Prostate Cancer Outcomes Research Articles

Rurality and outcomes in prostate cancer: role of socioeconomic status and educational attainment

Abstract Background/Introduction Patients diagnosed with prostate cancer (PC) have a higher cardiovascular disease (CVD) prevalence and mortality risk. Rurality have been associated with up to 33% higher CVD risk and 44% higher all-cause mortality risk in patients with PC. Purpose Analyze the impact of rurality (from both patient and provider perspectives) on the development of adverse outcomes after a PC diagnosis according to socioeconomic and educational status. Methods We included men aged ≥66 with a new primary PC diagnosis (defined as ICD-10 = C61) from 2009-2017 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The primary outcomes were CVD (comprising heart failure, atrial fibrillation, acute myocardial infarction, peripheral artery disease, and ischemic stroke), PC-specific mortality (PCsm), cardiovascular disease mortality (CVDm), and all-cause mortality. Patients living in areas with a population of <2,500 or <20,000, not adjacent to a metropolitan area, were considered to have a positive rural status. The provider status (metropolitan vs. non-metropolitan) was defined according to the 2013 National Center for Health Statistics' Urban-Rural Classification Scheme for Counties. Low socioeconomic status (SES) was defined according to Yost Index quintiles. Low educational status was defined according to percentiles of people >25 years old with less than a high school diploma. Multivariable Fine-Gray models, accounting for competing mortality/type of mortality, and Cox regression models were applied. Results We included 75,221 patients with PC (Picture 1), of which 1,828 were from rural areas and 362 were from rural areas with providers from non-metropolitan areas. Among patients from rural areas under the care of non-metropolitan providers, 82.6% had low SES (Yost Index ≤ 2). In this subgroup, patients from rural areas with non-metropolitan providers had 30% higher CVD risk (sHR 1.30; 95% CI 1.04-1.62) and 44% higher all-cause mortality risk (sHR 1.44; 95% CI 1.14-1.83; Picture 2) when compared to patients with low SES from urban or rural areas with providers from metropolitan areas. Additionally, within patients from rural areas with non-metropolitan providers, the median % of people with only high school diploma was 38.3 (IQR 36.2-40.9). Among those with low educational status (≤41% of high school county-rate), patients from rural areas with non-metropolitan providers had a 35% higher associated CVD risk (sHR 1.35; 95% CI 1.06-1.71), 54% higher associated CVDm risk (sHR 1.54; 95% CI 1.01-2.36), and a 32% higher associated all-cause mortality risk (sHR 1.32; 95% CI 1.04-1.66). Conclusion Patients with PC from rural areas with non-metropolitan providers have higher rates of low SES and low educational status and suffer from up to 54% higher associated risks of adverse outcomes, emphasizing the role of multiple domains of the Social Determinants of Health in health outcomes.

Educational attainment and cardiovascular outcomes in prostate cancer: observations from 3700 men in 6 countries in the RADICAL PC study

Abstract Background Educational attainment has been associated with improved cardiovascular outcomes in individuals with or at high risk for cardiovascular disease (CVD). There is little information on the relationship between education and CVD outcomes in individuals with cancer. Also, we have limited understanding of what mediates the relationship between education and these outcomes. Purpose To evaluate the relationship between educational attainment in patients with PC and CVD event (CVE) or all-cause mortality. Methods We prospectively studied 3,778 men with PC from 55 sites in 7 countries (median age 69 years), 46% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Educational attainment was classified as those who attained primary school education vs. those who attained high school education vs. those who attained greater than high school education. Participants were followed for a median of 2.5 years from enrolment to document CVE: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism, and atrial fibrillation. The primary outcome for this analysis was CVE or death. All outcomes were evaluated by Cox proportional hazards models adjusted sequentially for age, race, physical activity levels, tobacco use, and alcohol use. Results Among 3,778 participants, 726 (19%) achieved primary school education, 1,001 (27%) high school, and 2,051 (54%) greater than high school education. On univariate analysis, as compared with participants with greater than high school education, those with high school education and primary school education had respective HR (95% CI) of 1.33 (1.05-1.69) and 2.19 (1.71-2.83). Adding age, race, tobacco, and alcohol use to the Cox model progressively attenuated the association between education and the primary outcome. Eventually, after adjustment for these characteristics and physical activity levels, the relationship between education and the primary outcome was no longer significant (Table). Conclusion This finding suggests that patterns of tobacco and alcohol use and physical activity, which are modifiable behaviors, account for the relationship between education and death or CVE in patients with prostate cancer.Table

Exploring Ethnic Variability in Aryl Hydrocarbon Receptor Signaling: Delineating Differences in Prostate Cancer Outcomes Between African American and Caucasian Populations

Exploring Ethnic Variability in Aryl Hydrocarbon Receptor Signaling: Delineating Differences in Prostate Cancer Outcomes Between African American and Caucasian Populations

LINC01518 predicts poor prognosis of prostate cancer and promotes its progression by regulating hsa-miR-320a/CNKSR2 axis

