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Background: Active surveillance (AS) has been increasingly proposed as the preferential initial management strategy for low-risk prostate cancer (PC), while in high-risk PC the indication for surgery has widened., Objective: To evaluate the development of risk group distribution of patients undergoing radical prostatectomy (RP)., Design, Setting, and Participants: Retrospective database review of combined RP databases (2000-2015) of four large European centers (Créteil, Paris; San Rafaele, Milan; Martini Klinik, Hamburg; NKI, AvL, Amsterdam)., Outcome Measurements and Statistical Analysis: Clinical and pathological characteristics per year of surgery. Eligibility for AS was defined according to Prostate Cancer Research International Active Surveillance criteria: cT≤2c, cN0/X, cM0/X, PSA ≤10ng/ml, prostate-specific antigen density <0.2ng/ml/ml, one to two positive biopsies, and Gleason score ≤6, high-risk disease as: cT≥3, c N1, cM1, PSA >20ng/ml, and/or Gleason ≥8., Results and Limitations: In total, 28572 patients had complete clinical and 24790 complete pathological data available. The absolute number of RPs increased: 401, 975, 2344, and 2504 in 2000, 2005, 2010, and 2015, respectively. The proportion of cases considered suitable for AS decreased: 31%, 32%, 18%, and 5%, while the cases considered high risk increased: 10%, 8%, 16%, and 30%. The percentage of patients having only localized Gleason 6 disease after RP decreased: 46%, 34%, 14%, and 8% for all patients (p<0.01), as well as for AS-suitable patients: 70%, 54%, 41%, and 38% (p<0.01). Comparisons between centers were outside the scope of this article. Developments in diagnostics may have impacted on results., Conclusions: This European analysis confirmed the risk profile of patients undergoing RP shifting away of the most favorable disease spectrum. Patients with PC clinically considered suitable for AS and men having only localized Gleason 6 disease pathologically comprised a decreasing share of all RP performed. High-risk disease comprised an increasing share of all RPs., Patient Summary: The databases of four large European centers of prostate cancer surgery were analyzed. In recent years, the risk profile of patients shifted away of low-risk cancer, while high-risk cancer comprised a larger part of cases. This confirms the introduction of active surveillance for low-risk prostate cancer and increase in potentially curative options for high-risk disease., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Vascular targeted photodynamic therapy with TOOKAD® is a new therapeutic option for localized prostate cancer management. The objectives of this study were to assess the feasibility of radical prostatectomy after vascular targeted photodynamic therapy and describe functional and oncologic outcomes., Materials and Methods: We retrospectively included in study 45 patients who underwent salvage radical prostatectomy after vascular targeted photodynamic therapy for recurrent prostate cancer at a total of 14 surgical centers in Europe between October 2008 and March 2017. Of the 42 radical prostatectomies performed 16 were robot-assisted, 6 were laparoscopic and 20 were open surgery. Primary end points were morbidity and technical difficulties. Secondary end points were early and intermediate postoperative functional and oncologic outcomes., Results: Median operative time was 180 minutes (IQR 150-223). Median blood loss was 200 ml (IQR 155-363). According to the surgeons the surgery was easy in 29 patients (69%) and difficult in 13 (31%). Nerve sparing was feasible in 14 patients (33%). Five postoperative complications (12%) were found, including 2 Clavien I, 2 Clavien II and 1 Clavien IIIB complications. Of the cases 13 (31%) were pT3 and 21 (50%) were pT2c. Surgical margins were positive in 13 patients (31%). Prostate specific antigen was undetectable at 6 to 12 months in 37 patients (88%). Nine patients underwent complementary radiotherapy. Four patients had final prostate specific antigen greater than 0.2 ng/ml at a median followup of 23 months (IQR 12-36). At 1 year 27 patients (64%) were completely continent (no pads) and 10 (24%) had low incontinence (1 pad). Four patients (11%) recovered potency without treatment and 23 (64%) recovered potency with appropriate treatment., Conclusions: Salvage radical prostatectomy after vascular targeted photodynamic therapy treatment was feasible and safe without difficulty for most of the surgeons.

Background: Ultrasensitive prostate-specific antigen (USPSA) is useful for stratifying patients according to their USPSA-based risk. Aim of our study was to determine the usefulness of USPSA as predictor of biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP)., Methods: This retrospective study included 213 prostate cancer patients who had a postoperative USPSA between 0.01 and 0.2 ng/mL and at least 2 years of follow-up. We developed predictive models for BCR with PSA ≥0.2 and ≥0.5 ng/mL., Results: A total of 103 patients (48.3%) had BCR at a median follow-up of 13.3 months. Higher postoperative USPSA (odds ratio [OR] = 4.73, P < 0.01), bilateral positive surgical margin in both sides (OR = 1.32, P = 0.044), higher average PSA rise (OR = 1.67, P = 0.031), ISUP grade group ≥3 (OR = 1.48, P = 0.003), and shorter interval since RARP (OR = 0.58, P < 0.001) were independent predictors of BCR with PSA ≥0.2 ng/mL. Higher postoperative USPSA (OR = 3.85, P < 0.01), bilateral positive surgical margin (OR = 1.34, P = 0.011), ISUP grade group ≥3 (OR = 1.5, P = 0.002), and shorter interval since RARP (OR = 0.61, P = 0.001) were independent predictors of BCR with PSA ≥0.5 ng/mL. The areas under the curve for the first and second model were 0.865 and 0.834, respectively., Conclusion: Ultrasensitive PSA after RARP is a useful prognostic indicator of BCR which could guide postoperative risk stratification and layout follow-up scheduling., (© 2018 Wiley Periodicals, Inc.)

