Appraising the relevance of DNA copy number loss and gain in prostate cancer using whole genome DNA sequence data.

A variety of models have been proposed to explain regions of recurrent somatic copy number alteration (SCNA) in human cancer. Our study employs Whole Genome DNA Sequence (WGS) data from tumor samples (n = 103) to comprehensively assess the role of the Knudson two hit genetic model in SCNA generation in prostate cancer. 64 recurrent regions of loss and gain were detected, of which 28 were novel, including regions of loss with more than 15% frequency at Chr4p15.2-p15.1 (15.53%), Chr6q27 (16.50%) and Chr18q12.3 (17.48%). Comprehensive mutation screens of genes, lincRNA encoding sequences, control regions and conserved domains within SCNAs demonstrated that a two-hit genetic model was supported in only a minor proportion of recurrent SCNA losses examined (15/40). We found that recurrent breakpoints and regions of inversion often occur within Knudson model SCNAs, leading to the identification of ZNF292 as a target gene for the deletion at 6q14.3-q15 and NKX3.1 as a two-hit target at 8p21.3-p21.2. The importance of alterations of lincRNA sequences was illustrated by the identification of a novel mutational hotspot at the KCCAT42, FENDRR, CAT1886 and STCAT2 loci at the 16q23.1-q24.3 loss. Our data confirm that the burden of SCNAs is predictive of biochemical recurrence, define nine individual regions that are associated with relapse, and highlight the possible importance of ion channel and G-protein coupled-receptor (GPCR) pathways in cancer development. We concluded that a two-hit genetic model accounts for about one third of SCNA indicating that mechanisms, such haploinsufficiency and epigenetic inactivation, account for the remaining SCNA losses.

Aiming for a holistic integrated service for men diagnosed with prostate cancer - Definitions of standards and skill sets for nurses and allied healthcare professionals.

PURPOSE: To establish a comprehensive set of recommendations for the service structure and skill set of nurses and allied healthcare professionals in prostate cancer care. METHODS: Using components of formal consensus methodology, a 30-member multidisciplinary panel produced 53 items for discussion relating to the provision of care for prostate cancer patients by specialist nurses and allied healthcare professionals. Items were developed by two rounds of email correspondence in which, first, items were generated and, second, items refined to form the basis of a consensus meeting which constituted the third round of review. The fourth and final round was an email review of the consensus output. RESULTS: The panel agreed on 33 items that were appropriate for recommendations to be made. These items were grouped under categories of "Environment" and "Patient Pathway" and included comments on training, leadership, communication and quality assessment as well as specific items related to prostate diagnosis clinics, radical treatment clinics and follow-up survivor groups. CONCLUSIONS: Specialist nurses and allied healthcare professionals play a vital role alongside urologists and oncologists to provide care to men with prostate cancer and their families. We present a set of standards and consensus recommendations for the roles and skill-set required for these practitioners to provide gold-standard prostate cancer care. These recommendations could form the basis for development of comprehensive integrated prostate cancer pathways in prostate cancer centres as well as providing guidance for any units treating men with prostate cancer.

Evolution and oncological outcomes of a contemporary radical prostatectomy practice in a UK regional tertiary referral centre.

