PURPOSE Guidelines for prostate cancer (PCA) germline testing (GT) have expanded, with impact on clinical management and hereditary cancer assessment. African American (AA) men have lower engagement in GT, with concern for widening disparities in genetically informed care. We evaluated the germline spectrum in a cohort of men with PCA enriched for AA men who underwent GT to inform tailored genetic evaluation strategies. METHODS Participants included AA and White men with PCA tested with a 14-gene PCA panel: ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, and TP53. Germline analysis was performed per standard clinical testing and variant classification protocols. Data were compared with Fisher's exact, chi-squared, or two sample t-tests, as appropriate. Multivariable analysis was conducted using Akaike's Information Criterion. The significance level was set a priori at .05. RESULTS The data set included 427 men all tested using the 14-gene PCA panel: AA (n = 237, 56%) and White (n = 190, 44%). Overall, the pathogenic/likely pathogenic (P/LP) variant rate was 8.2%, with AA men having lower rates of P/LP variants then White men (5.91% v 11.05%, respectively; P = .05). Borderline associations with P/LP variant status were observed by race (AA v White; odds ratio = 0.51; P = .07) and age (> 50 v ≤ 50 years; odds ratio = 0.48; P = .06). The P/LP spectrum was narrower in AA men ( BRCA2, PALB2, ATM, and BRCA1) than White men ( BRCA2, ATM, HOXB13, CHEK2, TP53, and NBN). A significant difference was noted in rates of variants of uncertain significance (VUSs) between AA men and White men overall (25.32% v 16.32%; P = .02) and for carrying multiple VUSs (5.1% v 0.53%, P = .008). CONCLUSION Germline evaluation in a cohort enriched for AA men highlights the narrower spectrum of germline contribution to PCA with significantly higher rates of multiple VUSs in DNA repair genes. These results underscore the imperative to engage AA men in GT, the need for larger panel testing in AA men, and the necessity to incorporate novel genomic technologies to clarify VUS to discern the germline contribution to PCA. Furthermore, tailored genetic counseling for AA men is important to ensure understanding of VUS and promote equitable genetics care delivery.
10595 Background: Indications for prostate cancer (PCA) germline testing (GT) have greatly expanded, necessitating thousands of men to seek genetic evaluation through traditional genetic counseling and alternate delivery approaches. Therefore, there is an important need for patient-reported outcomes among men undergoing genetic testing which has been understudied. PROGRESS (Prostate Cancer Genetic Risk, Experience, and Support Study) was therefore developed to garner men’s experience with PCA germline testing. Here we provide an interim update on recruitment and results from registry participants. Methods: PROGRESS is a patient-driven registry of clinical, genetic, and patient-experience information among men undergoing PCA genetic testing. Survey covers demographic information, PCA history, mode of genetic counseling, satisfaction, decisional conflict, intention to share genetic results with family and physicians, attitude towards genetic testing, knowledge of cancer genetics, medical literacy, and numeracy. Descriptive statistics summarized results with counts and percentages for categorical variables and mean and standard deviation for continuous variables. All analyses were performed with SAS 9.4 (Cary, NC). Results: Current enrollment is 217 participants. Among 140 men with complete demographics, 93.57% are White, 98.6% non-Hispanic/Latino, 85% with bachelor’s degree or higher. Among 143 respondents, 60% reported a diagnosis of PCA. Among 85 men who reported on Gleason score, 24.7% had Gleason > = 8. Regarding family history, 23.5% reported a 1st/2nd degree relative with PCA and 58.1% reported a 1st/2nd degree relative with any cancer. Among 150 men who reported genetic results, 40.7% had a genetic mutation, 18% reported having a VUS, and 10.7% reported not knowing their results. Among 185 men who reported on mode of genetic evaluation, 58.4% met with a genetics professional and 21.7% reported their doctor had discussed genetic testing. Satisfaction was high (n = 121) (highest score 30; mean score 27.92 + 2.73) and decisional conflict was low (n = 138) (mean score 26.07 + 10.18; range 16-80). Majority of 140 respondents discussed their results with their family (93.6%). Knowledge of cancer genetics was modest, with correct responses among 140 respondents of 50.1% + 28.1. Conclusions: Current participants of the PROGRESS Registry report high satisfaction with their genetic evaluation process. However, resources are needed to increase knowledge and understanding of genetic results. Greater engagement of African American males is critically needed to garner diverse perspectives and develop resources for men and their families applicable across populations. Target goal of the registry is 500 males; men can be referred to participate in the PROGRESS Registry at www.progressregistry.com .
