ABSTRACT Background Emerging evidence indicates significantly poorer overall survival for men with metastatic prostate cancer in resource‐limited settings than in high‐income countries. However, there is less understanding of the overall survival of non‐metastatic disease, which could inform early treatment strategies. Objective To prospectively examine factors associated with the National Comprehensive Cancer Network (NCCN) risk stratification and overall survival in 741 Black South African men with non‐metastatic prostate cancer, some of whom also had co‐morbidities (≥ 2 other chronic conditions). Methods Baseline data on social and health factors were collected. Follow‐up of participants monitored overall survival over a median of 4.3 (3.5–5.0) years. We used multivariable proportional ordinal regression to examine factors associated with non‐metastatic prostate cancer risk stratification. Kaplan‐Meier, Cox proportional hazards regression, and Pohar‐Perme methods were used to calculate overall survival and assess associations. Results Our findings showed a generally favourable prognosis of non‐metastatic prostate cancer with a 5‐year overall survival of 79.0% (75.6–82.6) while the 5‐year age‐standardised net survival was 91.0% (95% CI 86.0–97.0). Overall survival differed significantly by the different NCCN risk groups, emerging early and widening over time, with the lowest survival in the high‐risk groups. Only older age at diagnosis (Hazard Ratio per one‐year increase:1.05 (95% CI: 1.02–1.08)), diabetes (HR: 1.70 (95% CI: 1.08–2.67)), and depression (HR: 1.67 (95% CI: 1.09–2.57)) at study recruitment were associated with poorer overall survival. Furthermore, only older age at diagnosis (HR: 1.04 (95% CI: 1.02–1.07)) was associated with higher non‐metastatic prostate cancer risk. Conclusions These findings emphasise the need to address early diagnosis and comorbidities in non‐metastatic prostate cancer, which could improve overall survival.

PURPOSEAfrican ancestry and family history (FHx) of prostate cancer (CaP) are among the few established CaP risk factors. Few studies have evaluated the association of FHx of CaP with the risk of this disease in African men.METHODSUsing the Men of African Descent and Carcinoma of the Prostate (MADCaP) network, we evaluated the association of self-reported FHx of CaP in fathers and brothers in a case-control study of 2,505 prostate cancer cases and 2,222 age-matched controls ascertained from seven centers across Africa. We compared the association of FHx and a 451-SNP polygenic risk score (PRS).RESULTSCompared with controls, CaP cases had a higher proportion of fathers and/or brothers with a history of CaP overall, as well as in men age <60 or ≥60 years, and in those with/without aggressive CaP (P < .001). A CaP diagnosis in fathers was associated with an odds ratio (OR) of 3.90 (95% CI, 2.66 to 5.72), 3.13 (95% CI, 2.02 to 4.86) in brothers, and 3.41 (95% CI, 2.51 to 4.64) in fathers and/or brothers. A one-unit PRS change was associated with an OR of 1.92 (95% CI, 1.72 to 2.13). Estimates for the PRS effect did not change substantially when FHx was included in the model.CONCLUSIONFHx is a strong predictor of CaP in African men. PRS is also associated with CaP largely independently of FHx. FHx may not always be reliably reported in Africa but the magnitude of recall or reporting bias is unlikely to have negated the observed association.

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. Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.

Abstract Background Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first‐line treatment for stage IV PCa. Objective To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT. Design, Setting, and Participants Men diagnosed with prostate cancer (3/22/2016–10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate‐specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start. Outcomes Measures and Statistical Analysis We used Kaplan–Meier statistics to estimate OS and Cox regression models to identify predictors of OS. Results and Limitations Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64–73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%–noncalculable), while biochemical progression‐free survival was 2.36 years (95% CI: 2.03%–3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%–6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%–7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%–5.83%), and hemoglobin at diagnosis <13.5 g/dL (HR 2.90, 95% CI: 1.28%–6.56%) were associated with worse OS. Conclusions In this study, we identified factors associated with poor OS among Black South African men with stage IV PCa treated with ADT. These factors may be useful in identifying patients for upfront treatment escalation, including the use of docetaxel chemotherapy or escalation of therapy at the time of biochemical progression. Patient Summary In this study, we found that high alkaline phosphatase level, anemia at diagnosis, and high PSA nadir after initiation of androgen deprivation therapy are associated with worse overall survival among Black South African men treated with androgen deprivation therapy for metastatic prostate cancer.

