As HRR testing becomes a cornerstone of personalized care in metastatic prostate cancer (mPC), how do we ensure it’s implemented equitably and effectively across all clinical settings? Arun Azad unpacks the real-world barriers to implementing HRR testing in mPC, from clinician education and workflow integration to funding, access, and persistent misconceptions. He highlights the importance of multidisciplinary collaboration, reflex testing, and targeted advocacy to ensure equitable access across diverse clinical settings. “We’re denying some patients the opportunity to have another therapy that could extend their life and improve their quality of life if we don’t do the testing,” Azad warns, underscoring the urgency of closing the gap. View transcript .
Chapters 00:00 Barriers to integrating HRR testing13:21 Can advocacy reduce HRR testing gaps? 14:01 Checklist: How to implement HRR testing
Meet the expert
Arun Azad is a Professor of Medical Oncology at the University of Melbourne and a Consultant Medical Oncologist at the Peter MacCallum Cancer Centre in Melbourne, Australia. Azad has served in leadership roles across multiple international clinical trial steering committees. He is the Translational Chair of the Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group and Urologic Oncology Chair at the Clinical Oncology Society of Australia. He also contributes to international standards of care as a member of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines Committee for prostate cancer.
Disclosures: Honoraria from Aculeus Therapeutics, Amgen, Arvinas, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Ipsen, Janssen, Merck Serono, Merck Sharpe Dohme, Novartis, Noxopharm, Pfizer, Sanofi, Telix, and Tolmar. Member of scientific advisory board for Amgen, Arvinas, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Ipsen, Janssen, Merck Serono, Merck Sharpe Dohme, Novartis, Noxopharm, Pfizer, Sanofi, Telix, and Tolmar. Travel and accommodation support from Amgen, Astellas, Bayer, Hinova, Janssen, Merck Serono, Novartis, Pfizer, and Tolmar. Research funding from Aptevo Therapeutics (institutional), Astellas (investigator), Astellas (institutional), AstraZeneca (institutional), AstraZeneca (investigator), Bayer (institutional), Bionomics (institutional), Bristol Myers Squibb (institutional), Eli Lilly (institutional), Exelixis (institutional), Gilead Sciences (institutional), GlaxoSmithKline (institutional), Hinova (institutional), Ipsen (institutional), Janssen (institutional), MedImmune (institutional), Merck Serono (investigator), Merck Serono (institutional), Merck Sharpe Dohme (institutional), Novartis (institutional), Pfizer (institutional), Sanofi (institutional), and SYNthorx (institutional). Member of steering committee for AstraZeneca, Arvinas, Astellas, Exelixis, Janssen, Pfizer, and Merck Sharpe Dohme.
- There are many challenges for institutions to do HRR testing. The first one is actually reminding physicians to actually do the testing or to refer patients for testing. But once that's done, there are still other challenges, coordinating the sample collection and processing for testing, sending the samples off, and then getting the testing results back and then incorporating those into the patient workflow. So, there are many challenges, but the first challenge actually is for the physicians to actually remember to do the testing in the first place. So, I think once upon a time, there was HRR testing and molecular testing for patients with cancer, was something that was very much reserved for academic and metropolitan centres. But really now that is no longer the case in in many countries, and that's because molecular testing, if we think even beyond HRR testing for prostate cancer patients, just molecular testing for patients with cancer is really standard of care for many different cancers. And so, really to be able to deliver best care for patients, whether they're in an academic, metropolitan, or in a community or regional setting, we really need to be able to access molecular testing, and that includes HRR testing for prostate cancer patients. And so, I think increasingly, we're seeing that both academic and community centres, both in metropolitan and regional areas, can access HRR testing. And so, this is very important because all patients need access to this information. And I don't think this is as much of a barrier as it once was. I still think the biggest challenge is actually getting people to do the testing. It would be wonderful if we actually had reflex testing where patient gets a diagnosis of metastatic prostate cancer, for example, and just automatically had molecular testing, including HRR testing done. But in most systems around the world, that's not the case. It still relies on the physician to actually do the testing. And it may seem like not a big barrier, but in busy clinics with many patients in the clinic and time pressures, it's easy to forget. And I think part of the challenge also in prostate cancer is that we haven't really incorporated previously a lot of molecular and HRR testing on patients. In some other cancers, that's been more common as they've been targeted therapies in the clinic for longer than in prostate cancer. It's only really been emergence of PARP inhibitors in prostate cancer in recent years that has spurred the HRR testing to be done. And so, I think it's also some of it is just physicians remembering, as they see more and more patients with prostate cancer, remembering to do that testing. And as we get more personalised therapies coming through in prostate cancer, I do feel like physicians will get better at remembering that. There's no doubt that funding and reimbursement is critical. I would say that HRR testing and molecular testing in general for patients with cancer, as the technology has improved, the prices come down, and it is more cost-effective than it once was, but there's no doubt that it's still expensive and needs funding. And there are different models in some countries that's funded through patients' private insurance. In other countries, it's done through a single-payer government-funded testing. And there are other countries in the world