Alicia Morgans: Hi. This is Alicia Morgans, GU medical oncologist and Associate Professor of Medicine at Northwestern University in Chicago. I am so excited to have here with me today, a friend and colleague, Dr. Mary-Ellen Taplin, who is a Professor of Medicine at Harvard Medical School, as well as a GU medical oncologist at the Dana-Farber Cancer Institute. Thanks so much for being here today, Mary-Ellen.

Mary-Ellen Taplin: Oh, my pleasure, Alicia.

Alicia Morgans: Wonderful. So I wanted to talk with you about a really exciting presentation that happened at ASCO, really a little bit outside of the prostate cancer box, but also very much within the current prostate cancer box. You and the team did some work on something called ProGen, which is video education or in-person genetic counseling for men with prostate cancer, which is such a timely study, as we really struggle to make sure that we have the capacity to meet the needs of patients with prostate cancer in terms of genetic counseling. Can you tell us a little bit about this study and how your team performed it?

Mary-Ellen Taplin: Sure. Well, the background, Alicia, is that several years ago, it was reported that approximately 10% of men with prostate cancer had germline mutations in DNA repair genes and other cancer susceptibility genes. At that time, our current model of delivering genetic counseling at Dana-Farber was all in-person counseling. It was actually quite time-consuming. The patients routinely would meet with the counselors for 30 to 60 minutes before getting their blood drawn for the counseling.

So as the need to screen more prostate cancer patients, but also patients with pancreatic cancer, melanoma, were coming online, we were interested in testing a more efficient model to deliver genetic counseling. So we decided to test the video model. As you probably know, there are other models, phone calls, for instance.

But we made an eight-minute video that was geared toward prostate cancer patients specifically, that described why they were eligible for germline testing, what the incidence was. We introduced cascade testing. We introduced some of the issues with life insurance and other types of insurance around genetic counseling. So it was all within this eight-minute video.

So our eligibility included anyone with potentially life-threatening prostate cancer. We wanted the eligibility to be large. So it could be someone with a high-risk localized prostate cancer, up to an advanced metastatic castration-resistant prostate cancer. We sort of had a loophole in the eligibility as well, that included anyone that the treating physician thought warranted germline testing because of family history or age or other things. So it was quite a diverse group, which I think is an important point.

And we randomized the patients in a three-to-one fashion to watching this eight-minute video and then doing the testing or meeting in person with a genetic counselor and getting a more in-person counseling session.

And the protocol was open at three places, Dana-Farber, Karmanos in Detroit, and UT Southwestern, and very popular, very popular, among the patients. We enrolled 600 men, I think, short of two years, and our results are being presented at ASCO. And what we found, the top-line results of what we found, were patient satisfaction and acceptance of testing, which was quite high at 95%, was equal in the two cohorts. The patients felt equally informed with the video, short video, eight minutes, compared to the in-patient counseling. So that was reassuring as these new models are rolling out.

What we found was the incidence of clinically significant mutations was 13%. It's pretty much what we expected based on publications in prostate cancer by Pritchard et al and others. And of those with mutations, a quarter of them were BRCA1 and BRCA2, and then the long list of others that we'll be seeing in the presentation were a much smaller frequency.

So we're learning what we're seeing for alterations, both in the germline and somatically in prostate cancer patients, this study is important because it's helping us learn efficient models of testing. It's helping us understand who should be tested, the incidence of positive results. We have an incredibly rich cohort of variants of uncertain significance, which I don't have time to go into today, but we're excited to learn more about those variants in prostate cancer natural history.

And, of course, the cascade testing, Alicia, is paramount to this area of investigation. And I can give you one example of a patient of mine who was in the trial. I introduced it to him. He went off to the genetic clinic, had the testing. I saw him back in a usual Lupron® interval in three months, came with his wife and his daughter, and he had been positive. His daughter was tested, and she had already had bilateral mastectomy.

So, the impact of work like this for saving lives in general because of education in delivery around germline testing it was standard of care in breast and ovarian cancer culture, but for prostate cancer in our clinical setting, it was all new. I'm embarrassed to say, I used to take a prostate cancer family history, but I kind of left it at that. And now I've been educated to the importance of taking a very extended family history and really thinking about each patient as an individual and thinking about genetic counseling and testing.

Alicia Morgans: Yeah. I think it is a massive change that has happened over the last few years, which is one of the reasons that it's been hard to really implement the guidelines that the NCCN has, which actually mirror the study actually quite closely, because, at this point, anyone with high-risk, localized disease, all the way through metastatic and mCRPC patients, all of these individuals should have germline testing. And it's strongly suggested for those metastatic patients to also have their tissue testing done, which wasn't necessarily part of this trial but is such an important part of care that we've learned about. And I so appreciate that you and the team actually took on something that is not in your normal wheelhouse of translational and therapeutic studies, but really an implementation study, that I think could help us disseminate this practice through practices across the country, and hopefully globally.

