PROCLAIM Study Reveals Impact of Germline Genetic Testing on Prostate Cancer Clinical Decisions - Neal Shore

November 15, 2022

Neal Shore shares insights from his presentation about the PROCLAIM trial - a study examining the impact of germline genetic testing on prostate cancer clinical decisions. Dr. Shore underscores the importance of expanding testing beyond traditional criteria, given the prevalence of pathogenic germline variants among both qualifying and non-qualifying patients under NCCN criteria. Notably, the trial's inclusivity extended to racially diverse cohorts, with 21% of participants identifying as non-white. This highlighted disparities in the understanding of genetic variants across different races, especially for non-white populations, underscoring the need for further genetic research and understanding in these communities. Ultimately, the study found that the results from genetic testing significantly impacted clinical utilization, follow-up criteria, and recommendations for cascade family testing, shaping future clinician decision-making. Despite limitations and challenges, Dr. Shore advocates for democratizing access to universal germline testing, while stressing the urgency of overcoming inequity and disparity in genetic testing.


Neal D. Shore, MD, FACS is the Medical Director for the Carolina Urologic Research Center. He practices with Atlantic Urology Clinics in Myrtle Beach, South Carolina

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts

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Alicia Morgans: Hi, I'm so excited to be talking with Dr. Neal Shore about an ASCO 2022 presentation that he gave on the PROCLAIM trial. Neal, can you tell us a little bit about this study?

Neal Shore: Yeah. So honored to tell you about it on behalf of my co-authors. Our oral presentation at ASCO 2022 this year was entitled Democratizing Germline Genetic Testing and its Impact on Prostate Cancer Clinical Decision-Making. We had presented, in 2021 at a podium presentation, on this regarding our findings of 1,000 patient trial of patients who were in NCCN and outside NCCN criteria, and I'm going to get to that in a second.

We know that 10-17% of patients have a pathogenic germline variant when they're newly diagnosed, you'll pick up another 50% in the castration-resistant disease category. But when we started this study in the end of 2019, there was really very limited real-world documentation about post germline genetic testing and what were community clinicians doing with that information.

So, we designed our study called the PROCLAIM, 15 community and academic U.S. urology sites, and by design, we wanted to make sure that about 50% of the patients we included would've met the NCCN criteria and that 50% did not meet the criteria. So we called it in criteria, out of criteria. We used an 84 gene panel, and really what was pretty cool, Alicia, was that 21% of our 1,000 patients study were in patients who identified as non-white. So going with that important theme of trying to overcome inequity and disparity, we were proud of that finding.

Ultimately, what we found in looking at the 2019 NCCN criteria, 50% of the patients that had a PGV met the criteria and 50% of the patients who had a pathogenic variant didn't meet the criteria. Of the 10% total who had a PGV, a pathogenic variant, 12% were white and 5% were non-white. Now, interestingly, the obverse, 44% of the white population had variants of uncertain significance compared to about 70% of the non-white that had variants of uncertain significance. I think that speaks to the fact that so much of our genetic testing and interrogation has been normalized for the white population, North American, and European. And so we need to do a better job of looking at the non-white populations. Four out of the five top PGVs we found were in DDRs, or DNA damage repair alterations.

When we asked the clinicians what was the impact of these results, it was statistically significant the amount of change in follow up criteria, clinical utilization, and a very important aspect of recommending cascade family testing. So we felt incredibly proud of this. And these were in community and academic sites that were largely not doing germline testing at all. There's still a lot of education that needs to be performed. Some patients were getting recommendations because of their VUS findings, which that needs to be better educated upon as we recognize that we can't make clinical utility decisions based upon that. But nonetheless, that was a finding. There are always limitations to a study. The fact that this was community-based, maybe we would've seen different results in oncologic practices or academic practices. But nonetheless, 27% of the clinicians told us that they thought that these findings would influence their decisions and patients going forward.

So ultimately, at the end of the day, our recommendation in this study was to try and encourage the democratization for universal testing with any patient diagnosed. NCCN still says if you're grade group 1 and 2 and you don't have a significant first or second degree family relative of a malignancy, breast, ovarian, colorectal, prostate, you should not get the germline testing. But my experience, and I think others would correlate this is, so often that family history is so unreliable by the patient and even their caregiver. The caveat to all of this is we want to make this accessible to get the test, whether it's blood-based, germline, or saliva-based, but of course, cost is always an issue as well.

Alicia Morgans: I love this work, and really, to your point, congratulate you on having such a high proportion of non-white participants engaging in this. I wonder about the UVS information that you have and are there concrete steps that we can take to try to improve our germline testing in non-white populations to try to really characterize these variants so that we know which are benign and which are pathogenic.

Neal Shore: Yeah, it's such an important question. There's even a higher likelihood when you're doing liquid-based testing and somatic of getting CHIPs, clonal hematopoiesis, in the non-white population even more so. So, yeah, it's so important. We need to be really putting our efforts towards where these patients are. At least in the U.S., the demographics are changing. Hopefully we'll continue to see a free-flow of immigration into the country, and that creates for greater diversity. And we find sometimes that will be here, for example, in some populations, 17% positive germline, we'll find other populations that may be as low as 7% from newly diagnosed. On the flip side with somatic testing, we'll see upwards of 30% somatic-positive findings for homologous recombinant repair alterations. Sometimes it's 20% depending upon your population.

But it's largely been done in the Caucasian community, so I think we need to do a much better job of going where the patients are and helping them get access to Black, Latino, and not just African American, but Afro-Caribbean, African African. I know ASCO has made this a very important initiative for them, I know the work of our colleagues, Silke Gillessen and Aurelius Omlin at APCCC, it's a big, important initiative for them as well. And you and I have talked about this, and I think this is how we'll enhance global healthcare.

Alicia Morgans: Well, I could not agree more and I look forward to our community continuing to engage patients all around the world to try to better characterize these variants and really inform the practices that we have and achieve the outcomes that we aspire to for our patients. Thank you so much for doing this work, congratulations again, and I, as always, appreciate your time and your expertise.

Neal Shore: Thank you so much, Alicia.