Incidence Of Prostate Cancer Research Articles

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.

In Vitro Antitumor Effect of Oils Rich in CBD and THC Cannabis Extract in Canine Prostate Carcinoma Cell Lines

Prostate cancer is one of the leading causes of cancer-related deaths worldwide, even when diagnosed at an early stage in humans and dogs. Dogs have a significant incidence of spontaneous prostate cancer, which is highly similar to human androgen-independent prostate cancer and represents a valuable model for comparative studies. Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) are the two main cannabinoids extracted from Cannabis sativa and have demonstrated antiproliferative and anti-invasive properties in different tumor types. In this study, CBD or THC-rich extracts inhibited the proliferation of two canine prostatic carcinoma cell lines, PC1 and PC2, showing an IC50 of 3.43 and 3.57 μM for CBD rich extracts, and 4.90 and 4.48 μM THC rich extracts, respectively. Cell death was also observed with both Annexin V and Propidium iodide staining for the canine cell lines. These results provide new information concerning the use of rich oil in canine PC and open a promising opportunity for further in vitro and in vivo studies to establish the mechanisms of action of these compounds using dogs as a natural model for prostatic carcinoma.

Assessment of age specific serum Prostate Specific Antigen (PSA) levels for Indian population: A retrospective analysis at a tertiary healthcare facility.

Prostate-specific antigen (PSA) is a key marker for prostate cancer screening, but its utility is debated, prompting exploration of PSA derivatives for improved accuracy. While racial variations in serum PSA levels are documented, limited data exists for the Indian population. Given increasing life expectancy and heightened awareness of prostate cancer, this study aims to establish age-specific PSA ranges in an Indian cohort, contributing vital insights for population-specific screening and diagnosis. A cross-sectional study was conducted on 4860 men with lower urinary tract symptoms (LUTS). Data, collected from April 2016 to March 2023, included age, PSA levels, digital rectal examination (DRE), and biopsy results. Statistical analysis involved Spearman's correlation, descriptive statistics, and confidence intervals. Of the studied participants, 809 underwent prostatic biopsy, revealing malignancy in 500 cases. Age-specific PSA values were studied in 4170 subjects and showed positive correlation with increasing age and prostate size. Most cancers were metastatic (66%), emphasizing the need for early detection. Age-specific PSA ranges were lower in the Indian population compared to the West. This study's Indian cohort exhibited higher PSA values than some previous Indian studies but lower than Western populations, aligning with global trends. The rising incidence of prostate cancer in India underscores the importance of understanding the disease burden. PSA levels exhibit race-specific variations, cautioning against direct extrapolation of Western data to the Indian population. This study contributes age-specific PSA ranges for an Indian cohort, facilitating nuanced prostate cancer screening strategies.

Serum glycosylated hemoglobin and prostate cancer risk: Results from a systematic review and dose-response meta-analysis

ObjectivesTo evaluate the correlation between serum glycosylated hemoglobin (HbA1c) levels and the risk of prostate cancer incidence and mortality, providing a comprehensive analysis to inform preventative and clinical strategies. MethodsA systematic review and meta-analysis was conducted including studies based on their documentation of prostate cancer incidence and mortality related to HbA1c levels, with a minimum of 3 risk-related data levels. The Newcastle-Ottawa Quality Assessment Scale (NOQAS) was used for quality assessment and risk of bias evaluation. We employed generalized least squares (GLS) to assess the linear trend within individual studies and combined these estimates using a random effects model. Additionally, we utilized a restricted cubic spline (RCS) model to investigate potential nonlinear trends. ResultsA total of 13 studies were included in the quantitative synthesis ultimately. The quantitative analysis did not find a significant association between HbA1c levels and prostate cancer incidence. However, a significant positive correlation was revealed between HbA1c levels and both cancer-specific mortality (CSM) and all-cause mortality (ACM), with a 1% increase in HbA1c levels associated with a 26% increase in CSM and a 21% increase in ACM. ConclusionThe HbA1c level is significantly associated with increased prostate cancer mortality. The results highlight the importance of considering blood sugar control in the comprehensive risk assessment for prostate cancer, particularly among the nondiabetic population.

Prostate cancer and solid organ transplantation: patient management and outcomes.

