Prostate Cancer Disparities Research Articles

MP12-17 PREDICTING THE IMPACT OF IMPROVING QUALITY OF CARE AT MINORITY-SERVING HOSPITALS ON NATIONAL RACIAL/ETHNIC DISPARITIES: EFFECTS ON THE DEFINITIVE TREATMENT OF BREAST, COLON, LUNG, AND PROSTATE CANCER

You have accessJournal of UrologyCME1 Apr 2023MP12-17 PREDICTING THE IMPACT OF IMPROVING QUALITY OF CARE AT MINORITY-SERVING HOSPITALS ON NATIONAL RACIAL/ETHNIC DISPARITIES: EFFECTS ON THE DEFINITIVE TREATMENT OF BREAST, COLON, LUNG, AND PROSTATE CANCER Marco Paciotti, Nguyen David-Dan, Zhiyu (Jason) Qian, Edoardo Beatrici, Gene Cone, Maya Marchese, Adam S. Kibel, and Quoc-Dien Trinh Marco PaciottiMarco Paciotti More articles by this author , Nguyen David-DanNguyen David-Dan More articles by this author , Zhiyu (Jason) QianZhiyu (Jason) Qian More articles by this author , Edoardo BeatriciEdoardo Beatrici More articles by this author , Gene ConeGene Cone More articles by this author , Maya MarcheseMaya Marchese More articles by this author , Adam S. KibelAdam S. Kibel More articles by this author , and Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003227.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: A large proportion of minorities receive care at a relatively small number of MSHs. Facility-level disparities, namely in access to definitive treatment, between MSHs and non-MSHs likely contribute to national patient-level racial/ethnic disparities. We aim to estimate the effect of eliminating disparities in the rate of delivery of definitive treatment between minority-serving hospitals (MSH) and non-MSHs on national racial/ethnic disparities in breast, colon, lung, and prostate cancer. METHODS: We identified patients 40 years old or older in the National Cancer Database from 2004 to 2015 eligible for definitive treatment for breast, colon, prostate, and non-small cell lung cancers (NSCLC). Institutions in the top decile of proportion of minority (Black and Hispanic) patients were defined as MSHs. We estimated the adjusted odds ratio (AOR) of receiving definitive treatment at an MSH using a logistic model for each cancer site. We then used the estimated coefficients to derive the predicted difference in the average probability of getting treated if the quality of MSH increased to the level of a non-MSH. RESULTS: A total of 2,444,623 patients from 1,334 hospitals were included in the study (breast: 1,236,033 (50.6%), colon: 199,179 (8.2%), NSCLC: 257,057 (10.5%), prostate: 752,354 (30.8%)). Overall, 222,770 (9.1%) patients were treated at MSHs while 2,221,853 (90.9%) were treated at non-MSHs. For each cancer, patients treated at MSHs were significantly less likely to undergo definitive therapy (breast: AOR 0.78 (95%CI 0.65-0.94); colon: AOR 0.77 (95%CI 0.65 – 0.91); lung: AOR 0.80 (95%CI 0.68-0.94); prostate: 0.75 (95%CI 0.63-0.90)). If patients at MSHs received definitive treatment at the same rate as patients in non-MSHs, the national probability of minority patients receiving definitive therapy would significantly increase for all cancers (breast: +1.09% (95%CI: 1.08 – 1.10); colon: +4.34% (95%CI: 4.30 – 4.38); lung: +2.41% (95%CI: 2.40 – 2.43); and prostate: +4.25% (95%CI: 4.24 – 4.27)). This represents 5,322 additional minority patients accessing definitive. CONCLUSIONS: We found that patients treated at MSH for breast, colon, NSLSC, and prostate cancer are significantly less likely to receive definitive treatment for their treatment-eligible disease compared to patients treated at non-MSHs. Equalizing facility-level access to definitive cancer treatment between MSHs and non-MSHs would reduce patient-level national racial/ethnic disparities. Source of Funding: NA © 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 Marco Paciotti More articles by this author Nguyen David-Dan More articles by this author Zhiyu (Jason) Qian More articles by this author Edoardo Beatrici More articles by this author Gene Cone More articles by this author Maya Marchese More articles by this author Adam S. Kibel More articles by this author Quoc-Dien Trinh More articles by this author Expand All Advertisement PDF downloadLoading ...

