Racial Disparities In Prostate Cancer Research Articles

Investigating MRI-Associated Biological Aspects of Racial Disparities in Prostate Cancer for African American and White Men.

Understanding the characteristics of multiparametric MRI (mpMRI) in patients from different racial/ethnic backgrounds is important for reducing the observed gaps in clinical outcomes. To investigate the diagnostic performance of mpMRI and quantitative MRI parameters of prostate cancer (PCa) in African American (AA) and matched White (W) men. Retrospective. One hundred twenty-nine patients (43 AA, 86 W) with histologically proven PCa who underwent mpMRI before radical prostatectomy. 3.0 T, T2-weighted turbo spin echo imaging, a single-shot spin-echo EPI sequence diffusion-weighted imaging, and a gradient echo sequence dynamic contrast-enhanced MRI with an ultrafast 3D spoiled gradient-echo sequence. The diagnostic performance of mpMRI in AA and W men was assessed using detection rates (DRs) and positive predictive values (PPVs) in zones defined by the PI-RADS v2.1 prostate sector map. Quantitative MRI parameters, including Ktrans and ve of clinically significant (cs) PCa (Gleason score ≥ 7) tumors were compared between AA and W sub-cohorts after matching age, prostate-specific antigen (PSA), and prostate volume. Weighted Pearson's chi-square and Mann-Whitney U tests with a statistically significant level of 0.05 were used to examine differences in DR and PPV and to compare parameters between AA and matched W men, respectively. A total number of 264 PCa lesions were identified in the study cohort. The PPVs in the peripheral zone (PZ) and posterior prostate of mpMRI for csPCa lesions were significantly higher in AA men than in matched W men (87.8% vs. 68.1% in PZ, and 89.3% vs. 69.6% in posterior prostate). The Ktrans of index csPCa lesions in AA men was significantly higher than in W men (0.25 ± 0.12 vs. 0.20 ± 0.08 min-1; P < 0.01). This study demonstrated race-related differences in the diagnostic performances and quantitative MRI measures of csPCa that were not reflected in age, PSA, and prostate volume. 3 TECHNICAL EFFICACY: Stage 2.

PARP-ish: Gaps in Molecular Understanding and Clinical Trials Targeting PARP Exacerbate Racial Disparities in Prostate Cancer.

PARP is a nuclear enzyme with a major function in the DNA damage response. PARP inhibitors (PARPi) have been developed for treating tumors harboring homologous recombination repair (HRR) defects that lead to a dependency on PARP. There are currently three PARPi approved for use in advanced prostate cancer (PCa), and several others are in clinical trials for this disease. Recent clinical trial results have reported differential efficacy based on the specific PARPi utilized as well as patient race. There is a racial disparity in PCa, where African American (AA) males are twice as likely to develop and die from the disease compared to European American (EA) males. Despite the disparity, there continues to be a lack of diversity in clinical trial cohorts for PCa. In this review, PARP nuclear functions, inhibition, and clinical relevance are explored through the lens of racial differences. This review will touch on the biological variations that have been explored thus far between AA and EA males with PCa to offer rationale for investigating PARPi response in the context of race at both the basic science and the clinical development levels.

Abstract 7467: Multi-omics analysis reveals high chronic inflammation in African Americans compared to Native African Men with prostate cancer

Abstract Men of African descent have the highest prostate cancer (PCa) mortality rates in the United States and globally. Studies suggested that tumor subtypes or gene expression profiles had the greatest influence on overall racial/ethnic survival, accounting for 24% of the disparities in PCa and remains even when controlled for access to care and stage at presentation. Moreover, the tumor microenvironment plays an essential role in tumor progression, aggressiveness, therapeutic response, and patient outcomes. Additionally, the association of the genomic findings with patient ancestry and other characteristics, such as tumor biology and transcriptomic alterations, remains poorly understood. Here, we performed a multi-Omics approach (N=447) to unravel the complexity of tumor heterogeneity and understand disease progression &amp; distinct tumor biology influenced by genetic ancestry. We performed Whole Exome (Normal/tumor paired) Sequencing matched with Methyl Seq and Whole transcriptomic Sequencing for three datasets of our African, African American Men (AAM), and European Men (EAM). Additionally, we ran Spatial NanoString high-plex GeoMx-DSP at the protein and RNA levels for a total of 118 treatment-naive PCa patients (around 500 ROIs). Simultaneously, we added matched genome-wide Sequencing (whole transcriptome) for these patients. The cohort comprised 87 AAM, 3 unknown, and 28 EAM self-reported individuals. To verify the self-reported race, the genomic ancestry was qualified using genotype and Admixture analysis. To further validate differentially expressed genes at the protein level, we performed multi-plex histological staining of 40 markers to determine the spatial resolution and neighborhood clustering within the tumor and the microenvironment. In parallel, we performed scMultiOmics sequencing (scRNA &amp; scATAC-Seq) at a single-cell resolution (6000 cells/sample at 25K reads per cell) from an additional 12 patients (9 AAM &amp; 3 EAM). Our results demonstrate that patients who self-report as AAM or Nigerian are assigned to high African (&amp;gt; 70%) Ancestry with either Yoruba (Nigeria) and/or Bantu subpopulation in the Sub-Saharan area. Additionally, high African Ancestry patients are diagnosed at a younger age and show advanced pathology stages compared to patients with European Ancestry. AAM with Yoruba descent express significantly higher immune-inflammatory signatures (IFNG-signaling pathway) compared to the Nigerian-Yoruba subpopulation. Our scRNA-Seq analysis shows that AAM has myeloid cells that infiltrate within the tumor cells. The infiltrations of these cells change with age, Gleason Grade, and pathology stage. Our study provides new insight into how genetic ancestry impacts immune signatures in AAM/African and contributes to PCa racial disparities. Citation Format: Isra Elhussin, Ezra Baraban, Tamara L. Lotan, Cathy Handy Marshall, Emmanuel Antonarakis, Moray J. Campbell, Melissa Davis, Michael Dixon, Isaac Kim, Stefan Ambs, Rick Kittles, Adam B. Murphy, Clayton Yates. Multi-omics analysis reveals high chronic inflammation in African Americans compared to Native African Men with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7467.