128 Background: Indications for prostate cancer (PCA) germline testing (GT) have greatly expanded, with genetics delivery being implemented in a variety of ways. Here we evaluate factors related to men’s experience with genetic evaluation (GE) in the PCA Genetic Risk, Experience, and Support Study – PROGRESS Registry. Methods: Men took online surveys that covered demographics, PCA history, mode of GE, and measures of patient-reported outcomes (PROs) (satisfaction [Demarco 2004] [Score 6-30; higher=greater satisfaction], decisional conflict [O’Connor 1995] [Score 16-80; higher=greater conflict], attitude re: GT [Marteau 2001] [Score 1-7; higher=perceived benefit], and knowledge of cancer genetics [Erblich 2005] [% correct of 15 questions]). Data were summarized using descriptive statistics. Multiple linear regression modeling assessed relationships between characteristics, mode of GE, and PROs. Significance level was a nominal α = 0.05 (SAS v9.4). Results: PROGRESS reached accrual goal (n=500). Characteristics (among n=414): 87.7% White, 6.0% Asian, 87.7% bachelor’s degree or higher. Among n=422, 46.9% reported PCA diagnosis. Among n=416 who reported genetic results, 27.9% had pathogenic/likely pathogenic variants (P/LPV), 14.7% had VUS, and 9.9% did not know. Mode of GE was delivered: by genetics professional (GP) (24.9% in-person,10.5% phone, 6% telehealth), by doctor (21.1%), from website (20.8%), by genetics lab (5%), and by video (10.8%). Some reported not having pretest discussion (23.7%) or not knowing (8.1%). From multiple regression models, several factors including race, mode of GE, education, and genetic results were related to PROs. Conclusions: Several factors may impact men’s experience with PCA GE, deserving further study into root causes particularly related to diverse populations and genetics care delivery models to support men and their families. [Table: see text]
10502 Background: Germline testing (GT) for prostate cancer (PCA) is central to metastatic disease management, PCA screening strategies, and hereditary cancer assessment. African American (AA) males have a higher burden of PCA, yet have lower engagement in germline testing which limits understanding of genetic contribution to PCA. Here we evaluated the germline spectrum of AA and White males with PCA undergoing clinical multigene panel testing (MGPT) to inform germline testing strategies with attention to equity. Methods: Study participants included AA men and White men with PCA who underwent a 14-gene MGPT between April 2012 - December 2020 at a clinical diagnostic laboratory (Ambry Genetics). Exclusions were men with known pathogenic variants reported in their families or who had prior genetic testing. MGPT included: ATM, BRCA1, BRCA2, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, TP53. Sanger or next generation sequencing analysis was performed per standard clinical testing protocol. Variant classification was per ACMG 5-tier system. Descriptive statistics summarized results with counts and percentages for categorical variables and mean and standard deviation for continuous variables. Data were compared with Fisher’s exact, Chi-squared, two proportion z-test, or two sample t-test, as appropriate. Significance level was set a priori at 0.05. Results: The dataset included genetic and clinical data from 427 males who had undergone MGPT: White males (n = 190; 45.5%) and AA males (n = 237; 55.5%). Mean age at diagnosis was 59 + 9.3 years. Among men whose Gleason score was indicated (72%), 47% had Gleason > = 8. Majority of men indicated having a 1st/2nd degree relative with PCA (68.97%) or 1st/2nd degree relative with any cancer (99.2%). In the entire cohort, 8.2% tested positive for a pathogenic/likely pathogenic variant; AA males (n = 14, 5.91%) and White males (n = 21, 11.05%). VUS only was reported in 21.31% of the overall cohort with a significant difference noted between AA and White males (25.32% vs. 16.32%, respectively; p = 0.0238). Mutation spectrum in AA males included: BRCA2 (n = 7), PALB2 (n = 3), ATM (n = 3), and BRCA1 (n = 1). Among White males, a wider spectrum of mutations was observed: BRCA2 (n = 6), ATM (n = 5), HOXB13 (n = 5), CHEK2 (n = 2), TP53 (n = 1), and NBN (n = 2). The proportion of AA males with multiple VUS was significantly higher than for Caucasian males (5.1% vs. 0.53%, p = 0.003). Conclusions: Clinical germline testing among AA males reveals a narrow spectrum of mutations in key DNA repair genes, with important implications for precision therapy and hereditary cancer assessment. Furthermore, AA males had significantly higher rates of multiple VUS, indicating critical need for greater inclusion of diverse populations in genetic studies to discern the pathogenic spectrum contributing to PCA aggressiveness and risk.
10598 Background: Germline genetic testing is important for prostate cancer management, clinical trial eligibility and hereditary cancer risk assessment. Despite this, genetic testing is underutilized and there is a shortage of genetic counselors. To address these gaps, we designed a webtool to provide patient-driven genetic education and conducted a randomized non-inferiority trial to compare it with traditional pre-test genetic counseling. Methods: TARGET is a multi-center randomized controlled trial comparing standard pre-test genetic counseling versus web-based genetic education (intervention) (NCT04447703). The study protocol was previously published (PMID 35710085). Briefly, patients with prostate cancer who met criteria for germline testing (based on tumor features, ancestry or family history) were randomized to pre-test genetic education through genetic counseling vs a 9-module webtool created by the study team and Prostate Cancer Foundation. The primary endpoint was non-inferiority in reducing decisional conflict between the webtool and genetic counseling by a margin of 4 (set in advance) on the validated Decision Conflict Scale. Analysis of covariance was used to compare decisional conflict between groups. All participants opting for testing received a 51-gene Invitae panel, with results delivered to the patient and their provider. Results: 346 patients with prostate cancer with a mean age of 63.7 years were randomized to genetic counseling (n=174) or web-based genetic education (n=172). Compared to baseline, there were reductions in decisional conflict in both arms following pre-test genetic education (Table). Adjusting for study site and baseline decisional conflict, the test of non-inferiority in reducing decisional conflict between arms was statistically significant (difference = -0.04, 95% CI: -∞ to 1.95, p<0.001). Overall 265 (76.6%) participants underwent genetic testing, including 146 (83.9%) in the genetic counseling and 119 (69.2%) in webtool arm, with the following results: negative (49.4%), variant of uncertain significance (35.5%) and pathogenic variant (15.1%). Conclusions: Delivery of pre-test genetic education through a webtool was non-inferior to genetic counseling in reducing decisional conflict. These results support a new standard of care for the use of patient-driven digital webtools for expanding access to pretest genetic education and informed decision-making for prostate cancer genetic testing. Clinical trial information: NCT04447703 . [Table: see text]
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