White Prostate Cancer Patients Research Articles

Real-world analyses of mortality risk after androgen deprivation therapy initiation in Black vs. White patients with prostate cancer.

84 Background: 2 studies found significantly longer overall survival in Black vs. White patients with metastatic castration-resistant prostate cancer (PCa): a 2019 meta-analysis of 9 phase III trials and a 2020 registry study. Our real-world data study compared all-cause mortality risk for Black vs. White PCa patients. Compared to the prior studies, our study encompasses a broader scope and is not exclusive to men with castration-resistant PCa. Methods: Data were collected from the Decision Resources Group Real World Evidence repository, which links medical and prescription claims, and US Electronic Healthcare Records. The analysis set included PCa patients who received ≥1 androgen deprivation therapy (ADT) injection between 1991-2020. Cox regression was used to compare all-cause mortality rates between White and Black patients. Multivariable regression model accounted for the following variables: baseline metastasis, BMI, oncology vs. urology setting, antagonist vs. agonist, personal major adverse cardiovascular event (MACE) history, tobacco history, baseline PSA (>4 vs. ≤4 ng/mL), race (White vs. Black), statin use, increasing age per year, ethnicity (non-Hispanic vs. Hispanic), increasing ADT exposure per year, diabetes, hypertension, and family MACE history. Results: 44,439 patients were included for the all-patient analyses. 34,762 patients were included in the Black vs White analyses: 5,817 and 28,945 were Black and White, respectively. Overall, mortality risk was 2.6% and 17% at 1 and 4 years after ADT initiation, respectively. Mortality risk after ADT initiation was 1.6% and 2.6% at 1 year and 11.7% and 18.1% at 4 years for Black and White patients, respectively. Both unadjusted (HR=1.66, 95% CI 1.53-1.80, p<0.05) and adjusted (HR=1.24, 95% CI 1.01-1.52, p<0.05) mortality risks were higher for White vs. Black patients. Conclusions: All-cause mortality incidence was higher in White vs. Black patients. Adding to the body of evidence, our research also reveals that Black race is associated with a protective effect on survival for all-cause mortality in men undergoing ADT. Potential hypotheses for higher mortality in White vs. Black patients include survival bias to MACE (i.e., Black patients may have died from PCa before having MACE), survival bias to be diagnosed with PCa (i.e., Black patients may have higher rate of CV death and kidney failure prior to PCa diagnosis), and protective effects of higher BMI in Black patients against cancer cachexia. The large size (~45,000 patients from a database with >300 million patients), long follow-up (10 years for some patients), recent clinical experience (99% from 2010-2020), and diversity of the dataset give weight to the results being an accurate representation of current clinical experience. Future studies should confirm our findings that White PCa patients have higher mortality risk and investigate the above hypotheses.

Social Drivers of Cancer Risk and Outcomes Among African American Men.

Social risk factors play an important role in minority health and cancer health disparities. Exposure to stress and stress responses are important social factors that are now included in conceptual models of cancer health disparities. This report summarizes results from studies that examined stress exposure and responses among African Americans. Data from studies that were conducted as part of a transdisciplinary and translational research center are also presented to provide additional insight about the nature of racial differences in specific stressors among African American and White prostate cancer patients.

Abstract A001: Differential alternative RNA splicing and transcription events between Black and White prostate cancer patients involve genes promoting cancer aggressiveness and associate with patient survival