Introduction: The extent of lymph node dissection (LND) and its potential survival benefit are still a matter of debate. Aim of our review was to summarize the latest literature data regarding the surgical templates, the potential oncological benefits, the functional outcomes and the complications of extended lymph node dissection (eLND) during robot-assisted radical prostatectomy (RARP)., Evidence Acquisition: We systematically reviewed all relevant studies using PubMed, MEDLINE, Embase, American Urological Association (AUA), European Society of Medical Oncology (ESMO) and European Association of Urology (EAU) guidelines., Evidence Synthesis: A narrative synthesis of all relevant publications on surgical templates, complications, oncological and functional outcomes of robot assisted eLND was undertaken., Conclusions: A great deal of evidence supports that an extended template of LND is not only technically feasible but also safe in the context of RARP. It is really promising that in the era of minimally invasive surgery, parameters like the lymph node yield and the detection rates of positive lymph nodes during LND have become highly comparable with open series. The extended approach has already proved its benefits in terms of proper patient staging but more studies are needed with regard to functional outcomes and oncological benefits of this procedure.

Chromatin immunoprecipitation (ChIP)-seq analyses of transcription factors in clinical specimens are challenging due to the technical limitations and low quantities of starting material, often resulting in low enrichments and poor signal-to-noise ratio. Here, we present an optimized protocol for transcription factor ChIP-seq analyses in human tissue, yielding an ∼100% success rate for all transcription factors analyzed. As proof of concept and to illustrate general applicability of the approach, human tissue from the breast, prostate, and endometrial cancers were analyzed. In addition to standard formaldehyde fixation, disuccinimidyl glutarate was included in the procedure, greatly increasing data quality. To illustrate the sensitivity of the optimized protocol, we provide high-quality ChIP-seq data for three independent factors (AR, FOXA1, and H3K27ac) from a single core needle prostate cancer biopsy specimen. In summary, double-cross-linking strongly improved transcription factor ChIP-seq quality on human tumor samples, further facilitating and enhancing translational research on limited amounts of tissue., Competing Interests: The authors declare that they have no conflict of interest.

Objective: To investigate the effectiveness of motor imagery (MI) for technical skill and non-technical skill (NTS) training in minimally invasive surgery (MIS)., Subjects and Methods: A single-blind, parallel-group randomised controlled trial was conducted at the Vattikuti Institute of Robotic Surgery, King's College London. Novice surgeons were recruited by open invitation in 2015. After basic robotic skills training, participants underwent simple randomisation to either MI training or standard training. All participants completed a robotic urethrovesical anastomosis task within a simulated operating room. In addition to the technical task, participants were required to manage three scripted NTS scenarios. Assessment was performed by five blinded expert surgeons and a NTS expert using validated tools for evaluating technical skills [Global Evaluative Assessment of Robotic Skills (GEARS)] and NTS [Non-Technical Skills for Surgeons (NOTSS)]. Quality of MI was assessed using a revised Movement Imagery Questionnaire (MIQ)., Results: In all, 33 participants underwent MI training and 29 underwent standard training. Interrater reliability was high, Krippendorff's α = 0.85. After MI training, the mean (sd) GEARS score was significantly higher than after standard training, at 13.1 (3.25) vs 11.4 (2.97) (P = 0.03). There was no difference in mean NOTSS scores, at 25.8 vs 26.4 (P = 0.77). MI training was successful with significantly higher imagery scores than standard training (mean MIQ score 5.1 vs 4.5, P = 0.04)., Conclusions: Motor imagery is an effective training tool for improving technical skill in MIS even in novice participants. No beneficial effect for NTS was found., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