BackgroundProstate cancer (PCa) is the most common malignancy of the male genitourinary system. Understanding the molecular mechanism of PCa and its prognostic markers will assist in the selection of better treatment.AimTo explore the role of LINC01518 in the development of PCa and its prognostic value, and to understand its specific regulatory mechanism.MethodsThe levels of LINC01518, hsa-miR-320a, and CNKSR2 mRNA were detected by RT-qPCR. ROC curve was constructed to evaluate the prognostic value of LINC01518 in PCa. The effects of LINC01518 on the functions of PCa cells were demonstrated by CCK-8, Transwell test, and the detection of apoptotic markers, after LINC01518 knockdown. The interaction between hsa-miR-320a and LINC01518 or CNKSR2 mRNA was examined by constructing luciferase vectors.ResultsLINC01518 was abnormally expressed in PCa cells and tumor tissues, and knockdown of it inhibited the growth of PCa cells. LINC01518 predicted castration-resistant prostate cancer (CRPC) outcomes in PCa patients with AUC of 0.803, sensitivity and specificity of 75.4% and 74.6%, respectively. Hsa-miR-320a mimics reduced luciferase activity in PCa cells transfected with WT-LINC01518/CNKSR2 plasmids. Knocking down LINC01518 reduced CNKSR2 level, and this regulatory effect disappeared with the inhibition of hsa-miR-320a.ConclusionHigh levels of LINC01518 predicted poor prognosis in PCa patients and promoted CNKSR2 expression by competitively binding hsa-miR-320a, contributing to the progression of PCa.

The mendelian randomized study revealed the association of prostatitis with prostate cancer risk

In recent observational studies, a potential link between prostatitis and prostate cancer (PCa) has been hinted at, yet the causality remains ambiguous. In our endeavor to scrutinize the conceivable causal nexus between prostatitis and PCa, we embarked upon a Mendelian randomization (MR) study. MR circumvents arbitrary groupings by employing genetic variations that have a strong association with the exposure as instrumental variables to infer causal relationships between exposures and outcomes. The etiology of PCa remains elusive. Given that prostatitis and prostate cancer occupy the same anatomical region, MR can more effectively delineate their relationship by mitigating confounding variables. This method can indirectly elucidate disease correlations, thereby contributing to cancer prevention strategies. FinnGen Consortium data were used for the prostatitis genome-wide association study (GWAS), including 74,658 participants. UK biobank baseline data (ncase = 3436, ncontrol = 459574), European Bioinformatics Institute Database (ncase = 79148, ncontrol = 61106), and IEU openGWAS database (ncase = 79148, ncontrol = 61106) were used for PCa outcomes, mostly for European population samples. Data from the GWSAs for prostatitis were compared with data from the three GWASs for PCa, respectively, in an analysis of an MR. Utilizing the inverse variance weighting (IVW) methodology as our primary analytical framework, we delved into a meticulous exploration of the conceivable causal association between prostatitis and PCa. Furthermore, we deployed supplementary methodologies, including Maximum Likelihood, MR-Egger, weighted median, and MR-PRESSO, to thoroughly assess and scrutinize the causality aspect comprehensively. Cochran’s Q statistic is employed as a metric to quantify the heterogeneity inherent in instrumental variables. The inverse variance weighted analysis revealed no discernible effect of prostatitis on PCa in the three PCa GWAS databases (odds ratio [OR]: 1.001, 95% Confidence Interval [CI]: 0.999–1.002, p = 0.28), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40), (OR: 1.015, 95% CI: 0.981–1.050, p = 0.40). Similarly, employing MR-Egger did not yield substantial evidence (OR: 0.999, 95% CI: 0.999–1.002, p = 0.89), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07), (OR: 1.103, 95% CI: 1.006–1.209, p = 0.07). The weighted median analysis also failed to provide convincing support for the impact of prostatitis on the incidence of PCa (OR: 1.001, 95% CI: 1.000-1.002, p = 0.064), (OR: 0.989, 95% CI: 0.946–1.034, p = 0.64), (OR: 0.989, 95% CI: 0.945–1.036, p = 0.65). The results of the MR showed no causality from prostatitis to PCa.

Ultralow Prostate-Specific Antigen (PSA) Levels and Improved Oncological Outcomes in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Patients Treated with Apalutamide: A Real-World Multicentre Study.

Background/Objectives: Androgen receptor-targeted agents have significantly improved the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific antigen (PSA) levels are key prognostic markers, with rapid and deep reductions associated with better outcomes. This study aims to assess the association between the new PSA cut-offs and survival in mHSPC patients treated with Apalutamide. Methods: We conducted a multicentre, retrospective analysis of mHSPC patients treated with Apalutamide between March 2021 and January 2023. Overall survival (OS) and radiographic progression-free survival (rFPS) were analyzed and stratified by the following PSA ranges: <0.02 ng/mL (ultralow), 0.02-0.2 ng/mL, and >0.2 ng/mL. Cox regression was applied to identify variables associated with OS and rPFS. Results: Among 193 patients, 34.2% had de novo mHSPC, with the majority classified as M1b. A total of 58.2% (110) of our cohort achieved ultralow PSA levels, with 20.6% between 0.02 and 0.2 ng/mL, and 21.2% of PSA levels > 0.2 ng/mL. Most patients reached ultralow PSA within six months. Low-volume, metachronous, and M1a subgroups displayed a higher prevalence of patients reaching ultralow PSA levels. At 18 months, OS was 100% in the ultralow PSA group, 94.4% for the 0.02-0.2 ng/mL group, and 67.7% in the >0.2 ng/mL group. Similarly, rPFS at 18 months was 100%, 93.5%, and 50.7%, respectively. Cox regression revealed that both ultralow PSA levels and ISUP grade had a significant impact on OS (HR of 8.256 and 0.164, respectively). For rPFS, only ultralow PSA levels had a significant impact (HR = 0.085). Conclusions: This real-world study of mHSPC patients treated with Apalutamide plus ADT revealed that achieving ultralow PSA levels is strongly associated with better oncological outcomes.

