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Rashid Sayyid: Hello everyone, this is Rashid Sayyid. I'm a urological oncology fellow at the University of Toronto. And along with Zach Klaassen, assistant professor and program director at Augusta University, we'll be discussing the paper titled Racial Differences in Germline Genetic Testing for Prostate Cancer: A Systematic Review. This paper was recently published in Equity in Cancer Care.

We know that the NCCN currently recommends germline genetic testing for prostate cancer patients with a positive family history, high or very high risk disease, regional or metastatic spread, Ashkenazi Jewish ancestry, or patients who have intraductal or cribriform histology in their pathology. And we know that the genes are commonly looked at include BRCA1 and 2, ATM, CHEK2, ML1, MSH2, MSH6, and PMS6. We also know that Black patients, or African American patients, have a known higher risk disease features. As such, given these features, we would theoretically expect that such patients would undergo an increased frequency of genetic testing. We also know in this space that there are known disparities in equitable access to prompt, high-quality cancer care. And these have been associated with well-described racial disparities in clinical outcomes.

So the question is, does this same disparity in access to care translate to genetic testing in a population that should, in theory, have more frequent testing performed? And why does this even matter? And this is because we know that we now have mutation-driven treatments, for example, PARP inhibitors for BRCA1/2 and ATM mutated patients. And we also know that family members of patients with known genetic mutations can be informed about their disease risk, and as such undergo risk adapted screening measures.

And so, the study objective, the systematic review, was to evaluate whether racial ethnic disparities in germline genetic testing also exist for prostate cancer patients. And so, to accomplish this, the authors conducted a systematic review of PubMed, Web of Science, and Embase from January 1996 to May 2021. January 1996 was chosen as a starting point, given that that was the day that BRCA testing, the first available germline genetic test, was FDA approved in the United States. The authors included studies describing prostate cancer population undergoing germline genetic testing, and importantly reported the utilization rates across racial ethnic groups. Specifically, studies of men undergo somatic testing as opposed to germline testing or biomarker/proteomic testing were excluded from this analysis. And this study was limited to studies of US cohorts and included all study types, meaning RCTs, cohort studies, case control, et cetera.

As is typical with these systematic reviews, and in accordance with the PRISMA guidelines, the studies were independently extracted by multiple authors in numerous steps with independent verification performed by a third author. Furthermore, after the studies were abstracted, the studies were categorized either as reflective of routine clinical care, meaning if the tests were done to inform clinical decisions as opposed to those which were research studies where the results were only used for research purposes did not affect clinical care.

Among the research studies, these were further classified into either being racially targeted, meaning that if researchers made specific and intentional efforts to recruit patients of a specific race or if the inclusion criteria were explicitly based on race, or they were non racially targeted. And the reason that the authors made this distinction is to try to understand how these studies are performed and if there are any efforts to include these often underrepresented, marginalized populations. And at this point, I'll turn it over to Zach to discuss the remainder of the paper.

Zach Klaassen: Thanks so much, Rashid. So this is the PRISMA diagram for the study. You can see this was a comprehensive database search of 5,189 manuscripts. Ultimately 4,309 records were screened, 414 assessed for eligibility in the full text, and 91 studies were included. So, one important point is that there was several publications with the same population. So, they were able to take these 91 studies, combine them into 50 unique study populations, which ultimately made up the cohort for this analysis.

This first table looks at the racial breakdown of men receiving germline testing in the US from a research standpoint. I've highlighted, in the green box at the top, the comparator, which is the US demographic population in 2021. If we look at this, 13.4% of the population was African American, 76.3% was white, 5.9% Asian, 0.2% Native Hawaiian or Pacific Islander, 1.3% American Indian or Alaska Native, 18.5% Hispanic/Latino, and 2.4% Ashkenazi Jewish. When we look at the studies that looked at research specific testing, we see that there's actually a bit of an overrepresentation of African American men, 21.6%, a little bit of an underrepresentation of white at 64.3%, and then a bit of a underrepresentation for Hispanic/Latino at 6.5%, and slightly overrepresentation for Ashkenazi Jewish at 3.2%.