Men of African descent have the highest prostate cancer (CaP) incidence and mortality rates, yet the genetic basis of CaP in African men has been understudied. We used genomic data from 3,963 CaP cases and 3,509 controls recruited in Ghana, Nigeria, Senegal, South Africa, and Uganda, to infer ancestry-specific genetic architectures and fine-mapped disease associations. Fifteen independent associations at 8q24.21, 6q22.1, and 11q13.3 reached genome-wide significance, including four novel associations. Intriguingly, multiple lead SNPs 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 CaP differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African CaP associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

fracture and show reduced overall survival due to aging co-morbidities.Since oncogenes and DNA damage drive senescent growth arrest, we hypothesize that stable MGUS and SMM pre-malignant PCs exhibit senescence features.Methods: We performed gene set enrichment analysis (GSEA) of a published human PC gene array dataset (GSE5900).Immunostaining and fluorescent in situ hybridization were performed to evaluate senescence in MGUS, SMM and MM patient PCs and trephine bone biopsies from MGUS and SMM patients that progressed or not to MM. Lastly, quantitative PCR was used to validate senescence gene expression changes in MGUS, SMM, and MM PCs.Results: MGUS and SMM PCs exhibited significant enrichment for senescence phenotyping gene sets that were distinct from aging.PCs from bone marrow aspirates were identified as senescent based on the Loss of LMNB1 (LoL, < 50%) and senescence associated distension of satellites (SADS, ≥3/cell).PCs from patients with stable MGUS (N=4) exhibited increased percentage of senescent PCs compared to SMM and MM, while stable vs progressing SMM PCs (stable vs progressed ≤5 years, n=6-8) were unchanged.However, PCs from stable, but not progressing SMM, had increased expression of senescence genes (CDKN2A, TP53, BCL2, and IL1B).Both stable MGUS and SMM PCs showed a significant increase in the expression of the retrotransposable element, L1HS, which is increased with senescence, compared to PCs from SMM progressors.Trephine biopsy cells were scored as senescent based on LoL and loss of nuclear HMGB1.Stable MGUS patients exhibited increased percentage of senescent PCs compared to MM and MGUS patients that progressed ≤10 years (n=20-40).Senescent PCs in trephine biopsies correlated with senescence in the bone marrow microenvironment (BMME).Of interest, MGUS and SMM PCs from patients that progressed ≤10 years both exhibited a significant loss in neighboring senescent BMME compared to stable MGUS and SMM PCs.Conclusions: Overall, we demonstrate the presence of stage-specific senescence features in PCs from stable MGUS and SMM patients; these features are decreased in PCs from SMM progressors and MM, consistent with the protective effect of senescence against tumorigenesis.Thus, evaluating PC senescence in MGUS and SMM may have prognostic value to identify patients that will progress to MM. Importantly, given the increased risk for osteoporotic fracture and reduced overall survival in stable MGUS patients, the senescence-related protection against MM may come at the expense of premature aging.Ongoing studies are evaluating the safety and therapeutic utility of ablating pre-malignant senescent cells in MGUS and SMM.