MP77-03 THE EFFECT OF NEIGHBORHOOD ARCHETYPE ON PROSTATE CANCER-SPECIFIC MORTALITY FOR WISCONSIN MEN

You have accessJournal of UrologyCME1 Apr 2023MP77-03 THE EFFECT OF NEIGHBORHOOD ARCHETYPE ON PROSTATE CANCER-SPECIFIC MORTALITY FOR WISCONSIN MEN Ashanda R. Esdaille, Arighno Das, Glenn Allen, Daniel Shapiro, Kyle Richards, E. Jason Abel, David Jarrard, and Tudor Borza Ashanda R. EsdailleAshanda R. Esdaille More articles by this author , Arighno DasArighno Das More articles by this author , Glenn AllenGlenn Allen More articles by this author , Daniel ShapiroDaniel Shapiro More articles by this author , Kyle RichardsKyle Richards More articles by this author , E. Jason AbelE. Jason Abel More articles by this author , David JarrardDavid Jarrard More articles by this author , and Tudor BorzaTudor Borza More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Socioeconomic factors are associated with prostate cancer (PCa) disparities. This study aimed to identify the association between rurality and neighborhood deprivation on prostate cancer-specific mortality (PCSM) for men diagnosed and treated in Wisconsin. METHODS: Wisconsin Cancer Reporting System (WCRS) data were used to identify all men diagnosed with PCa between 1995-2010. These data were merged with rural-urban commuting area (RUCA) codes to identify patients living in rural, small town, and urban areas. Deprivation was measured by the Area of Deprivation Index (ADI) at the census block group level using the Neighborhood Atlas®, a validated composite measure which allows for rankings of neighborhoods by socioeconomic disadvantage based on income, education, employment, and housing quality. ADIs were categorized into quartiles. Differences in baseline demographic and clinicopathologic characteristics were determined using chi-square tests. Cox proportional hazards models were used to estimate the effect of neighborhood archetype and deprivation on PCSM, adjusted for age, clinical grade, stage, diagnosis year +/- treatment. RESULTS: 62,474 men with PCa were identified with a median follow up of 5.7 years (primary) and 9.6 years (sensitivity analyses). 41,885 men (67%) resided in urban areas, 7,102 (11%) in small towns and 13,487 (22%) in rural areas. Men living in rural areas were diagnosed at older ages and more commonly had nodal and metastatic disease (p<0.001). Among all three neighborhood archetypes, definitive treatment increased in later time periods with overall higher rates of surgery versus radiation. In small towns, radiation was more prevalent. In comparison to men living in urban areas, there was no increased risk of PCSM for men in rural or small town areas (p=0.09-0.56). Further, there was no difference in PCSM risk for advantaged men living in urban, rural or small town areas (p=0.39-0.93). Disadvantaged rural men had increased risk of PCSM compared to disadvantaged urban men (Q3: aHR=1.2 (95% CI 1.0-1.35, p=0.042). This trend was not observed in men residing in the most deprived neighborhoods (Q4: p=0.21-0.53). CONCLUSIONS: Men living in rural areas had more aggressive disease on presentation in comparison to men residing in small towns and urban areas, possibly reflecting differences in screening patterns. Overall, there was no difference in PCa-specific deaths by neighborhood archetype; however, differences in deprivation status within the archetypes underscore the association between lack of neighborhood-level resources and oncologic outcome. Source of Funding: Esdaille: AUA/UCF Research Scholar Award Grant# 017-822959 © 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 Ashanda R. Esdaille More articles by this author Arighno Das More articles by this author Glenn Allen More articles by this author Daniel Shapiro More articles by this author Kyle Richards More articles by this author E. Jason Abel More articles by this author David Jarrard More articles by this author Tudor Borza More articles by this author Expand All Advertisement PDF downloadLoading ...

Regulation of Prostate Androgens by Megalin and 25-hydroxyvitamin D Status: Mechanism for High Prostate Androgens in African American Men.

These findings link vitamin D deficiency and the megalin protein to increased levels of prostate androgens, which may underpin the disparity in lethal prostate cancer in African America men.

Source of funding and enrollment disparity in prostate cancer (PCa) clinical trials.

40 Background: Previously we have reported enrollment disparities in PCa clinical trials. Funding source can influence minority representation in clinical trials. Hence, we aimed to evaluate the impact of source of funding on enrollment disparities in PCa clinical trials. Methods: MEDLINE and EMBASE were searched to identify phase II/III PCa trials. All relevant trials reporting age by 65 years were considered eligible for inclusion. Trials recruiting from the United States (US) were considered eligible for analysis by race and ethnicity. The trial proportions of age, or racial/ethnic subgroup category and the global incidence in the corresponding age subgroup (from the global burden of disease database), or the US-population-based incidence in the corresponding racial/ethnic subgroup (from SEER 21 database) were used to compute enrollment incidence ratio (EIR) at each trial. EIRs with corresponding 95% confidence intervals (CI) were then meta-analyzed using a random-effects model and stratified by sources of funding (industry, US-government, and others [academic and non-US govt]). A univariate meta-regression was conducted to assess the temporal changes in EIR by each funding category. Results: Of 127 trials recruiting from the US, 89 (70%) reported race, and 35 (27%) reported ethnicity. Among those, 57 (64%), 14 (16%), and 18 (20%) trials reported industry, US-government, and other sources of funding, respectively. Of those reporting ethnicity, 23 (66%), 4 (11%), and 8 (23%) trials reported industry, US-government, and other sources of funding, respectively. Among the 287 eligible trials, 49 trials (17%) reported age by 65 years. Of those, 36 (73%), 6 (12%), and 7 (13%) reported industry, US-government, and other sources of funding, respectively. In terms of racial/ethnic enrollment, Black patients were significantly under-represented in industry funded trials (0.33; 0.27-0.41). No significant disparity was observed in US-government funded trials (0.75: 0.57-1.00). The P-value of interaction was &lt;0.0001. Hispanics were significantly under-represented in industry funded clinical trials (0.56; 0.43-0.74). The number of US-government funded trials reporting Hispanics were small (&lt;10) which precluded any meaningful statistics. No significant disparity was observed in terms of older adults (EIR: 1.00; 95% CI: 0.95; 1.05) overall and by funding sources. Black patients’ representation in industry funded PCa trials has significantly decreased over the last three decades. No significant change was observed in US-government funded PCa trials over the last three decades (P:0.004). Conclusions: Black and Hispanic men with PCa are likely to be under-represented in industry sponsored clinical trials. Black patients’ representation in industry sponsored trials has declined over time, thus widening the cancer-care inequities in these patients.

Health disparities in metastatic hormone-sensitive prostate cancer (mHSPC) presentations and outcomes among Hispanic Americans (HA) versus non-Hispanic Whites (NHW).