Objective: To develop a novel tool to increase the number of patients with prostate cancer eligible for active surveillance (AS) without increasing the risk of unfavourable pathological features (i.e., misclassification) at radical prostatectomy (RP)., Patients and Methods: Overall, 16 049 patients with low- or intermediate-risk prostate cancer treated with RP were identified. Misclassification was defined as non-organ confined or grade group ≥3 disease at RP. The coefficients of a logistic regression model predicting misclassification were used to develop a risk score. We then performed a systematic analysis of different thresholds to discriminate between patients with or without unfavourable disease and we compared it to available AS criteria., Results: Overall, 5289 (33.0%) patients had unfavourable disease. At multivariable analyses, PSA level, clinical stage, biopsy grade group, the number of positive cores, and PSA density were associated with the risk of unfavourable disease (all P < 0.001). The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were associated with a lower risk of misclassification (13%) compared to other criteria. Overall, 3303 (20.6%) patients were eligible according to the PRIAS protocol. The adoption of an 18% threshold according to the risk score increased the proportion of eligible patients from 20.6% to 29.4% without increasing the risk of misclassification as compared to the PRIAS criteria., Conclusions: The use of a novel risk score for AS selection would result in an absolute increase of 10% in the number of patients eligible for this approach without increasing the risk of misclassification., (© 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.)

In plant breeding the use of molecular markers has resulted in tremendous improvement of the speed with which new crop varieties are introduced into the market. Single Nucleotide Polymorphism (SNP) genotyping is routinely used for association studies, Linkage Disequilibrium (LD) and Quantitative Trait Locus (QTL) mapping studies, marker-assisted backcrosses and validation of large numbers of novel SNPs. Here we present the KeyGene SNPSelect technology, a scalable and flexible multiplexed, targeted sequence-based, genotyping solution. The multiplex composition of SNPSelect assays can be easily changed between experiments by adding or removing loci, demonstrating their content flexibility. To demonstrate this versatility, we first designed a 1,056-plex maize assay and genotyped a total of 374 samples originating from an F2 and a Recombinant Inbred Line (RIL) population and a maize germplasm collection. Next, subsets of the most informative SNP loci were assembled in 384-plex and 768-plex assays for further genotyping. Indeed, selection of the most informative SNPs allows cost-efficient yet highly informative genotyping in a custom-made fashion, with average call rates between 88.1% (1,056-plex assay) and 99.4% (384-plex assay), and average reproducibility rates between duplicate samples ranging from 98.2% (1056-plex assay) to 99.9% (384-plex assay). The SNPSelect workflow can be completed from a DNA sample to a genotype dataset in less than three days. We propose SNPSelect as an attractive and competitive genotyping solution to meet the targeted genotyping needs in fields such as plant breeding., Competing Interests: The KeyGene® SNPSelect and combinatorial sequence barcodes technologies are protected by patents and patent applications owned by Keygene N.V.. KeyGene is a registered trademark of Keygene N.V. Other trademarks are the property of their respective owners. This does not alter our adherence to PLOS ONE policies on sharing data.

Lymph node (LN) metastases in urological malignancies correlate with poor oncological outcomes. Accurate LN staging is of great importance since patients can benefit from an optimal staging, accordingly aligned therapy and more radical treatments. Current conventional cross-sectional imaging modalities [e.g., computed tomography (CT) and magnetic resonance imaging (MRI)] are not accurate enough to reliably detect early LN metastases as they rely on size criteria. Radical lymphadenectomy, the surgical removal of regional LNs, is the gold standard of invasive LN staging. The LN dissection is guided by anatomic considerations of lymphatic drainage pathways of the primary tumor. Selection of patients for lymphadenectomy heavily relies on preoperative risk stratification and nomograms and, as a result a considerable number of patients unnecessarily undergo invasive staging with associated morbidity. On the other hand, due to individual variability in lymphatic drainage, LN metastases can occur outside of standard lymphadenectomy templates leading to potential understaging and undertreatment. In theory, metastases from the primary tumor need to pass through the chain of LNs, where the initial node is defined as the sentinel LN. In theory, identifying and removing this LN could lead to accurate assessment of metastatic status. Radiotracers and more recently fluorescent dyes and superparamagnetic iron oxide nanoparticles (SPION) are injected into the primary tumor or peritumoral and the sentinel LNs are identified intraoperatively by a gamma probe, fluorescent camera or a handheld magnetometer. Preoperative imaging [e.g., single-photon emission computed tomography (SPECT)/CT or MRI] after tracer injection can further improve preoperative planning of LN dissection. While sentinel LN biopsy is an accepted and widely used approach in melanoma and breast cancer staging, its use in urological malignancies is still limited. Most data published so far is in penile cancer staging since this cancer has a typical echelon-based lymphatic metastasizing pattern. More recent data is encouraging with low false-negative rates, but its use is limited to centers with high expertise. Current guidelines recommend sentinel LN biopsy as an accepted alternative to modified inguinal lymphadenectomy in patients with pT1G2 disease and non-palpable inguinal LNs. In prostate cancer, a high diagnostic accuracy could be demonstrated for the sentinel approach. Nevertheless, due to lack of data or high false-negative rates in other urological malignancies, sentinel LN biopsy is still considered experimental in other urological malignancies. More high-level evidence and longitudinal data is needed to determine its final value in those malignancies. In this manuscript, we will review sentinel node imaging for urologic malignancies., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Fibroblasts are abundantly present in the prostate tumor microenvironment (TME), including cancer-associated fibroblasts (CAFs) which play a key role in cancer development. Androgen receptor (AR) signaling is the main driver of prostate cancer (PCa) progression, and stromal cells in the TME also express AR. High-grade tumor and poor clinical outcome are associated with low AR expression in the TME, which suggests a protective role of AR signaling in the stroma against PCa development. However, the mechanism of this relation is not clear. In this study, we isolated AR-expressing CAF-like cells. Testosterone (R1881) exposure did not affect CAF-like cell morphology, proliferation, or motility. PCa cell growth was not affected by culturing in medium from R1881-exposed CAF-like cells; however, migration of PCa cells was inhibited. AR chromatin immune precipitation sequencing (ChIP-seq) was performed and motif search suggested that AR in CAF-like cells bound the chromatin through AP-1-elements upon R1881 exposure, inducing enhancer-mediated AR chromatin interactions. The vast majority of chromatin binding sites in CAF-like cells were unique and not shared with AR sites observed in PCa cell lines or tumors. AR signaling in CAF-like cells decreased expression of multiple cytokines; most notably CCL2 and CXCL8 and both cytokines increased migration of PCa cells. These results suggest direct paracrine regulation of PCa cell migration by CAFs through AR signaling., (© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