As Rashid delineated, there was untargeted and targeted research. So untargeted, we see that was about roughly the same as the US population for African American 12.7%. Slightly higher, 85.8% for white. And then, essentially underrepresented for the rest of the groups, as you can see here at 0% for majority and 0.3% for Hispanic/Latino. When we talk about the racially targeted research, this was 19 studies. By targeted, the strategies for recruitment were several, including recruitment to geographic areas, enriched for race and ethnicity of interest, targeted advertisements including letters, newspaper, radio, media, and health fairs, male-based recruitment, and recruitment at racially concentrated cultural affairs or fraternities. Looking at these studies in detail, we see that this targeted research did lead to more African Americans, 29.6%, compared to the general population, less white patients at 44.9%, appropriate compared to the US demographics for Asian at 6.3%, and slightly less than the US demographic population for Hispanic/Latino at 12.0%.

The second set of studies or populations was looking at routine clinical care, and this was only four studies. And this is where we started to see some interesting disparities. As you can see here, again, the reference being US demographics in 2021, only 7.2% in routine clinical care for African Americans, so about half of what would be expected for the US population. About the same as the US population for white at 72.6%.

Underrepresentation for Asians at 2.4%. And certainly for native Hawaiian Pacific Islanders, American Indian, and Alaska native, no representation at all at 0%. Significantly underrepresented for Hispanic/Latino at 1.8%. And slightly overrepresentation for Ashkenazi Jewish at 5.3%, with the US demographic in 2021 set at 2.4%. So, we do see some differences between whether this is research germline genetic testing or routine clinical care, particularly where it comes to underrepresented minorities.

This looks at these four populations for clinical care, a little bit more detail. We can see here that the majority of the commercial brand for testing was Invitae. Several studies with wide variation in size, 169 patients up to 3,600 patients. And we see here, the number of African American men was 16.6%, about appropriate. But then, we see down to 6.6% and 6.3% in some other studies, which is remarkably less than the US demographic population. For Caucasian men, we do see roughly similar to the US demographic in the high 60% to low 80%.

Several important discussion points from this study. This was the first systematic review showing significant racial and ethnic differences in germline genetic testing for prostate cancer in the US. And as we discussed, this differs based on whether studies were performed for research or in routine clinical care. The proportion of Black men with prostate cancer in published studies on germline genetic testing is about 22%, which is higher than the proportion of Black men in the US population at roughly 13.4%. The percentage of Asian, native Hawaiian/Pacific Islanders, American Indian, Alaska native, and Hispanic/Latino was underrepresented in both routine clinical and research populations compared to the US demographics.

Indeed, there's a significant need for community-based research within the US racially, ethnically represented populations to determine several important points. First, quantitative gaps in access to germline genetic testing as part of clinical care for prostate cancer, the qualitative barriers that lead to these gaps, and what interventions are able to successfully mitigate these gaps.

Furthermore, the reason for minority underrepresentation in clinical practice for germline genetic testing is multifold. First, there's a general mistrust of genetic and genomic testing among Black men and other historically marginalized groups in clinical settings. Importantly, provider and system-level factors are also important, as 33% of urologists do not perform germline genetic testing or make referrals to a genetic counselor. And finally, minority patients are often seen in low resource settings, are less likely to have private insurance, and more likely to be on public insurance, which all of these factors affect access to genetic testing and counseling.

In conclusion, most studies that report germline genetic testing rates by race and ethnicity are in research settings. Many of these studies use targeted recruitment methods and subsequently had a greater proportion of Black men than clinical and US population-based studies. Third, other historically marginalized populations are not well represented, and there remains a knowledge gap regarding the extent of racial disparities in the use of germline genetic testing, particularly in the clinical setting. We thank you very much for your attention. We hope you enjoyed this UroToday Journal Club discussion.