OBJECTIVE: To investigate the clinical and pathological trends, over a 10-year period, in robot-assisted laparoscopic prostatectomy (RALP) in a UK regional tertiary referral centre. PATIENTS AND METHODS: In all, 1 500 consecutive patients underwent RALP between October 2005 and January 2015. Prospective data were collected on clinicopathological details at presentation as well as surgical outcomes and compared over time. RESULTS: The median (range) age of patients throughout the period was 62 (35-78) years. The proportion of preoperative high-grade cases (Gleason score 8-10) rose from 4.6% in 2005-2008 to 18.2% in 2013-2015 (P < 0.001). In the same periods the proportion of clinical stage T3 cases operated on rose from 2.4% to 11.4% (P < 0.001). The median prostate-specific antigen (PSA) level at diagnosis did not alter significantly. Overall, 11.6% of men in 2005-2008 were classified preoperatively as high-risk by National Institute for Health and Care Excellence criteria, compared with 33.6% in 2013-2015 (P < 0.001). The corresponding proportions for low-risk cases were 48.6% and 17.3%, respectively. Final surgical pathology showed an increase in tumour stage, Gleason grade, and nodal status over time. The proportion of pT3 cases rose from 43.2% in 2005-2008 to 55.5% in 2013-2015 (P < 0.001), Gleason score 9-10 tumours increased from 1.8% to 9.1% (P < 0.001) and positive nodal status increased from 1.6% to 12.9% (P < 0.001) between the same periods. Despite this, positive surgical margin rates showed a downward trend in all pT groups across the different eras (P = 0.72). CONCLUSION: This study suggests that the patient profile for RALP in our unit is changing, with increasing proportions of higher stage and more advanced disease being referred and operated on. However, surgical margin outcomes have remained good.

General application of the National Institute for Health and Clinical Excellence (NICE) guidance for active surveillance for men with prostate cancer is not appropriate in unscreened populations.

UNLABELLED: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance (AS) is a well-recognised management strategy to minimise the morbidity associated with radical treatment of prostate cancer. The National Institute for Health and Clinical Excellence guidelines initially suggested that all men with low-risk prostate cancer should first be offered AS. The cohort of men with upstaging and upgrading of prostate cancer from diagnosis to final pathology has been described in North American and European populations. As the rate of PSA testing in Britain is lower than North America and parts of Europe, the risk of more advanced disease at diagnosis of prostate cancer is higher. The present study is one of the first to examine this cohort in a British population and found the rate of features of advanced disease (extracapsular extension, seminal vesicle involvement and Gleason 4 + 3, or 8-10) to be 37.2%. OBJECTIVE: To determine if the National Institute for Health and Clinical Excellence (NICE) guidelines for men with low-risk prostate cancer were generally applicable in unscreened populations. PATIENTS AND METHODS: Retrospective analysis of prospectively collected case series from a single tertiary care centre in England. In all, 700 consecutive men treated for prostate cancer from 2005 by robot-assisted laparoscopic prostatectomy (RALP) were included. Patients satisfying NICE criteria for low-risk disease (PSA level < 10 ng/mL and Gleason score ≤ 6 and cT1-2a) had their pathological samples analysed for advanced disease, defined as extracapsular extension (ECE: pT3), seminal vesicle involvement (SVI), Gleason sum 7, or 8-10 or node-positive disease. RESULTS: In all, 275 patients (39.2%) met the NICE low-risk criteria, but pathologically advanced disease was found in 37.2% of this group. There was ECE in 71 patients (25.8%), 10 had SVI (3.6%), nine (3.3%) had Gleason score 7(4 + 3), and 12 had Gleason sum 8-10 (4.4%). CONCLUSIONS: The NICE guidance was developed largely on data from North America where populations are highly screened using PSA testing. In the UK, many men with low-risk disease features have high-risk disease and the general applicability of the NICE guidance is questionable in unscreened populations. We recommend that radical therapy is discussed as an alternative option to active surveillance.

Laparoscopic pyeloplasty in a solitary kidney.

BACKGROUND: A 40-year-old male presented with right-sided abdominal pain and no lower urinary tract symptoms. Examination was unremarkable, apart from mild right renal angle tenderness. INVESTIGATIONS: Renal function, full blood count and C-reactive protein levels were all normal. Ultrasound of renal tract, abdominal computed tomography (CT) and (99m)Tc-mercaptoacetyltriglycine (MAG3) renogram confirmed ureteropelvic junction obstruction. DIAGNOSIS: The ureteropelvic junction obstruction of the right kidney was identified, with a crossing lower pole renal vessel as the possible cause. An absent left kidney was also noted. MANAGEMENT: Laparoscopic transperitoneal dismembered Anderson-Hynes pyeloplasty was performed, with posterior transposition of the crossing lower pole vessel.