31 Background: Multiple retrospective studies conducted have demonstrated disparities in access to care and treatment rates for prostate cancer between HA and NHW. We sought to understand the differences in prostate cancer presenting characteristics, prognosis, and outcomes between the two ethnic groups who presented to the University of Arizona Cancer Center (UACC), which serves a large Hispanic community. Methods: A retrospective analysis of mHSPC adenocarcinoma patients who presented to UACC from 2016 to 2022 was conducted. Patients must have had genetic testing to be included. Patients with no metastasis and incomplete data were excluded. Continuous data were analyzed using t-tests or Wilcoxon Rank sum tests depending on whether they were normally distributed. Categorical variables were analyzed using X2 Tests or Fisher's exact tests. Time to Event data was analyzed using Kaplan-Meier Methods. Results: 83 patients were included with 38.5% HA. No difference was observed between the ethnic groups by median age at presentation (66 years), race (90% white), obesity (40% BMI&gt;30), personal cancer history (10%), or family history of cancer (48%). HA were more likely to have a smoking (69%) and alcohol (63%) history compared to NHW (54% and 39%, respectively; p= 0.04). On presentation, 56% of HA were ECOG 0 compared to 22% of NHW (p=0.001). At the time of diagnosis, HA had median PSA levels of 111.5 ng/ml compared to 52.6 ng/ml in NHW (p=0.12). Gleason Grade Group ≥4 in 73% HA vs 79% in NHW (p=0.61). 41% of HA presented with T4 disease compared to 14% of NHW (p=0.01). 69% of HA presented with N1 disease vs 61% of NHW (p=0.85). 41% of HA presented with visceral metastasis, M1c, compared to 16% of NHW (p=0.04). The median time to first-line (1L) treatment was 1 month in HA compared to 3 months for NHW (p&lt;0.01). 84% of all patients had 1L combination therapy. Abiraterone plus ADT was 1L in 47% of HA compared to 20% of NHW (p=0.06). ADT plus androgen receptor blocker was 1L in 41% of NHW compared to 28% of HA (p=0.06). Median PSA response 3 months after starting treatment was 0.8 ng/ml in HA vs 3.96 ng/ml NHW (p=0.05). The median time to 2L was 20 months for HA vs 11 months in NHW (p=0.05). Conclusions: HA in our study presented with higher PSA, more locally advanced disease, and increased rates of visceral metastases, necessitating a shorter time interval to 1L therapy. HA demonstrated a more favorable response to 1L treatment, noted by lower PSA at 3 months and time to the next line of treatment. Overall survival was not calculated due to the small sample size with only 11 (1 HA vs 10 NHW) total deaths. The Hispanic Americans Prostate Cancer Comprehensive Genomic Profiling Study's (THAPCA-GPS) future investigations aim to delineate the pathogenetic differences between HA and NHW and may reduce healthcare disparities and improve clinical outcomes in HA patients.

Serum Androgen Metabolites Correlate with Clinical Variables in African and European American Men with Localized, Therapy Naïve Prostate Cancer.

Dihydrotestosterone (DHT) and testosterone (T), which mediate androgen receptor nuclear translocation and target gene transcription, are crucial androgens and essential molecular triggers required for the proliferation and survival of prostate cancer cells. Therefore, androgen metabolism is commonly targeted in the treatment of prostate cancer. Using a high-pressure liquid chromatographic assay with tandem mass spectral detection, we determined the serum levels of metabolites produced during DHT/T biosynthesis in African American (AA) and European American (EA) men with localized, therapy naïve prostate cancer. Serum progesterone and related metabolites were significantly lower in AA men than in EA men, and these differences were associated with rapid disease progression. Multivariate analysis revealed significant differences between a subset of intermediate androgen metabolites between AA and EA men and between men with <=3 + 4 and >=4 + 3 Gleason score disease. AA men have a significantly higher frequency of single nucleotide polymorphisms in CYP11B1 and CYP11B2, enzymes that regulate corticosterone-aldosterone conversion. Finally, higher levels of T and pregnenolone were associated with a lower risk of progression-free survival only in AA men. This work provides new insight into androgen metabolism and racial disparities in prostate cancer by presenting evidence of dysregulated androgen biosynthesis in therapy naïve disease that correlates with clinical variables.

Role, race, and place: Prostate cancer disparities in Patients' and Partners' health outcomes and psychosocial factors.

This study aimed to examine the effects of participant role (patient vs. partner), race (white vs. non-white), and place (less vs. more neighborhood deprivation) on health outcomes (quality of life [QOL] and symptoms) and stress-coping-related psychosocial factors (appraisals of illness and coping resources). This descriptive study included 273 patients and their partners (dyads) who transitioned from PCa treatment to self-management. We used established, psychometrically sound measures to assess health outcomes and psychosocial factors and conducted multilevel modeling analyses. Compared to partners, patients reported worse physical QOL; less frequent anxiety; less pain and fatigue; less bothersome hormonal problems; more bothersome urinary and sexual problems; greater self-efficacy; and more instrumental support. Compared to their white counterparts, non-white dyads reported better overall, emotional, and functional QOL; less depression; more positive appraisals, and greater self-efficacy. Compared to dyads in low ADI neighborhoods, dyads in high ADI (more deprived) neighborhoods reported worse social QOL; more bothersome urinary, sexual, and hormonal symptoms; and less interpersonal support. White patients reported the highest emotional support among all groups, while white partners reported the lowest emotional support. Our findings underscore the need to consider social determinants of health at multiple levels when investigating PCa disparities. Considering neighborhood-level socioeconomic factors, in addition to race and role, improves our understanding of the PCa disparities in QOL, symptoms, and psychosocial factors among patients and partners. Targeted multilevel supportive care interventions should tailor to the needs of racially diverse PCa patients and partners residing in deprived neighborhoods are needed.

Prostate cancer disparities among American Indians and Alaskan Natives in the United States.