N-linked fucosylated glycans are biomarkers for prostate cancer with a neuroendocrine and metastatic phenotype.

Prostate cancer (PCa) is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged Matrix Assisted Laser Desorption Ionization (MALDI) imaging of formalin-fixed, paraffin embedded (FFPE) prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes. We found that N-glycan fucosylation was abundant in neuroendocrine prostate cancer as well as adenocarcinomas at time of prostatectomy that eventually developed recurrent metastatic disease. Analysis of patient derived xenografts revealed that this fucosylation signature was enriched differently across metastatic disease organ sites, with the highest abundance in liver metastases. These data suggest that N-linked fucosylated glycans could be an early tissue biomarker for poor PCa outcomes. Implications: These studies identify that hyper-fucosylated N-linked glycans are enriched in neuroendocrine prostate cancer and conventional prostate adenocarcinomas that progress to metastatic disease, thus advancing biomarker discovery and providing insights into mechanisms underlying metastatic disease.

Associations of prostate tumor immune landscape with vigorous physical activity and prostate cancer progression.

Vigorous physical activity has been associated with lower risk of fatal prostate cancer. However, mechanisms contributing to this relationship are not understood. We studied 117 men with prostate cancer in the University of North Carolina Cancer Survivorship Cohort (UNC CSC) who underwent radical prostatectomy, and 101 radiation-treated prostate cancer patients in FASTMAN. Structured questionnaires administered in UNC CSC assessed physical activity. In both studies, digital image analysis of H&E-stained tissues was applied to quantify Tumor Infiltrating Lymphocytes (TILs) in segmented regions. Nanostring gene expression profiling in UNC CSC and microarray in FASTMAN were performed on tumor tissue and a 50-gene signature utilized to predict immune cell types. Vigorous recreational activity, reported by 34 (29.1%) UNC men, was inversely associated with TILs abundance. Tumors of men reporting any vigorous activity versus none showed lower gene expression-predicted abundance of Th, exhausted CD4 T cells and macrophages. T cell subsets, including Treg, Th, Tfh, exhausted CD4 T cells, and macrophages were associated with increased risk of biochemical recurrence, only among men with ERG-positive tumors. Vigorous activity was associated with lower prostate tumor inflammation and immune microenvironment differences. Macrophages and T cell subsets, including those with immunosuppressive roles and those with lower abundance in men reporting vigorous exercise, were associated with worse outcomes in ERG-positive prostate cancer. Our novel findings contribute to our understanding of the role of the tumor immune microenvironment in prostate cancer progression, and may provide insight into how vigorous exercise could affect prostate tumor biology.

Determining Long-term Prostate Cancer Outcomes for Active Surveillance Patients Without Early Disease Progression: Implications for Slowing or Stopping Surveillance

Background and objectiveActive surveillance (AS) of prostate cancer (PCa) is the standard of care for low-grade disease, but there is limited guidance on tailoring protocols for stable patients. We investigated long-term outcomes for patients without initial progression and risk factors for upgrade. MethodsMen on AS with Gleason grade group (GG) 1 PCa on three serial biopsies, ≥5 yr without progression, and ≥10 yr of follow-up were included. Outcomes were upgrade (GG ≥2), major upgrade (GG ≥3), progression to treatment, metastasis, PCa-specific survival, and overall survival. Cox proportional hazards regression models were used to estimate the associations between patient characteristics and risk of upgrade. Key findings and limitationsA total of 774 men met the inclusion criteria. At 10, 12, and 15 yr, upgrade-free survival rates were 56%, 45%, and 21%; major upgrade–free survival rates were 88%, 83%, and 61%; treatment-free survival rates were 86%, 83%, and 73%; metastasis-free survival rates were 99%, 99%, and 98%; and overall survival rates were 98%, 96%, and 95%, respectively. PCa-specific survival was 100% at 15 yr. On a multivariable analysis, year of diagnosis, age, body mass index (BMI), and biopsy core positivity were associated with upgrade (all p < 0.01), whereas age and prostate-specific antigen (PSA) density were associated with major upgrade. Conclusions and clinical implicationsPatients without progression for 5 yr on AS had modest rates of upgrade and low rates of metastasis, and mortality at 15 yr of follow-up. Year of diagnosis, older age, increased BMI, and increased biopsy core positivity were associated with upgrade, whereas older age and greater PSA density were associated with an increased risk of major upgrade. A subset of these patients may benefit from deintensification of AS protocols. Patient summaryThere are little reported data or clinical guidelines for patients with prostate cancer (PCa) who are stable for many years on active surveillance (AS). We show, in a large cohort, that PCa patients without progression for 5 yr on AS have modest rates of upgrade and very low rates of metastasis, and mortality rates at 15 yr of follow-up, and that older age, increased body mass index, and increased PCa volume are associated with an increased likelihood of future upgrade. This study supports continued AS in this patient population and deintensification in select patients.