To analyse the management and outcomes of individuals diagnosed with prostate cancer either before or after organ transplantation, as the impact of organ transplantation and associated immunosuppression on the incidence, progression, and mortality of prostate cancer remains an area of substantial clinical interest and uncertainty. We conducted a retrospective analysis of patients from two tertiary care centres who had solid organ transplantation and were diagnosed with prostate cancer before or after organ transplantation. Data collected included demographics and clinical information. The cohort consisted of 110 patients with a median (interquartile range [IQR]) age at prostate cancer diagnosis of 62 (56.6-67.2) years and a median (IQR) age at transplantation of 58.6 (52.7-65.3) years. Renal transplantation was the most common (54%). The median (IQR) prostate-specific antigen concentration at prostate cancer diagnosis was 6.2 (4.5-10) ng/mL, and the distribution of American Urological Association risk groups was: low risk, 36%; intermediate risk, 50%; and high risk, 14%. In all, 45 (41%) patients were diagnosed with prostate cancer prior to transplantation. Management included radical prostatectomy (RP; 62%), prostate radiotherapy (RT; 13%), and active surveillance (AS; 18%). During a median (IQR) follow-up of 5.8 (2.5-10) years from prostate cancer diagnosis, one (2%) patient developed metastatic disease. In all, 65 (59%) patients were diagnosed with prostate cancer subsequent to organ transplantation. Management included AS (29%), RT (45%), and RP (15%). During a median (IQR) follow-up of 5.3 (1-8.4) years, three patients (5%) developed metastatic disease. There were no deaths from prostate cancer. A diagnosis of localised prostate cancer should not preclude solid organ transplantation, and the presence of a transplant does not appear to substantially impact risk of prostate cancer progression.

CACA guidelines for holistic integrative management of prostate cancer

Prostate cancer (PC) is an epithelial malignancy occurring in the prostate. PC ranks second in incidence among all male malignancies globally by the latest statistics from the World Health Organization. Notably, China has seen a more rapid increase in PC incidence compared to developed European and American nations. By 2022, the newly reported cases and deaths due to PC in China increased to 134,200 and 47,500, respectively. Thus, early diagnosis and standardized treatment for prostate cancer in China remain far-reaching objectives. Burgeoning research on advanced PC and castration-resistant prostate cancer in recent years have paved the way for a new era of integrated treatment methods including novel endocrine drugs, chemotherapy, targeted therapy, and immunotherapy. Future therapies involve precision treatment guided by genetic testing and individualized integrated treatment as part of a multidisciplinary integrated diagnosis and treatment model for PC. The Genitourinary Oncology Committee of the China Anti-Cancer Association (CACA-GU) has invited multidisciplinary experts across fields including surgery, oncology, pathology, radiology, herbal medicine, physiatry, and psychology to collaboratively write, discuss, and revise guidelines on managing PC. The CACA Guidelines for Holistic Integrative Management of Prostate Cancer includes epidemiology, screening and diagnosis, treatment for localized PC, diagnosis and treatment of PC recurrence after radical prostatectomy, management of metastatic PC, traditional Chinese medicine diagnosis and treatment of PC, and rehabilitation from PC. This guideline aims to standardize the clinical diagnosis and treatment management of PC in China. It is more aligned with China’s clinical practice, highlights Chinese characteristics, and bears significant clinical importance.

8815 ANPEP regulates one-carbon metabolism in prostate cancer

Abstract Disclosure: A. El-Kenawi: None. R. Putney: None. A. Berglund: None. K. Yamoah: None. African American men (AAM) experience disproportionately higher rates of both prostate cancer (PCa) incidence and mortality compared to their European American counterparts (EAM). To investigate some of the biological factors which contribute to these disparities, we carried out an unbiased genomic expression analysis of PCa by ancestry using the matched GRID and VANDAAM cohorts. In this analysis, we discovered aminopeptidase N (ANPEP, APN, CD13), to be the most differentially expressed functional gene in both self-identified and ancestry derived AAM compared with EAM. Further computational analyses revealed that ANPEP correlates with signatures of cholesterol transport, estrogen and androgen receptor (AR) signaling. The functional role of ANPEP in regulating cholesterol metabolism and AR signaling remains unclear. Further computational analyses demonstrate that expression of ANPEP predominantly correlates with various amino acid transporters. In addition, comprehensive metabolomic characterization revealed that ANPEP-overexpressing cells exhibit altered level of one-carbon metabolism metabolites. The one-carbon metabolic pathway regulates amino acids homeostasis and epigenetic mechanisms. Metabolomics-based approach to assess the consumption of over 15 amino acids in patient-derived explants validate enrichment of one-carbon metabolism circuits in AAM. Thus, we further investigated whether ANPEP impact high methylation capacity by performing genome-wide methylation profiling in cells. We unraveled that ANPEP overexpression is associated with elevated methylation of DNA. Our future studies will assess whether ANPEP regulation of methylation capacity have an impact on AR binding to DNA. Presentation: 6/3/2024

Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa.

Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

Clinicopathological Study of Prostate Diseases and Its Correlation with PSA Level, Size of Prostate and Gleason’s Scoring System in Case of Prostatic Carcinoma

Background: Prostate gland diseases significantly impact adult males globally, with an increasing prevalence due to aging populations. The primary conditions affecting the prostate are inflammation, benign prostatic hyperplasia (BPH), and tumors, with BPH being the most common. Prostatic carcinoma is also prevalent, with a high lifetime risk. Prostate cancer incidence increases with age, and early detection relies on digital rectal examination, transrectal ultrasonography, and PSA testing. Aim of the study: The study aims to find out correlation between PSA, Gleasons scoring system and HER-2/NEU gene in prostatic cancer. Methods: This study, conducted from July 2017 to June 2019 at BIRDEM General Hospital, enrolled 110 male patients aged 50-100 with clinical signs of prostatic diseases. Patients provided written informed consent and met specific inclusion criteria. Specimens were obtained via TURP, simple or radical prostatectomy, preserved in 10% neutral buffered formalin and examined for pathological lesions. PSA levels were measured using an immunoassay, and Gleason scoring was used for carcinoma categorization. Data were collected via questionnaires and analyzed using SPSS software. Result: The study analyzed 110 prostatic disease cases, with patients averaging 67.7 years. The most common diagnosis was BPH with inflammation (50.9%), followed by BPH without inflammation (35.5%) and adenocarcinoma (13.6%). Urgency (80%), increased micturition frequency (78.2%), poor stream (78.2%), and urinary retention (77.3%) were the most common symptoms. There was a significant correlation between serum PSA levels and prostate size (p < 0.001), with higher PSA levels indicating larger prostates and a higher likelihood of adenocarcinoma. The most frequent Gleason score was 4+4=8 (40%). HER2/neu overexpression showed a marginal correlation with PSA levels (p=0.053). Conclusion: The study found that the most common age group for prostatic diseases was 61-70 years. Benign prostatic hyperplasia (BPH) was the most frequent lesion. Grade II (31-50g) prostate size was common on ultrasound. Most patients had a PSA level of 0-5 ng/ml, aiding early diagnosis and reducing morbidity

The Possible Role of Progesterone Receptors in Prostate Cancer Incidences in the Iraqi Population.

Prostate cancer (PCa) is one of the leading diseases causing mortality. It comes in the third rank of common cancer types. It is considered extremely a complicated cancer type since it occurs in highly steroid-responsive and dependent tissues. Many factors are considered to play an important role in the disease progression of PCa, with some functioning at the molecular level. After applying the exclusion criteria, 200 patients who underwent proctectomy were included in this study. Following receiving patient consent, blood samples were withdrawn from patients, DNA was extracted, and precise polymerase chain reaction (PCR) amplification was conducted using specifically designed primers. The resulting amplicons were sequenced and analyzed. The progesterone receptor B (PGRB) DNA from patients showed four distinctive single-nucleotide polymorphisms (SNPs) at sites 11:101128812, 11:101128924, 11:101128949, and 11:101128986, which altered the amino acid sequences to Y>N, A>D, T>I, and C>R, respectively, compared to control. These SNPs resided in sensitive sites that either affected the control elements or promoted alterations in the protein configuration. This DNA change diminished the PGR gene function and promoted an imbalance in the encoded PGR protein structure and expression. Many factors may play a role in PCa manifestation, with steroids and progesterone initially noted as factors. Many studies have dealt with the hormonal effect on PCa; however, few have ultimately determined the molecular impact on disease progression. The presence of pathogenic SNPs in the enhancing region of the gene may impact the expression level of PGR. High or low expression levels may negatively affect gene function, which can be considered a reliable factor in prostate tumorigenesis.