Americans Indians and Alaska Natives face disparities in cancer care with lower rates of screening, limited treatment access, and worse survival. Prostate cancer treatment access and patterns of care remain unknown. We used Surveillance, Epidemiology, and End Results data to compare incidence, primary treatment, and cancer-specific mortality across American Indian and Alaska Native, Asian and Pacific Islander, Black, and White patients. Baseline characteristics included prostate-specific antigen (PSA), Gleason score (GS), tumor stage, 9-level Cancer of the Prostate Risk Assessment risk score, county characteristics, and health-care provider density. Primary outcomes were first definitive treatment and prostate cancer-specific mortality (PCSM). American Indian and Alaska Native patients were more frequently diagnosed with higher PSA, GS greater than or equal or 8, stage greater than or equal to cT3, high-risk disease overall (Cancer of the Prostate Risk Assessment risk score ≥ 6), and metastases at diagnosis than any other group. Adjusting for age, PSA, GS, and clinical stage, American Indian or Alaska Native patients with localized prostate cancer were more likely to undergo external beam radiation than radical prostatectomy and had the highest rates of no documented treatment. Five-year PCSM was higher among American Indian and Alaska Natives than any other racial group. However, after multivariable adjustment accounting for clinical and pathologic factors, county-level demographics, and provider density, American Indian and Alaska Native patient PCSM hazards were no different than those of White patients. American Indian or Alaska Native patients have more advanced prostate cancer, lower rates of definitive treatment, higher mortality, and reside in areas of less specialty care. Disparities in access appear to account for excess risks of PCSM. Focused health policy interventions are needed to address these disparities.

Abstract C045: Investigating molecular and genetic contributions to racial disparities in prostate cancer by integrating multi-omic datasets available in public

Abstract African-American males are disproportionately affected by prostate cancer in comparison to other racial and ethnic groups. African-American males have increased risk for the disease, experience higher incidence and mortality rates, and present higher grade and stage prostate tumors than Caucasian men. To determine molecular mechanisms beyond racial disparities in prostate cancer, molecular and genetic profiles of prostate tumor samples from different ethnic groups are developed. For example, DNA sequencing in the form of target-based array or whole exome and genome sequencing revealed SNPs, genetic mutations, deletions, and amplifications linked to prostate cancer subgroups. Comparative analysis of DNA sequences of prostate cancer cells have pinpointed areas of interest that suggest race specific mutations. Moreover, differentially expressed genes between prostate tumor tissue samples from African and Caucasian ancestries are identified using RNA sequencing and microarray-based methods. Abnormal levels of gene expression are measured by the levels of mRNA. Furthermore, epigenetic modifications, such as DNA methylation levels were examined, identifying CpG sites that are differentially methylated among ethnic groups. To comprehensively examine molecular and genetic contributions to racial disparities in prostate cancer, we compiled over 200 published studies that profiled genome, epigenome, and transcriptome in prostate tumor tissues from diverse ethnic groups. Specifically, we categorized studies according to their method and organized the identified features that offer insight into racial disparities in prostate cancer. For instance, we reviewed over 100 studies that identify reproducible genetic alterations found in prostate cancer patients from African ancestry from DNA sequencing experiments. We also reviewed over 50 studies that utilized RNA sequencing to measure gene expression levels in prostate tumor tissues from African-American male samples, identifying genes and signaling pathways abnormally dysregulated in the disease. In addition, we reviewed over 25 studies quantifying epigenetic modifications to determine key and reproducible epigenetic alterations linked to aggressiveness of the disease from African American. Subsequently, we identified socioeconomic factors that are associated with molecular features contributing to the increased risk for prostate cancer in African-American men. Overall, we evaluated multiple molecular and genetic features that contribute to racial disparities in prostate cancer. This may provide researchers with valuable background knowledge and perspective for identifying biomarkers for specific prostate cancer subgroups. Citation Format: Alexandria J. Hightower, Suhn K. Rhie, Sara M. Falzarano, Sarah Buxbaum. Investigating molecular and genetic contributions to racial disparities in prostate cancer by integrating multi-omic datasets available in public [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C045.

Abstract C043: Aberrant mRNA splice variants as novel prognostic biomarkers for tumor aggressiveness and treatment resistance in African American prostate cancer

Abstract African Americans (AAs) have among the highest incidence of prostate cancer (PCa) and mortality attributable to this disease, and AA PCa disparities remains a clinical challenge. Specifically, AAs are 1.6 times more likely to develop PCa, and 2.4 times more likely to die from this disease compared to European Americans (EAs). A number of studies have shown that higher mortality and recurrence rates of PCa in AA men were observed even after adjustment for socioeconomic factors, suggesting that intrinsic biological difference may account for part of the PCa disparities. Our recent genomic study has identified global splicing events as critical drivers for promoting AA and EA PCa disparities. In this study, we utilized population-specific cell lines as in-vitro AA and EA PCa models to evaluate the molecular functions of the aberrant splice variants involved in cancer aggressiveness and drug resistance. Comprehensive functional assays (such as MTT, apoptosis, invasion, kinase activity assays, and western blotting analysis in PCa cells treated with vehicle or small molecule drugs, etc.) were employed to elucidate the functional roles of an oncogenic splice variant, PIK3CD-S, in AA and EA PCa cells in response to drug treatments. Immunohistochemistry and RNAScope assays were performed to examine the expression profile of PIK3CD-L (full length) and PIK3CD-S variants in an independent PCa cohort derived from AA and EA patients. Higher PIK3CD-S/PIK3CD-L expression ratios were detected in AA PCa cell lines and patient specimens. In addition, the functional validations have indicated that the higher PIK3CD-S/PIK3CD-L expression ratio in AA PCa cells potentially contributes to the higher cell proliferative and invasive capacities. By targeting splicing mechanism and/or PI3K isoforms using specific small molecule inhibitors in AA and EA cell models, we further explored the functional mechanisms of these oncogenic splice variants underlying the drug resistance. In conclusion, our molecular mapping/validation and functional analysis suggest that high PIK3CD-S/PIK3CD-L expression profile may contribute to the PCa aggressiveness and treatment resistance in AA PCa, potentially serving as a precision prognostic biomarker and novel drug target in advanced PCa Citation Format: Siyoung Ha, Himali Gujrati, Bi-Dar Wang. Aberrant mRNA splice variants as novel prognostic biomarkers for tumor aggressiveness and treatment resistance in African American prostate cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C043.