Prostate cancer disparities in clinical and survival patterns among Black and Latino patients considering nativity: findings from the California Cancer Registry.

We investigated clinical characteristics and prostate cancer (PCa) survival patterns among Latino patients considering nativity compared to non-Latino Black (NLB) and non-Latino White (NLW) patients. We used data from the California Cancer Registry (1995-2021), which included 347,540 NLW, 50,032 NLB, and 75,238 Latino PCa patients. Frequencies of sociodemographic and clinical variables were assessed with Chi-square tests. Multivariable regression models were fitted to evaluate determinants of treatment reception, Gleason upgrade, and survival differences. Exploratory analyses were conducted grouping Latino cases into US-born and non-US-born by country-of-origin. Compared to NLW, NLB cases had the greatest proportion of younger patients, whereas non-US-born Latino patients had the greatest proportion of low socio-economic status and uninsured patients. Non-US-born Latinos showed greater proportion of diagnoses completed with <6 core biopsies, Gleason >8, stage IV tumors and metastasis. Multivariable analyses showed that compared to NLW, Latino patients were as likely to receive treatment, whereas NLB cases were less likely (OR = 0.81, 95% CI: 0.67-0.98, p = 0.029). Compared to NLW, Non-US-born Latino cases were less likely to die of PCa (HR = 0.78; 95% CI = 0.64-0.94, p=0.011), with no difference reported for NLB cases. Considering sociodemographic and clinical characteristics, non-US-born Latino PCa patients had better survival than NLW. This highlights the need to identify key determinants of these survival differences, and the importance of sociodemographic and clinical determinants in survival disparities. Our study emphasizes the importance of considering nativity among Latino patients to understand PCa disparities and outcomes in this population.

Abstract A062: Glycemic control and risk of total and advanced prostate cancer in Veterans with diabetes: analysis of disparities by race/ethnicity

Abstract Introduction Access to quality healthcare is considered a key driver in the multifactorial process giving rise to racial inequities in two of the most common complex diseases in adult men in the US - prostate cancer and diabetes. Whether inequities in diabetes treatment and outcomes, and/or related metabolic and hormone signaling pathways contribute to racial differences in prostate cancer outcomes in an equal access setting is unknown. Our objective is to determine if associations between glycemic control assessed by routine clinically measured hemoglobin A1c (A1c), among men with diabetes and risk of total and advanced prostate are similar in Black and White men receiving care from the Veterans Health Administration (VHA). Methods We used clinical data from the VHA to construct a longitudinal cohort of male Veterans &amp;gt;=45 years of age with diagnosed diabetes free of any cancer from 01/01/2010 to 12/31/2019. We classified men with total prostate cancer if the date of prostate cancer diagnosis preceded any other cancer diagnosis. Advanced prostate cancer was classified as prostate cancer diagnosis with Gleason score &amp;gt;=8, or PSA &amp;gt;=100 ng/mL, or metastasis, or death from prostate cancer. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for time-updated annual mean A1c (&amp;lt;7% [ref]; 7-8%; &amp;gt;8%) and total and advanced prostate cancer risk adjusted for age; marital status; rurality, smoking; annual primary care visits; service-connected disability; comorbidities; statin use; and oral diabetes medication use for non-Hispanic Black (NHB) and non-Hispanic White (NHW) men separately. Results Among 736,964 Veterans with diabetes, we observed 31,330 prostate cancer events including 6,779 advanced prostate cancers. For NHW men, poor glycemic control (A1c &amp;gt;8%) and moderate control (A1c 7-8%) were associated with a 19% (HR=0.81; 95%CI=0.78-0.84) and 8% lower risk (HR=0.92; 95%CI=0.89-95) of total prostate cancer incidence (p-trend&amp;lt;0.001). Among NHB men, inverse associations were attenuated for poor (HR=0.90; 95% CI=0.86-0.95) and moderate (HR=1.01; 95% CI=0.96-1.06) glycemic control and total prostate cancer risk (p-trend &amp;lt;0.001). For advanced prostate cancer, associations were inverse for poor (HR=0.90; 95% CI=0.83-0.97) and moderate glycemic control (HR=0.90; 95% CI=0.84-0.97) and advanced prostate cancer risk in NHW men, while non-statistically significant associations were observed in NHB men with poor HR=1.06; 95%CI=0.96-1.18) and moderate glycemic control (HR=1.04; 95%CI=0.94-1.16). Conclusion In the largest equal access healthcare system in the US, inverse associations for glycemic control and risk of total and advanced prostate cancer varied by race/ethnicity with stronger inverse associations observed in NHW men compared to NHB men. Whether the racial differences in diabetes treatment and care contribute to the observed disparities in total and advanced prostate cancer risk could inform precision public health efforts aimed at reducing inequities in both diabetes and prostate cancer outcomes. Citation Format: Michael T. Marrone, Kinfe G. Bishu, Neal Axon, Hermes Florez, Robert L. Grubb, Mulugeta Gebregziabher. Glycemic control and risk of total and advanced prostate cancer in Veterans with diabetes: analysis of disparities by race/ethnicity [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A062.