Abstract Black patients suffer disproportionately from prostate cancer (PCa) progression to lethal disease compared with Asian and White patients. Comparing the molecular landscape of PCa in Black and White men has the potential to identify targets for development of new precision medicine interventions. Alternative RNA splicing and transcription events (ARS/Ts) can alter gene function. Cancer may exploit ARS/Ts to enhance proliferation, metastasis, and drug resistance. Here, we isolated RNA from fresh frozen PCa specimens and tumor-associated normal (TAN) specimens from 35 self-reported Black and 37 self-reported White patients diagnosed with Gleason-high or -low PCa and undergoing radical prostatectomy or biopsy. Analysis of follow-up clinical data for patients participating in our study show an increased hazard ratio of PCa progression among Black patients compared to White patients (HR = 2.13 and p < 0.05). We performed comparative transcriptomic analysis between Gleason-high or -low tumor and TAN samples among Blacks, among Whites, or between Blacks and Whites with Gleason-high or –low PCa. Among differential ARS/Ts identified between tumors and TANs among Blacks, 532 are unique to Gleason-high and 673 are unique to Gleason-low. Among differential ARS/Ts between Blacks and Whites, 360 are unique to Gleason-high and 242 are unique to Gleason-low. Interestingly, we found that even in TANs, there are 802 differential ARS/Ts between Blacks and Whites, with 459 and 343 in Gleason-high and Gleason-low, respectively. Among the genes undergoing differential ARS/Ts between Blacks and Whites are FGFR1, AKT1, H6PD, MDM2, and RAD51D in Gleason-high and CDK7 and VEGFA in Gleason-low. Notably, the number of genes undergoing ARS/Ts between Blacks and Whites with Gleason-high or -low tumors was higher than the number of genes undergoing differential aggregate gene expression between Blacks and Whites. Using gene set enrichment analysis, we found that genes undergoing ARS/Ts function in cancer relevant pathways. For example, the genes undergoing ARS/Ts between Blacks and Whites with Gleason-high or -low tumors were enriched in spermatogenesis and P53 hallmark pathways, respectively. Importantly, survival analysis shows a number of differential ARS/Ts between Blacks and Whites with Gleason-high or -low tumors are individually associated with progression-free survival. In summary, we have investigated the biology of PCa and TAN tissue between Black and White patients at the exon level. A number of genes undergoing newly identified differential ARS/Ts between Blacks and Whites are in genes reported to promote cancer aggressiveness and a number are in genes whose function in cancer was unreported prior to our findings, and a number are associated with patient progression-free survival. Our findings have identified novel targets with potential for precision oncology for PCa. Estimation of genetic ancestry of study participants and in vitro and in vivo validation of prioritized targets for PCa biology are underway. Citation Format: Muthana Al Abo, Wen-Chi Foo, Lauren Howard, Monika Anand, Daniel J. George, Steven R. Patierno, Jennifer A Freedman. Differential alternative RNA splicing and transcription events between Black and White prostate cancer patients involve genes promoting cancer aggressiveness and associate with patient survival [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A001.

Abstract 984: Race- and ancestry-related metabolites and SNPs associated with response to secondary hormonal therapy in metastatic castration-resistant prostate cancer

Abstract The number of new cases and deaths from prostate cancer (PCa) is highest for Black men compared with other racial and ethnic groups, and Black PCa patients have a shorter average survival as well as a greater risk of tumor recurrence than men of other racial and ethnic groups. However, recent studies have shown that Black PCa patients have a better response to certain therapeutic regimens than White PCa patients. This study focuses on addressing the critical need to determine novel relationships between ancestry-related genetic variation and PCa aggressiveness and response to secondary hormonal therapy in metastatic castration-resistant PCa (mCRPC). We conducted correlative science in a DoD Prostate Cancer Clinical Trials Consortium (PCCTC) prospective multicenter study of secondary hormonal therapy in mCRPC stratified by race, Abi Race. This study enrolled 50 self-reported Black and 50 self-reported White mCRPC patients, and such patients received abiraterone and prednisone until disease progression or adverse event. We performed metabolic profiling using serum samples from fasting patients at baseline and after treatment. In addition, we performed genome-wide genotyping using genomic DNA from whole blood specimens from patients at baseline. We then identified race- and ancestry-related metabolite and SNP variations that associated with outcome using a penalized Cox model approach. In addition, we used Ingenuity Pathway Analysis (IPA) and Lasso Analysis to further study race-related metabolites and SNPs. From these analyses, we identified sphingolipids such as ceramide as race-related metabolites associated with outcome as well as SNPs in Sphingosine Kinase Type 1-Interacting Protein (SKIP) associated with outcome. In addition, our analyses suggest that sphingolipids such as ceramides and SKIP may regulate cancer-related biofunctions differently in Black and White mCRPC patients undergoing abiraterone treatment. Both sphingolipids and SKIP are components of the Sphingosine Rheostat, the regulatory component of sphingolipid cellular metabolism often exploited by various cancers, in which ceramides displays a pro-apoptotic role whereas sphingosine-1-phosphate (S1P) is associated with an anti-apoptotic role and is indirectly regulated by SKIP via regulating the activity of Sphingosine Kinase (SPK1). Evaluation of the function of these sphingolipids and SKIP in PCa cell drug response and aggressiveness are currently underway. These findings are furthering understanding of race- and ancestry-related biological factors that influence response to secondary hormonal therapy in mCRPC and have the potential to impact selection of patients for secondary hormonal therapy and to mitigate PCa disparity. Citation Format: Sean Alan Piwarski, Tyler Allen, Bonnie LaCroix, Lauren Howard, Morgan Paul, Nick Bachelder, Alex Sibley, Steve Patierno, Terry Hyslop, Kouros Owzar, Daniel George, Jennifer Freedman. Race- and ancestry-related metabolites and SNPs associated with response to secondary hormonal therapy in metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 984.