Abstract A018: Geographic disparities in aggressive prostate cancer varies by region-specific environmental and sociodemographic characteristics: A statewide analysis

Abstract Background: Although the overall 5-year survival rate for prostate cancer (PCa) is relatively high, there are substantial differences in survival by stage at diagnosis. In contrast to men diagnosed with localized or regional stage PCa, both of which have a 5-year survival rate of nearly 100%, only 31% of patients survive five years after being diagnosed with distant or metastatic disease. Given PCa remains the second leading cause of cancer death among U.S. men, targeted PCa screening interventions centered on early detection for men at risk for more aggressive PCa subtypes appear warranted. Under a Precision Public Health approach, the application of geospatial analysis to cancer surveillance data can help to identify and “narrow down” geographic areas where rates of aggressive PCa are higher than expected to target for intervention. Thus, the primary objective of this study was to conduct a geospatial scan to identify clusters of aggressive PCa in a State-wide analysis. Given well-known racial disparities and associations between socioeconomic status and PCa stage at diagnosis and survival, the secondary objective was to evaluate geographic variation, or changes in aggressive PCa clusters, by area-level sociodemographics and environmental exposures. Methods: The study population included 82,580 patients diagnosed with incident PCa from the Pennsylvania (PA) State Registry from 2005-2015. Patient addresses were geocoded. Patient clinical data from the registry (age, race/ethnicity, insurance status) were linked via geocodes to area-level sociodemographic measures generated from the US Census Bureau at the census tract level, and to Environmental Quality Indices (Air, water, soil) from the Environmental Protection Agency (EPA) at the county level. Aggressive PCa was evaluated using 3 separate definitions based on TNM staging and/or Gleason grade. A Bayesian geoadditive modeling approach identified census tract clusters with higher than expected rates of aggressive PCa, adjusted for individual-level factors (age, race, diagnosis year) (Baseline model). The baseline model was then compared to models that included sociodemographic and/or environmental measures by evaluating changes in model fit (DIC), cluster size, and relative risk (RR). Results: We identified 3 main clusters in PA where rates of aggressive PCa were higher than expected near Philadelphia, Altoona, and Pittsburgh. Clusters of aggressive PCa in Philadelphia were eliminated and could be fully explained after adjustment for sociodemographic characteristics (insurance, poverty, etc), but not environmental measures. In contract, clusters of aggressive PCa in Pittsburgh were only reduced after adjustment for environmental variables, particularly water quality. Conclusion: PCa screening interventions could be prioritized in high risk cluster areas. Results are novel in that they preliminarily suggest that the type of intervention and focus of future etiologic studies in aggressive PCa might vary by geographic location, even within a single State. Citation Format: Daniel Wiese, Kevin A. Henry, Carolyn Fang, Adam Reese, Mary Daly, Camille Ragin, Shannon M. Lynch. Geographic disparities in aggressive prostate cancer varies by region-specific environmental and sociodemographic characteristics: A statewide analysis [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A018.

Abstract IA041: Basic science mechanisms associated with bone tumor microenvironment and health disparities in breast and prostate cancer

Abstract Prostate cancer (PCa) and breast cancer (BCa) are leading causes of cancer related deaths in American men and women, and morbidity is due to metastasis preferentially to bone. Compared to Caucasian American (CA), African American (AA) men and women have a higher bone density, as well as mortality rate due to bone metastasis. Recent studies have shown that high mobility group two (HMGA2), a non-histone chromatin binding protein, plays a critical role in promoting epithelial-mesenchymal transition (EMT) and metastasis. HMGA2 full-length/wild-type and truncated (without the 3’UTR) isoforms have been shown to be overexpressed in several cancers, however their distinct roles in metastasis have not been reported. Our laboratory focuses on tumor-micronenvironmental interactions, particularly, how PCa cells interact with bone at the metastatic site. We have previously published that PCa cells may degrade hydroxyapatite, the major inorganic component of bone, to release calcium which promotes paracrine cell proliferation and migration, and this signaling increases with increased bone density. We hypothesize that EMT is associated with prostate health disparities and that HMGA2 isoforms may play differential roles at the bone metastatic site. We examined EMT marker expression in breast and prostate patient tissue and cell lines by immunohistochemistry (IHC), RNA In Situ Hybridization (RISH), western blot, and real-time PCR. Next, LNCaP PCa cell line stably overexpressing either full length or truncated HMGA2 was co-cultured with low (100 mg) or high (200 mg) hydroxyapatite, demineralized bone matrix or human ground bone matrix, for 6 days followed by collection of condition media (CM). CM was added to parental LNCaP cells for various time points followed by analysis of paracrine cell proliferation using MTS assay, cell migration across collagen using boyden chamber, and the effect on various pathways using western blot analysis. EMT marker (Snail and Cathepsin L) protein expression was higher in AA normal and cancer tissue compared to CA, while it was intermediate in Bahamian tissue. Wild-type HMGA2 mRNA expression was higher in metastatic patient tissue compared to truncated HMGA2, and higher in AA compared to CA tissue. CM taken from LNCaP cells overexpressing wild-type and truncated HMGA2 co-cultured with hydroxyapatite, demineralized bone matrix or ground bone matrix when added to parental LNCaP cells led to higher paracrine cell proliferation and paracrine cell migration. This was associated with MAPK activation that could be abrogated by MAPK inhibitor, UO126. These results indicate that EMT is higher in AA compared to CA. Additionally, both wild-type and truncated HMGA2 interaction with bone matrix promotes paracrine cell proliferation and migration via ERK signaling. Our study shows that wild-type and truncated isoforms of HMGA2 mediate PCa/bone interactions which may lead to increased bone metastasis, particularly in African American men that have higher bone density. Citation Format: Taaliah Campbell, Ohuod Hawsawi, Bor-Jang Hwang, Liza J. Burton, Quentin Loyd, Veronica Henderson, Simone Howard, Camille Ragine, Robin Roberts, Andrew Gachii, Valerie Odero-Marah. Basic science mechanisms associated with bone tumor microenvironment and health disparities in breast and prostate cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA041.