Objective: To perform the first validation of a full procedural virtual reality robotic training module and analysis of novice surgeon's learning curves., Design: Participants completed the bladder neck dissection task and urethrovesical anastomosis task (UVA) as part of the prostatectomy module. Surgeons completed feedback questionnaires assessing the realism, content, acceptability and feasibility of the module. Novice surgeons completed a 5.5-hour training programme using both tasks., Setting: King's College London, London., Participants: 13 novice, 24 intermediate and 8 expert surgeons completed the validation study., Results: Realism was scored highly for BDN (mean 3.4/5) and UVA (3.74/5), as was importance of BDN (4.32/5) and UVA (4.6/5) for training. It was rated as a feasible (3.95/5) and acceptable (4/5) tool for training. Experts performed significantly better than novice group in 6 metrics in the UVA including time (p = 0.0005), distance by camera (p = 0.0010) and instrument collisions (p = 0.0033), as well as task-specific metrics such as number of unnecessary needle piercing points (p = 0.0463). In novice surgeons, a significant improvement in performance after training was seen in many metrics for both tasks. For bladder neck dissection task, this included time (p < 0.0001), instrument collisions (p = 0.0013) and total time instruments are out of view (p = 0.0251). For UVA, this included time (p = 0.0135), instrument collisions (p = 0.0066) and task-specific metrics such as injury to the urethra (p = 0.0032) and bladder (p = 0.0189)., Conclusions: Surgeons found this full procedural VR training module to be a realistic, feasible and acceptable component for a robotic surgical training programme. Construct validity was proven between expert and novice surgeons. Novice surgeons have shown a significant learning curve over 5.5 hours of training, suggesting this module could be used in a surgical curriculum for acquisition of technical skills. Further implementation of this module into the curriculum and continued analysis would be beneficial to gauge how it can be fully utilised., (Copyright © 2017. Published by Elsevier Inc.)