One question I have, it certainly didn't seem to impact the satisfaction because there was great satisfaction in both groups, but what did patients do if they had questions after the video? Was there a way for them to engage and sort some of those things out?

Mary-Ellen Taplin: Yeah. They were assigned a genetic counselor at the time of the video. And after they watched the video and had blood tests drawn, the patients who had positive findings, including variants of unknown significance, had a phone call with a genetic counselor and then were offered a visit. Very few of them came in for the visit after the phone call, but they were offered that. And the services of the genetic counseling team were available to people who were negative, but most of them were satisfied that they were negative and that they didn't have to pursue it any further.

Alicia Morgans: That's great because I think that one thing that patients could fear or clinicians might fear in terms of implementing something like this, is what if questions come up, whether they're about legal implications, which I know were covered in the video but may still be questions in patients' minds, or cascade testing questions, it's really important to have ... To close that loop with the genetic counselors being available on the backend, so that's great.

And as you think about this particular trial, potentially altering practice, as I think that it could, certainly, if others have access to these videos, which have clearly been tested and are a successful way to communicate this information, how do you see this kind of rolling out to other practices if they choose to implement something like this?

Mary-Ellen Taplin: Yeah. So this one trial has changed the delivery of genetic counseling in all of the Dana-Farber, which is quite a big institute. So the patients will all be watching videos and having their blood drawn, and only patients who are positive will be seen in person if they want it, or they'll have a phone call.

So, with the amount of patients that need to be tested, this is very scalable. And the way we were doing it in the not-too-distant future, like last year, just really is not tenable, and I think that's true for every institution.

So our video was very specific to the study. It had a lot of trial language, a lot of Dana-Farber-specific language, but our genetics group has videos that are available certainly for academic institutions that we can share, and I'm sure others will be made for people to work with.

Alicia Morgans: And that's great. And I think that the bottom line is if you provide the education in a way that's easy for patients to obtain, particularly in a setting where they can't necessarily come to the clinic because of COVID, they can get the information they need. They can be actually quite satisfied with that. They can have the follow-up on the backend with a phone call or an in-person visit, and then cascade testing can happen, which as you mentioned in your story, has significant implications for loved ones and for their health. And as a prostate cancer oncologist, it's exciting to know that you potentially prevented breast cancer in a patient that you've never even seen, so that is wonderful.

As you think about this, what would your bottom line be to folks who are thinking about integrating genetic counseling, as per the guidelines, into their clinical practices, whether they are urology oncology practices or medical oncology practices, any words of advice or guidance?

Mary-Ellen Taplin: I think, number one, is to understand the importance and who your targeted patient audience is. I think, number two, is to develop an SOP for testing that works for you. I don't think one size fits all. And there are resources out there from some of the companies that do genetic testing that I know some of the offices have found helpful, Color Genomics, Ambrey, there's several of them and then stick to it.

I think the problem with doing something new is you get excited about it in the moment. You think about it for the next five patients, and then you forget about it again because we're all busy.

So trying to get an SOP that works for you, your practice, your staff, and your patients, taking the time to do that from the beginning, and then making sure that it can roll along in your practice fairly seamlessly so that it doesn't get left behind.

Alicia Morgans: That is great advice, and I appreciate it. I also really look forward to hearing some follow-up on these variants of unknown significance that you're going to be following. You have a cohort of over 660 patients. So I'm sure there will continue to be a lot learned from this trial. This is just really the first piece of information that we have.

So, thank you so much for sharing this and for doing the work in the first place because I think that many of us don't think about implementation science, but that is the way that discoveries are actually brought into the clinic, and that's the way that we ultimately change and deliver care. So thank you for your efforts and for sharing your time today.

Mary-Ellen Taplin: Yeah. I'd just like to call out my co-investigator, Dr. Huma Rana, who's presenting this at ASCO this weekend. And also to note that this trial was funded through gracious donations to Dana-Farber for research in general and prostate cancer research.

So, at this time when all institutes are struggling financially, it's important to remember that these donations are so much appreciated and go directly to impacting patient care, preventing and treating, and sometimes curing cancers.

Alicia Morgans: Absolutely. Well, congratulations to Dr. Rana and the entire study team. And thank you so much to the donors who made this possible. Even the smallest donations can add together to make huge change, as you've shown. So thank you so much for your insights, your time, and for your work.

Mary-Ellen Taplin: Oh, best of luck. Thank you.