Abstract C062: Metabolic rewiring: A role for adenosine-inosine axis in African-American prostate cancer

Abstract African-American (AA) men have a 60% higher incidence of prostate cancer (PCa) compared to European-American (EA) men. An understanding of the altered biological responses and the factors that lead to health disparity in PCa is unclear. Metabolism defines the physiological state of the cell and metabolic reprogramming is a hallmark of cancer. Thus, studying the metabolic landscape will be crucial for understanding the biological changes that might contribute to this disparity. Analysis of 190 metabolites across PCa/benign adjacent tissue pairs from ancestry typed AA and EA men done in our laboratory, revealed altered levels of nucleosides adenosine and inosine. High inosine to adenosine ratio was observed in AA men compared to EA men. In line with this, the enzyme adenosine deaminase (ADA), which converts adenosine to inosine was found elevated in AA men, potentially explaining the high inosine to adenosine ratio in AA PCa. The consequences of the accumulation of these metabolites on AA PCa progression are unknown. This study will address the knowledge gap on the effects adenosine-inosine alterations in AA PCa and attempt to dissect its role in effecting an aggressive phenotype in PCa. To determine the role of elevated ADA in PCa, it was overexpressed in AA(MDA-PCa-2A) and EA PCa (LNCaP) cell lines (termed ADA OE). Phenotypic examination of these cells revealed high ADA enzyme activity decreases the cell-ECM adhesion. Molecular analyses revealed that upon ADA OE there is a reduction in Tenascin C(TNC), a matrix protein known for its anti-adhesive properties. TNC-rich microenvironment facilitates reactive stromal induction and high motility. This TNC-mediated reprogramming enhances the metastatic ability and PCa progression in bone. TNC induction was observed in stromal cells (DPT44) upon treatment with ADA OE conditioned media and inosine addition. PCa progression on bone was assessed using a cancer cell-bone in vitro co-culture system. High inosine and adenosine levels enabled better attachment of PCa cells to the bone. These findings suggest that an altered adenosine/inosine axis could facilitate adhesion decrease and modulate the stromal microenvironment to aid in the metastatic dissemination and migration towards the bone. Adenosine-inosine alterations could serve as a biomarker for metastatic PCa. We will further analyze the inosine and adenosine levels in patient samples and correlate them with various clinical outcomes in PCa. Our study so far shows high inosine to adenosine ratio in biopsy positive patient samples compared to biopsy negative samples. Our next steps of analysis include correlating the metabolite levels with (i)Biochemical recurrence (BCr) (ii)Time to attaining castration resistance (iii)Time to metastasis (iv)Response to Androgen deprivation in patients after BCr. Based on our current findings, we expect the inosine to adenosine ratio in plasma or urine to serve as a predictive marker for PCa incidence or progression in AA men. In addition, the enzyme ADA could serve as a potential therapeutic target for AA PCa. Citation Format: Christy Charles. Metabolic rewiring: A role for adenosine-inosine axis in African-American prostate cancer [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C062.

Abstract A042: Addressing prostate cancer disparities through the Inclusive Cancer Care Research Equity (iCCaRE) for Black men consortium