Background: To establish objective benchmarks at the level of a competent robotic surgeon across different exercises and metrics for the RobotiX Mentor virtual reality (VR) simulator suitable for use within a robotic surgical training curriculum., Methods: This retrospective observational study analysed results from multiple data sources, all of which used the RobotiX Mentor VR simulator. 123 participants with varying experience from novice to expert completed the exercises. Competency was established as the 25th centile of the mean advanced intermediate score. Three basic skill exercises and two advanced skill exercises were used., Setting: King's College London., Participants: 84 Novice, 26 beginner intermediates, 9 advanced intermediates and 4 experts were used in this retrospective observational study., Results: Objective benchmarks derived from the 25th centile of the mean scores of the advanced intermediates provided suitably challenging yet also achievable targets for training surgeons. The disparity in scores was greatest for the advanced exercises. Novice surgeons are able to achieve the benchmarks across all exercises in the majority of metrics., Conclusion: We have successfully created this proof-of-concept study, which requires validation in a larger cohort. Objective benchmarks obtained from the 25th centile of the mean scores of advanced intermediates provide clinically relevant benchmarks at the standard of a competent robotic surgeon that are challenging yet also attainable. That can be used within a VR training curriculum allowing participants to track and monitor their progress in a structured and progressional manner through five exercises. Providing clearly defined targets, ensuring that a universal training standard has been achieved across training surgeons., Competing Interests: Competing interests: NR acknowledges financial support from the Vattikuti Foundation. PH acknowledges financial support from the Royal College of Surgeons of England in the form of an Intercalated BSc research award. KA and PD acknowledge financial support from the National Institute for Health Research (NIHR) Biomedical Research Centre-based Guy’s and St Thomas’s NHS Foundation trust. PD also acknowledges the support of the Medical Research Council Centre for Transplantation, London Deanery, London School of Surgery, Guy’s and St. Thomas’ Charity, European Union, Vattikuti Foundation and Olympus., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Accurate prediction of survival after radical prostatectomy (RP) is important for making decisions regarding multimodal therapies. There is a lack of tools to predict prostate cancer-related death (PCRD) in patients with high-risk features., Objective: To develop and validate a prognostic model that predicts PCRD combining pathologic features and using competing-risks analysis., Design, Setting, and Participants: This was a retrospective multi-institutional observational cohort study of 5876 patients affected by high-risk prostate cancer. Patients were treated using RP and pelvic lymph node dissection (PLND) in a multimodal setting, with median follow-up of 49 mo., Outcome Measurements and Statistical Analysis: For PCRD prediction, a multivariate model with correction for competing risks was constructed to evaluate pathologic high-risk features (pT3b-4, Gleason score ≥8, and pN1) as predictors of mortality. All possible associations of the predictors were combined, and then subgroups with similar risk of PCRD were collapsed to obtain a simplified model encoding subgroups with significantly differing risk. Eightfold cross-validation of the model was performed., Results and Limitations: After applying exclusion criteria, 2823 subjects were identified. pT3b-4, Gleason score ≥8, and pN1 were all independent predictors of PCRD. The simplified model included the following prognostic groups: good prognosis, pN0 with 0-1 additional predictors; intermediate prognosis, pN1 with 0-1 additional predictors; poor prognosis, any pN with two additional predictors. The cross-validation yielded excellent median model accuracy of 88%. The retrospective design and the short follow-up could limit our findings., Conclusions: We developed and validated a novel and easy-to-use prognostic instrument to predict PCRD after RP+PLND. This model may allow clinicians to correctly counsel patients regarding the intensity of follow-up and to tailor adjuvant treatments., Patient Summary: Prediction of mortality after primary surgery for prostate cancer is important for subsequent treatment plans. We present an accurate postoperative model to predict cancer mortality after radical prostatectomy for high-risk prostate cancer., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aims: To determine whether preoperative prostate/pelvic anatomical structures and intraoperative fascia preservation (FP) predict continence recovery after robot-assisted radical prostatectomy (RARP)., Methods: Between January 2012 and March 2016, 439 prostate cancer (PCa) patients with normal preoperative continence were retrospectively included. FP score was defined as the extent of FP from base to apex of the prostate, quantitatively assessed by the surgeon. Anatomical prostate structures were measured on endorectal preoperative Magnetic Resonance Imaging. The International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) was used to assess urinary incontinence (UI). Cox analysis was used to determine predictive factors for early continence recovery. Finally a binary logistic regression analysis was performed to develop a risk calculator., Results: At a median follow up of 12.1 months 50.8% of men reported UI. In the Cox multivariate analysis longer membranous urethral length (MUL; P < 0.0001; OR 1.309; CI 1.211, 1.415) and shorter inner levator distance (ILD; P < 0.0001; OR 0.904; CI 0.85, 0.961) were predictors of earlier continence recovery. In the multivariate binary logistic regression analysis longer MUL (P < 0.0001; OR 1.565, CI 1.362, 1.798), shorter ILD (P < 0.0001; OR 0.819, CI 0.742, 0.904) and higher FP score (P = 0.024; OR 1.089, CI 1.011, 1.172) were independent predictors of continence outcome. The risk calculator predicted continence recovery between 1.3% and 99%., Conclusions: Preoperative longer MUL and shorter ILD, but also intraoperative FP independently improve continence recovery after RARP. The risk calculator could be used to identify patients at high risk of UI., (© 2017 Wiley Periodicals, Inc.)

The integration of medical imaging technologies into diagnostic and therapeutic approaches can provide a preoperative insight into both anatomical (e.g. using computed tomography, magnetic resonance imaging, or ultrasound), as well as functional aspects (e.g. using single photon emission computed tomography, positron emission tomography, lymphoscintigraphy, or optical imaging). Moreover, some imaging modalities are also used in an interventional setting (e.g. computed tomography, ultrasound, gamma or optical imaging) where they provide the surgeon with real-time information during the procedure. Various tools and approaches for image-guided navigation in cancer surgery are becoming feasible today. With the development of new tracers and portable imaging devices, these advances will reinforce the role of interventional molecular imaging., (Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.)