Abstract C001: Global disparities in prostate cancer burden: An analysis of the GLOBOCAN 2020 database

Abstract Background: Prostate cancer (PCr) is one of the most common cancers among men globally, with considerable variations in incidence and death rates between racial/ethnic groups and geographical regions. With more than 1.4 million new cases reported in 2020, the global burden of PCr is predicted to double over the next two decades, to 2.9 million new cases and approximately 700,000 fatalities. Understanding the disparities in PCr is crucial for designing targeted treatments, and interventions and addressing health inequities. This study seeks to provide a comprehensive analysis of the recent global trends in PCr, focusing on incidence, mortality, and disparities in disease burden. Methods:This study analyzed age-standardized PCr incidence and mortality rates from the GLOBOCAN 2020 database for 174 countries, categorized by region and income level. Descriptive statistics and regression analyses were used to investigate the relationships between PCr rates and socioeconomic factors like the Human Development Index (HDI) and healthcare expenditure (HE). The study evaluated PCr distribution across age and geography, with statistical significance set at p < 0.05. Results:PCr incidence rates were highest in developed regions like Northern America (73.8/100,000), Western Europe (69.1/100,000), and Australia/New Zealand (88.2/100,000), and lowest in Eastern Asia (10.5/100,000) and Northern Africa (9.7/100,000). Mortality patterns were similar, with highest rates in the Caribbean (29.3/100,000) and Sub-Saharan Africa (26.6/100,000), and lowest in Eastern Asia (4.1/100,000) and Northern Africa (8.3/100,000). While incidence correlated positively with the HDI (p<0.001), mortality showed no significant association after adjusting for HE. Conclusion:This global analysis revealed major disparities in PCr incidence and mortality rates. Incidence was higher in developed regions, while mortality was elevated in economically disadvantaged areas. Further research is needed to understand the complex genetic, environmental, and socioeconomic factors driving these disparities. Key Takeaways: There is a continued need for targeted interventions to reduce the global burden of PCr and address disparities in disease burden. Citation Format: Olumide Arigbede, Sarah G. Buxbaum, Sara Falzarano, Suhn K. Rhie. Global disparities in prostate cancer burden: An analysis of the GLOBOCAN 2020 database [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 C001

Abstract C178: Uptake of prostate cancer screening services in men living with HIV in Trinidad and Tobago

Abstract Background: Compared to other groups, Black men have a higher incidence and mortality of prostate cancer (PCa). Worldwide, the Caribbean region has one of the highest age-standardized PCa incidences with 76 cases per 100,000 population per year. PCa incidence in predominantly Afro-Caribbean countries ranges from 160 in Barbados to 304 men diagnosed per 100,000 in Jamaica. In Tobago, 10% of adult men over 40yrs were found to be diagnosed with PCa. Additionally, men living with HIV (MLWH) are more susceptible and vulnerable to cancer due to their immune-compromised status. Thus, in the Caribbean, there is a pressing need for clinic-based PCa screening in MLWH. Objective: A preliminary quality improvement evaluation of a prostate cancer screening (PSA test) program targeting MLWH in Trinidad and Tobago from January 2019 to May 2024. Methodology: The electronic health information system from a large clinic was used to abstract prostate cancer screening (PSA) delivery. No personal identifiers were collected from the system to protect the privacy of individuals and abide by Trinidad and Tobago’s data protection law. According to NCCN guidelines, since most of our patients were Afro-Caribbean or Mixed, this study treated all MLWH aged < 75yrs as men with high risk and used 3 ng/mL as the threshold; the threshold was 4 ng/mL for MLWH >75yrs. Evaluation of quality improvement of interventions approach was applied. Descriptive analyses were conducted using SPSS. Results: Between January 2019 and May 2024, a total of 2,442 MLWH were eligible to participate in the PSA screening clinic. The average age was 54.0 (age range: 40- 90). 62.9% were Afro-Caribbean, 17.6% were Mixed, 7.4% were East Indian/Indian, and 0.6% were Caucasian. 45.6% of MLWH completed at least secondary education. 26.2% reported having steady partners and 82.5% reported their sexual orientation was heterosexual. Among all MLWH who attended the clinic, 2,127 (87.1%) were referred for PSA tests and 1,640 (77%) MLWH received their PSA tests. For PSA results collected from participants aged 40-75, 86.6% were ≤ 3 ng/mL and 13.4% were > 3 ng/mL. Additionally, among PSA results of participants aged over 75, 51.9% were < 4 ng/mL and 48.1% were ≥ 4 ng/mL. Discussion: To the best of our knowledge, this study is the first of its kind in the Caribbean region. Among MLWH, PSA screening rate was relatively high at 77%. Not too surprising, the PSA results showed 13% of men under 75 and almost 50% of men over 75 had elevated PSAs requiring confirmatory screening and follow-up. Hence, we conclude that a whole-person care approach that includes cancer prevention with prostate cancer screening can be effective. We thus recommend an implementation and dissemination science approach to create strategies for adopting, implementing, sustaining, and disseminating clinic-based prostate cancer-related prevention to reduce related morbidity and mortality among MLWH within the Caribbean and the Americas. Citation Format: Jonathan Edwards, Gaole Song, Gregory Boyce, Selena Todd, Sharon Soyer, Tessa Galindo, Kimlin Ashing, Jeffrey Edwards. Uptake of prostate cancer screening services in men living with HIV in Trinidad and Tobago [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 C178.