Introduction Serum free light chain (sFLC) are important for diagnosis and prognosis of plasma cell dyscrasias and are known to be affected by kidney function and inflammatory conditions. However, African Americans (AA) have been reported to have significantly higher Kappa (κ) and Lambda (λ) sFLC levels than European Americans (EA) in a biobanked population, even after adjusting for kidney function (El-Khoury et al., Lancet Haem 2022). Data on race-adjusted reference ranges for sFLC and sFLC ratio (sFLCr) remain limited. We hypothesize that an adjustment in sFLC reference ranges for individuals of African and European ancestry is needed. Methods We analyzed serum samples from 738 healthy Black South African (SA) and 3402 US individuals (AA+EA) as part of an international study screening for individuals at high risk of multiple myeloma (MM) and precursor conditions. Self-identification as Black or having family history of hematologic cancer or MM precursor were key eligible criteria. sFLC levels were measured using the Optilite® Freelite assay (The Biding Site). All participants were screened for Monoclonal Gammopathy of Undetermined Significance (MGUS; M protein concentration ≥ 0.2 g/L) by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. Serum Cystatin C (Optilite®) was used to calculate estimated Glomerular Filtration Rate (eGFR) with CKD-EPI Cystatin C Equation (2012) formula for 752 individuals (568 SA, 184 AA). Clinical data was collected using validated questionnaires at study enrollment. Group medians were compared with Wilcoxon tests. Abnormal sFLCr was defined as any value outside the normal reference range with the involved sFLC above the manufacturer's normal reference range. We used 95% central interval (CI) values to compute new sFLCr reference values for each group. Results After excluding individuals with Heavy Chain-MGUS, our study population consisted of 654 SA, 326 AA, and 2,551 EA. Median age was 52 (IQR 46-59), 56 (IQR 50-65, and 58 (IQR 50-64) for the three groups, respectively. There was a female predominance in the AA (74%) and EA (73%) groups compared to SA (52%). Chronic kidney disease (CKD) was self-reported in 0.2%, 1% and 1% of the three groups, respectively. Calculated median eGFR was 118 ml/min (IQR 106-134) for SA and 112 (IQR 98-123) for AA. HIV positivity was higher (23%) in SA than the other groups (<1%) and 99% were under treatment (Tenofovir 92%, which is known to be nephrotoxic). The median free κ was higher in SA (32 mg/l, IQR 24.8-46) than AA (18.1 mg/l, IQR 14.4-23, +80%, p<0.01) and EA (13.7 mg/l, IQR 10.8 - 17.1, +133%, p<0.01). Similarly, median free λ was higher in SA (24.6 mg/l, IQR 18.8-33.4) than AA (15 mg/l, IQR 11.7-19.3, +64%, p<0.01) and EA (11.9, mg/l IQR 9.1-15.5, +106%, p<0.01). 92% of SA, 43% of AA, and 16% of EA had κ values above the normal range. Similarly, 43% of SA, 10% of AA, and 3% of EA had λ values outside the normal range. Median sFLCr was higher in SA (1.34, IQR 1.13-1.65) than AA (1.25, IQR 1.03-1.48, p<0.01), and EA (1.18, IQR 0.99-1.39, p<0.01) (Fig 1). Using the standard manufacturer ranges, 25% of SA, 11% of AA and 3% of EA had abnormal sFLCr and involved FLC. Decreasing eGFR, increasing age, HIV positivity, and the cohort (SA, AA, or EA) were all significant predictors of changes in sFLCr in univariate analysis. In multivariate logistic regression, increasing age, HIV positivity, and decreasing eGFR were independent predictors of abnormal sFLCr (Table 1) for SA or AA compared to EA. In SA with normal renal function (eGFR >60 ml/min), excluding those with free κ and λ outside the 95% CI, we identified a new reference (95% CI) for FLCr of 0.80-2.38. Conclusions This is the first report of sFLC measurements in an African population screened for MG and compared to AA and EA. We observe a significantly higher sFLC for Black (SA and AA) than White individuals (EA), independent of renal function. This difference could be due to genetic background and socioeconomic and environmental factors (e.g., HIV epidemiology). In contrast with previous reports (Zemlin, et al, J Clin Pathol 2015), HIV was associated with higher FLCr, maybe with a possible role of nephrotoxic HIV drugs. Here, standard reference ranges do not apply to SA participants. While further validation is needed, we propose to use a different sFLC range for African ancestry populations with normal renal function. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

5046 Background: Men in sub-Saharan Africa (SSA) are disproportionately affected by prostate cancer (PCa), and many have metastatic disease (mPCA) at presentation. In SSA, androgen deprivation therapy (ADT) is the first-line treatment for mPCa, and often the only available therapy. Treatment failure and death is common. We identified predictors of overall survival (OS) in Black South African (SA) men with mPCa on ADT. Methods: We performed a retrospective analysis of prospectively gathered data from men diagnosed with mPCA (3/22/2016 - 10/30/2020) at Chris Hani Baragwanath Hospital in Johannesburg, which was also a study site for the concurrent Men of African Descent and Carcinoma of the Prostate study. We included men with mPCA treated with ADT (received at least 1 dose of luteinizing hormone-releasing hormone agonist and/or had surgical castration), who had ≥1 PSA level drawn ≥12 weeks after ADT start. OS was defined from ADT start to death. PSA progression (PSA-P) definition was adapted from PCWG 3. Cox regression models were used to identify predictors of OS. PSA-P was treated as a time-dependent covariate. Results: Of 200 men with mPCa, we excluded 6 who did not receive ADT and 41 without sufficient data for PSA-P analysis. Of 153 men, 26.8% were <65 years old and 12% had a family history of PCa. Median PSA at diagnosis was 71.5 ng/mL (interquartile range (IQR) 20.7-432.6), median alkaline phosphatase level (ALP) 108 IU/L (79-224) and median hemoglobin (Hb) 13 g/dL (IQR 10-15). Median PSA nadir was 2.8 ng/mL (IQR 0.55-17.93). The rate of PSA-P at 1- and 2-years was 12.1% [95%CI 5.9-17.8] and 37.5% [95%CI 26.1-47.2]. The median follow-up was 2.75 years, and the 3-year OS was 61.9% [95%CI 52.7-72.6]. Cox proportional hazard ratio (HR) models of risk factors for OS are shown in Table 1. PSA-P was a strong predictor of OS. Men with PSA nadir >4ng/mL after ADT start had a HR for death of 3.77 [1.86-7.62]. Men with ALP >150 IU/L and those with Hb <13.5g/dL at diagnosis were also at higher risk for death (HR 3.09 [1.64-5.83] and HR 2.00 [1.28-6.56] respectively). Conclusions: Among Black men in SA treated with ADT for mPCA, PSA-P strongly predicts OS. In this cohort, high ALP and anemia at diagnosis, and PSA nadir >4ng/mL after ADT start are associated with higher risk for death. These factors can be used identify high risk men with mPCA, for whom early treatment escalation to chemotherapy should be considered. [Table: see text]