Abstract B004: Dealing with prostate cancer racial disparity: Galeterone and next-generation galeterone analog VNPP433-3β potently inhibits proliferation of prostate cancer cells from African American patient by degrading AR and Mnk1/2

Abstract Prostate cancer incidence and mortality rates are remarkably higher in African-American (AA) men as compared to their European-American (EA) counterparts even after factoring in socio economic status. The disproportionate incidence of prostate cancer and associated mortality in African men is currently becoming more evident as Several studies have reported significant variations in genetic, molecular, epigenetic, microRNA, and cell signaling pathways in patients of Caucasian and African race. As androgen is implicated in prostate cancer progression and about 90% of the cases are Androgen-dependent, blocking androgen action is an effective strategy in treating prostate cancer. Previously, we reported that galeterone and VNPP433-3β, a next generation galeterone analog potently inhibit metastatic castration resistant prostate cancer of Caucasian origin in vitro and in vivo by degrading AR/AR-V7 and Mnk1/2. Since the prostate cancer patients of African descent express significant levels of AR and Mnk1/2, we investigated the efficacy of galeterone and VNPP433-3β in treating prostate cancer of African men. Cell proliferation assay using the cell lines MDA-PCa 2b and RC77 T/E derived from AA prostate cancer patient demonstrates that galeterone and VNPP433-3β can effectively inhibit prostate cancer of African descent at very low concentration. These cell lines are Androgen-sensitive and further biochemical studies reveal that galeterone and VNPP433-3β degrade AR and Mnk1/2 in RC77 T/E and MDA-PCa 2b cell lines, thereby inhibiting its proliferation. Galeterone and VNPP433-3β significantly decrease the half-life of AR in these cell lines by increasing the rate of ubiquitination and proteasomal degradation of AR. Therefore, galeterone and VNPP433-3β hold significant promise for the clinical management of prostate cancer in patients of African descent Citation Format: Elizabeth Thomas, Retheesh Sulochana Thankan, Puranik Purushottachar, Vincent C.O. Njar. Dealing with prostate cancer racial disparity: Galeterone and next-generation galeterone analog VNPP433-3β potently inhibits proliferation of prostate cancer cells from African American patient by degrading AR and Mnk1/2 [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B004.

Abstract B111: Population genetics identifies distinct subsets of prostate cancer risk variants between men of European, African and East Asian ancestry

Abstract Introduction Genome-wide association studies (GWAS) have identified Single Nucleotide Polymorphisms (SNPs) or variants associated with prostate cancer risk. The contribution of human genetic variation to racial disparities in prostate cancer is still not clearly understood. Men of African ancestry have the highest risk of prostate cancer, followed by European ancestry and lowest in men with East Asian ancestry. Prostate cancer is the most common cancer in human males, but non-human large primates do not develop prostate cancer naturally. This study investigated the population genetics of prostate cancer SNPs to identify those that were unique to ancestral groups, and also comparative genomics of human risk alleles and orthologous alleles in primates. Methods Prostate cancer SNPs were obtained from previous GWAS studies in the GWAS Catalog (https://www.ebi.ac.uk/gwas/home), and the GWAS Diversity Monitor Database (https://gwasdiversitymonitor.com). SNPs identified from discovery stages in AFR and EAS populations were included even when they did not replicate in EUR populations. Using Ensemble Release 109 (https://www.ensembl.org), the risk allele frequencies (RAF) in European (EUR), African (AFR) and East Asian (EAS) populations were obtained from the 1000 Genomes project and other population genetics data available on Ensembl. Population RAFs were used to identify variants that were present in only one ancestral group and not shared by other ancestral groups. A SNP was considered unique to a population if it was present in &amp;gt;1% of that population, but present in &amp;lt;.01% of the others. The risk alleles in Homo sapiens were compared to the orthologous ancestral primate allele using genome alignments from 10 primate species. Results 520 prostate cancer-associated SNPs were identified. 484 were shared between EUR, AFR and EAS populations. 10 SNPs were unique to EUR (on chromosomes 1, 2, 5, 8, 11, 17, 21, 22), 19 to AFR (on chromosomes 1, 5, 6, 8, 13, 17, 22) and 7 to EAS (on chromosomes 2, 10, 12, 13) populations. The gene sets involved by these SNPs were different in each ancestral group, with some overlap between EUR and AFR genes sets, but no overlap with the EAS genes set. The risk allele for all the 36 SNPs that were unique to EUR, AFR or EAS populations was different from the ancestral primate allele. Conclusion Prostate cancer SNPs unique to EUR, AFR and EAS populations were identified and are likely to be driving the genetic component of prostate cancer racial disparities. The genes involved were different between populations, which could have biological consequences and lead to distinct cancer phenotypes in men from different ancestral groups. The unique SNPs all had alleles different from the ancestral primate allele, suggesting that these variants emerged after human speciation and ‘Out of Africa’ human migration events. Citation Format: Chidi N. Molokwu, Evi O. Useh, Suresh Venugopal. Population genetics identifies distinct subsets of prostate cancer risk variants between men of European, African and East Asian ancestry [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B111.