Church Attendance and Mobility Limitation Among Black and White Men With Prostate Cancer

Prostate cancer is a significant impediment that can reduce physical functional status. Mobility is fundamental for quality of life and church attendance to be associated with improved physical functioning. Few studies have examined how religious participation have implications for mobility limitation among men in general and among prostate cancer survivors in particular. The purpose of this study was to assess the association between church attendance and mobility limitation among Black and White prostate cancer patients and survivors. Data for this investigation were drawn from the Diagnosis and Decisions in Prostate Cancer Treatment Outcomes Study that consisted of 804 Black and White men with complete information on the primary outcome and predictor variables. Mobility limitation was the primary outcome variable, and church attendance was the main independent variable. The analytic sample was almost equally divided between Black (N = 382) and White men (N = 422). The proportion of Black men reporting mobility limitation (30.09%) more than doubled the corresponding percentage for White men (14.7%). Black men had a higher proportion of individuals who reported weekly church attendance (49.2% vs. 45.0%). Fully adjusted modified Poisson regression models produced results indicating that respondents attending church weekly had a lower mobility limitation prevalence (PR = 0.56, 95% CI [0.39, 0.81]) than those never attending church. Results from this study contribute to the body of evidence asserting the health benefits of church attendance. These findings suggest that health providers should consider how religion and spirituality can present opportunities for improved outcomes in prostate cancer patients and survivors.

Abstract PO-100: Ancestry-related variation in Sphingosine Kinase Type 1-Interacting Protein (SKIP) and Sphingosine Kinase 1 (SPHK1) and response to secondary hormonal therapy in metastatic castration-resistant prostate cancer

Abstract The number of cases and deaths from prostate cancer (PCa) is highest for African American (AA) men compared with men of other racial and ethnic groups, and AA men more frequently have more aggressive disease. However, recent studies have shown that AA PCa patients have a better response to certain therapeutic regimens than white PCa patients. We conducted a DoD Prostate Cancer Clinical Trials Consortium (PCCTC) prospective study of secondary hormonal therapy (HT) in metastatic castration-resistant PCa (mCRPC) patients stratified by race, Abi-Race. This study enrolled 50 AA and 50 white patients with mCRPC and received abiraterone and prednisone daily until disease progression or adverse event. AA men had higher rates of Prostate Specific Antigen (PSA) response and time to PSA progression. Herein we focus on correlative science in the context of Abi-Race to determine novel relationships between ancestry-related genetic variation and response and time to progression on secondary HT in mCRPC. An exploratory genome-wide analysis assessing the role of genotypic and local ancestry variation with respect to time to progression identified a missense variant in Sphingosine Kinase Type 1-Interacting Protein (SKIP) with predicted pathogenicity and potentially high ancestral variation. SKIP plays a role in modulating the conversion of sphingosine to sphingosine-1-phosphate (S1P) by regulating Sphingosine Kinase 1 (SPHK1) activity within the cytosol. S1P is a potent lipid mediator that plays a role in multiple cancer-promoting biofunctions. SKIP directly binds and inhibits SPHK1 activity, resulting in the decreased production of S1P and S1P-associated cell signaling. The relationship between SKIP and SPHK1 and response to secondary HT in mCRPC was investigated. We knocked down SKIP or SPHK1 in LN95 prostate cancer cells and assessed resulting alterations in proliferation with or without abiraterone. Knockdown of SKIP increased proliferation in untreated cells and knockdown cells were more resistant to treatment with abiraterone compared with the control group. Conversely, knockdown of SPHK1 decreased proliferation in untreated cells and knockdown cells were more sensitive to treatment with abiraterone compared with the control group. In addition, we are measuring changes in sphingosine and S1P in serum samples we collected from fasting Abi-Race patients at baseline and cycle 4 of treatment to investigate ancestry-related sphingosine and S1P variations and associated outcomes. Lastly, we are further investigating the potential function of the variant in SKIP associated with time to progression on secondary HT in mCRPC. These findings will further the understanding of ancestry-related biological factors that influence response to secondary HT in mCRPC and could have direct implications for the timing and selection of AA patients for secondary HT and those needing additional therapy. Ultimately, such strategies have the potential to mitigate prostate cancer disparities. Citation Format: Sean A. Piwarski, Tyler A. Allen, Dadong Zhang, Alexander B. Sibley, Patrick Healy, Brendon M. Patierno, Bonnie L. LaCroix, Rick A. Kittles, Kouros Owzar, Terry Hyslop, Steven R. Patierno, Daniel J. George, Jennifer A. Freedman. Ancestry-related variation in Sphingosine Kinase Type 1-Interacting Protein (SKIP) and Sphingosine Kinase 1 (SPHK1) and response to secondary hormonal therapy in metastatic castration-resistant prostate cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-100.