e20032 Background: Monoclonal gammopathy of undetermined significance (MGUS) is the precursor to multiple myeloma (MM). MM disproportionately affects black individuals, but the cumulative risk of progression from MGUS to malignancy does not differ by race. Hence, the racial disparities in MM incidence appear to arise from differences in the occurrence of MGUS. Nonetheless, MGUS has been studied mainly in white populations; the study that first described the natural history of MGUS was conducted by Kyle, et al. (2006) in 97.3% white Olmsted County, Minnesota. Methods: We determined the prevalence of MGUS among black South African men >30 years of age at the Chris Hani Baragwanath Academic Hospital in Johannesburg. We conducted serum protein electrophoresis (SPEP) and free light chain (FLC) quantification and used the same criteria for MGUS as the Olmsted County studies: a monoclonal protein on SPEP or an abnormal FLC-ratio plus elevation in the appropriate FLC. We also investigated the association between MGUS and various clinical and behavioral factors. Results: The prevalence of MGUS in our cohort (n=386) was 8.03% (95%CI 5.32-10.74), nearly 1.6-fold higher than in Olmsted County males. In a univariable logistic regression model, MGUS was associated with HIV status (odds ratio (OR) 2.39, 95%CI 0.95-5.51), but in the adjusted model that also included body mass index (BMI) and cigarette use, the magnitude of the association decreased to an OR of 2.17 and was not statistically significant. MGUS was associated with current (vs. never) cigarette smoking in both univariable (OR 5.2, 95%CI 1.53-24.0) and multivariable (OR 4.11, 95%CI 1.08-20.4) models. Conclusions: Not only did we find the prevalence of MGUS in black South African men to be substantially higher than in white populations, but we also report that MGUS cases are associated with potentially modifiable risk factors. Building on this pilot study, a larger study is currently underway powered to confirm the relationship between MGUS and HIV, as well as between MGUS and cigarette smoking, in a black African population inclusive of both genders. Future studies designed to evaluate genetic and matched-environmental contributions may elucidate racial disparities and facilitate the development of strategies to prevent plasma cell malignancies.[Table: see text]