Abstract A106: Examining the role of social connection on allostatic load and quality of life in African American prostate cancer survivors

Abstract Background. Racial disparities in prostate cancer (PC) survivorship persist despite clinical advancements. Chronic stress may contribute to these disparities, with allostatic load (AL) considered a measure of such stress. Associations between AL and survivorship outcomes such as quality of life (QoL) are documented, yet less is known about factors influencing these relationships. Social connections (SC) (e.g., social networks, social support) are associated with improved QoL in survivors, yet which aspects of SC and which pathways linking SC to QoL remain unclear. Additionally, little is known about the SC of African American PC survivors (AAPCS) and how these relate to QOL, stress, and AL. This study explores the relationship between SC, stress (perceived and AL) and QOL in in 48 AAPCS enrolled in Men Moving Forward, a randomized trial to improve body composition through lifestyle change. Methods. At baseline, participants completed surveys including: the Cohen Social Network Index assessing 3 aspects of social networks: network size (# of ties with regular contact), diversity (# of roles with regular contact) and embeddedness (# of domains with 4 or more regular contacts); Patient-Reported Outcomes Measurement Information System (PROMIS) measures of social support (companionship, emotional and informational support); the perceived stress scale, and PROMIS measures of physical function, anxiety, depression, fatigue, sleep disturbance, social function, and pain intensity. The latter were used to generate summative physical (PQOL) and mental (MQOL) health standardized T-scores (U.S. population mean=50, SD=10). AL scores used 15 criterion reflecting neuroendocrine, cardiovascular, immune, and metabolic systems. Each criterion was assigned a score of 0 or 1: 1 if in the high-risk range based on clinical guidelines. An index score was generated by summing high-risk indicators. Pearson correlations were used to explore the relationship between aspects of SC and QOL and SC and stress variables. Results. The average AL score was 5.8 (SD ± 2.3) of a maximum 15. No significant correlations were found between any SC domains and AL. However, negative associations were identified between network size (r=-.313, p=0.030), emotional support (r=-.319, p = 0.027), companionship (r=-.313, p=0.030) and perceived stress. A positive association was found between loneliness and perceived stress (r=.521, p&amp;lt;0.000). MQOL was positively related to network size (r=.364, p=0.011), emotional support (r=.366, p=0.011), and companionship (r=.288, p=0.047). Loneliness was negatively associated with MQOL (r=-.626, p&amp;lt;0.000) and PQOL (r=-.407, p=0.006). Conclusions. These findings suggest SC has a positive impact on survivorship in AAPCS, and that structural and functional aspects of SC may be involved. Currently, limited resources are available for PC survivors, and even fewer are tailored for AAPCS. Future efforts to improve survivorship for AAPCS should consider assessing social networks and access to social support when initiating survivorship care. Citation Format: Iwalola A. Awoyinka, Kathryn Flynn, Deepak Kilari, Kathryn Bylow, Jennifer Knight, Jamila Kwarteng, Anjishnu Banerjee, Kirsten M. Beyer, Staci Young, Patricia Sheean, Paula Papanek, Melinda Stolley. Examining the role of social connection on allostatic load and quality of life in African American prostate cancer survivors [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A106.

Abstract C086: Prostate cancer: Integrative multi-omics profiling in patients of African descent

Abstract In the United States and globally, prostate cancer (PCa) mortality rates are highest among men of African descent. Previous studies suggested that tumor subtypes or gene expression profiles had the greatest influence on overall racial/ethnic survival accounting for 24% of the disparities in PCa and remains even when controlled for access to care and stage at presentation. Moreover, the tumor microenvironment plays an essential role in tumor progression, aggressiveness, therapeutic response, and patient outcomes. Additionally, the association of the genomic findings with patient ancestry and other characteristics, such as tumor biology and transcriptomic alterations, remains poorly understood. Here we performed a multi-Omics approach to unravel the complexity of tumor heterogeneity and understand disease progression &amp; distinct tumor biology influenced by genetic ancestry. We performed Spatial NanoString high-plex GeoMx-DSP (Digital Spatial Profiler) at the protein and RNA levels for a total of 118 treatment-naive PCa patients (around 500 ROIs). Simultaneously, we ran matched genome-wide sequencing (whole transcriptome) for these patients. The cohort comprised 87 AAM, 3 unknown, and 28 EAM self-reported individuals. To verify the self-reported race, the genomic ancestry was qualified using genotype and Admixture analysis. To further validate differentially expressed genes at the protein level, we performed multi-plex histological staining of 40 markers to determine the spatial resolution and neighborhood clustering within the tumor and the microenvironment. In parallel, we performed scMultiOmics sequencing (scRNA &amp; scATAC-Seq) at a single-cell resolution (6000 cells/sample at 25K reads per cell) from an additional 12 patients (9 AAM &amp; 3 EAM). We will use the multi-omics integration method (CoGap) to build a structural, spatial map that reflects tissue/system phenotype and to understand the complementary role of multi-omics (genome, transcriptome, and metabolite) interrelation/influence on the disease processes. Our results demonstrate that patients who self-report as AAM or Nigerian are assigned to high African (&amp;gt; 70%) Ancestry with either Yoruba (Nigeria) and/or Bantu subpopulation in the Sub-Saharan area. Additionally, high African Ancestry patients are diagnosed at a younger age and show advanced pathology stages compared to patients with European Ancestry. Moreover, AAM with high African Ancestry has significantly (p-value 0.05) higher CD8 +ve cells infiltration. Interestingly, segmentation and gating of the immune cell populations showed increased expression of CD8+ve cells colocalization with PD-1 signaling within African Ancestry patients. Our study provides new insight into how genetic ancestry impacts immune signatures in AAM and contributes to PCa racial disparities. Our findings could lead to new therapeutic strategies using immune modulators drugs to decrease the global disease burden, especially among men at high risk for PCa, such as AAM of African descent. Citation Format: Isra Elhussin, Ezra Baraban, Tamara L. Lotan, Cathy Handy Marshall, Emmanuel Antonarakis, Moray J. Campbell, Melissa Davis, Michael Dixon, Isaac Kim, Stefan Ambs, Rick Kittles, Adam B. Murphy, Clayton Yates. Prostate cancer: Integrative multi-omics profiling in patients of African descent [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C086.