Objectives: The pre-treatment risk of seminal vesicle (SV) invasion (SVI) from prostate cancer is currently based on nomograms which include clinical stage (cT), Gleason score (GS) and prostate-specific antigen (PSA). The aim of our study was to evaluate the staging accuracy of 3T (3T) multi-parametric (mp) Magnetic Resonance Imaging (MRI) by comparing the imaging report of SVI with the tissue histopathology. The additional value in the existing prediction models and the role of radiologists' experience were also examined., Methods: After obtaining institutional review board approval, we retrospectively reviewed clinico-pathological data from 527 patients who underwent a robot-assisted radical prostatectomy (RARP) between January 2012 and March 2015. Preoperative prostate imaging with an endorectal 3T-mp-MRI was performed in all patients. Sequences consisted of an axial pre-contrast T1 sequence, three orthogonally-oriented T2 sequences, axial diffusion weighted and dynamic contrast-enhanced sequences. We considered SVI in case of low-signal intensity in the SV on T2-weighted sequences or apparent mass while diffusion-weighted and DCE sequences were used to confirm findings on T2. Whole-mount section pathology was performed in all patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI (index test) for the prediction of histological SVI (reference standard) were calculated. We developed logistic multivariable regression models including: clinical variables (PSA, cT, percentage of involved cores/total cores, primary GS 4-5) and Partin table estimates. MRI results (negative/positive exam) were then added in the models and the multivariate modeling was reassessed. In order to assess the extent of SVI and the reason for mismatch with pathology an MRI-review from an expert genitourinary radiologist was performed in a subgroup of 379 patients., Results: A total of 54 patients (10%) were found to have SVI on RARP-histopathology. In the overall cohort sensitivity, specificity, PPV and NPV for SVI detection on MRI were 75.9%, 94.7%, 62% and 97% respectively. Based on our sub-analysis, the radiologist's expertise improved the accuracy demonstrating a sensitivity, specificity, PPV and NPV of 85.4%, 95.6%, 70.0% and 98.2%, respectively. In the multivariate analysis PSA (odds ratio [OR] 1.07, p=0.008), primary GS 4 or 5 (OR 3.671, p=0.007) and Partin estimates (OR 1.07, p=0.023) were significant predictors of SVI. When MRI results were added to the analysis, a highly significant prediction of SVI was observed (OR 45.9, p<0.0001). Comparing Partin, MRI and Partin with MRI predictive models, the areas under the curve were 0.837, 0.884 and 0.929, respectively., Conclusions: MRI had high diagnostic accuracy for SVI on histopathology. It provided added diagnostic value to clinical/Partin based SVI-prediction models alone. A key factor is radiologist's experience, though no inter-observer variability could be examined due to the availability of a single expert radiologist., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment., Methods: This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml -1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment., Results: After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations., Conclusions: In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

Background: Non-technical skills (NTS) are being increasingly recognised as vital for safe surgical practice. Numerous NTS rating systems have been developed to support effective training and assessment. Yet despite the additional challenges posed by robotic surgery, no NTS rating systems have been developed for this unique surgical environment. This study reports the development and validation of the first NTS behavioural rating system for robotic surgery., Methods: A comprehensive index of all relevant NTS behaviours in robotic surgery was developed through observation of robotic theatre and interviews with robotic surgeons. Using a Delphi methodology, a panel of 16 expert surgeons was consulted to identify behaviours important to NTS assessment. These behaviours were organised into an appropriate assessment template. Experts were consulted on the feasibility, applicability and educational impact of ICARS. An observational trial was used to validate ICARS. 73 novice, intermediate and expert robotic surgeons completed a urethrovesical anastomosis within a simulated operating room. NTS were tested using four scripted scenarios of increasing difficulty. Performances were video recorded. Robotic and NTS experts assessed the videos post hoc using ICARS and the standard behavioural rating system, NOn-Technical Skills for Surgeons (NOTSS)., Results: 28 key non-technical behaviours were identified by the expert panel. The finalised behavioural rating system was organised into four principle domains and seven categories. Expert opinion strongly supported its implementation. ICARS was found to be equivalent to NOTSS on Bland-Altman analysis and accurately differentiated between novice, intermediate and expert participants, p = 0.01. Moderate agreement was found between raters, Krippendorff's alpha = 0.4. The internal structure of ICARS was shown to be consistent and reliable (median Cronbach alpha = 0.92, range 0.85-0.94)., Conclusion: ICARS is the first NTS behavioural rating system developed for robotic surgery. Initial validation has shown it to be an effective and reliable tool. Implementation of ICARS will supported structured training and assessment of NTS within the robotic surgical curriculum.