Abstract B084: Multi-Stakeholder Engagement to Create Equity in Prostate Cancer Outcomes through Identifying Community Priorities in Early Detection Research

Abstract Introduction: Black individuals have a two-fold higher rate of prostate cancer death in the US compared with other groups. This is the largest racial inequity in US cancer-related deaths. Annual prostate-specific antigen (PSA) testing among Black individuals starting at age 45 years could reduce mortality by 30% compared with current screening practices. Few current practice guidelines make race-conscious screening recommendations due to a lack of trial data on screening in Black populations; only 0-3% of participants in practice-informing PSA screening trial cohorts were Black. An equity-informed approach is required to ensure that trial designs reflect the priorities and perspectives of Black individuals to ensure their participation in future research. Methods: We partnered with the Black and African-descent Collaborative for Prostate Cancer ACtion (BACPAC) to conduct a survey to identify community priorities in prostate cancer early detection research. Respondents were asked to rate the importance of 15 research topics, then select the three topics most critical for research. Members of the BACPAC Virtual Research Community (VRC), a nationally representative group of 2,016 Black prostate cancer survivors and community members, were invited to participate. Eligible members were Black prostate cancer survivors and family members/caregivers of Black prostate cancer survivors. Those who met the inclusion criteria were emailed a unique link to complete the online survey. Results: 1,557 eligible VRC members received a survey link, 1,224 surveys were completed (78.6% response rate). 60% of respondents were survivors, 38% were family members/caregivers, and 2% were both. More than 80% of respondents rated each of the 15 research topics as moderately to very important. Topic rankings revealed two overarching priority areas, representing 6 out of 15 topics included in the survey. These areas were 1) the use of reflex testing in the setting of elevated PSA to aid detection of clinically significant cancer and 2) establishing optimal timing for initiation or interval of PSA testing for prostate cancer screening. Regarding use of reflex testing, 97.7% of respondents prioritized blood (44.3%), urine (27.8%), or MRI (25.6%) reflex testing. Regarding timing of PSA testing, 51.5% of respondents prioritized customized screening schedules based on personal risk factors, with 24.9% selecting to improve rates of screening and 26.6% selecting to improve detection of clinically significant cancers, and 25% of respondents prioritized initiating screening at age 45 to improve early detection of prostate cancer. Conclusion: Our survey identified critical research topics that are of high importance to Black prostate cancer survivors and their families/caregivers. Our findings bridge a critical gap in prostate cancer early detection research, from which Black individuals have been historically excluded. Involving Black prostate cancer survivors in research design may help ensure that Black individuals are better represented in future clinical trials. Citation Format: Jenney R. Lee, Sung Min Kim, Erika M. Wolff, Yohali Burrola-Mendez, Dante' Morehead, Ben Young, Raymond Miller, Robert Ginyard, Frank Fields, Marty Chakoian, Patrick Bingham, Daniel VanArsdale, Mike Crosby, Tony Minter, Thomas Farrington, John Masembe, Burcu Darst, Ruth Etzioni, Adam Murphy, Sam L Washington, Jonathan Shoag, Yaw A Nyame. Multi-Stakeholder Engagement to Create Equity in Prostate Cancer Outcomes through Identifying Community Priorities in Early Detection Research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B084.