Survival Outcomes by Race and Ethnicity in Veterans With Nonmetastatic Castration-Resistant Prostate Cancer

Racial and ethnic disparities in prostate cancer are poorly understood. A given disparity-related factor may affect outcomes differently at each point along the highly variable trajectory of the disease. To examine clinical outcomes by race and ethnicity in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) within the US Veterans Health Administration. A retrospective, observational cohort study using electronic health care records (January 1, 2006, to December 31, 2021) in a nationwide equal-access health care system was conducted. Mean (SD) follow-up time was 4.3 (3.3) years. Patients included in the analysis were diagnosed with prostate cancer from January 1, 2006, to December 30, 2020, that progressed to nmCRPC defined by (1) increasing prostate-specific antigen levels, (2) ongoing androgen deprivation, and (3) no evidence of metastatic disease. Patients with metastatic disease or death within the landmark period (3 months after the first nmCRPC evidence) were excluded. The primary outcome was time from the landmark period to death or metastasis; the secondary outcome was overall survival. A multivariate Cox proportional hazards model, Kaplan-Meier estimates, and adjusted survival curves were used to evaluate outcome differences by race and ethnicity. Of 12 992 patients in the cohort, 826 patients identified as Hispanic (6%), 3671 as non-Hispanic Black (28%; henceforth Black), 7323 as non-Hispanic White (56%; henceforth White), and 1172 of other race and ethnicity (9%; henceforth other, including American Indian or Alaska Native, Asian, Native Hawaiian or Other Pacific Islander, unknown by patient, and patient declined to answer). Median time elapsed from nmCRPC to metastasis or death was 5.96 (95% CI, 5.58-6.34) years for Black patients, 5.62 (95% CI, 5.11-6.67) years for Hispanic patients, 4.11 (95% CI, 3.96-4.25) years for White patients, and 3.59 (95% CI, 3.23-3.97) years for other patients. Median unadjusted overall survival was 6.26 (95% CI, 6.03-6.46) years among all patients, 8.36 (95% CI, 8.0-8.8) years for Black patients, 8.56 (95% CI, 7.3-9.7) years for Hispanic patients, 5.48 (95% CI, 5.2-5.7) years for White patients, and 4.48 (95% CI, 4.1-5.0) years for other patients. The findings of this cohort study of patients with nmCRPC suggest that differences in outcomes by race and ethnicity exist; in addition, Black and Hispanic men may have considerably improved outcomes when treated in an equal-access setting.

Exploring the Association Between Online Health Information and Racial Disparities in Prostate Cancer

Exploring the Association Between Online Health Information and Racial Disparities in Prostate Cancer

Deregulated microRNAs Involved in Prostate Cancer Aggressiveness and Treatment Resistance Mechanisms.

Prostate cancer (PCa) is the most frequently diagnosed cancer and the second leading cause of cancer deaths among American men. Complex genetic and epigenetic mechanisms are involved in the development and progression of PCa. MicroRNAs (miRNAs) are short noncoding RNAs that regulate protein expression at the post-transcriptional level by targeting mRNAs for degradation or inhibiting protein translation. In the past two decades, the field of miRNA research has rapidly expanded, and emerging evidence has revealed miRNA dysfunction to be an important epigenetic mechanism underlying a wide range of diseases, including cancers. This review article focuses on understanding the functional roles and molecular mechanisms of deregulated miRNAs in PCa aggressiveness and drug resistance based on the existing literature. Specifically, the miRNAs differentially expressed (upregulated or downregulated) in PCa vs. normal tissues, advanced vs. low-grade PCa, and treatment-responsive vs. non-responsive PCa are discussed. In particular, the oncogenic and tumor-suppressive miRNAs involved in the regulation of (1) the synthesis of the androgen receptor (AR) and its AR-V7 splice variant, (2) PTEN expression and PTEN-mediated signaling, (3) RNA splicing mechanisms, (4) chemo- and hormone-therapy resistance, and (5) racial disparities in PCa are discussed and summarized. We further provide an overview of the current advances and challenges of miRNA-based biomarkers and therapeutics in clinical practice for PCa diagnosis/prognosis and treatment.

Abstract B036: Immune cell profiling of human prostate tumors identifies a protective and pathological role for intratumoral mast cells in the development of biochemical recurrence and metastasis

Abstract Background: Immunobiological factors may, in part, contribute to racial disparities in prostate cancer (PCa), the second leading cause of cancer-related death for US men. African American (AA) men face a greater risk of developing PCa and having a poorer outcome of this disease, compared to Caucasian American (CA) men. The goal of this study is to identify immune-specific differences influencing PCa health disparity as well as PCa progression. Methods: Ex vivo tumor biopsies were obtained following radical prostatectomy (RP) from 51 treatment-naïve patients (26 AA, 25 CA) under approved IRB protocols. Total RNA from fresh frozen tissue was isolated and amplified by PCR using NanoString multiplexed target enrichment protocols. We evaluated differences in resulting transcripts by self-reported race, pathology, and other clinical and pathologic features. Relative abundances of immune cell subsets were determined using computational methods, including previously published deconvolution algorithms, to estimate cellular content. Results: We identified differentially expressed genes between AA and CA tumors that are characterized by genes regulating Natural Killer (NK) cell function and Wnt signaling cancer pathways. Among the entire cohort, high expression of two of these differentially expressed genes, DVL2 and MAP3K5, were associated with worse biochemical recurrence (BCR)-free and metastasis-free survival. No difference in immune cell abundance was observed by self-reported race. Strikingly, among the entire cohort, low abundance of intratumoral mast cells was also associated with worse PCa pathology and poorer BCR-free and metastasis-free survival. Conclusions: Using a race-matched military cohort, we found that AA and CA tumors differ in the expression levels of Wnt and NK signaling-related pathways, yet cellular estimations of immune abundance did not significantly differ. Remarkably, the level of mast cell abundance within tumors at time of RP may be protective and prolong BCR-free and metastasis-free survival of patients. These types of in-depth immune profiling assessments have the potential to guide precision medicine and treatment decisions in the clinic. Disclaimer: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions or policies of Uniformed Services University of the Health Sciences (USUHS), The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense (DoD), the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. Citation Format: Cara Schafer, Jiji Jiang, Sally Elsamanoudi, Darryl Nousome, Denise Young, Yingjie Song, Isabell Sesterhenn, Gregory Chesnut, Shyh-Han Tan. Immune cell profiling of human prostate tumors identifies a protective and pathological role for intratumoral mast cells in the development of biochemical recurrence and metastasis [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B036.