Abstract IA33: The immunogenomic landscape of primary prostate cancer in African-American men

Abstract African-American (AA) men have a 1.5-fold higher incidence of prostate cancer (PCa) than non-Latino White (WH) men and are nearly 2.5 times more likely to die from their disease. These disparities are likely due to a combination of social, environmental, and biological factors. Discerning the biological determinants of aggressive PCa in AA men remains a critical and unmet need in cancer health disparities research. Although there have been several large-scale genome sequencing studies that identified unique molecular drivers in primary and metastatic PCa, these have included few AA patients, even fewer with potentially lethal PCa, and have generally lacked clinical outcome data. Work by our group and others demonstrates that the most common somatic genomic alterations in primary PCa (such as ERG rearrangement and PTEN deletion) occur at significantly different frequencies in AA and WH men, providing the first direct evidence for molecular differences between PCa arising in AA and WH patients. Similarly, gene expression studies by other groups have consistently found that various immune response pathways are more highly expressed in PCa arising in AA compared to WH patients. However to date, few studies have integrated somatic molecular subtype data with immune tumor microenvironment (TME) characterization across different populations. To begin to address these knowledge gaps, we have studied primary PCa tissues from a unique cohort comprising 200 self-identified AA and 200 WH patients, matched by grade and other clinical-pathologic parameters, with long-term follow-up for biochemical recurrence and metastasis. This cohort is unique in that it is highly enriched for high-risk disease and has now been profiled for somatic genomic, epigenomic, transcriptomic and tumor microenvironment landscapes, enabling one of the first integrative molecular portraits of AA PCa. We find that tumor infiltrating T-lymphocyte density is significantly correlated with underlying tumor molecular subtype and oncologic outcomes, but does not vary by racial ancestry. In contrast, using a combination of transcriptomic, methylation and quantitative immunohistochemical analyses, we demonstrate that tumor infiltrating B-lymphocyte density is significantly higher among AA compared to WH PCa patients, irrespective of molecular subtype, and trends towards improved outcomes. Citation Format: Tamara L. Lotan. The immunogenomic landscape of primary prostate cancer in African-American men [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA33.

Lack of Racial Survival Differences in Metastatic Prostate Cancer in National Cancer Data Base (NCDB): A Different Finding Compared to Non-metastatic Disease.

Background: Inconsistent findings have been reported in the literature regarding racial differences in survival outcomes between African American and white patients with metastatic prostate cancer (mPCa). The current study utilized a national database to determine whether racial differences exist among the target population to address this inconsistency.Methods: This study retrospectively reviewed prostate cancer (PCa) patient data (N = 1,319,225) from the National Cancer Database (NCDB). The data were divided into three groupings based on the metastatic status: (1) no metastasis (N = 318,291), (2) bone metastasis (N = 29,639), and (3) metastases to locations other than bone, such as brain, liver, or lung (N = 952). Survival probabilities of African American and white PCa patients with bone metastasis were examined through parametric proportional hazards Weibull models and Bayesian survival analysis. These results were compared to patients with no metastasis or other types of metastases.Results: No statistically supported racial disparities were observed for African American and white men with bone metastasis (p = 0.885). Similarly, there were no racial disparities in survival for those men suffering from other metastases (liver, lung, or brain). However, racial disparities in survival were observed among the two racial groups with non-metastatic PCa (p < 0.001) or when metastasis status was not taken into account (p < 0.001). The Bayesian analysis corroborates the finding.Conclusion: This research supports our previous findings and shows that there are no racial differences in survival outcomes between African American and white patients with mPCa. In contrast, racial disparities in the survival outcome continue to exist among non-metastatic PCa patients. Further research is warranted to explain this difference.

Ethnicity and insurance status predict metastatic disease presentation in prostate, breast, and non-small cell lung cancer.