Background Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant expansion of plasma cells that always precedes the development of multiple myeloma. Recent U.S.-based screening studies utilizing matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) reported a high prevalence of monoclonal gammopathies (MGs) among Blacks. One study observed among Blacks over age 50 years, a high prevalence of MGUS (17%) as well as low-level MGs below the detection threshold of serum protein electrophoresis/immunofixation (SPEP/IFX) assays, termed monoclonal gammopathy of indeterminate potential (MGIP, 31% prevalence). In the current study, we aimed to define the prevalence of MGs by MALDI-TOF MS in a Black population in South Africa and evaluate its association with risk factors (e.g., obesity). Methods Individuals who self-identify as Black African and aged >=40 years were recruited from Soweto, Johannesburg, South Africa to participate in the study. Those with a prior diagnosis of a plasma cell dyscrasia and/or any cancer history requiring active therapy were excluded. Serum samples of participants were analyzed using the Binding Site Group's EXENT® assay based on MALDI-TOF MS for the quantification of M-proteins. M-proteins >=0.2 g/L were categorized as MGUS, and those <0.2 g/L were MGIP. This concentration threshold of 0.2 g/L was the lower detection limit of SPEP/IFX-determined by serial dilution sensitivity testing comparing MALDI-TOF MS and SPEP/IFX assays, performed and provided by the manufacturer and reported in a prior study. Participants’ heights and weights were measured at enrollment and used to calculate body mass index (BMI, kg/m2). All participants completed a survey querying sociodemographic factors, clinician-diagnosed comorbidities, and lifestyle factors. Logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for exposure and MGUS/MGIP associations. Results As of June 2022, 738 participants enrolled in the study. Median age was 52 years (range, 40-79), and 52% were female. 3% reported an educational status of college graduate or above. Ethnic background of participants included 38% IsiZulu, 20% Sesotho, 13% IsiXhosa, 13% Setswana, 5% Tsonga, 4% Sepedi, 4% Seswati, and 1% Tshivenda. The prevalence of MGUS and MGIP was 12% and 17% in the entire cohort and 13% and 18% in those aged >=50 years. MGUS was predominantly IgG (89%), followed by IgA (7%) and IgM (4%). MGIP was predominantly IgM (81%), followed by IgA (15%) and IgG (4%). In univariate analysis, MGs were associated with increasing 10-year age intervals (OR, 1.40; 95% CI, 1.17-1.67). Mean BMI was 27 kg/m2, and 27% of participants were obese (>=30 kg/m2). Adjusting for age, sex, and education, obesity was associated with all MGs (OR, 1.49; 95% CI, 1.01-2.20). Obesity was associated with MGIP (OR, 1.94; 95% CI, 1.20-3.12) and not with MGUS (OR, 1.04; 95% CI, 0.58-1.82). Diabetes was also associated with MGIP (OR, 2.98; 95% CI, 1.19-7.19). HIV was reported in 23% of participants, among whom 99% reported current HIV treatment. HIV was not associated with MGUS or MGIP. All other comorbidities, including cardiovascular disease, stroke, COPD/emphysema, arthritis, liver disease, and chronic kidney disease, were reported in <=1% of participants. As for lifestyle factors, heavy alcohol consumption (>=30 g/day) was associated with MGUS (OR, 2.76; 95% CI, 1.47-5.51). Heavy smoking (>10 pack-years) had a trend toward association with MGUS (OR, 1.81; 95% CI, 0.98-3.32). Short sleep (<=6 hours/day) was associated with MGIP (OR, 2.11; 95% CI, 1.22-3.59). Conclusion These results are the first to describe a high prevalence of MGUS detected by MS (13%) for a Black African cohort aged >=50 years, consistent with high prevalence estimates of MS-detected MGUS recently reported in U.S. Blacks. Obesity and diabetes were associated with MGIP, an entity that currently bears unknown etiology. We, however, did not observe associations for obesity and related comorbidities with MGUS, possibly due to limited sample size. Nonetheless, these first results along with other observed novel risk factor associations (e.g., MGUS and heavy alcohol consumption) in our expanding South African cohort provide clues to pathophysiological mechanisms of MGs and may inform interception strategies in preventing their progression.