Racial differences in the utilization of MRI-guided biopsy before prostate cancer diagnosis.

5093 Background: Most low-risk prostate cancer (PCa) patients undergo active surveillance (AS). Compared with Whites, Blacks are more likely to opt for AS and suffer a higher risk of cancer progression while on AS. A primary concern of AS is the likelihood of missing clinically significant cancer. Transrectal ultrasound-guided biopsy is the most common method for diagnosing and grading PCa; however, this method often misses anterior PCa. Magnetic resonance imaging (MRI) allows clinicians to identify better and detect PCa; however, current guidelines on MRI-guided biopsy (MRI-GB) are inconsistent. This population-based study aimed to examine the utilization of MRI-GB 6 months before PCA diagnosis over time by race in the US. Methods: We used SEER-Medicare data to identify men diagnosed with PCa between January 1, 2012, to December 31, 2017, and excluded patients missing the date of diagnosis, being diagnosed at death, enrolled in HMO, or having no continuous A and B coverage six months before diagnosis. We used the CPT codes to identify prostate biopsy and MRI use. Multivariable logistic regression was used to evaluate racial disparity in MRI use six months before PCa. The model included covariates age, race, SEER region, marital status, state buy-in for Medicare (a poverty indicator), education, income, Charlson comorbidity index, and procedure (MRI) year. Results: Among 38,612 eligible men, MRI use six months before PCa diagnosis increased from 2012 to 2017 (3.2% to 24.3% among Whites, 1.8% to 14.2% among Blacks). Compared with Whites, Blacks were 38% less likely to receive pre-diagnosis MRI (OR=0.62, 95% CI 0.52-0.74). Besides race, having state buy-in for Medicare (OR=0.44; 95% CI 0.30-0.65) and geographic regions (Central vs. West OR=0.40; 95% CI 0.34-0.45) were strong predictors of lower utilization of MRI. Conclusions: The gap in the utilization of MRI may exacerbate racial disparities in PCa. Future studies are needed to identify potential barriers to adopting MRI for PCa workups.

Effect of type of definitive treatment on race-based differences in prostate cancer-specific survival.

Racial and ethnic disparities in prostate cancer (PCa)mortality are partially mediated by inequities in quality of care. Intermediate- and high-risk PCa can be treated with either surgery or radiation, therefore we designed a study to assess the magnitude of race-based differences in cancer-specific survival between these two treatment modalities. Non-HispanicBlack (NHB)and non-HispanicWhite (NHW)men with localized intermediate- and high-risk PCa, treated with surgery or radiation between 2004 and 2015 in the Surveillance, Epidemiologyand End Results database were included in the study and followed until December 2018. Unadjusted and adjusted survival analyses were employed to compare cancer-specific survival by race and treatment modality. A model with an interaction term between race and treatment was used to assess whether the type of treatment amplified or attenuated the effect of race/ethnicity on prostate cancer-specific mortality (PCSM). 15,178 (20.1%) NHB and 60,225 (79.9%) NHW men were included in the study. NHB men had a higher cumulative incidence of PCSM (p = 0.005) and were significantly more likely to be treated with radiation than NHW men (aOR: 1.89, 95% CI: 1.81-1.97,p < 0.001). In the adjusted models, NHB men were significantly more likely to die from PCa compared withNHW men (aHR: 1.18,95% CI:1.03-1.35, p = 0.014), and radiation was associated with a significantly higher odds of PCSM (aHR: 2.10,95% CI:1.85-2.38, p < 0.001) compared with surgery. Finally, the interaction between race and treatment on PCSM was not significant, meaning that no race-based differences in PCSM were found within each treatment modality. NHB men with intermediate- and high-risk PCa had a higher rate of PCSM than NWH men in a large national cancer registry, though NHB and NHW men managed with the same treatment achieved similar PCa survival outcomes. The higher tendency for NHB men to receive radiation was similar in magnitude to the difference in cancer survival between racial and ethnic groups.

Access to definitive treatment and survival for intermediate-risk and high-risk prostate cancer at hospital systems serving health disparity populations.