BackgroundEthnicity and insurance status have been shown to impact odds of presenting with metastatic cancer, however, the interaction of these two predictors is not well understood. We evaluate the difference in odds of presenting with metastatic disease in minorities compared to white patients despite access to the same insurance across three common cancer types.MethodsUsing the National Cancer Database, a multilevel logistic regression model that estimated the odds of metastatic disease was fit, adjusting for covariates including year of diagnosis, ethnicity, insurance, income, and region. We included adults diagnosed with metastatic prostate, non–small cell lung cancer (NSCLC), and breast cancer from 2004 to 2015.ResultsThe study cohort consisted of 1 191 241 prostate cancer (PCa), 1 310 986 breast cancer (BCa), and 1 183 029 NSCLC patients. Private insurance was the most protective factor against metastatic presentation. Odds of presenting with metastatic disease were 0.190 [95% CI, 0.182‐0.198], 0.616 [95% CI, 0.602‐0.630], and 0.270 [95% CI, 0.260‐0.279] for PCa, NSCLC, and BCa compared to uninsured patients, respectively. Private insurance provided the most significant benefit to non‐Hispanic White PCa patients with 81% reduction in odds of metastatic presentation and conferred the least benefit to African‐American NSCLC patients at 30.4% reduction in odds of metastatic presentation.ConclusionsInsurance status provided the single most protective effect against metastatic presentation. This benefit varied for minorities despite similar insurance. Reducing metastatic disease presentation rates requires addressing social barriers to care independent of insurance.

Leukocyte telomere length is associated with aggressive prostate cancer in localized prostate cancer patients.

BackgroundTelomeres play important roles in cancer initiation and progression. The aim of this study is to investigate whether leukocyte telomere length (LTL) is associated with aggressive prostate cancer (PCa).MethodsWe measured relative LTL in a cohort of 1,889 white PCa patients who were treated and followed up at the University of Texas MD Anderson Cancer Center and assessed its associations with aggressive disease characteristics at diagnosis and biochemical recurrence (BCR) after active treatments (radical prostatectomy and radiotherapy). We further used a Mendelian randomization (MR) approach to compute a weighted genetic risk score (GRS) predictive of LTL using 10 established LTL-associated genetic variants and determined whether this GRS is associated with aggressive PCa.FindingsLTL was significantly shorter in patients with higher Gleason scores at diagnosis. Dichotomized at the median value of LTL, patients with short LTL exhibited a 2.74-fold (95% confidence interval, 1.79–4.18, P = 3.11 × 10−6) increased risk of presenting with GS≥8 disease than those with long LTL in multivariate logistic regression analysis. Moreover, shorter LTL was significantly associated with an increased risk of BCR (hazard ratio = 1.53, 95% confidence interval, 1.01–2.34) compared to longer LTL in localized patients receiving prostatectomy or radiotherapy with a significant dose-response association (P for trend = 0.017) in multivariate Cox proportional hazards regression analysis. In MR analysis, genetically predicted short LTL was also associated with an increased risk of BCR (HR=1.73, 95% CI, 1.08–2.78).InterpretationOur results showed for the first time that LTL was shorter in PCa patients with high Gleason scores and that short LTL and genetically predicted short LTL are associated with worse prognosis in PCa patients receiving prostatectomy or radiotherapy.FundingCancer Prevention and Research Institute of Texas (CPRIT) grant (RP140556), National Cancer Institute Specialized Program of Research Excellence (SPORE) grant (CA140388), and MD Anderson Cancer Center start-up fund.

Abstract 4204: Racial difference in the risk of secondary bladder cancer following radiation therapy among prostate cancer patients