where, you know, it just isn't available. It's only really accessible to patients who have the resources to actually pay for it. And so, there's no doubt that funding and reimbursement is a challenge. And when these tests are funded, either through patient's insurance or through single-payer government-funded system, there's no doubt that we've seen that the uptake of molecular testing, including HRR testing for prostate cancer goes up. And there's no doubt that training for physicians and across disciplines and doctors in general is really important to get HRR testing done. We often focus a lot of that attention on medical oncologists who manage a lot of patients with metastatic cancers, if you think about molecular testing for patients with cancer. And so, there's no doubt that educating medical oncologists is really important, particularly those who perhaps treat many cancers and not just focusing on prostate or urological cancers, but treat many cancers and making them aware of the fact that there are PARP inhibitors in the clinic and these are available for patients with HRR and or BRCA mutations. But at the same time, prostate cancer is interesting because there are other disciplines involved in the management of prostate cancer patients. And in many countries, urologists actually manage patients with advanced prostate cancer right throughout the patient's journey, and so they need to be educated. Radiation oncologists and even nuclear medicine physicians, you know, using theranostic treatments are also increasingly involved in the care of patients with prostate cancer. So, it's really imperative that we educate all of these craft groups, which is more of a challenge, but also is something that we must do, because all of these groups are involved in the care of patients with advanced prostate cancer. There are misconceptions about, you know, personalised therapy or precision medicine for prostate cancer patients. I think there's some therapeutic nihilism, and I don't think this is necessarily restricted to any particular craft group or specialty group, but I think some feel like PARP inhibitors have a fairly limited role in the management of advanced prostate cancer patients. Approximately 7% of patients have BRCA mutations, and these are the mutations that are most sensitive to PARP inhibitors, for example. And so, some physicians actually will say, "Oh, look, I do all this testing, and I only find a few positive results. Why should I bother doing all this testing?" Because, of course, there are other reasons to do the testing, including other mutations that may be relevant to PARP inhibitors or other therapies. So, I think there is some misconceptions there around the potential benefit of PARP inhibitors, but also increasingly other personalised medicine therapies. And so, it's really important that we educate all of the craft groups again about this, that you know, PARP inhibitors can only be given in patients who have a BRCA or HRR mutation, and they can only be found if you do the testing. So, we're denying patients, some patients at least, the opportunity to have another therapy that could extend their life and improve their quality of life if we don't do the testing. So, education is critical to help overcome those misconceptions. Yeah, education is at all facets. I mean, understanding the data, understanding the importance of testing, yes, and actually doing the testing. There are often misconceptions around, for example, what's the difference between somatic and germline mutations in the HRR genes. Of course, somatic mutations are ones which are in the tumour only, and germline mutations are ones which are in the patient's own DNA. And there's many misconceptions around that. For example, so patients will sometimes... So, a common scenario, for example, is that patients don't have any tumour tissue available and they won't then get any HRR testing done, but actually, you can do germline testing on a patient's blood sample, which is very easy to obtain. And 50% of HRR mutations can actually be found in the germline, so patients' own DNA. So, that's just one example of how when you're implementing this in the real-world setting, you know, the misconceptions or lack of knowledge about these mutations and how they can be identified can actually be a barrier to testing and, again, identifying mutations. Well, yeah, I think anecdotally anyway, a feeling would be that sometimes patients who are older, you know, will not get testing done because there's a perception that, "Oh, you know, HRR mutations and, in particular, BRCA mutations are more likely to be found in younger patients, so why bother? Why bother testing?" And that's actually not the case. Age is not a... You know, older patients can also be identified with these HRR alterations. And, you know, as part of that misconception also is that, "Well, older patients won't be able to tolerate a PARP inhibitor, so why would we do the testing?" But again, you know, there are many factors that come into tolerability of PARP inhibitors, and age is only one of them. So, again, I don't think that should be a reason. I think there's no doubt that with some of the complexities around trying to explain to patients why you're doing, you know, molecular testing, HRR testing in prostate cancer patients, that some patients from, culturally and linguistically, you know, diverse sort of groups may be less likely to get testing 'cause it's just harder to explain these things sometimes to patients if, you know, their primary language is not the one that's spoken most commonly in the country that they live in. And I think that, you know, historically as well, there's probably also been patients, you know, in regional and perhaps more likely very remote, you know, settings who live a long way from major centres and even, you know, major regional centres who have probably missed out on molecular testing as well for prostate cancer patients. So, I think those are some of the groups that have historically missed out, and we clearly need to do better to make sure that they're all included and get their HRR testing done. It's always a challenge, isn't it, to understand how you can improve