Objective With increases in chronic disease, men with prostate cancer are likely to have at least one other chronic health condition. The burden and complexity of each additional chronic disease may complicate prostate cancer treatment and reduce survival. In this paper, we describe the frequency of multimorbid chronic diseases, HIV and depression among men in Soweto, South Africa (SA) with and without prostate cancer and determine whether the presence of multimorbid diseases is associated with metastatic and high-risk, non-metastatic prostate cancer. Methods A population-based case-control study on prostate cancer was conducted among black men in Soweto. All participants completed a baseline survey on sociodemographics, lifestyle, and comorbid medical conditions. All participants completed a depression screening survey and HIV testing at enrolment. Blood pressure measurements and blood testing for fasting glucose, total cholesterol, and high-density lipoprotein were performed on a subset of randomly selected cases and controls. For men with prostate cancer, clinical T staging was assessed with the digital rectal examination, the diagnosis was confirmed with a biopsy and PSA levels were assessed at presentation. The metastatic staging was assessed by bone scans, and this was confirmed with PSMA PET scans, CT scans and X-rays, standard for our resource-constrained setting. Normal PSA scores were used as an inclusion criterion for controls. Results Of the 2136 men (1095 with prostate cancer and 1041 controls) included in the analysis, 43.0% reported at least one chronic metabolic disease; 24.1% reported two metabolic diseases; 5.3% reported three metabolic diseases; and 0.3% reported four metabolic diseases. Men with prostate cancer were more likely to report a multimorbid chronic metabolic disease compared to controls (p<0.001) and more likely to test positive for HIV (p = 0.05). The majority of men (66.2%) reported at least one metabolic disease, tested negative for HIV and had a negative depression screen. The clinical characteristics of men with prostate cancer, were as follows: 396 (36.2%) had a Gleason score of 8 and above; 552 (51.3%) had a PSA score of >20ng/ml; 233 (21.7%) had confirmed metastatic prostate cancer at diagnosis. Older age was associated with metastatic prostate cancer (OR = 1.043 95% CI:1.02–1.07) and NCCN defined high-risk non-metastatic prostate cancer (OR = 1.03 95% CI:1.01–1.05), whilst being hypertensive was protective (OR = 0.63 95% CI:0.47–0.84 and OR = 0.55 95% CI:0.37–0.83) respectively for metastatic and high-risk, non-metastatic prostate cancer. Conclusion The high prevalence of multimorbid metabolic diseases and HIV among men with prostate cancer represents a public health concern in South Africa. There is a need to effectively address multiple chronic diseases among men with prostate cancer by incorporating coordinated care models.

Background: Both multiple myeloma and its precursor, mono-clonal gammopathy of undetermined significance (MGUS), occur twice as often within Black compared with White populations, suggesting that racial disparities lie within the development of MGUS. Nonetheless, MGUS has been studied mainly in White cohorts; the study that first described the natural history of MGUS was conducted in 97.3% White Olmsted County, Minnesota.Methods: We determined the prevalence of MGUS among 386 Black South African (SA) men>30 years at Chris Hani Baragwanath Hospital in Johannesburg. We conducted serum protein electro-phoresis and free light chain quantification to define MGUS by the same criteria as the Olmsted County studies. We also inves-tigated the association between MGUS and various clinical factors, including human immunodeficiency virus (HIV) infection and smoking.Results: We found the prevalence of MGUS to be 8.03% [95% confidence interval (CI), 5.32-10.74], nearly 1.6-fold higher than in the White Olmsted County male population. In a univariable logistic regression model, MGUS was associated with HIV status (OR, 2.39; 95% CI, 0.95-5.49), but in an adjusted model that included body mass index and cigarette use, the association was not statistically significant. Those who were current (vs. never) cigarette smokers were more likely to have MGUS in both univari-able (OR, 5.60; 95% CI, 2.16-17.42) and multivariable models (OR, 4.49; 95% CI, 1.63-14.56). Conclusions: The prevalence of MGUS in Black SA men is substantially higher than in White populations and may be asso-ciated with HIV status and cigarette use.Impact: Racial disparities in MGUS exist and may be associated with potentially modifiable risk factors.

Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Results Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608-0.707, OR 2.37-5.71) than for African individuals (AUC 0.502-0.585, OR 0.95-2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Conclusions Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.

African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. Between 2016 and 2020, we recruited 2,200 PCa cases and 1,985 age-matched controls into a multi-center, hospital-based case–control study in Senegal, Ghana, Nigeria, and South Africa. Participants completed an epidemiologic questionnaire, and anthropometric factors were measured at clinic visit. Multivariable logistic regression was used to examine associations of overall and central obesity with PCa risk, measured by body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), respectively. Among controls 16.4% were obese (BMI ≥ 30 kg/m2), 26% and 90% had WC > 97 cm and WHR > 0.9, respectively. Cases with aggressive PCa had lower BMI/obesity in comparison to both controls and cases with less aggressive PCa, suggesting weight loss related to cancer. Overall obesity (odds ratio: OR = 1.38, 95% CI 0.99–1.93), and central obesity (WC > 97 cm: OR = 1.60, 95% CI 1.10–2.33; and WHtR > 0.59: OR = 1.68, 95% CI 1.24–2.29) were positively associated with D’Amico intermediate-risk PCa, but not with risks of total or high-risk PCa. Associations were more pronounced in West versus South Africa, but these differences were not statistically significant. The high prevalence of overall and central obesity in African men and their association with intermediate-risk PCa represent an emerging public health concern in Africa. Large cohort studies are needed to better clarify the role of obesity and PCa in various African populations.