Although socioeconomic and racial disparities in prostate cancer (CaP) have been attributed to patient-level and physician-level factors, there is growing interest in investigating the role of the facility of care in driving cancer disparities. We sought to examine the receipt of guideline-concordant definitive treatment, time to treatment initiation (TTI), and overall survival (OS) for men with CaP receiving care at hospital systems serving health disparity populations (HSDPs). We retrospective analyzed the National Cancer Database (2004-2016). We identified men with intermediate-risk or high-risk CaP eligible for definitive treatment. The primary outcomes were receipt of definitive treatment and TTI within 90 days of diagnosis. The secondary outcome was OS. We defined HSDPs as minority-serving hospitals-facilities in the highest decile of proportion of non-Hispanic Black (NHB) or Hispanic cancer patients-and/or high-burden safety-net hospitals-facilities in the highest quartile of proportion of underinsured patients. We used mixed-effect models with facility-level random intercept to compare outcomes between HSDPs and non-HSDPs among the entire cohort and among men who received definitive treatment. We included 968 non-HSDPs (72.2%) and 373 HSDPs (27.8%) facilities. Treatment at HSDPs was associated with lower adjusted odds of receipt of definitive treatment (aOR 0.64; 95% CI 0.57-0.71; P < 0.001), lower odds of TTI within 90 days of diagnosis (aOR 0.74; 95% CI 0.68-0.79; P < 0.001), and worse OS (aHR 1.05; 95% CI 1.02-1.09; P = .003) when accounting for covariates. However, no difference was found in OS if patients received definitive treatment (aHR 1.03; 95% CI 0.99-1.07; P = 0.1). NHB men at HSDPs had worse outcomes than NHB men treated at non-HSDPs as well as NHW men treated at HSDPs. Patients treated at HSDPs were less likely to receive timely definitive treatment and had worse OS, independent of their race. NHB men have worse outcomes than NHW at HSDPs. Thus, NHB men with CaP are doubly disadvantaged since they are more likely to be treated at hospitals with worse outcomes and have worse outcomes than other patients at those same institutions.

Disparities in prostate cancer

Despite substantial advances in early detection/prevention and treatments, and improved outcomes in recent decades, prostate cancer continues to disproportionately affect Black men and is the secondleading cause of cancer death in this subgroup. Black men are substantially more likely to develop prostate cancer and are twice as likely to die from the disease compared with White men. In addition, Black men are younger at diagnosis and face a higher risk of aggressive disease relative to White men. Striking racial disparities endure along the continuum of prostate cancer care, including screening, genomic testing, diagnostic procedures, and treatment modalities. The underlying causes of these inequalities are complex and multifactorial and involve biological factors, structural determinants of equity (i.e., public policy, structural and systemic racism, economic policy), social determinants of health (including income, education, and insurance status, neighborhood/physical environment, community/social context, and geography), and health care factors. The objective of this article is to review the sources of racial disparities in prostate cancer and to propose actionable recommendations to help address these inequities and narrow the racial gap.

Differential Expression of miRNAs Contributes to Tumor Aggressiveness and Racial Disparity in African American Men with Prostate Cancer.

Prostate cancer is the leading cancer in incidence and second leading cause of cancer mortality in US men. African American men have significantly higher incidence and mortality rates from prostate cancer than European American men. Previous studies reported that the disparity in prostate cancer survival or mortality can be explained by different biological backgrounds. microRNAs (miRNAs) regulate gene expression of their cognate mRNAs in many cancers. Therefore, miRNAs may be a potentially promising diagnostic tool. The role of miRNAs in prostate cancer aggressiveness and racial disparity has not been fully established. The goal of this study is to identify miRNAs associated with aggressiveness and racial disparity in prostate cancer. Here we report miRNAs that are associated with tumor status and aggressiveness in prostate cancer using a profiling approach. Further, downregulated miRNAs in African American tissues were confirmed by qRT-PCR. These miRNAs have also been shown to negatively regulate the expression of the androgen receptor in prostate cancer cells. This report provides a novel insight into understanding tumor aggressiveness and racial disparities of prostate cancer.

Abstract 5762: New perspective on racial disparities in prostate cancer: identification of new molecular subsets using whole-mount radical prostatectomy

Abstract Introduction: Prostate cancer is a heterogenous multifocal disease. We hypothesize that different tumor foci may harbor distinct driver molecular aberrations, making it a more complex disease and difficult to manage. To avoid overlooking smaller tumor foci with clinical and biological significance, we used an innovative approach to understand the genetic underpinnings of each tumor foci based on the molecular analysis of whole-mount radical prostatectomy specimens rather than a systematic sampling of dominant nodules alone. Our study aimed to identify distinct molecular subsets of prostate cancer, if any, and correlate them with clinical outcomes in Caucasians (CA) and African Americans (AA). Method: We randomly selected 834 whole-mount radical prostatectomy tissues including 463 (56%) CA and 371 (44%) AA. We used combined dual immunohistochemistry (IHC) for ERG and SPINK1 and dual RNA in-situ hybridization (ISH) for ETV1 and ETV4. The racial disparity in aberrant oncogene expression was analyzed by the Chi-squared test. The recurrence-free survival (RFS) of patients with distinct molecular subsets of prostate cancer was examined by the Kaplan-Meier method and cox-ph models. The Gleason’s grades of prostate biopsies were summarized by spaghetti plot and compared by linear mixed models. Results: Patients with localized prostate cancer expressing none, one, two, and three of four oncogenes were 16.4%, 58.4%, 21.7%, and 3.5%, respectively. The expression of ERG and SPINK1 was negatively correlated (odds ratio (OR)=0.38, 95% CI 0.29-0.51, p&amp;lt;.001). Compared with CA, AA had a lower incidence of ERG (38.8% vs 60.3%), a higher incidence of SPINK1 (63.3% vs 35.6%), and similar incidences of ETV1 (9.4% vs 9.3%) and ETV4 (4.6% vs 3.9%). Importantly, ETV1 expression was associated with a worse RFS in CAs (hazard ratio (HR)=2.49, 95% CI 1.15-5.38, p=.02). ETV4 expression was associated with a worse RFS in AA (HR=3.11, 95% CI 1.32-8.04, p=.01). In addition, ETV4 expression was associated with lymph node metastasis in AA (OR=4.0, 95% CI 1.06-12.44, p=.02) but not in CA (OR=0.56, 95% CI 0.03-2.85, p=.57). For those who had multiple biopsies before radical prostatectomy, Gleason’s grade increased with time in AA (0.23 per year, p&amp;lt;.001) but was unchanged in CA. ERG expression was associated with a lower Gleason grade (-0.20, p=.03). ETV4 was associated with a higher Gleason grade (0.50, p=.02). Conclusion: Our findings showed the molecular heterogeneity between CA and AA who had localized prostate cancer, and supported ETV1 and ETV4 as prognostic markers that can be incorporated into clinical practice to better predict prostate cancer recurrence after radical prostatectomy in CA and AA, respectively. Citation Format: Wei Zhao, Pin Li, Shannon Carskadon, Craig Rogers, James Peabody, Mani Menon, Dhananjay Chitale, Sean Williamson, Nilesh Gupta, Nallasivam Palanisamy. New perspective on racial disparities in prostate cancer: identification of new molecular subsets using whole-mount radical prostatectomy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5762.