Abstract Background: The prostate cancer (CaP) disparities experienced by Black men (BM) in the US is a microcosm of the burden of CaP seen in BM globally. The complexity of CaP disparities and the need for a unique approach to better understand and address a complex chronic disease, such as CaP, underscores the need for consortium research that is multilevel, collaborative, translational, and global. In response to this need, we brought together CaP survivors, advocates, scientists and clinicians to form the inclusive Cancer Care Research Equity (iCCaRE) for Black Men Consortium. Aim: Our overall goal is to optimize CaP diagnosis experiences, treatment and survivorship based on the Science of Survivorship (S.O.S). Our primary aim was to develop a consortium co-led by CaP scientists and survivors with multiple S.O.S research projects supported by research cores/services across multiple institutions. Methodology: The consortium was developed to comprise multiple individuals with complementary expertise and resources working collaboratively to achieve the common purpose of eliminating CaP disparities globally. Building on the expertise, resources, and relationships of collaborating CaP investigators, survivors and advocates, the iCCaRE Consortium was proposed to “advance health equity and reduce disparities in CaP” by studying the within-group differences among ethnically diverse BM and comparing US-born BM to their ancestral populations, including West African immigrant men in the US and indigenous West African men. Results: Through the Department of Defense Health Equity Research and Outcomes Improvement Consortium (HEROIC) Award, the iCCaRE Consortium was launched in 2022. There are five pilot projects (PPs), each co-led by a scientist PI and community PI: PP1 will plan and develop a Virtual Robot Assistant (ViRA) that will provide SDOH navigation services, psycho-oncology support and emotional support for BM newly diagnosed with CaP. PP2 will develop and analyze the impact of a patient-centered home cancer care system on health-related Quality of Life (HRQOL), access to healthcare, and PROs. PP3 will plan and develop a ViRA to improve HRQOL in Black CaP survivors. PP4 will employ the social determinants of migrant health framework to understand and address the needs of sub-Saharan African immigrant CaP survivors. PP5 will explore how biological factors induced by cancer cells contribute to poor mental health of CaP survivors. The PPs are supported by an Administrative Core, Translational Research &amp; Clinical Intervention Service, Data Management and Analytics Services, Partnership Engagement Services, Pathology Resource &amp; Biospecimen Core, Methodology and Measures Services and Digital Health &amp; Human Services. Conclusion: The iCCaRE Consortium will “improve HRQOL to enhance outcomes and overall health and wellness for those impacted by CaP” by developing and implementing Artificial Intelligence interventions that address social determinants of health, psycho-oncology support and emotional support for newly diagnosed CaP patients. Citation Format: Folakemi Odedina, Roxana Dronca, Kimlin Ashing, Ernest Kaninjing, Solomon Rotimi, Che Ngufor, Arnold Merriweather, Jennifer Crook, Manisha Salinas, Fathi Parisa, Sha’Reff Rashad, John McCall, Ebenezer Erefah, Ayinde Yahaya. Addressing prostate cancer disparities through the Inclusive Cancer Care Research Equity (iCCaRE) for Black men consortium [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A042.

Abstract A080: The immunological signatures of African American prostate cancer as biological determinants of disease disparity

Abstract Background: Prostate cancer (PCa) is currently the second leading cause of cancer-related deaths among men in the United States. African American men suffer the highest incidence of disease morbidity and mortality compared to other racial groups. Although socio-economic, cultural, epidemiological, and genomic factors have been described to contribute to cancer health disparities in African American men, there is a knowledge gap regarding how the tumor immune landscape shapes aggressive disease patterns in this patient population, and whether their tumor microenvironment (TME) is amenable to immune modulation. This study aims to identify distinct and targetable immunosuppressive phenotypes and immunological signatures in prostate tumors of AA patients. Methodology: Peripheral blood from consented African American (AA) and Caucasian American (CA) patients undergoing prostatectomy at Moffitt Cancer Center were analyzed by Luminex multiplex cytokine/chemokine assay and comprehensive immune profiling via multi-parameter flow cytometry. Also, multiparameter immune profiling of freshly resected PCa specimens obtained from these same patients after prostatectomy was performed. In addition, multiplex immunohistochemical staining was performed on prostate tumor tissue microarrays to compare the proportions and phenotypes of T cells in the prostate TME of AA and CA patients. Lastly, the immunomodulatory potential of AZD5153, a bivalent Bromodomain 4 (BRD4) inhibitor was investigated on orthotopic prostate tumor-bearing humanized mouse models under racially defined settings, followed by comprehensive flow cytometry immunophenotypic profiling of tumor-infiltrating immune cells in the resected mice prostate tumors at clinical endpoints. Results: Prostate tumors of AA patients harbored higher proportions of CD4+ regulatory T cells (Tregs) and lower proportions of CD8+ T cells relative to CA patients. Furthermore, the immunophenotypic analysis of T cells showed higher expression of immune checkpoint molecules in AA compared to CA patients. Serum analysis revealed cytokine and chemokine expression signatures that are skewed towards a more immunosuppressive profile in AA compared to CA patients. Treatment with AZD5153 led to an increase in the survival time and a more striking reduction in tumor volume of AA-matched prostate tumor-bearing humanized mice relative to CA-matched prostate tumor-bearing humanized mice. A decrease in the proportion of tumor-infiltrating Tregs and a reduction in the expression of immune checkpoint molecules were also observed in prostate tumors from AA-matched humanized mice relative to CA-matched humanized mice. Conclusion: Our findings support the contributory role of racially distinct immunophenotypes and immune signatures in PCa disparity, and highlight the potential immunotherapeutic benefits of BRD4 inhibitors, such as AZD5153 in AA PCa patients. Citation Format: Saheed O. Oseni, Arup Bag, Oluwaseyi Oluwatola, Natalie DeMars, Dennis Adeegbe. The immunological signatures of African American prostate cancer as biological determinants of disease disparity [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A080.

Application of GIS and SPSS for prostate cancer and health disparity detection in Texas

Application of GIS and SPSS for prostate cancer and health disparity detection in Texas

Application of GIS and SPSS for prostate cancer and health disparity detection in Texas

Application of GIS and SPSS for prostate cancer and health disparity detection in Texas

Abstract B078: Implementing a transdisciplinary framework to build capacity for complex collaboration among academic and non-academic partners