Abstract Purpose: Radiation therapy has been found associated with increased risk of secondary bladder cancer diagnosis among prostate cancer patients. It is unknown whether this association varies by race. This study aimed to investigate whether the association between radiation and secondary bladder cancer differs for white vs. black prostate cancer patients. Methods: Data on white or black men who were diagnosed with primary localized prostate cancer in Louisiana between 2004 and 2013 and received radiation only or surgery only were obtained from Louisiana Tumor Registry. We excluded those who developed secondary bladder cancer within 180 days of the prostate cancer diagnosis or had follow-up less than 180 days or with unknown tumor size or Gleason score. Every patient was followed up until the end of 2016. The exposure variable was treatment (radiation only vs. surgery only). The outcome variable was the diagnosis of secondary bladder cancer and the time from prostate cancer diagnosis to secondary bladder cancer diagnosis or to loss to or end of follow-up. Covariates included age at diagnosis, marital status, insurance, census tract level poverty, tumor size, and Gleason score group. The competing risk survival analysis was applied. Death during follow-up was considered as competing event. Analysis was stratified by race. Results: Of 10,861 white and 5,117 black prostate cancer patients, 52.7% and 56.8% received only radiation respectively. Regardless of race, patients who only received surgery were younger, more likely to be married, privately insured, live in low poverty census tract, and have smaller or lower grade tumor (P &amp;lt;0.0001 for each in both racial groups). Among white prostate cancer patients who received surgery only vs. radiation only, 31 (0.60%) vs. 127 (2.22%) of them developed secondary bladder cancer (P &amp;lt; 0.0001). Among black surgery only vs. radiation only patients, 14 (0.63%) vs. 29 (1.00%) of them developed a secondary bladder cancer (P = 0.16). The median follow-up time was 8.9, 8.0, 8.3, and 7.6 years for white surgery, white radiation, black surgery, and black radiation patients, respectively. After adjusting for covariates, the hazard ratio (95% confidence interval) [HR (95% CI)] of developing secondary bladder cancer was 2.70 (1.58, 4.61) for white radiation patients compared to white surgery patients; 0.95 (0.31, 2.89) for black radiation patients compared to black surgery patients. Compared to white surgery patients, the HR (95% CI) of developing secondary bladder cancer was 1.16 (0.61, 2.22) and 1.38 (0.74, 2.56) for black surgery and black radiation patients, respectively. Conclusions: Radiation is associated with increased risk of secondary bladder cancer among white prostate cancer patients, but not among black patients. Early screening of secondary bladder cancer need to be emphasized among white prostate cancer patients who received radiation therapy. Citation Format: Lu Zhang, Mei-Chin Hsieh, Qingzhao Yu, Xiao-Cheng Wu. Racial difference in the risk of secondary bladder cancer following radiation therapy among prostate cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4204.

Disparities in hospitalization outcomes among African-American and White prostate cancer patients

ObjectivesThis paper aims to determine whether racial disparities exist in hospitalization outcomes among African-American and White hospitalized prostate cancer patients in the United States. We evaluated racial differences among matched groups of patients in post-operative complications, hospital length of stay and in-hospital mortality. MethodsWe identified a total of 183,856 men aged 40 years and older with a primary diagnosis of prostate cancer, of which 58,701 underwent prostatectomy, through the Nationwide Inpatient Sample, and matched all African-American patients with White patients on: 1) Demographics, 2) Demographics+Clinical presentation and 3) Demographics+Clinical presentation+Treatment. Multivariable regression analyses were conducted in SAS and estimates were reported with 95% confidence intervals. ResultsAfrican-American patients were more likely to be admitted with metastatic disease (24.8%) compared with White patients matched on demographics (17.9%), and demographics+presentation (23.6%). However, 23.9% of African-American patients received surgery compared with 38.2% and 34.2% of Whites matched on demographics and demographics+presentation, respectively. White patients had lower in-hospital mortality compared with African-American patients matched on demographics (OR: 0.72, 95% CI: 0.66-0.79), demographics+presentation (OR: 0.88, 95% CI: 0.81-0.96), but was no longer significantly lower when matched on demographics, presentation and treatment (OR: 0.92, 95% CI: 0.85–1.00). ConclusionThere were significant racial differences in outcomes among prostate cancer patients within the inpatient setting, even after accounting for demographic and presentation differences.

The association between hypertension and prostate cancer.

A 2016 meta-analysis documented a possible association between hypertension and prostate cancer. We retrospectively reviewed our 3200 prostate cancer patients that were aged 51 to 76 years to determine the frequency of hypertension. Data was gathered on age, race (African American and white), hypertension, diabetes, and body mass index (BMI). Patients were subdivided into three groups: age 51 to 60 years, age 61 to 70 years, and age 71 to 76 years. Our study population consisted of 1388 (43%) African American patients and 1812 (57%) white patients. Hypertension was found in 1013 (73%) of African American patients and 1290 (72%) of white patients. Diabetes was found in 35% of African American patients and 24% of white patients. BMI over 30 kg/m2 (obesity) was found in 47% of African American patients and 45% of white patients. We found the frequency of hypertension to be 73% in African American and 72% in white patients, 18% and 44% relatively higher in African American vs white patients, respectively, compared with the general population (62% in African American vs 50% in white patients). The study also found a similar frequency of hypertension among African American and white prostate cancer patients, despite an approximate 12% difference in the general population. Based on these findings, we suggest that prostate cancer and hypertension share a common androgen-mediated mechanism and further prospective studies are recommended to confirm that hypertension is a risk factor for prostate cancer.