Abstract 6114: Race-associated base excision repair defects alter the DNA damage landscape in prostate cancer

Abstract Prostate cancer is the most diagnosed cancer among men in the United States. African American men are diagnosed with and succumb to prostate cancer at higher rates than other demographic groups. However, the biological drivers contributing to poorer outcomes in African American men compared to European American men with prostate cancer are still poorly defined. One understudied area is DNA repair defects, which drive genomic instability in cancers. Defects in homologous recombination are often at the forefront of repair defects examined and exploited for therapeutic intervention. However, defects in other DNA repair pathways may contribute to poor disease outcomes and chemoresistance. We demonstrated that defects in the base excision repair (BER) pathway contribute to chemoresistance and alter growth in breast cancer. Others have also shown chemoresistant effects from dysregulated BER protein expression in gastric, colorectal, and ovarian cancers. Examination of the TCGA database show dysregulation of key BER protein like X-ray cross complementing protein 1 (XRCC1) and DNA polymerase β (POLβ) are common across several cancers. Therefore, we decided to explore DNA damage and repair defects in prostate cancer to explore if altered DNA repair contributes to poorer outcomes in African American men. To measure DNA repair defects in formalin-fixed paraffin-embedded (FFPE) tissues, we employed a novel assay, Repair Assisted Damage Detection (RADD), which measures DNA lesions within the tissues. RADD fluorescently tags DNA lesions for quantification and is compatible with immunohistochemistry detection of DNA repair or other proteins of interest. Using the tissue microarrays, we used RADD to discover that prostate tumors from African American patients have more uracil and pyrimidine lesions, elevated uracil DNA glycosylase (UNG) levels, and reduced XRCC1 levels than European American tumors, which indicate defects in the BER pathway. In addition, these men had higher uracil monophosphate (UMP) and lower expression of folate cycle metabolites, suggesting that metabolic rewiring may also contribute to the dysregulation of BER. Defects in the BER pathway may offer new therapeutic opportunities for African American prostate cancer patients. These defects may be targeted by therapeutics which pressure the BER pathways. This work demonstrates that functional detection of DNA repair defects through RADD offers new insight into race-specific DNA repair defects offering new molecular targets or therapeutic strategies to reduce racial disparities in prostate cancer. Citation Format: Kaveri Goel, Kimiko Krieger, Manoj Sonavane, Arun Sreekumar, Natalie R. Gassman. Race-associated base excision repair defects alter the DNA damage landscape in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6114.

MP77-04 RACIAL DISPARITIES IN FUTURE DEVELOPMENT OF LETHAL PROSTATE CANCER BASED ON PSA LEVELS IN MIDLIFE

You have accessJournal of UrologyCME1 Apr 2023MP77-04 RACIAL DISPARITIES IN FUTURE DEVELOPMENT OF LETHAL PROSTATE CANCER BASED ON PSA LEVELS IN MIDLIFE Matthew Davis, Alexander Stephens, Chase Morrison, Sami Majdalany, Rafe Affas, Sohrab Arora, Nicholas Corsi, Ivan Rakic, Akshay Sood, Craig Rogers, and Firas Abdollah Matthew DavisMatthew Davis More articles by this author , Alexander StephensAlexander Stephens More articles by this author , Chase MorrisonChase Morrison More articles by this author , Sami MajdalanySami Majdalany More articles by this author , Rafe AffasRafe Affas More articles by this author , Sohrab AroraSohrab Arora More articles by this author , Nicholas CorsiNicholas Corsi More articles by this author , Ivan RakicIvan Rakic More articles by this author , Akshay SoodAkshay Sood More articles by this author , Craig RogersCraig Rogers More articles by this author , and Firas AbdollahFiras Abdollah More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous literature has examined prostate cancer (PCa) mortality in a Scandinavian population based on midlife PSA results. The aim of our study was to examine racial disparities in PCa mortality based on midlife PSA results in a North American population. METHODS: Our cohort included self-identified White and Black men aged 40-59 years, who received their first PSA through our health system between the years 1995 and 2019. Next, patients were divided into 4 categories based on age as follows: 40 to 44, 45 to 49, 50 to 54, and 55 to 59 years. First PSA testing represented the main predictor of interest, and it was categorized based on median and 90th percentile for each age category. Fine-Gray regression was used to examine the impact of the value of PSA at first testing on the risk of developing lethal PCa (i.e. PCa-specific mortality) by race after accounting for all confounders including Charlson comorbidity index among others. Cancer-specific mortality and overall mortality were obtained by linking our database to the Michigan Vital Records registry. RESULTS: A total of 112,967 men met inclusion criteria, of whom 82,084 (73%) were White and 30,883 (27%) were Black. Median and 90th percentile PSA were 0.7 and 2.0 ng/ml, respectively, in White men compared to 0.7 and 2.1 ng/ml, respectively, in Black men. For White men aged 40 to 44, 45 to 49, 50 to 54, and 55 to 59 years, median PSA was respectively 0.6, 0.7, 0.7, and 0.9 ng/ml compared to 0.6, 0.7, 0.8, and 0.9 ng/ml in Black men. The 90th percentile PSA in White men was respectively 1.3, 1.6, 2.0, and 2.8 ng/ml compared to 1.4, 1.8, 2.4, and 3.8 ng/ml in Black men. For the same age categories, the estimated rate of lethal PCa at 20 years was significantly higher in Black men when using the 90th percentile PSA cutoff (see Table 1). Median (IQR) follow-up was 6.7 (2.9 - 14.4) years for White men and 9.9 (4.4 - 16.4) years for Black men. On multivariable analysis, these findings were confirmed. CONCLUSIONS: Our findings suggest that Black men are significantly more likely to develop lethal PCa based on previously published midlife first-time PSA cutoffs. This information suggests that a lower midlife PSA cutoff could be considered amongst Black men. To the best of our knowledge, our report is the first to examine the racial disparities in lethal PCa based on first-time PSA results in a diverse North American cohort. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1102 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew Davis More articles by this author Alexander Stephens More articles by this author Chase Morrison More articles by this author Sami Majdalany More articles by this author Rafe Affas More articles by this author Sohrab Arora More articles by this author Nicholas Corsi More articles by this author Ivan Rakic More articles by this author Akshay Sood More articles by this author Craig Rogers More articles by this author Firas Abdollah More articles by this author Expand All Advertisement PDF downloadLoading ...