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 A038: Uncovering the role of social determinants of health in racial disparities in cancer incidence in Alabama

Abstract Purpose Black-White racial disparities have long been recognized in cancer incidence. National estimates may not reflect racial disparities in individual states. In Alabama (AL), a primarily rural underserved state, Black Americans are more often diagnosed with breast, prostate and colorectal cancer (CRC), with Black men more often diagnosed with lung cancer. Although rurality and area-level deprivation, as social determinants of health (SDoH), have been associated with cancer, their role in explaining racial disparities in cancer incidence remains unknown. We assessed racial disparities in breast, prostate, CRC and lung cancer incidence in AL. Methods We used the Alabama Statewide Cancer Registry (ASCR) to collect data on incident cases of breast, prostate, CRC and lung cancers diagnosed between January 1, 2010 and December 31, 2019. We categorized cases according to age group (0-14, 15-19, 20-24, 25-34, 35-44, 45-64, 65-84, ≥85 years), racial/ethnic group (non-Hispanic Black/White), rural-urban status (defined by AL Rural Health Association), and national area deprivation index (ADI) quartile (Q1-Q4) of census tract at diagnosis. For each combination of these variables, we calculated age-adjusted incidence per 100,000. We conducted bivariate descriptive analysis of incidence rates by race, and rural-urban status and ADI quartile stratified by race. Results Incidence of breast, prostate and CRC cancer was higher in Black versus White individuals (breast 143 vs 127; prostate 206 vs100; CRC males 57.2 vs 45.4, CRC females 42.7 vs 32.6). Lung cancer incidence was higher in Black males and White females (Black vs White: males 82.7 vs 77.6; females 36.9 vs 49.9). In all cancers, racial differences in incidence existed by rural versus urban status (breast Black 142 vs 144, breast White 131 vs 124; prostate Black 204 vs 207, prostate White 101 vs 99.4; male CRC Black 60 vs 55.3, male CRC White 47.7 vs 43, female CRC Black 43.5 vs 42.3, female CRC White 35.2 vs 30.2; male lung Black 84.5 vs 81.7, male lung White 85.1 vs 70.2, female lung Black 31.4 vs 40.1, female lung White 54.4 vs 45.6). In all cancers, racial differences in incidence also existed by ADI status (reporting Q1 vs Q4) [breast Black 190 vs 130, breast White 144 vs 118; prostate Black 269 vs 189, prostate White 109 vs 101; CRC male Black 64.2 vs 56.7, CRC male White 41.2 vs 49.7, CRC female Black 43.4 vs 43.5, CRC female White 29.5 vs 36.6; lung male Black 73.7 vs 91, lung male White 57.9 vs 97.6, lung female Black 41 vs 37.7, lung female White 40.8 vs 60.7]. Conclusions In AL, racial differences in incidence rates for each of the most common cancers exist overall and by key SDoH. Generally, Black individuals have higher rates of cancer, particularly those in rural and low ADI areas. Next, we will perform a decomposition analysis to decompose the Black/White differences in incidence into a portion explained and unexplained by rural-urban status and ADI. Ultimately, these results may inform interventions in a rural underserved state with a large Black population at higher risk of cancer. Citation Format: Mackenzie E. Fowler, Hayden Reeves, Melissa J. Smith, Geetanjali Saini, Mahak Bhargava, Ritu Aneja. Uncovering the role of social determinants of health in racial disparities in cancer incidence in Alabama [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 A038.

