastatic prostate cancer whether that be hormone sensitive, castration resistant or de novo disease. Also, men with localized prostate cancer who had a Gleason score of 8 or higher, men who were diagnosed with prostate cancer at age 55 or younger, and men with persistent or rising prostate-specific antigen after prostatectomy were also eligible.

Additionally, eligible men included those with potential biomarkers of lethal prostate cancer, including a family history of close relatives with specific cancers that would enrich for underlyingBRCAmutations. For example, men with prostate cancer and a family history of ovarian cancer were included.

We excluded subjects who had previously had genetic counseling or germline genetic testing, as well as men who had an active hematologic cancer because we would not be able to send a blood or saliva sample [for] them. We also excluded men who did not have potentially lethal prostate cancers.

Subjects were accrued across 3 sites: Dana-Farber Cancer Institute, the Barbara Ann Karmanos Cancer Institute, and UT Southwestern Medical Center. This could allow for geographic diversity among the subjects accrued.

The study was randomized controlled. Eligible subjects were approached and asked if they wanted to participate in the study. Those who consented to the study662 subjectswere randomized 3:1 to video education or in-person genetic counseling. They then scheduled their video-education visit or their genetic counseling visit. At the end of that visit, they were asked if they wanted to undergo germline genetic testing.

In both arms, a very high uptake of germline genetic testing was observed, with no significant differences between arms in terms of demographic characteristics or outcomes. High satisfaction was also reported in both arms at the first time point. Additional analyses of surveys 4 months and 12 months out from result disclosure are pending.

What were the results that were presented during the 2020 ASCO Virtual Scientific Program?

Men who consented to genetic testing underwent a 67-gene panel through a commercial laboratory. This panel-based test looked at genes involved in homologous recombination repair, as well as other DNA damage repair pathways. Other outcomes of interest included a family history of cancer, genetic testing satisfaction, the Multidimensional Impact of Cancer Risk Assessment score, which looks at the impact of genetic testing on distress, uncertainty, and positive experiences, as well as family communication of genetic test results.

At present, we have results available on the genetic testing outcomes, which as I said, showed that 13% of subjects had a positive genetic test result and thatBRCA1/2pathogenic variants account for 32% of subjects with positive results. We also have data on completion of intervention and completion of genetic testing. In the genetic counseling arm, 88% of subjects received their intervention. Of those who received genetic counseling, 98% consented to genetic testing. In the video-education arm, 93% received the intervention of an 8-minute educational video. Of those who received that intervention, 99% consented to genetic testing.

No real difference in consent to genetic testing was observed between arms in terms of those who received their intervention. Obviously, there was some drop-off of consented subjects who did not undergo their intervention.

Regression models were performed to determine if any specific clinical factors of interest such as metastatic prostate cancer, age at diagnosis of prostate cancer 55 years or younger, Gleason score, or hormone-sensitivity [status] were predictive of having a positive genetic test result. Separately, [the models determined] whether [these factors] were predictive ofBRCAstatus.

One significant result showed that an age of less than 65 at the time of prostate cancer diagnosis was associated with a higher likelihood of having a positive genetic test result. Despite that statistically significant result, it is important to point out that 8% of subjects over the age of 65 diagnosed with prostate cancer had a positive result. Personally, I would not use age at diagnosis to determine which patients would quality for germline genetic testing.

What are the clinical implications of these findings?

We can harness technology and technological advances such as video education to improve access to germline genetic testing as it can be impactful in someones cancer treatment, as well as in risk stratification for subjects and their family members.

It is important to note that genetic counseling is still important and genetic counselors still provide a valuable service. The emphasis of this study was placed on moving genetic counseling to the backend so that genetic counselors and their efforts could be focused on patients who had positive test results or those who were anxious about their negative or variant results and wanted to discuss those further with an expert.

Rana HQ, Stopfer JE, Petrucelli N, et al. A randomized controlled trial of video-education or in-person genetic counseling for men with prostate cancer (ProGen). J Clin Oncol. 2020;38(suppl 15)1507. doi:10.1200/JCO.2020.38.15_suppl.1507

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Study Analyzes the Role of Genetic Counseling in Men With Prostate Cancer - OncLive