Purpose: The updated Winter nomogram is the only nomogram predicting lymph node invasion (LNI) in prostate cancer (PCa) patients based on sentinel node (SN) dissection (sLND). The aim of the study was to externally validate the Winter nomogram and examine its performance in patients undergoing extended pelvic lymph node dissection (ePLND), ePLND combined with SN biopsy (SNB) and sLND only. The results were compared with the Memorial Sloan Kettering Cancer Center (MSKCC) and updated Briganti nomograms., Methods: This retrospective study included 1183 patients with localized PCa undergoing robot-assisted laparoscopic radical prostatectomy (RARP) combined with pelvic lymphadenectomy and 224 patients treated with sLND and external beam radiotherapy (EBRT), aiming to offer pelvic radiotherapy only in case of histologically positive SNs. In the RARP population, ePLND was applied in 956 (80.8%) patients,while 227 (19.2%) patients were offered ePLND combined with additional SNB., Results: The median numbers of removed nodes were 10 (interquartile range, IQR = 6-14), 15 (IQR = 10-20) and 7 (IQR = 4-10) in the ePLND, ePLND + SNB, and sLND groups, respectively. Corresponding LNI rates were 16.6%, 25.5% and 42%. Based on the AUC, the performance of the Briganti nomogram (0.756) in the ePLND group was superior to both the MSKCC (0.744) and Winter nomogram (0.746). The Winter nomogram, however, was the best predictor of LNI in both the ePLND + SNB (0.735) and sLND (0.709) populations. In the calibration analysis, all nomograms showed better accuracy in the low/intermediate risk patients, while in the high-risk population, an overestimation of the risk for LNI was observed., Conclusion: The SN-based updated nomogram showed better prediction in the SN population. The results were also comparable, relative to predictive tools developed with (e)PLND, suggesting a difference in sampling accuracy between SNB and non-SNB. Patients who benefit most from the nomogram would be those with a low/intermediate risk of LN metastasis.

