Remote genetic testing has the potential to increase the uptake of testing in large integrated healthcare systems

Dr Bruce Montgomery - University of Washington, Seattle, USA

The work that we presented at ASCO GU was related to this area of precision oncology that is what is called germline testing, which means testing men with advanced prostate cancer in this case for the presence of an alteration that they might have inherited from one of their parents. That is a national guideline and the reasons for the national recommendation is that by testing men with metastatic prostate cancer we can find alterations in their normal DNA that led to them developing advanced prostate cancer. Those alterations not only are important for their family – if nobody in the family knows that they carry this alteration – but it also allows us to design therapy for a subset of patients who carry one of these alterations. Some of them are genes like what’s called BRCA1 or BRCA2 and the presence of those alterations in a man’s DNA who has advanced prostate cancer, the majority of the time make the cancer susceptible to targeted therapies – things like PARP inhibitors or in some cases immunotherapy – to the point that we can actually do a remarkably effective treatment for these men. But they don’t work unless we know that the patients have them.

The other part of this, which I alluded to earlier, is that if a family doesn’t know that there is the presence of one of these inherited alterations in the family then they can’t do essentially personalised healthcare. So, for example, if we determine that a man carries a BRCA2 gene, all of the other family members that he has that are related by blood have a 50/50 chance of having inherited that gene. If nobody knows about it then there isn’t much they can do about it. In, for example, women if they carry one of these genes they have a roughly 40% lifetime risk of developing breast cancer and 20% risk of developing ovarian cancer. Those risks can be mitigated by a number of other interventions so this can potentially be lifesaving in family members as well.

So the idea of testing men for these alterations is really something that carries a lot of importance. The issue is that the approach of testing these men is something that isn’t happening as frequently as we would like and there are many reasons for that. This would be an hour-long conversation to go through them all. But our study was designed to see if we could augment what is the standard approach. The standard approach is that the provider talks to the patient in the clinic, they then send them to the laboratory after consenting them, they have blood drawn, tests get sent off, the result comes back. If it’s positive the patient is referred to a genetic counsellor. Each of the points of ordering and then going to visits can be a barrier for patients completing testing.

So out in the community and in the VA, which is where this study specifically was done, the uptake of testing is about 10% of the men who have metastatic prostate cancer whereas what we would like is as close to 100% as possible. So the study that we did was to approach men who had a diagnosis of metastatic prostate cancer in the VA who had previously participated in a genetic study called The Million Veteran Program which allowed us to see in the electronic medical record that they did or didn’t have a diagnosis of metastatic prostate cancer and might be eligible for this testing. What we then did after identifying them would be to send them a letter saying we’re doing this study, we’re going to be offering you genetic testing to see whether you have, in fact, inherited a genetic alteration which may have had something to do with your diagnosis. If they didn’t want to be approached they had the option to what’s called opt out, to just say, ‘Please don’t call me, don’t contact me.’ We ended up contacting about 2,000 veterans who had metastatic prostate cancer who did not opt out. That contact came in the form of informational materials, a consent form, information about why germline testing might be important to them as per what we just talked about a moment ago. Then if we didn’t hear back from them they were again given the option to opt out by contacting us and saying, ‘No, I’m not interested.’ We would then call them, go through the consent form with them and determine whether they, in fact, were both appropriate and wanted to participate in the germline testing.

If they’d said yes, we would then send them what’s called a saliva kit, a spit kit. This test is done at home, on your own time, and there are a number of commercial assays that are used that are the same type of test although they don’t test exactly the same genes that we do. So these spit kits can be sent to anybody anywhere who has a mailbox. Ultimately we were able to complete testing, meaning consent, send the kit and have the kit come back to the laboratory directly, about 25% of the men who were initially approached. Which, again, isn’t the near 100% that we would like; on the other hand it’s 2½ times the uptake that is being seen in the community through the standard process.

Interestingly, about 50 men of the roughly 500 who participated in the testing had an alteration which was in their normal DNA that may have played a role in their development of prostate cancer. We offered them post-test counselling through our genetic counsellors, again mostly by phone or by video, whichever the patient preferred. Then as part of this they were also offered what’s called facilitated communication and testing of any of their first-degree family members that wanted to undergo testing. That is also a very important part of this because even though, for example, one member of the family can be found to carry an alteration, the ability of the family member who has that alteration to communicate why this is important to the rest of the family, it’s a tall order for somebody who doesn’t have a background in medicine or genetics to actually tell them why this is important and what to do about it. So this pilot program offered the proband, somebody who carried one of these alterations, facilitated communication by genetic counsellors with their first-degree family members and then we actually also facilitated the cost of the testing – it was free to first-degree family members. Ultimately about 30 of the patients who had an alteration participated and we facilitated testing for their first-degree relatives. So it is something that can be done as well.

The takeaway from this study is that using an approach which is entirely remote so that it’s possible to reach essentially anyone anywhere who has a phone and has a mailbox, can be approached and can complete testing. By doing this approach, which actually does not require a huge amount of investment in terms of money or even effort on the part of, for example, the research coordinators or the genetic counsellors. It’s not a matter of effort, it’s simply that you can actually test a very large number of patients without spending an hour of pre-test counselling, having somebody going through the process, of insurance approval for testing and subsequent post-test counselling. We can actually achieve uptake that, as of right now, is significantly higher than what is happening in the community overall. Being able to complete testing in these patients can help them, can help their family and ultimately just improve their care. So that’s really what we were trying to do and luckily we were able to succeed in improving some of the uptake of germline testing through this mechanism.

What is next for this study?

The next study for this is to implement it, again through a research study. Doing it more broadly in the VA as a whole, rather than limiting it to this group of folks who have participated in another genetic testing study and try to reach more veterans who could potentially benefit. We’ll be looking at the uptake through point of care testing for patients versus this approach and see whether, for example, in a broader population of veterans with advanced prostate cancer we’re able to achieve the same results. And incorporating into the approach ways that we think might improve people’s interest in completing the testing because, again, not everybody necessarily is all that interested in genetics and finding approaches that make their understanding of how this might affect them and their family more significant. A more informed consumer is obviously a better consumer. We don’t think of patients as consumers but in this situation when we’re reaching out directly we want them to feel comfortable. By testing different approaches to giving them information and providing the subsequent testing itself we just want to optimise the uptake so that instead of 25% of people being tested through this approach we’re much closer to what we would really like which is as close to 100% as possible.

So that is the next step. We hope that this kind of approach which we don’t at all think can replace point of care testing but can augment standard testing and particularly for patients who don’t live next to an academic medical centre, folks that are out in rural areas, for example, and subspecialty oncology care is not necessarily easily accessible. We think that those patients in particular are folks who could particularly benefit from this sort of approach