A Systems Approach to Interrogate Gene Expression Patterns in African American Men Presenting with Clinically Localized Prostate Cancer.

An emerging theory about racial differences in cancer risk and outcomes is that psychological and social stressors influence cellular stress responses; however, limited empirical data are available on racial differences in cellular stress responses among men who are at risk for adverse prostate cancer outcomes. In this study, we undertook a systems approach to examine molecular profiles and cellular stress responses in an important segment of African American (AA) and European American (EA) men: men undergoing prostate biopsy. We assessed the prostate transcriptome with a single biopsy core via high throughput RNA sequencing (RNA-Seq). Transcriptomic analyses uncovered impacted biological pathways including PI3K-Akt signaling pathway, Neuroactive ligand-receptor interaction pathway, and ECM-receptor interaction. Additionally, 187 genes mapping to the Gene Ontology (GO) terms RNA binding, structural constituent of ribosome, SRP-dependent co-translational protein targeting to membrane and the biological pathways, translation, L13a-mediated translational silencing of Ceruloplasmin expression were differentially expressed (DE) between EA and AA. This signature allowed separation of AA and EA patients, and AA patients with the most severe clinical characteristics. AA patients with elevated expression levels of this genomic signature presented with higher Gleason scores, a greater number of positive core biopsies, elevated dehydroepiandrosterone sulfate levels and serum vitamin D deficiency. Protein-protein interaction (PPI) network analysis revealed a high degree of connectivity between these 187 proteins.

Financial toxicity and strain among men receiving prostate cancer care in an equal access healthcare system.

PURPOSE: To examine financial toxicity and strain among men in an equal access healthcare system based on social determinants and clinical characteristics. METHODS: Observational study among men receiving prostate cancer care (n = 49) at a Veterans Health Administration (VHA) facility. Financial hardship included overall financial strain and financial toxicity due to healthcare costs. Financial strain was measured with one item asking how much money they have leftover at the end of the month. Financial toxicity was measured with the Comprehensive Score for Financial Toxicity (COST) scale. RESULTS: Comprehensive Score for Financial Toxicity scores among participants indicated moderate levels of financial toxicity (M = 24.4, SD = 9.9). For financial strain, 36% of participants reported that they did not have enough money left over at the end of the month. There were no racial or clinically related differences in financial toxicity, but race and income level had significant associations with financial strain. CONCLUSION: Financial toxicity and strain should be measured among patients in an equal access healthcare system. Findings suggest that social determinants may be important to assess, to identify patients who may be most likely to experience financial hardship in the context of obtaining cancer care and implement efforts to mitigate the burden for those patients.

Resiliency and Allostatic Load among Veterans at Risk for Adverse Prostate Cancer Outcomes.

Objective: To examine the relationships between resiliency, sociodemographic factors, and allostatic load among male Veterans. Design/Study Participants: Cross-sectional study with minority (African American or Hispanic) and non-minority (White) male Veterans undergoing prostate biopsy. Setting: Veterans Affairs Medical Center located in Charleston, SC. Main Outcome Measures: Self-reported resilience measured using the two item sub-scale from the Connor-Davidson Resiliency Scale and allostatic load determined from biomarkers measured in blood. Results: In this small sample, bounce-back resilience and allostatic load level had a significant negative correlation, while adaptation resilience and allostatic load were slightly correlated, but the association was not statistically significant. Sixty-six percent of participants reported that they were able to adapt and 40% reported they were able to bounce back. Higher income and lower PSA level were significantly correlated with greater adaptation resilience. Minority men were significantly more likely than non-minority men to report that they are able to bounce back. Married men were also significantly more likely than unmarried men to report that they were able to bounce back. Conclusion: It may be important to target resiliency training programs to Veterans based on their social determinants and to examine the effects of these programs on allostatic load.

Six Weeks of Fluoroquinolone Antibiotic Therapy for Patients With Elevated Serum Prostate-specific Antigen Is Not Clinically Beneficial: A Randomized Controlled Clinical Trial.

OBJECTIVE: To evaluate asymptomatic men with elevated serum prostate-specific antigen (PSA) to determine whether a 6-week course of fluoroquinolone antibiotics lowers serum PSA and affects recommendations for prostate biopsy. MATERIALS AND METHODS: A randomized, single-center prospective trial of 150 men with an initial elevated PSA was conducted. Patients were randomized to 6 weeks of ciprofloxacin or observation. Those patients with persistently elevated PSA were recommended to proceed with transrectal ultrasound-guided 12-core biopsy. Those with reduced PSA were offered transrectal ultrasound-guided biopsy but could opt to continue serial digital rectal examination/PSA. Patients were followed an average of 4.6 years to assess trends in PSA and biopsy results. RESULTS: Of 136 men who completed the trial, 63 were in the treatment and 73 were in the observation group. The average PSA change from baseline was borderline statistically significant with a change of -0.68 ng/mL in the treatment arm and 0.01 ng/mL in the observation arm (P = .052). Of those who underwent biopsy, prostate cancer was diagnosed in the first biopsy in 24 (63%) of the treatment vs 27 (52%) of the observation group (P = .60) over follow-up. CONCLUSION: In a cohort of asymptomatic men with elevated PSA, there was only a borderline statistically significant change in serum PSA between patients randomized to a 6-week course of fluoroquinolones vs observation, and there was no difference in positive prostate biopsy results. Our clinical recommendation is one should not treat patients with elevated serum PSA with antibiotics in the absence of clinical symptoms of prostatitis.