Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences.

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

Improving risk stratification in a community-based African American population using cell cycle progression score.

BACKGROUND: Current clinical nomograms such as American Urological Association/National Comprehensive Cancer Network (AUA/NCCN) risk categories or CAPRA may not always reflect prostate cancer (PCa) risk among African American men. We evaluated the usefulness of adding a commercially available cell cycle progression (CCP) score to improve risk stratification in a community-based African American population. METHODS: Biopsy tissues from 150 African American and 60 Caucasian men were obtained from a single community urologic oncology practice in Memphis, TN. The biopsy samples were evaluated with a commercially available CCP panel (Prolaris). Clinical variables such as Gleason score, prostate-specific antigen (PSA), age, clinical stage, and extent of disease were combined to determine a single category of low-, intermediate-, or high-risk. AUA risk stratification for cancer aggressiveness was then compared between the CCP score vs. the clinical parameters to determine potential risk improvement by the CCP score. RESULTS: Based on the clinical parameters, of the 150 African American men evaluated, 20% were classified as low-risk, 40% were classified as intermediate-risk, and 40% were classified as high-risk. Of the 60 Caucasian men evaluated, 42% were low-risk, 42% were intermediate-risk, and 17% were high-risk. However, when re-evaluating the African American patients using the CCP score, 30% of the patients were determined to be more aggressive than the clinical low-risk category. Similarly, 21.67% of the patients were found to be more aggressive than the clinical intermediate-risk category, and 23.33% of the patients were more aggressive than the high-risk category. When compared to our Caucasian cohort, 12% of the low-risk patients, 8% of the intermediate-risk patients, and 10% of the high-risk patients were found to be more aggressive by the CCP score. Overall, 24% of African American men vs. 10% of Caucasian men were reclassified to a higher risk by CCP score. When we compared the mean CCP score in the African American population vs. the Caucasian population, the mean CCP score in the AUA low-risk was 3.2 vs. 2.9; 3.4 vs. 3.2 in the AUA intermediate-risk; and 3.8 vs. 3.5 in the AUA high-risk category, respectively. Despite the higher mean CCP score in the African American population, the difference between the African American men and the Caucasian men was not significant (P=0.064 for low-risk, P=0.204 for intermediate-risk, and P=0.209 for high-risk). CONCLUSIONS: Our data extends the evidence that CCP score derived from a biopsy specimen can be clinically useful. Our findings showed that the CCP score could stratify 10-year mortality risk in African American men beyond the current clinicopathologic features, which may better prepare patients for follow-up visits and discussions with their health care provider(s) and enhance their ability to select the most appropriate treatment option.

Effect of a resident physician educational program on pediatric emergency department pharmacy interventions and medication errors.

PURPOSE: To determine the effects of a resident physician educational program in a pediatric emergency department (ED) on pharmacy interventions and medication errors, particularly dose adjustments, order clarifications, and adverse drug events (ADE). METHODS: The ED pharmacist recorded all interventions and medication errors on weekdays from 3 to 11 pm during a 9-month period, consisting of a preobservational (Quarter 1), observational (Quarter 2), and interventional (Quarter 3) phases. Program implementation occurred in Quarter 3, with an initial 3-hour lecture during the ED orientation, followed by daily patient case discussions. Weekly interventions and errors were analyzed using statistical process control u-chart analyses. Chi-square analyses of independence were also performed. Resident and ED staff feedback on the program was obtained through anonymous internet-based surveys. RESULTS: A total of 3507 interventions were recorded during the 9-month period. Chi-square approximation and interval estimation of odds ratio showed a statistically significant decrease between Quarters 1 and 3 in the number of dose adjustments (95% confidence interval [CI], 0.324-0.689) and order clarifications (95% CI, 0.137 to 0.382) after initiation of the program. The decline in ADE, while not as substantial (95% CI, 0.003 to 1.078), still achieved a level of significance (90% CI, 0.006 to 0.674). Survey results were positive toward the program. CONCLUSIONS: The implementation of a resident physician educational program in our pediatric ED significantly decreased the number of medication errors, increased resident physician awareness of the potential for errors, and increased ED pharmacist utilization.