Age-related racial disparities in prostate cancer patients: A systematic review

ABSTRACTObjective. Prostate cancer mortality rates have decreased over recent decades, but racial disparities in prostate cancer survival still present as a serious challenge. These disparities may be impacted by age; in fact, African-American men younger than age 65 have prostate cancer mortality rates nearly three times greater than that of White men. Therefore, a systematic literature review was conducted in Medline and EMBASE databases focusing on articles comparing survival and mortality rates for prostate cancer patients across age and race.Design. Articles included were based on the following criteria: (1) included African-American and White prostate cancer patients residing in the US; (2) measured racial disparities across distinct age categories with at least one category below and one above age 65; and (3) addressed racial disparities in terms of overall survival or mortality.Results. Twenty eight articles compared survival and mortality disparities between African-American and White prostate cancer patients across different age categories. Of the 28 articles, 19 articles (68%) showed disparities decreased with age, 8 articles (29%) showed disparities constant with age, and 1 article (3%) showed disparities increased with age.Conclusions. More often the survival and mortality gap between African-American and White prostate cancer patients decreases with age. Additional studies are needed to elucidate other factors that may influence racial disparities in prostate cancer patients. These results provide insight into the racial disparities in prostate cancer and suggest more resources should be directed towards decreasing the disparity gap in younger prostate cancer patients.

Why men get or don’t get treated for locally advanced prostate cancer: Physicians’ perspectives.

e16068 Background: Locally advanced prostate cancer treatment can improve survival. Yet, African American are more likely than white prostate cancer patients to go untreated. We found that 13% of b...

Sociocultural determinants of men's reactions to prostate cancer diagnosis

To develop a better understanding of how men react to being diagnosed with prostate cancer and identify factors that influence these responses, we conducted an observational study to identify sociocultural predictors of men's psychological reactions. Participants were 70 African American and 124 white prostate cancer patients who completed a structured telephone interview that evaluated psychological reactions in terms of intrusive thoughts about cancer and attempts to avoid cancer-related thoughts and feelings. Perceptions of disease-specific stress, cultural beliefs and values, and social constraints were also assessed during the interview. There were no racial differences in men's reactions to being diagnosed with prostate cancer; however, greater perceptions of disease-specific stress, increasing levels of present temporal orientation, and more social constraints had significant positive effects on avoidant reactions. Greater perceptions of stress also had a significant positive effect on intrusive thoughts. The results of this study highlight the need for individualized approaches to help men address their thoughts and feelings about being diagnosed with prostate cancer. These efforts should include strategies that help men to communicate more effectively with social support resources and address cultural beliefs and values related to temporal orientation.

Racial Differences in Quality of Life Following Prostate Cancer Diagnosis

To evaluate the effects of race on QOL while adjusting for subjective stress and religiosity among African American and white prostate cancer patients. Although racial differences in quality of life (QOL) have been examined between African American and white prostate cancer patients, it is not known whether differences exist while adjusting for psychological and cultural factors. We predicted that African American men would report poorer emotional and physical functioning after adjusting for these factors and that greater subjective stress and lower levels of religiosity would be associated with poorer well-being. We conducted an observational study of QOL among 194 African American and white men who were recruited from February 2003 through March 2008. Race had a significant effect on emotional functioning after adjusting for perceptions of stress and religiosity. Compared with white men, African American men (P = .03) reported significantly greater emotional well-being. Greater subjective stress was associated significantly with poorer emotional functioning (P = .0001) and physical well-being (P = .0001). There were no racial differences in physical functioning (P = .76). The results of this study highlight the importance of developing a better understanding of the context within which racial differences in QOL occur and translating this information into support programs for prostate cancer survivors.

Effects of zoledronate (Z) on bone mineral density (BMD) among African Americans (AA) with advanced prostate cancer, without skeletal metastases, receiving androgen ablation therapy