You have accessJournal of UrologyGlobal Health/Humanitarian (MP67)1 Sep 2021MP67-18 CLINICAL CHARACTERISTICS OF PROSTATE CANCER PATIENTS IN WEST AND SOUTH AFRICA IN THE MEN OF AFRICAN DESCENT AND CARCINOMA OF THE PROSTATE (MADCAP) CONSORTIUM STUDY Mohamed Jalloh, Denzel Zhu, Ilir Agalliu, Caroline Andrews, Evan Kovac, Ben Adusei, Nana Yaa Snyper, James Mensah, Victoria Okyne, Ann Hsing, Akindele Adebiyi, Olufemi Ogunbiyi, Olayiwola Shittu, Peter Olabode, Maxwell Nwegbu, Oseremen Aisuodionoe-Shadrach, Pedro Fernandez, Hayley Irusen, Audrey Pentz, Maureen Joffe, Elvira Singh, Judith Jacobson, Alfred Neugut, Thomas Rohan, Lamine Niang, Serigne Gueye, and Timothy Rebbeck Mohamed JallohMohamed Jalloh More articles by this author , Denzel ZhuDenzel Zhu More articles by this author , Ilir AgalliuIlir Agalliu More articles by this author , Caroline AndrewsCaroline Andrews More articles by this author , Evan KovacEvan Kovac More articles by this author , Ben AduseiBen Adusei More articles by this author , Nana Yaa SnyperNana Yaa Snyper More articles by this author , James MensahJames Mensah More articles by this author , Victoria OkyneVictoria Okyne More articles by this author , Ann HsingAnn Hsing More articles by this author , Akindele AdebiyiAkindele Adebiyi More articles by this author , Olufemi OgunbiyiOlufemi Ogunbiyi More articles by this author , Olayiwola ShittuOlayiwola Shittu More articles by this author , Peter OlabodePeter Olabode More articles by this author , Maxwell NwegbuMaxwell Nwegbu More articles by this author , Oseremen Aisuodionoe-ShadrachOseremen Aisuodionoe-Shadrach More articles by this author , Pedro FernandezPedro Fernandez More articles by this author , Hayley IrusenHayley Irusen More articles by this author , Audrey PentzAudrey Pentz More articles by this author , Maureen JoffeMaureen Joffe More articles by this author , Elvira SinghElvira Singh More articles by this author , Judith JacobsonJudith Jacobson More articles by this author , Alfred NeugutAlfred Neugut More articles by this author , Thomas RohanThomas Rohan More articles by this author , Lamine NiangLamine Niang More articles by this author , Serigne GueyeSerigne Gueye More articles by this author , and Timothy RebbeckTimothy Rebbeck More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002028.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Men of African descent have the highest burden of aggressive prostate cancer (PCa). However, the clinical features of PCa within sub-Saharan Africa (SSA) are understudied. Our objective was to characterize the clinical features of men with PCa in SSA, and to compare demographic/clinical features of PCa between West (WA) and South Africa (SA). METHODS: Between 2016 and 2020, we recruited 2,588 histologically-confirmed PCa patients into a multi-center study in Senegal, Ghana, Nigeria and South Africa via the MADCaP Consortium. Participants completed a detailed questionnaire which collected information on demographics, lifestyle, PCa family history, and lower urinary symptoms (LUTS) assessed through the International Prostatism Symptom Score (IPSS); medical history and PCa clinical features were extracted through review of medical charts. We used Student t-test, Wilcoxon sign-rank test or χ2 test to compare patients’ characteristics by region. RESULTS: Among 2588 men with PCa, 1325 (51.2%) were recruited in WA and 1263 (49.8%) in SA. The majority (78.9%) of patients had high D’Amico risk PCa. PCa patients in WA were older at diagnosis (68.3±8.0 years) compared to SA patients (66.5±8.0, p<0.001). Median PSA at diagnosis was higher in WA cases (93.9, IQR: 26.5-450.9) compared to SA cases (28.5, IQR: 12.8-100.9, p<0.001). PCa cases in WA also had a higher prevalence of moderate/severe LUTS (63.7%) compared to PCa cases in SA (49.4%). Clinically invasive disease (stage T3+) was more prevalent in WA compared to SA (64.5% vs. 20.2%, p<0.001). However, the distribution of aggressive Gleason Group 4-5 PCa was similar between WA (39.9%) and SA (38.1%). The majority of patients were treated with hormone-therapy in both WA (42.2%) and SA (61.8%). However, in SA, a large proportion of patients are treated with radiation therapy (27.6%), while this treatment was rarely used in WA. CONCLUSIONS: Men in Africa present with very high-risk PCa. Patients in WA had characteristics of more advanced disease at presentation than their SA counterparts, indicated by a higher PSA, prevalence of adverse clinical features, and a greater proportion of prostatic symptoms. This data further emphasizes the need for the development of PCa screening guidelines within SSA. Source of Funding: Supported in part by the National Cancer Institute, National Institutes of Health (NIH) Grants No. U01-CA184374 and NIH 5 P30-CA06516 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e516-e517 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Jalloh More articles by this author Denzel Zhu More articles by this author Ilir Agalliu More articles by this author Caroline Andrews More articles by this author Evan Kovac More articles by this author Ben Adusei More articles by this author Nana Yaa Snyper More articles by this author James Mensah More articles by this author Victoria Okyne More articles by this author Ann Hsing More articles by this author Akindele Adebiyi More articles by this author Olufemi Ogunbiyi More articles by this author Olayiwola Shittu More articles by this author Peter Olabode More articles by this author Maxwell Nwegbu More articles by this author Oseremen Aisuodionoe-Shadrach More articles by this author Pedro Fernandez More articles by this author Hayley Irusen More articles by this author Audrey Pentz More articles by this author Maureen Joffe More articles by this author Elvira Singh More articles by this author Judith Jacobson More articles by this author Alfred Neugut More articles by this author Thomas Rohan More articles by this author Lamine Niang More articles by this author Serigne Gueye More articles by this author Timothy Rebbeck More articles by this author Expand All Advertisement PDF downloadLoading ...