MP12-18 RACIAL DISPARITY IN PROSTATE CANCER DIAGNOSIS: A COMPARISON OF PROSTATE BIOPSY RESULTS IN AFRICAN AMERICAN AND WHITE MEN USING AN MRI-BASED BIOPSY STRATEGY.

You have accessJournal of UrologyCME1 Apr 2023MP12-18 RACIAL DISPARITY IN PROSTATE CANCER DIAGNOSIS: A COMPARISON OF PROSTATE BIOPSY RESULTS IN AFRICAN AMERICAN AND WHITE MEN USING AN MRI-BASED BIOPSY STRATEGY. Ali Kasraeian, Miguel Alcantara, Kaitlyn Mola Alcantara, Adam Brochert, Joshua Yellin, Eliana Namen, Sean Parsons, Jamie Cesaretti, and Ahmad Kasraeian Ali KasraeianAli Kasraeian More articles by this author , Miguel AlcantaraMiguel Alcantara More articles by this author , Kaitlyn Mola AlcantaraKaitlyn Mola Alcantara More articles by this author , Adam BrochertAdam Brochert More articles by this author , Joshua YellinJoshua Yellin More articles by this author , Eliana NamenEliana Namen More articles by this author , Sean ParsonsSean Parsons More articles by this author , Jamie CesarettiJamie Cesaretti More articles by this author , and Ahmad KasraeianAhmad Kasraeian More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003227.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: African American (AA) men in the United States have an increased burden of morbidity and mortality from prostate cancer (PCa). The roles of factors related to both racial disparities and intrinsic biological traits remain to be determined. We quarried our prospective database of standard and MRI fusion prostate biopsies (tMRI/US FPB) to determine if any pre-biopsy characteristics predicted adverse tumor pathology. METHODS: Between January 2017 and September 2022, 828 men underwent prostate biopsy (PBx) using an MRI-based algorithm. Men with negative MRI underwent standard PBx (n=440), while those with lesion on mpMRI underwent tMRI/US FPB (n=388). All patients underwent mpMRI of the prostate, interpreted by a single radiologist using the PIRADS scoring system. 3D rendering of the regions of interest was performed by the radiologist prior to tMRI/US FPB performed by a single urologist using the Invivo UroNav Fusion Biopsy System. A standard 14-core PBx was performed at the same time in all tMRI/US FPB cases. Prospective data was collected and analyzed. RESULTS: Of the 828 men who underwent standard and tMRI/US FP with 14Bx (tMRI/US FP-14Bx), 593 presented with a rise in PSA, while 235 had a suspicious digital rectal exam. Prostate Cancer was found in 367/608 (60%) of the White men and 104/147 (70.8%) of AA men in our series (p=0.02). 224/608 (36.8%) of White men and 74/147 (50.3%) of AA men had a Gleason score of 7-10 (p=0.003). Age, DRE status, PIRADS score, and the incidence of Gleason 6 PCa were not found to be significantly different by race. 163/608 (26.8%) of White men and 20/147 (13.6%) of AA men had a PSA upon presentation of 0-3.9 ng/ml (p=0.001). The PSA levels of 4.0-9.9 ng/ml and PSA > 10 ng/ml at presentation were not significantly different. Of the 73/828 (8.8%) of men who identify as not White and not Black no significant difference was found for any tested factor but interestingly 19/73 (26%) presented with a PSA between 0-3.9 ng/ml versus Black men (p=0.02) which was almost identical to the effect seen relative to White men. CONCLUSIONS: In this dataset, it appears that AA men present with a higher PSA than White men. It is likely that this is related to disparities in access to care rather than biological intrinsic factors. Also, we did observe a higher incidence of Gleason 7-10 PCa in AA men, which one would expect in a cohort of patients who presented for biopsy in the community with a significantly higher PSA at initial presentation. Continuing education of primary care providers regarding the importance of PSA testing in the AA community should be emphasized by both the urological and primary care professional medical societies. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e140 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ali Kasraeian More articles by this author Miguel Alcantara More articles by this author Kaitlyn Mola Alcantara More articles by this author Adam Brochert More articles by this author Joshua Yellin More articles by this author Eliana Namen More articles by this author Sean Parsons More articles by this author Jamie Cesaretti More articles by this author Ahmad Kasraeian More articles by this author Expand All Advertisement PDF downloadLoading ...