Fitzsimmonsstokholm1906

BACKGROUND Although 5-alpha-reductase inhibitors (5ARIs) have been shown to benefit men with prostate cancer (PCa) on active surveillance (AS), their long-term safety remains controversial. Our objective is to describe the long-term association of 5ARI use with PCa progression in men on AS. MATERIALS/SUBJECTS AND METHODS The cohort of men with low-risk PCa was derived from a prospectively maintained AS database at the Princess Margaret (1995-2016). Pathologic, grade, and volume progression were the primary end points. Kaplan-Meier time-to-event analysis was performed and Cox proportional hazards regression was used to determine predictors of progression where 5ARI exposure was analyzed as a time-dependent variable. Patients who came off AS prior to any progression events were censored at that time. RESULTS The cohort included 288 men with median follow-up of 82 months (interquartile range 37-120 months). Among non-5ARI users (n = 203); 114 men (56.2%) experienced pathologic progression compared with 24 men (28.2%) in the 5ARI group (n = 85), (p  less then  0.001). Grade and volume progression were higher in the non-5ARI group compared with the 5ARI group (n = 82; 40.4% vs. n = 19; 22.4% respectively, p = 0.003 for grade progression; n = 87; 43.1% and n = 15; 17.7%, respectively for volume progression p  less then  0.001). Lack of 5ARI use was independently positively associated with pathologic progression (HR 2.65; CI 1.65-4.24), grade progression (HR 2.75; CI 1.49-5.06), and volume progression (HR 3.15; CI 1.78-5.56). The frequency of progression to high-grade (Grade Group 4-5) tumors was not significantly different between the groups. CONCLUSIONS Use of 5ARIs diminished both grade and volume progression without an increased risk of developing Grade Groups 4-5 disease.BACKGROUND Black men have significantly higher incidence and are up to three times more likely to die of prostate cancer (PCa) than White men. Multiparametric magnetic resonance imaging-ultrasound fusion biopsy (FBx) has emerged as a promising modality for the detection of PCa. The goal of our study is to identify differences in utilization of FBx between Black and White men presenting with suspicion of PCa. METHODS We performed a retrospective review of Black and White men who presented with suspicion of PCa and required biopsy from January 2014 to December 2018. Multivariate logistic regression analysis was done to study the influence of race on the utilization of FBx. RESULTS Six hundred nineteen (Black 182, White 437) men were included in the study. Forty-one out of 182 (22.5%) Black men underwent FBx compared with 225/437 (51.5%) of White men (P  less then  0.001). After adjusting for age, race, prostate-specific antigen level, digital rectal exam, family history of PCa and health insurance provider, Black race was found to be a significant negative predictor of obtaining FBx (OR0.32, 95% CI 0.21-0.51, P  less then  0.001). Black race stayed an independent negative predictor (OR 0.36, 95% CI 0.20-0.64, P  less then  0.001) in the cohort of patients who were biopsy naïve; however, although reduced, there was no significant difference in the cohort with a prior negative biopsy (OR 0.51, 95% CI 0.19-1.36, P = 0.179). CONCLUSIONS Although FBx is a superior modality for early detection of PCa, we found that Black men were less likely to undergo FBx when presenting with PCa suspicion. Further investigation is needed to evaluate if this difference is patient preference or if there are underlying socioeconomic, cultural or provider biases influencing this disparity.BACKGROUND This systematic review and meta-analysis aimed to assess the prognostic value of sequential of abiraterone (ABI) and enzalutamide (ENZ) therapy in patients with castration-resistant prostate cancer (CRPC). METHODS PUBMED, Web of Science, Cochrane Library, and Scopus databases were searched for articles published prior to December 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they compared overall survival (OS), combined progression-free survival (PFS), combined prostate specific antigen (PSA)-PFS, and PSA response rates in CRPC patients receiving sequential ABI/ENZ or vice versa. PSA response to both the first and second agents was defined as a >50% decrease in PSA achieved with each of these agents. Formal meta-analyses were performed for these outcomes. RESULTS Ten studies with 1096 patients were eligible for the systematic review and eight studies with 643 patients for the meta-analysis. The ABI-to-ENZ sequence was significantly associated with better PFS (pooled hazard ratio (HR) 0.62, 95% confidential interval (CI) 0.49-0.78, P  less then  0.001), and PSA-PFS (pooled HR 0.48, 95% CI 0.38-0.61, P  less then  0.001) than the ENZ-to-ABI sequence. selleck kinase inhibitor PSA response rates of both agents were significantly better with the ABI-to-ENZ sequence (risk ratio 0.21, 95% CI 0.09-0.47, P  less then  0.001). In contrast, treatment sequence was not significantly associated with OS (pooled HR 0.77, 95% CI 0.59-1.01, P = 0.055). CONCLUSIONS ABI-to-ENZ sequential therapy in patients with CRPC was associated with better PFS, PSA-PFS, and PSA response rates. Regardless of sequencing, response to drug therapy was transient for both ABI and ENZ when either agent was used as a secondary therapy. Despite this, treatment sequencing is important to achieve the maximum possible benefit from available drugs in CRPC.We have previously reported that recombinant adeno-associated virus serotype 3 (AAV3) vectors transduce human liver tumors more efficiently in a mouse xenograft model following systemic administration. Others have utilized AAV8 vectors expressing miR-26a and miR-122 to achieve near total inhibition of growth of mouse liver tumors. Since AAV3 vectors transduce human hepatic cells more efficiently than AAV8 vectors, in the present studies, we wished to evaluate the efficacy of AAV3-miR-26a/122 vectors in suppressing the growth of human hepatocellular carcinoma (HCC) cells in vitro, and human liver tumors in a mouse model in vivo. To this end, a human HCC cell line, Huh7, was transduced with various multiplicities of infection (MOIs) of AAV3-miR-26a or scAAV3-miR-122 vectors, or both, which also co-expressed a Gaussia luciferase (GLuc) reporter gene. Only a modest level of dose-dependent growth inhibition of Huh7 cells (~12-13%) was observed at the highest MOI (1 × 105 vgs/cell) with each vector. When Huh7 cells were co-transduced with both vectors, the extent of growth inhibition was additive (~26%).