Purpose Health research in low- and middle-income countries can generate novel scientific knowledge and improve clinical care, fostering population health improvements to prevent premature death. Project management is a critical part of the success of this research, applying knowledge, skills, tools, and techniques to accomplish required goals. Here, we describe the development and implementation of tools to support a multifaceted study of prostate cancer in Africa, focusing on building strategic and operational capacity. Methods Applying a learning organizational framework, we developed and implemented a project management toolkit (PMT) that includes a management process flowchart, a cyclical center-specific schedule of activities, periodic reporting and communication, and center-specific monitoring and evaluation metrics. Results The PMT was successfully deployed during year one of the project with effective component implementation occurring through periodic cycles of dissemination and feedback to local center project managers. A specific evaluation was conducted 1 year after study initiation to obtain enrollment data, evaluate individual quality control management plans, and undertake risk log assessments and follow-up. Pilot data obtained identified areas in which centers required mentoring, strengthening, and capacity development. Strategies were implemented to improve project goals and operational capacity through local problem solving, conducting quality control checks and following compliancy with study aims. Moving forward, centers will perform quarterly evaluations and initiate strengthening measures as required. Conclusion The PMT has fostered the development of both strategic and operational capacity across project centers. Investment in project management resources is essential to ensuring high-quality, impactful health research in low- and middle-income countries.

Purpose Cancer of the prostate (CaP) is the leading cancer among men in sub-Saharan Africa (SSA). A substantial proportion of these men with CaP are diagnosed at late (usually incurable) stages, yet little is known about the etiology of CaP in SSA. Methods We established the Men of African Descent and Carcinoma of the Prostate Network, which includes seven SSA centers partnering with five US centers to study the genetics and epidemiology of CaP in SSA. We developed common data elements and instruments, regulatory infrastructure, and biosample collection, processing, and shipping protocols. We tested this infrastructure by collecting epidemiologic, medical record, and genomic data from a total of 311 patients with CaP and 218 matched controls recruited at the seven SSA centers. We extracted genomic DNA from whole blood, buffy coat, or buccal swabs from 265 participants and shipped it to the Center for Inherited Disease Research (Baltimore, MD) and the Centre for Proteomics and Genomics Research (Cape Town, South Africa), where genotypes were generated using the UK Biobank Axiom Array. Results We used common instruments for data collection and entered data into the shared database. Double-entered data from pilot participants showed a 95% to 98% concordance rate, suggesting that data can be collected, entered, and stored with a high degree of accuracy. Genotypes were obtained from 95% of tested DNA samples (100% from blood-derived DNA samples) with high concordance across laboratories. Conclusion We provide approaches that can produce high-quality epidemiologic and genomic data in multicenter studies of cancer in SSA.