Abstract Complex problems require a deep understanding of the issue and a collaborative approach to find sustainable solutions. Cancer disparities are complex and must be understood from a broad set of perspectives across the academic spectrum and non-academic sources (community members, community-based organizations, and policymakers). The Community and Cancer Science Network (CCSN) is a transdisciplinary network focused on addressing statewide cancer disparities. The CCSN grounds its approach in the principles of deep equity, systems-change, and the integration of biology to policy. It brings together diverse perspectives through a three-phase model: 1) Incubate ideas through co-learning among the team members to build shared vocabulary, knowledge, and integrate perspectives on the issue; 2) Innovate by using learnings to develop, prototype and pilot potential solutions; 3) Implement to further scale and embed solutions. Despite challenges, the commitment to this approach enabled our network to expand and strengthen transdisciplinary capacity in its partnerships. Now in its third year, CCSN encompasses four projects using its transdisciplinary approach: 1) a curriculum for biomedical researchers and community members to address mistrust and misunderstandings of disparities; 2) development of a shared measurement system to improve mammographic quality; 3) design and implementation of community-based action plans to address breast and lung cancer disparities, and 4) formation of a workgroup to explore the potential causes and solutions for prostate cancer disparities in the state. The projects are guided and supported through the framework by a leadership structure. To assess the impact of its approach on community-academic partnerships, CCSN assesses against a rubric developed in 2020 with its advisory team. The rubric measures partner perception of impact, values application, belonging, interconnectedness and shared purpose. CCSN looks at quantitative and qualitative data annually to generate insights on the strength of partnerships and how its leadership can build additional capacities. CCSN is currently finalizing its assessment of its third year of data. Initial findings suggest partnerships with sustained relationships and high levels of trust appear to weather challenges that accompany implementation of complex interventions. Results also indicate that partners are eager to consider implications for their own work and to connect with others doing similar work within CCSN as they experience similar challenges including navigating the pace of change. Incorporating varied perspectives into understanding cancer disparities and then developing and implementing solutions requires a thoughtful, deliberate and flexible approach. Our framework provides rigor without rigidity and allows academics and non-academics to build authentic and collaborative relationships which persist through adversity, facilitate a richer understanding of disparities and open doors for future partnerships. Citation Format: Tobi A. Cawthra, Laura Pinsoneault, Alexis Krause, Kristen Gardner-Volle, Kim Kinner, Jenelle Elza, Melinda Stolley. Implementing a transdisciplinary framework to build capacity for complex collaboration among academic and non-academic partners [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B078.

Abstract IA025: Utilizing Visium spatial transcriptomics to investigate prostate cancer disparity in men of African descent

Abstract People of African descent suffer more from cancer compared to other racial groups in terms of morbidity and mortality. Surveillance, Epidemiology, and End Results (SEER) reports Black men and women to have the highest diagnoses and highest cancer death rate. The reported cancer disparity statistic is also reflected by cancer type; prostate cancer was shown to be one of the top causes of cancer death in all cancer types, and the second leading cause of death, after lung cancer, in men. Men of African Descent, however, have more than a 2-fold increased mortality rate of prostate cancer compared to other ancestral populations. Cancer is considered a genetic disease, and prostate cancer has a heritability of 58%. Most studies however, do not capture the genetic heterogeneity found in men of African Descent, nor histological and morphological profiles that would provide prognostic and diagnostic markers for targeted and personalized therapeutic treatment options. Visium Spatial Transcriptomics is a method that maps transcriptomics data to the location within the tissue region that is being analyzed. Instead of being limited to a small piece of DNA or RNA, spatial transcriptomics enables high-resolution assessment of spatial gene expression across tissue sections. This technology assiduously probes the transcriptome of tissues samples in an untargeted way. Spatial Transcriptomics involves cutting edge technology that provides great potential to capture the cellular landscape of men with the heaviest burden of prostate cancer. The Visium platform by 10X Genomics is able to interrogate more than 10,000 transcripts per capture region. The protocol involves a comprehensive process from tissue collection to next generation sequencing following a bioinformatics pipeline. The complete protocol from beginning to end requires a collaboration of clinicians, pathologists, basic scientists, and bioinformaticians. This means that access to resources is imperative to the success of this technique. Unfortunately, low resource institutions are at a disadvantage in being able to perform the entire protocol. This fact is yet another type of health disparity. This observation, however, provides great opportunities to establish collaborations with other institutions. Closing the gap between higher and lower resource investigations would be vital in addressing prostate cancer health disparity using spatial transcriptomics. I will share my observation, learning, experimentation, and joint participation effort experience with Visium Spatial Transcriptomics in my quest to understand the genetic architecture of men of African descent that has them at a prolific risk for prostate cancer. Citation Format: Maxine S. Harlemon, Ana C. Millena, Bor-Jang Hwang, Valerie Odero-Marah. Utilizing Visium spatial transcriptomics to investigate prostate cancer disparity in men of African descent [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr IA025.

Prostate Cancer Disparities and Management in Southern Africa: Insights into Practices, Norms and Values.

Prostate cancer (PCa) is a leading cause of mortality in men of African origin. While men of African descent in high-income countries (HICs) demonstrate poor prognosis compared to their European counterparts, African men on the African continent, particularly Southern Africa have shown even higher PCa mortality rates. Extrinsic factors such as the socioeconomic status, education level, income level, geographic location and race contribute to PCa patient outcome. These are further deepened by the African norms which are highly esteemed and may have detrimental effects on PCa patients' health. Insights into African cultures and social constructs have been identified as key elements towards improving men's health care seeking behaviour which will in turn improve PCa patients' outcome. Compared to Southern Africa, the Eastern, Western and Central African regions have lower PCa incidence rates but higher mortality rates. The availability of cancer medical equipment has also been reported to be disproportionate in Africa, with most cancer resources in Northern and Southern Africa. Even within Southern Africa, cancer management resources are unevenly available where one country must access PCa specialised care in the neighbouring countries. While PCa seems to be better managed in HICs, steps towards effective PCa management are urgently needed in Africa, as this continent represents a significant portion of low-middle-income countries (LMICs). Replacing African men in Africa with African American men may not optimally resolve PCa challenges in Africa. Adopting western PCa management practices can be optimised by integrating improved core-African norms. The aim of this review is to discuss PCa disparities in Africa, deliberate on the significance of integrating African norms around masculinity and discuss challenges and opportunities towards effective PCa care in Africa, particularly in Southern Africa.