16031 Background: Bone health is a particular concern for patients undergoing androgen ablation for treatment of prostate cancer, as it has been known to cause bone loss. These issues are especially important in AA, who present with higher rates of advanced disease and are more likely to choose androgen ablation therapy than white patients. Bisphosophonates, such as Zoledronate (Z), are often used by cancer patients who experience bone metastases. We evaluated the effects of Ca/Vitamin D ± Z on skeletal related events and BMD on AA and white prostate cancer patients undergoing androgen ablation therapy. Methods: Prostate cancer patients receiving at least 3 months of androgen ablation were eligible. Exclusion criteria: Use of bisphosphonates in last 12 months, abnormal liver/kidney function, or prior bone disease. 42 patients were randomized, 51% of which are AA. Patients on the Z arm received 4 mg IV infusion of Z q 3 months over one year. Bone densities were evaluated at baseline and 13 months. Results: Interim analysis is available for patients who have completed the study as of Jan 2008. Three patients were taken off the study (one due to secondary cancer, two due to patient withdrawal). One patient withdrew due to jaw pain; follow up did not identify osteonecrosis. Two patients had lesions that may have been bone metastases; follow up testing was inconclusive. Patients treated with Z had higher BMD scores than control group patients. AA patients treated with Z also showed increased BMD values at 13 months. Conclusions: Z appears to have a positive effect on BMD in AA men with prostate cancer, an effect potentially more beneficial than previously reported for white men with prostate cancer. AA men with prostate cancer receiving long term androgen ablation should be considered for Z therapy to improve bone health. % Change in BMD All Control (C) All w/Z AA (C) AA w/Z Non AA (C) Non AA w/Z Lumbar Spine 0.75* 4.29* 2.53 3.76 -1.53* 5.08* Hip -2.39* 0.96* -1.19 0.77 -3.96* 1.26* Femur -0.90** 3.51* -1.77** 6.13* 0.23 -0.40 * = p value <.05, ** = .05–1.0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen, Novartis Oncology, sanofi-aventis

Novel mutations in tyrosine kinase domain of epidermal growth factor receptor in prostate cancer

4611 Background: We recently reported that EGFR protein overexpression is significantly more common in African American (AA) prostate cancer patients compared to White patients (Shuch et al. 2004 JCO, 22:4673–4677). In the current study, we further explore EGFR dysregulation in prostate cancer patients of different ethnicities by examining mutations in the EGFR tyrosine kinase (TK) domain. In addition to AA and White prostate cancer patients, we included South Korean patients in light of recent reports that EGFR mutations are more common in Asian patients with non-small cell lung cancer. Methods: Normal and tumor DNA from radical prostatectomy cases (n = 89: Koreans n = 36, AA n = 27, Whites n = 26) were studied for mutations in the EGFR TK domain using genomic DNA sequencing. Results: We identified 4/89 (5%) novel missense mutations in exons 19, 20 and 21 of TK domain: 3 in Koreans (8%, 95%, CI = 2%– 22%) and 1 in White (4%, 95% CI = 0.1%–20%) but none in AA. These mutations, which were not described before, are expected to affect TK activity based on the change of the amino acid phosphorylation pattern and the 3-dimensional structure of TK domain. We also identified 5 distinct synonymous DNA sequence changes in exons 20 and 21 in 31/89 (35%) patients. These synonymous sequence changes were not observed in the corresponding normal DNA in 8/31 (25.8%) patients, indicating the presence of de novo somatic mutation in those patients, and are likely to affect mRNA splicing leading to altered EGFR protein transcripts. Conclusions: Several independent mechanisms of EGFR dysregulation operate in prostate cancer including EGFR protein overexpression, missense mutations, and somatic synonymous sequence changes in the TK domain. Validation on a larger sample size in addition to functional studies are needed to determine the specific association between a patient’s ethnicity, EGFR dysregulation, and response to EGFR inhibitors in prostate cancer. No significant financial relationships to disclose.

Using north carolina medicare data to assess excess prostate cancer mortality among african americans

PURPOSE: To investigate the basis for the higher prostate cancer mortality rate for African American (AA) men, which is twice the rate for White men.METHODS: 221 AA and 979 White men with a primary diagnosis code of prostate cancer (“patients”) in the North Carolina Medicare Hospitalization claims from 1997 were compared with 1,326 AA and 5,874 White men of the same age with no cancer hospitalizations (“beneficiaries”) selected from the NC Medicare Enrollment files. Mortality rates were calculated as the cumulative percent of deaths using the hospital discharge date as day 1. AA and White age distributions were similar.RESULTS: Cumulative mortality percentages at 6, 12, and 18 months were, respectively, 4.5, 7.7, 10.9 for AA patients; 2.8, 6.5, 9.2 for White patients; 2.3, 3.8, 7.4 for AA beneficiaries; and 1.8, 3.1, 6.1 for White beneficiaries.CONCLUSIONS: AA prostate cancer patients had higher overall mortality than did White prostate cancer patients during the first year, but by 12-months the White-Black survival advantage for prostate cancer patients was similar in magnitude to the White-Black survival advantage among the non-cancer Medicare beneficiaries. AAs' higher prostate cancer mortality may derive from higher short-term case fatality rates, which may reflect differences in treatment and access to quality medical care, co-morbidities, and tumor characteristics such as stage and grade at diagnosis, and in part from the survival disadvantage for AA in the general population.