Abstract B068: Physical function and fitness of African American prostate cancer survivors at baseline of Men Moving Forward, a lifestyle intervention program

Abstract Background: Prostate cancer (PC) is the most commonly diagnosed cancer in American men with 1 in 8 men diagnosed in their lifetime. African American men have the highest rates of incidence and mortality for PC in the USA, due to a myriad of socio-biological factors. Fortunately, given advances in screening and treatment options the survival rate of PC is high with a 97% 5-year survival rate. However, PC treatments can cause muscle atrophy and reduced physical functioning and quality of life (QoL). Physical function and strength can serve as proxy measurements for cellular aging, longevity, and QoL. Handgrip is related to overall strength, upper limb function, bone mineral density, and mortality. Sit-to-stand measures leg strength and endurance and is used to evaluate fall risk. The 6-minute walk test (6MW) is used to assess aerobic capacity. Men Moving Forward (MMF) is one of the first community-based lifestyle programs developed with and for African American Prostate Cancer Survivors (AAPCS). This study examines objective and subjective physical function of MMF participants at baseline. Methods: MMF is a randomized, wait-list control trial with a 16-week group-based lifestyle intervention focused on physical activity, nutrition and QoL, led by local health coaches. Participants complete physical assessments and surveys at baseline, post-intervention and 12 months. Physical assessments consist of a blood draw, DXA scan, anthropometric measurements, handgrip strength, 30-second sit-to-stand, and 6MW (added with second cohort). Participants also answer surveys on their health and physical function. Pearson’s correlation was used to assess linear correlation between fitness measures and self-reported physical function. Results: At baseline, 100 AAPCS completed both the physical assessment and survey. Participants had a mean age of 65.8 ± 7.26 years, 49% were married/living with a partner, 47.6% were retired, and education levels varied. Top comorbidities include hypertension, obesity, diabetes, and hypercholesterolemia. Mean hand grip scores were 39.8 ± 7.5kg for right and 38.4 ± 7.7kg for left. Handgrip scores 28.2-44.0kg for men aged 64-69 are considered normal. Mean sit-to-stand (n=96) was 12.2 ± 4.3 reps in 30 seconds. Since 6MW was added later in the study, 68 men completed with a mean score of 0.42 ± 0.10 km. Normal ranges for men aged 65-69 is 15 reps for sit-to-stand and 0.572km for 6MW. 50% of participants rated their overall health as “good”, 21% as “very good”, and 20% as “fair” on a five-point Likert scale. PROMIS physical function measures had an average of 50.3 ± 7.3 for men at baseline. PROMIS physical function was weakly correlated with 6MW and sit-to-stand with r = 0.34, p-value=0.004 and r = 0.27, p- value=0.009, respectively. Conclusion: Data reflect the value of supporting AAPCS in lifestyle changes to improve physical function. Few efforts have addressed lifestyle among AAPCS, despite high prostate cancer burden. Future reports will examine the efficacy of MMF in improving physical function, overall health, and QoL. Citation Format: Margaret Y. Tovar, Iwalola Awoyinka, Patricia Sheean, Paula Papanek, Toni Uhrich, Sandra Contreras, Meheret Gebreegziabher, Estefania Alonso, Jayme Ewens, Shannon Reed, Diana Navarro Suarez, Kathleen O'Connell, Kathryn Flynn, Kathryn Bylow, Deepak Kilari, Melinda Stolley. Physical function and fitness of African American prostate cancer survivors at baseline of Men Moving Forward, a lifestyle intervention program [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 B068.