access to care with some of these groups of disadvantaged for whatever reason. Again, you know, I think that it's about having no preconceptions and just understanding that patients, even if they're older and whatever their cultural and linguistic background, wherever they live, you know, they have prostate cancer and they need to be tested. And so, I think that it's really just putting aside, you know, those perhaps preconceptions about, "Well, this patient's not gonna have a mutation." Or, "This patient wouldn't understand why I'm doing the testing." Or, "This patient wouldn't be able to tolerate a PARP inhibitor." You know, it's about putting that aside, actually doing the testing. You know, another key aspect of testing of course is if you pick up HRR, you know, mutations, some of them are hereditary, and then you have implications for not just the patient, but the family as well. So, even if you think the patient's sitting in front of you won't be able to tolerate a PARP inhibitor or may not be suitable for more systemic treatment, testing them is still important because it may have major implications for their family. So, that's even another reason why it's so important to test all groups, including some of these ones which perhaps historically have been underrepresented in HRR testing. Yeah, there are obviously many strategies to sort of improve HRR testing. I think, you know, key one, and I'm speaking from my experience in Australia here, was really getting government funding for BRCA and HRR testing to be done, really, BRCA testing to PARP inhibitors. And so, you know, without that push from physicians and patient advocacy groups and consumers and others to actually push the government to actually fund this, it wouldn't have happened. Of course, that can only happen if you actually have clinical trials that show that there's a reason to do the testing. So, you know, linked, you know, in this case, you know, finding a BRCA or an HRR alteration lets patients with prostate cancer have a PARP inhibitor. So, you have to do the clinical trials to actually show there's a benefit there. And that can only happen there, you know, through industry and the pharmaceutical industry specifically, as well as, you know, biotechnology companies that are doing the genomic testing. So, all of these groups are critical to actually making this happen and actually getting HRR testing being used, you know, being available, and then also being implemented in a widespread way in the real-world setting. There are emerging innovations. I think for the first thing I would say is that the technology just for doing testing on tumour tissue has really improved and is much more sophisticated and efficient now. And so, we're, once upon a time, where you may have only had, you know, a certain amount of funding from an insurance company or from a single-payer system to actually do just BRCA testing for HRR. Now for that same cost, you know, typically, you're able to run panels of 70 or 80 genes now looking at many different, you know, genes, some of which will actually be linked to probably future personalised therapies, so that'll be in addition to PARP inhibitors, which are linked to BRCA and HRR mutations. So, that's one aspect. The other aspect I think is circulating tumour DNA, or ctDNA, which is essentially like a liquid biopsy, so you take a blood sample, and it can do the same HRR and molecular testing of that. And it's pretty much almost as good really now as tumour tissue, if not as good. And so, that is really easy to use because it's literally, patient rolls up their sleeve, you a take a blood draw and can do the testing. You don't have to chase tumour tissue up or get a fresh biopsy. So, I think you'll see in coming years for HRR testing and prostate cancer that ctDNA testing will be used in a widespread fashion. In terms of advocacy, yes, there is definitely a role for advocacy, and I think this comes in different ways. I mean clearly, patients and patient representatives and consumers are critical, physicians as well, but there's also no doubt that, you know, the pharmaceutical industry has a key role here. And, you know, people might say it's self-interest, but again, if they don't do the clinical trials that show that HRR testing allows use of PARP inhibitors, improves outcomes for prostate cancer patients, you know, then we're not gonna actually get these tests and these drugs into the clinic. So, all of these groups, you know, are critical in terms of advocating for access to testing and have a key role to play. Yeah, I think the list, you know, would be probably number one, two, and three would be education, you know. And as part of education, you know, I think a lot of us know about these tests and know the benefit, but it's really about remembering to do the testing. And that's where education is just a reminder, you know, to actually do that testing. So, I think education is the absolute priority because if I look at a country like Australia, the testing is available. And, you know, the reason that testing is not being done as much as possible is that physicians are just forgetting in busy clinics. And so, I think that education is critical, not just for medical oncologists, but actually for other groups, so, you know, other specialty groups, urologists and radiation oncologists, nuclear medicine physicians, I think increasingly prostate cancer nurse, you know, specialists are increasingly part of our practise in Australia, but I think in many other countries. And they're fantastic for remembering these sorts of things because sometimes they're not caught up in the really busy, you know, clinics where you're, you know, trying to get through and manage sick patients. They have a bit more time to actually spend and go through, you know, checklist of topics and issues as well. So, I think they have a key role as well. So, I think it's about education, and it's not because people don't know this, it's about reminding them and reinforcing it so that eventually, it just becomes part of your normal workflow for prostate cancer patients. So, I think it's education, education. Education is the absolute key.
Arun Azad, MBBS, FRACP, PhD