Abstract C098: CYR61 expression in prostate cancer patients at City of Hope

Abstract In the US, African-American (AA) and Hispanic/Latino (H/L) men have higher rates of advanced prostate cancer (PCa), increased PCa-specific mortality, and are more likely to undergo metastasis than non-Hispanic White (NHW) men attributed to a lack of access to early screening, and a higher prevalence of risk factors such as obesity, diet, and genetic differences. Consequently, effective treatment of advanced PCa and elimination of racial and ethnic disparities for this malignancy require the identification of mechanisms of disease progression. In PCa, the cysteine-rich angiogenic inducer 61 (CYR61) contributes to malignant cell growth through interactions with extracellular ligands, such as integrins avb3 and a6b4. In previous studies, we have found that CYR61 is upregulated in metastatic PCa cell lines and knockdown of this protein significantly reduced metastatic cell proliferation, viability, prostasphere formation, and activation of the PI3/AKT pathway, indicating a potential utilization of CYR61 inhibition in the therapy of metastatic PCa. Interestingly, we have observed that in metastatic PCa cell models, IGF1 induction increased CYR61 protein expression. However, the correlation between PCa aggressiveness and levels of CYR61 in tumor-derived tissues from patients is poorly studied. Our goal with this study is to identify possible correlations in CYR61 expression that may reflect health disparities in PCa outcomes. We used in silico analyses from whole exome paired tumor/normal DNA sequencing and tumor RNA sequencing data available on 542 PCa cases in the City of Hope POSEIDON database to determine whether gene expression of CYR61 and IGF1 was correlated with genetic ancestry, Gleason score, and tumor purity. In univariate analyses, we found that H/L PCa cases had significantly higher levels of expression of CYR61 than NHW PCa cases (p = 0.043) and that both H/L and AA PCa cases had higher IGF1 expression levels, although only significant in AA (p=0.031). We also found that PCa patients with Gleason scores of 8 and higher had significantly lower expression of IGF1 than those with Gleason scores of 7 or less (p=0.006). Both CYR61 and IGF1 expression levels were significantly lower in those with luminal B (p=0.00000000053, p=0.000009, respectively) and with basal subtypes (p=0.00035, p=0.000069, respectively compared to luminal A subtype. Tumor purity was estimated by RNA-seq based on 141 genes specific to stroma and 141 genes specific to immune cells. CYR61 expression was significantly correlated with stromal and immune infiltration. These results suggest that reduced CYR61 expression is associated with more aggressive PCa. Additional analyses are ongoing to understand the interplay of variables of race and ethnicity, age, Gleason score, and tumor purity and to investigate outcomes of biochemical recurrence and death from PCa. Citation Format: Greisha L. Ortiz-Hernandez, Yuan Chun Ding, Susan L. Neuhausen. CYR61 expression in prostate cancer patients at City of Hope [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C098.

Abstract A039: Joint roles of proteomics and neighborhood-level social determinants of metastatic prostate cancer

Abstract Introduction: Striking racial disparities in prostate cancer (PCa) outcomes among American Black men warrant significant efforts to identify early predictors of lethal PCa, to avoid over- treatment of clinically favorable disease with minimal risk of progression. Building on prior work, this study examined independent and joint roles of proteomic markers and social determinants of health (SDOHs) in predicting prostate disease aggressiveness in a racially diverse cohort of men undergoing prostate biopsy. Methodology: A retrospective cohort of 300 men biopsied for prostate cancer was assembled at University Hospitals (UH) Seidman Cancer Center in Cleveland, Ohio between January 1, 2005-May 2022. An extensive medical chart review was performed to identify Black and White men undergoing transrectal ultrasound- guided biopsy that resulted in: (i) a negative biopsy in patients with a history of 1+ prior negative biopsy and no PCa history (“NEG”); (ii) a biopsy-detected PCa of Gleason sum 6 (“GL6”); and (iii) biopsy-detected PCa with nodal and/or distant metastases at initial cancer detection (“METS”). Prostate biopsy tissues were obtained on each patient, balancing 100 men per biopsy group, and balanced on race (1:1) within each biopsy group. Informed by findings from an untargeted analysis of the entire proteome of 60 patients (“Discovery cohort”), we conducted a targeted proteomics analysis of 16 protein markers generated from prostate biopsy tissue, using mass spectrometry, on n=240 patients (“Verification cohort”). Chi-square testing and Analysis of Variance (ANOVA) were used to assess associations between protein expression, neighborhood-level SDOHs, and biopsy group. Race-stratified analyses were performed to examine statistical interactions between study associations. Principal components (PC) analysis was used to identify protein markers that predicted the greatest variance in biopsy group. Multivariable logistic regression (MLR) was used to predict METS (vs. NEG and GL6, combined), as a function of PC-selected protein markers and census block-group level area deprivation index (ADI). Bonferroni correction was used to establish the threshold for the decision rule of statistical significance (alpha error 0.05/16 markers: p&amp;lt; 0.0031). Results: Median patient age was 68 years. Protein expression distributions were transformed into quintiles due to non-normality. Of 16 protein markers, 14 were significantly correlated with biopsy group, including PARP 1 and TGFB1, for which METS patients had the highest expression. ADI was strongly correlated with race but not protein expression. ADI was significantly higher in METS patients, followed by GL6 and lowest in NEG group; however no associations were seen for ADI with protein expression. Eight proteins were found to predict METS in PC and MLR analysis. Conclusions: These data support use of proteomics markers to predict a metastatic versus non-metastatic biopsy result. Next steps include deep exploration of proteome findings generated in the Discovery cohort, such as biological pathways. Citation Format: Jennifer Cullen, Tao Liu, Holly Hartman, Fangzhou Liu, Anood Alfahmy, Rini Ghosh, Ayesha Shafi, Julia Payne, Randy Vince, Lee Ponsky, Gregory MacLennan. Joint roles of proteomics and neighborhood-level social determinants of metastatic prostate cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A039.

