BACKGROUND After long-term androgen deprivation therapy, 25-30% prostate cancer (PCa) acquires an aggressive neuroendocrine (NE) phenotype. Dysregulation of YAP1, a key transcription coactivator of the Hippo pathway, has been related to cancer progression. However, its role in neuroendocrine prostate cancer (NEPC) has not been assessed. METHODS Immunohistochemistry was used to evaluate YAP1 protein levels during PCa initiation and progression. YAP1 knockdown and luciferase reporter assays were used to evaluate the ability of YAP1 to modulate Wnt/beta-Catenin signaling. RESULTS YAP1 expression was present in the basal epithelial cells in benign prostatic tissues, lost in low grade PCa, but elevated in high grade prostate adenocarcinomas. Interestingly, the expression of YAP1 was reduced/lost in both human and mouse NEPC. Finally, YAP1 knockdown in PCa cells activates Wnt/beta-Catenin signaling, which has been implicated in NE differentiation of PCa, supporting a functional involvement of the loss of YAP1 expression in NEPC development. CONCLUSIONS The expression of YAP1 is elevated in high grade prostate adenocarcinomas while lost in NEPC. Reduced YAP1 activates Wnt/beta-Catenin signaling in PCa cells. These results suggest that when applied to PCa patients, YAP1 inhibitors shall be used with caution.

Objective The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. Methods We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Results Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. Conclusion A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials.

Objectives: Bladder and prostate cancers occur with increasing prevalence in the ageing population. Our study aims to quantify the incidence of prostate cancer in patients undergoing cystoprostatectomy for bladder cancer and assess the impact of that incidental prostate cancer on oncological outcome. Methods and Materials: We retrospectively reviewed the pathology reports of 128 men who underwent cystoprostatectomy for bladder cancer. Results: Twenty-three men (18%) were found to have incidental prostate cancer. All incidental prostate cancers were organ confined and 91% were well or moderately differentiated. At a mean follow-up of 55 months the prostate cancer-free survival was 96%. Conclusion: The incidence of prostate cancer in cystoprostatectomy specimens is high. When the prostate is removed completely the presence of incidental prostate cancer does not influence the overall oncological outcome.

In patients undergoing supravesical urinary diversion for benign disease in whom the bladder remains in situ the risks of complications related to the defunctionalized bladder are more than 50% and 25% of patients subsequently need cystectomy. These patients should be offered primary cystectomy at urinary diversion.