Abstract C060: Social isolation and secondary appraisal mediate the association between race and functional well-being among prostate cancer survivors

Abstract Background: Disparities in prostate cancer (PCa) incidence and mortality persist among African Americans. Functional well-being plays a crucial role in the prognosis and survival of PCa patients. Prior studies show the association between African American race and health-related quality of life among PCa patients. However, no studies have examined possible mediational processes linking race to functional well-being in this population. Objective: To assess the association between race and functional well-being and the mediating pathways of clinical, social determinants, and psychological factors in PCa patients. Methods: We used clinic-based cohort data of PCa patients treated with radical prostatectomy from April 2017 through September 2021. We measured functional well-being, socioeconomic factors, social stressors, perceived stress, and primary and secondary appraisal by self-report. We obtained clinical variables such as disease stage, prostate-specific antigen (PSA) levels, and comorbidities through electronic medical records. We first conducted a path analysis based on linear regression to test the direct association between race and functional well-being, adjusting for age, marital status, education level, employment status, and income. We concurrently examined the mediational pathways linking race to functional well-being via mediators, including stage, PSA, primary appraisal, secondary appraisal, perceived stress, and social isolation. Results: A total of 163 participants (48 African American, 115 White) with a mean age of 66.7 years (SD=6.31) were included in the study. Participants' mean score of functional well-being was 20.32 (SD=6.70; Range=0-28). Compared to White individuals, African American participants exhibited significantly lower levels of functional well-being (b [95% CI] = -3.09 [-5.48, -0.72]). Mediation analyses linking race to functional well-being revealed that, compared to Whites, African Americans displayed significantly lower levels of secondary appraisal (b [95% CI] = -1.45 [-2.85, -0.05]), which, in turn, were associated with higher levels of functional well-being (b [95% CI] = 0.27 [0.01, 0.53]). In addition, African Americans also displayed higher levels of social isolation (b [95% CI] = 0.55 [0.14, 0.97]), which were significantly associated with lower levels of functional well-being (b [95% CI] = -0.91 [-1.64, -0.17]). Both indirect effects of race → secondary appraisal → functional well-being (b [95% CI] = -0.39 [-0.88, -0.01]) and race → social isolation → functional well-being (b [95% CI] = -0.50 [-1.06, -0.02]) were significant and explained 12.6% and 16.2%, respectively, of the total relationship between race and functional well-being. Conclusion: Social isolation and secondary appraisal mediate the association between race and functional well-being among prostate cancer survivors. There is a need to understand the lived experiences of Black men and develop interventions that mitigate the impact of social barriers and psychological stressors on functional well-being to advance health equity. Citation Format: Fatimata Sanogo, Junhan Cho, Trista Beard, Chanita Hughes Halbert. Social isolation and secondary appraisal mediate the association between race and functional well-being among prostate cancer survivors [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 C060.

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 >=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 >=8, or PSA >=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 (<7% [ref]; 7-8%; >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 >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<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 <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 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.

Abstract A086: Racial and ethnic disparities in prostate cancer survival in the Multiethnic Cohort Study (MEC)