Abstract C074: Patient-provider communication and receipt of definitive prostate cancer treatment by race and rurality

Abstract Background: Patient-provider communication (PPC) is critical in treatment decisions for cancer care, and it is unknown if improved communication may mitigate disparities in prostate cancer (PCa) outcomes by race and rurality. We examined associations between PPC and treatment receipt among Black and White patients diagnosed with incident PCa in the North Carolina Louisiana Prostate Cancer Project. Methods: Near-equal numbers of Black (n=1130) and White (n=1128) participants were recruited by rapid case ascertainment from 2004-2009. PPC was assessed from the baseline survey, where participants rated their cancer provider using three subscales adapted from the Primary Care Assessment Survey for contextual knowledge of the patient (CK: knowledge of patient’s medical history, home/work responsibilities, their worries, and the patient as a person), and communication content (CMN: doctor’s thoroughness of questions, attention, explanations of health problems, instructions about symptoms, and advice/help in making care decisions), and interpersonal treatment (IT: amount of time spent, patience, friendliness, caring, concern, and respect for patient). First-course treatment was ascertained from medical records and defined as definitive (surgery or radiation) compared to non-definitive treatment (all other). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for receipt of definitive treatment with logistic regression, adjusted for age at diagnosis, cancer aggressiveness, educational attainment, and marital status. Results: Black participants were diagnosed at younger ages (mean 62 vs. 64 years) with more aggressive disease (21% vs. 15%) and received surgery or radiation less often than White participants (73% vs. 77%). Median PPC subscales differed between Black and White participants (CK: 16 vs 15; CMN: 23 vs 24; IT: 22 vs 23), and between rural and urban participants (CK: 16 vs 16; CMN: 22 vs 24; IT: 21 vs 23). The odds of receiving definitive treatment was associated with positive communication content (1.12, 1.06-1.18), and interpersonal treatment (1.08, 1.02-1.14) among Black and White participants. Among urban participants, communication content (1.09, 1.05-1.15), and interpersonal treatment (1.09, 1.04-1.14) were associated with higher odds of definitive treatment. Among rural participants, higher communication content was associated with increased odds of receiving definitive treatment (OR 1.15, 95%CI: 1.04-1.28). We did not observe associations for contextual knowledge with the odds of receipt for definitive treatment subgroups. Conclusions: Positive patient-provider communication was associated with higher odds of receiving surgery/radiation in a historical cohort of PCa patients diagnosed between 2004-2009. Higher communication content and interpersonal treatment could promote uptake of contemporary guideline-based treatment recommendations for PCa. Future research will assess the validity and reliability of the communication subscales via annual follow-up questionnaires and associations with cancer-specific survival. Citation Format: Jeanny H Wang, Bria Carmichael, Shaun Jones, Hung-Jiu Tan, Deshira D. Wallace, Jennifer L. Lund, Lixin Song, Jeannette T. Bensen, Eboneé N. Butler. Patient-provider communication and receipt of definitive prostate cancer treatment by race and rurality [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C074.

Abstract A061: The impact of race and obesity on the prostate tumor microenvironment

Abstract Black Americans have the highest prostate cancer incidence and are twice as likely to die from their disease compared to Non-Hispanic White men, making this one of the largest cancer disparities between these two racial groups in the United States. While access to health care is one of the strongest contributors to this disparity, studies suggest biological distinctions exist between tumors from Black and Non-Hispanic White men. Furthermore, obesity is associated with worse prostate cancer outcomes, and research showing a stronger association between obesity and prostate cancer risk among Black men compared to Non-Hispanic White men suggests obesity and Black race may work in combination to create aggressive disease. Hence, we sought to thoroughly and precisely characterize tumors from Black men, with and without obesity, to identify tumor behavior and potential therapeutic options for this population, which to date, has not been done mostly because of the lack of racially diverse cohorts of prostate cancer. Also, we sought to determine the impact of obesity on the composition of the prostate tumor microenvironment, which to date remains unknown. Given that in the US obesity rates are over 40% and the pressing need to better address high-risk populations, it is critical to better understand how obesity and race impact disease biology. We hypothesized obesity and Black race, individually and combined, increase tumor immune infiltration, creating a distinct tumor microenvironment. Specifically, we hypothesized this microenvironment will be characterized by higher overall inflammation, but also will enable us to identify therapeutic targets that in time can lead to the creation of personalized treatments for this population. To test this hypothesis, we used a large and racially diverse patient cohort from men who underwent radical prostatectomy at the Veterans Affairs Medical Center in Durham, North Carolina. To analyze the tumor microenvironment at the single cell level and define spatial organization, we used imaging mass cytometry in tissue microarrays of tumor and normal prostate samples from patients similar in tumor stage. We created a customized marker panel to determine cell phenotype and expression of immune checkpoints. We detected 25 cell phenotypes in the prostate microenvironment and determined differential phenotypic abundance and interactions by race and obesity. Next, we will expand our study to include a larger number of samples and associate tumor microenvironment characteristics with patient recurrence, metastasis, and survival. In this study, we generated new insights into disease drivers in an understudied and disproportionately affected population and lay important groundwork for future research identifying novel therapeutic targets for high-risk populations, such as men with African descent and obesity. Citation Format: Gloria Cecilia Galvan, Simeon Mahov, Sungyong You, Simon Knott, Michael Freeman, Akil Merchant, Stephen J Freedland. The impact of race and obesity on the prostate tumor microenvironment [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A061.

