Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo. Our data suggest that ADT can functionally impair HR prior to the development of castration resistance and that, this potentially could be exploited therapeutically using PARP inhibitors in combination with androgen-deprivation therapy upfront in advanced or high-risk prostate cancer.

contributed equally to the present study. Objectives• To define terms and processes and agree on a minimum dataset in relation to transperineal prostate biopsy procedures and enhanced prostate diagnostics.• To identify the need for further evaluation and establish a collaborative research practice. Patients and Methods• A 19-member multidisciplinary panel rated 66 items for their appropriateness and their definition to be incorporated into the international databank using the Research and Development/University of California Los Angeles Appropriateness Method. • The item list was developed from interviews conducted with healthcare professionals from urology, radiology, pathology and engineering. Results• The panel agreed on 56 items that were appropriate to be incorporated into a prospective database.• In total, 10 items were uncertain and were omitted. These items were within the categories: definitions (n = 2), imaging (n = 1), surgical protocols (n = 2) and histology (n = 5). Conclusions• The components of a minimum dataset for transperineal prostate biopsy have been defined. • This provides an opportunity for multicentre collaborative data analysis and technique development.• The findings of the present study will facilitate prospective studies into the application and outcome of transperineal prostate biopsies.

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ObjectivesTo determine the accuracy of multiparametric magnetic resonance imaging (mpMRI) during the learning curve of radiologists using MRI targeted, transrectal ultrasonography (TRUS) guided transperineal fusion biopsy (MTTP) for validation. Patients and MethodsProspective data on 340 men who underwent mpMRI (T2-weighted and diffusion-weighted MRI) followed by MTTP prostate biopsy, was collected according to Ginsburg Study Group and Standards for Reporting of Diagnostic Accuracy standards. MRI data were reported by two experienced radiologists and scored on a Likert scale. Biopsies were performed by consultant urologists not 'blinded' to the MRI result and men had both targeted and systematic sector biopsies, which were reviewed by a dedicated uropathologist. The cohorts were divided into groups representing five consecutive time intervals in the study. Sensitivity and specificity of positive MRI reports, prostate cancer detection by positive MRI, distribution of significant Gleason score and negative MRI with false negative for prostate cancer were calculated. Data were sequentially analysed and the learning curve was determined by comparing the first and last group. ResultsWe detected a positive mpMRI in 64 patients from Group A (91%) and 52 patients from Group E (74%). The prostate cancer detection rate on mpMRI increased from 42% (27/64) in Group A to 81% (42/52) in Group E (P < 0.001). The prostate cancer detection rate by targeted biopsy increased from 27% (17/64) in Group A to 63% (33/52) in Group E (P < 0.001). The negative predictive value of MRI for significant cancer (>Gleason 3+3) was 88.9% in Group E compared with 66.6% in Group A. ConclusionWe demonstrate an improvement in detection of prostate cancer for MRI reporting over time, suggesting a learning curve for the technique. With an improved negative predictive value for significant cancer, decision for biopsy should be based on patient/surgeon factors and risk attributes alongside the MRI findings.