Abstract Background: Prostate cancer (PCa) survival has improved over the past 20 years due to advancements in treatment and screening. However, racial and ethnic disparities in PCa survival remain. Studying population differences in PCa survival may help identify underlying contributing factors. Methods: We conducted survival analyses among 10,651 African American, Latino, Native Hawaiian, Japanese American, and non-Hispanic White (NHW) men with an incident PCa diagnosis since 1993 who were part of the Multiethnic Cohort Study. Sub- hazard ratios (SHRs) and 95% confidence intervals (CI) were estimated using the Fine and Grey Subdistribution Hazards Model to account for competing risks in PCa-specific mortality, with age since diagnosis as the time metric. Multivariable models included age at PCa diagnosis, Gleason score, stage at diagnosis, and baseline values of education, initial treatment (radiation, surgery, hormone therapy, chemotherapy, or no active treatment), diabetes history, physical activity, BMI, smoking status, and dietary intakes linked to PCa progression (tomatoes, whole milk, fatty fish, processed meat, saturated fat, and alcohol). We also performed stratified analyses by tumor stage (localized or regional/distant) and Gleason score (≤7 or >7). Associations were considered statistically significant at P < 0.05. Results: Of 10,651 men diagnosed with PCa over 27 years of follow-up (mean duration, 8.4 years), 1,324 (12.4%) died of PCa. Those with lower Gleason scores were less likely to die than those with higher scores (6.8% of men with Gleason score ≤7 vs 21.3% of men with Gleason score >7, p<0.001). Likewise, men with localized disease were less likely to die than men with regional/distant disease (7.5% of men with localized disease vs. 29.2% of men with regional/distant disease, p<0.001). Japanese Americans had significantly lower mortality compared with NHWs (SHR=0.63, 95% CI:0.51, 0.79, p<0.001), consistently observed across stage and Gleason score: localized (SHR=0.64, 95% CI: 0.48, 0.87, p<0.001); regional/distant (SHR=0.63, 95% CI: 0.45, 0.88, p=0.01); Gleason ≤7 (SHR=0.61, 95% CI: 0.44, 0.86, p<0.001); and Gleason score >7 (SHR=0.59, 95% CI: 0.43, 0.79, p<0.001). PCa-specific mortality was significantly higher among African Americans compared to NHWs (SHR=1.31, 95% CI: 1.08-1.60, p=0.01). This difference was more pronounced for less aggressive tumors: localized (SHR=1.50, 95% CI: 1.15, 1.96, p<0.001); Gleason ≤7 (SHR=1.28, 95% CI: 0.95, 1.71, p=0.11). Lastly, we did not observe significant differences in PCa mortality for Latinos and Native Hawaiians compared to NHWs overall or by disease severity. Conclusions: Japanese American have ∼40% lower and African Americans have ∼30% higher PCa-specific mortality relative to NHWs, even after accounting for lifestyle/behavioral factors, stage, Gleason score, and treatment. Further investigations are needed to explore social and cultural factors that impact care as well as tumor-based characteristics that may vary between populations to understand these disparities in PCa mortality. Citation Format: Wei Xiong, Fei Chen, Ann S. Hamilton, David Conti, Raymond Hughley, David Bogumil, Anqi Wang, Song-Yi Park, Peggy Wan, Lynne R. Wilkens, Loïc Le Marchand, Brenda Y. Hernandez, Christopher A. Haiman. Racial and ethnic disparities in prostate cancer survival in the Multiethnic Cohort Study (MEC) [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 A086.

Estimating the Proportion of Overdiagnosis among Prostate, Breast, and Thyroid Cancers in China: Findings from the Global Burden of Disease 2019.

The incidence of prostate, breast, and thyroid cancers has increased in China over the past few decades. Whether and how much these increases can be attributed to overdiagnosis are less understood. This study aimed to estimate the proportion of overdiagnosis among these three cancers in China during 2004-2019. The age-specific cancer incidence, cancer mortality, and all-cause mortality in China were extracted from the Global Burden of Diseases 2019. The lifetime risk of developing and that of dying from each cancer were calculated using the life table method. The proportion of overdiagnosis of a cancer was estimated as the difference between the lifetime risk of developing the cancer and that of suffering from the cancer (including death, metastasis, and symptoms caused by the cancer), further divided by the lifetime risk of developing the cancer. The highest possible values of these parameters were adopted in the estimation so as to obtain the lower bounds of the proportions of overdiagnosis. Sensitivity analyses assuming different lag periods between the diagnosis of a cancer and death from the cancer were performed. The results showed that the lifetime risk of developing prostate, breast, and thyroid cancer increased dramatically from 2004 to 2019 in China, while the increase in the lifetime risk of dying from these cancers was less pronounced. The proportions of overdiagnosis among prostate, breast, and thyroid cancers were estimated to be 7.88%, 18.99%, and 24.92%, respectively, in 2004, and increased to 18.20%, 26.25%, and 29.24%, respectively, in 2019. The increasing trends were statistically significant for all three cancers (all p < 0.001). In sensitivity analyses, the proportions of overdiagnosis decreased, but upward trends over time remained for all three cancers. In conclusion, the overdiagnosis of prostate, breast, and thyroid cancers in China increased from 2004 to 2019, with the highest proportion seen in thyroid cancer and the most rapid increase seen in prostate cancer. Multifaceted efforts by policy makers, guideline developers, and clinicians are needed to tackle this problem.