Private economic impacts of late prostate cancer diagnosis: evidence from New Zealand's integrated data infrastructure

Prostate cancer outcomes significantly depend on its stage and grade at diagnosis. Early detection expands treatment options and improves prognosis and quality of life, especially for working-age men, preserving their ability to support their families and remain actively engaged in society. While research has extensively covered the health and psychological effects of prostate cancer, the socio-economic impacts remain less understood. This study uses data from New Zealand's Integrated Data Infrastructure (IDI) to examine the relationship between prostate cancer diagnosis and its effects on income and employment. Our analysis, focusing on early-stage and late-stage diagnoses, shows no significant employment differences in the 48 months post-diagnosis between prostate cancer patients and matched controls. However, we observe a reduction in monthly earnings post-diagnosis, with those diagnosed at a late stage experiencing a more substantial income decline.

Real-world outcomes following biochemical recurrence after definitive therapy with a short prostate-specific antigen doubling time: potential role of early secondary treatment.

The natural history of biochemical recurrence (BCR) managed with delayed hormonal therapy is well documented by data from Johns Hopkins. However, as many patients receive treatment prior to metastasis, we evaluated the natural history and role of prostate-specific antigen doubling time (PSADT) in a more contemporary cohort of BCR patients with nonmetastatic castration-sensitive prostate cancer (nmCSPC). Patients in the Veterans Health Administration (VHA; 01/01/06 to 06/22/20) with nmCSPC and BCR were divided into rapid ( ≤9 months) and less rapid ( >9 to ≤15 months) PSADT cohorts. Patients with PSADT >15 months were excluded as outcomes, even with delayed treatment, are excellent. Outcomes included time to first antineoplastic therapy after BCR, metastasis, metastasis-free survival (MFS), and overall survival (OS). Cox models adjusted for baseline demographics and clinical characteristics. Overall, 781 patients with BCR were identified (502 rapid; 279 less rapid PSADT). Rapid PSADT was associated with shorter time to first systemic antineoplastic therapy (median 11.4 vs. 28.3 months, adjusted hazard ratio [95% confidence interval] 2.17 [1.83-2.57]), metastasis (102.4 months vs. not reached, 1.79 [1.33-2.40]), MFS (76.1 vs. 106.3 months, 1.73 [1.33-2.24]), and OS (120.5 vs. 140.5 months, 1.76 [1.22-2.54]) versus less rapid PSADT. Most patients with rapid PSADT underwent secondary treatment within 1 year after BCR. More contemporary patients treated with early secondary treatment had better outcomes than historical data from patients who had delayed treatment. Whether these results reflect the benefits of early secondary treatment or overall improvements in prostate cancer outcomes over time requires further study.

PIONEER big data platform for prostate cancer: lessons for advancing future real-world evidence research.

Prostate Cancer Diagnosis and Treatment Enhancement through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer. PIONEER brings together 34 private and public stakeholders from 9 countries in one multidisciplinary research consortium with the aim of positively transforming the field of prostate cancer clinical care by answering pressing questions related to prostate cancer screening, diagnosis and treatment. PIONEER has developed a unique state-of-the-art big data analytic platform by integrating existing data sources from patients withprostate cancer. PIONEER leveraged this platform to address prioritized research questions, filling knowledge gaps in the characterization, management and core outcomes of prostate cancer across the different disease stages. The network has benefited from sustained patient and stakeholder involvement and engagement, but many challenges remain when using real-world data for big data projects. To continue to advance prostate cancer care, data need to be available, suitable methodologies should be selected and mechanisms for knowledge sharing must be in place. Now acting as the prostate cancer arm of the European Association of Urology's new endeavour, UroEvidenceHub, PIONEER maintains its goal of maximizing the potential of big data to improve prostate cancer care.

Epidemiology of Prostate Cancer in Africa: An In-Depth Review

Prostate cancer is a major health challenge in Africa, presenting significant regional disparities in incidence and outcomes. This review provides an in-depth examination of the epidemiology of prostate cancer on the continent, considering a range of factors that influence its prevalence and management. Genetic predispositions, including mutations in BRCA1, BRCA2, and HOXB13, play a crucial role, with African populations displaying unique genetic variants contributing to higher incidence rates. Environmental and lifestyle factors, such as diet, physical activity, and substance use, also impact prostate cancer risk. Traditional African diets, rich in fruits and vegetables, may offer protective benefits, while modern dietary patterns and sedentary lifestyles are linked to increased risk. Socioeconomic determinants, including access to healthcare, educational attainment, and financial barriers, significantly affect diagnosis and treatment, often leading to late-stage presentations. Hormonal and biological factors, such as androgen levels and age-related changes, further influence disease development. Infections, inflammatory conditions, and occupational exposures also contribute to risk. Cultural and behavioral influences, including traditional beliefs and health-seeking behaviors, impact prevention and management strategies. The review highlights the challenges faced by healthcare infrastructure and screening programs, emphasizing the need for improved access, public awareness, and tailored interventions. Addressing these factors through comprehensive public health strategies, including enhanced screening, lifestyle modifications, and cultural sensitivity, is essential for improving prostate cancer outcomes across Africa. Keywords: Epidemiology, Prostate Cancer, Africa, Genetic, Biological factor.