Objective: To investigate the association between benign prostatic hyperplasia (BPH) patterns, classified by magnetic resonance imaging (MRI), with lower urinary tract symptoms (LUTS) or continence, preoperatively and after robot-assisted laparoscopic radical prostatectomy (RARP)., Materials and Methods: This retrospective study included 49 prostate cancer patients, with prostate size >47 cm 3 , who underwent an endorectal MRI followed by RARP. Five BPH patterns were identified according to Wasserman, and additional prostate measurements were recorded. LUTS were assessed using the International Prostate Symptom Score and the PR25-LUTS-Questionnaire score. Continence was assessed using the International Consultation of Incontinence Questionnaire-Short Form., Results: BPH pattern 3 (44.9%) was identified most common, followed by pattern 5 (26.6%), 1 (24.5%), and 2 and 4 (both 2%). BPH patterns were significant predictors of preoperative LUTS, with pedunculated with bilateral transition zone (TZ) and retrourethral enlargement (pattern 5) causing more severe symptoms compared with bilateral TZ and retrourethral enlargement (pattern 3) and bilateral TZ enlargement (pattern 1), whereas pattern 3 was additionally associated with more voiding symptoms compared with pattern 1. None of the BPH patterns was predictive of postoperative LUTS and continence. Independent predictors of continence at 12 months were lower preoperative PR25-LUTS score (P = .022) and longer membranous urethral length (P = .025)., Conclusion: MRI is useful for classifying patients in BPH patterns which are strongly associated with preoperative LUTS. However, BPH patterns did not predict remnant LUTS or postoperative incontinence. Postoperative continence status was only associated with preoperative LUTS and membranous urethra length., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To develop benchmark scores of competency for use within a competency based virtual reality (VR) robotic training curriculum., Subjects and Methods: This longitudinal, observational study analysed results from nine European Association of Urology hands-on-training courses in VR simulation. In all, 223 participants ranging from novice to expert robotic surgeons completed 1565 exercises. Competency was set at 75% of the mean expert score. Benchmark scores for all general performance metrics generated by the simulator were calculated. Assessment exercises were selected by expert consensus and through learning-curve analysis. Three basic skill and two advanced skill exercises were identified., Results: Benchmark scores based on expert performance offered viable targets for novice and intermediate trainees in robotic surgery. Novice participants met the competency standards for most basic skill exercises; however, advanced exercises were significantly more challenging. Intermediate participants performed better across the seven metrics but still did not achieve the benchmark standard in the more difficult exercises., Conclusion: Benchmark scores derived from expert performances offer relevant and challenging scores for trainees to achieve during VR simulation training. Objective feedback allows both participants and trainers to monitor educational progress and ensures that training remains effective. Furthermore, the well-defined goals set through benchmarking offer clear targets for trainees and enable training to move to a more efficient competency based curriculum., (© 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Tumor localization provides crucial information for radiotherapy dose differentiation treatments, such as focal dose escalation and dose painting by numbers, which aim at achieving tumor control with minimal side effects. Multiparametric (mp-)MRI is increasingly used for tumor detection and localization in prostate because of its ability to visualize tissue structure and to reveal tumor characteristics. However, it can be challenging to distinguish cancer, particularly in the transition zone. In this study, we enhance the performance of a mp-MRI-based tumor localization model by incorporating prior knowledge from two sources: a population-based tumor probability atlas and patient-specific biopsy examination results. This information typically would be considered by a physician when carrying out a manual tumor delineation., Materials and Methods: Our study involves 40 patients from two centers: 23 patients from the University Hospital Leuven (Leuven), Leuven, Belgium and 17 patients from the Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands. All patients received a mp-MRI exam consisting of a T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI before prostatectomy. Thirty-one features were extracted for each voxel in the prostate. Among these, 29 were from the multiparametric-MRI, one was from the population-based tumor probability atlas and one from the biopsy map. T2-weighted images of each patient were registered to whole-mount section pathology slices to obtain the ground truth. The study was validated in two settings: single-center (training and test sets were from the same cohort); and cross-center (training and test sets were from different cohorts). In addition, automatic delineations created by our model were compared with manual tumor delineations done by six different teams on a subset of Leuven cohort including 15 patients., Results: In the single-center setting, mp-MRI-based features yielded area under the ROC curves (AUC) of 0.690 on a pooled set of patients from both cohorts. Including prevalence into mp-MRI-based features increased the AUC to 0.751 and including all features achieved the best performance with AUC of 0.775. Using all features always showed better results when varying the size of the training set. In addition, its performance is comparable with the average performance of six teams delineating the tumors manually. The error rate using all features was 0.22. The two prior knowledge features ranked among the top four most important features out of the 31 features. In the cross-center setting, combining all features also yielded the best performance in terms of the mean AUC of 0.777 on the pooled set of patients from both cohorts. In addition, the difference in performance between the single-center setting and cross-center setting was not significant., Conclusions: The results showed significant improvements when including prior knowledge features in addition to mp-MRI-based features in both single- and cross-center settings., (© 2016 The Netherlands Cancer Institute-Antoni van Leeuwenhoek. Medical Physics published by Wiley periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Purpose: To assess the efficacy of robotic-assisted laparoscopic sentinel lymph node (SLN) dissection (SLND) to select those patients with prostate cancer (PCa) who would benefit from additional pelvic external beam radiation therapy and long-term androgen deprivation therapy (ADT)., Methods and Materials: Radioisotope-guided SLND was performed in 224 clinically node-negative patients scheduled to undergo external beam radiation therapy. Patients with histologically positive SLNs (pN1) were also offered radiation therapy to the pelvic lymph nodes, combined with 3 years of ADT. Biochemical recurrence (BCR), overall survival, and metastasis-free (including pelvic and nonregional lymph nodes) survival (MFS) rates were retrospectively calculated. The Briganti and Kattan nomogram predictions were compared with the observed pN status and BCR., Results: The median prostate-specific antigen (PSA) value was 15.4 ng/mL (interquartile range [IQR] 8-29). A total number of 834 SLNs (median 3 per patient; IQR 2-5) were removed. Nodal metastases were diagnosed in 42% of the patients, with 150 SLNs affected (median 1; IQR 1-2). The 5-year BCR-free and MFS rates for pN0 patients were 67.9% and 87.8%, respectively. The corresponding values for pN1 patients were 43% and 66.6%. The PSA level and number of removed SLNs were independent predictors of BCR and MFS, and pN status was an additional independent predictor of BCR. The 5-year overall survival rate was 97.6% and correlated only with pN status. The predictive accuracy of the Briganti nomogram was 0.665. Patients in the higher quartiles of Kattan nomogram prediction of BCR had better than expected outcomes. The complication rate from SLND was 8.9%., Conclusions: For radioisotope-guided SLND, the high staging accuracy is accompanied by low morbidity. The better than expected outcomes observed in the lower quartiles of BCR prediction suggest a role for SLN biopsy as a potential selection tool for the addition of pelvic radiation therapy and ADT intensification in pN1 patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The following research questions were answered: (1) What are the training pathways followed by the current robot professionals? (2) Are there any differences between the surgical specialties in robot training and robot use? (3) What is their opinion about multidisciplinary basic skills training?, Methods: An online questionnaire was sent to 91 robot professionals in The Netherlands. The questionnaire contained 21 multiple-choice questions focusing on demographics, received robot training, and their opinion on basic skills training in robotic surgery., Results: The response rate was 62 % (n = 56): 13 general surgeons, 16 gynecologists, and 27 urologists. The urologists performed significantly more robotic procedures than surgeons and gynecologists. The kind of training of all professionals varied from a training program by Intuitive Surgical, master-apprenticeship with or without duo console, fellowship, and self-designed training programs. The training did neither differ significantly among the different specialties nor the year of starting robotic surgery. Majority of respondents favor an obliged training program including an examination for the basics of robot skills training., Conclusion: Training of the current robot professionals is mostly dependent on local circumstances and the manufacturer of the robot system. Training is independent of the year of start with robotic surgery and speciality. To guarantee the quality of future training of residents and fellows in robot-assisted surgery, clear training goals should be formulated and implemented. Since this study shows that current training of different specialities does not differ, training in robotic surgery could be started by a multidisciplinary basic skills training and assessment.

Aim: To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP)., Material and Methods: In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD., Results: Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7% ( n  = 671). Final Gleason score (GS) was 2-6 in 12.7% ( n  = 158), 7 in 52% ( n  = 649), and 8-10 in 35.4% ( n  = 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3%) had 0-3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p  < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% ( p  < 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS., Conclusion: Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.

Background: Prostate pedicle management is a crucial step during robot-assisted radical prostatectomy (RARP). Wide excision of prostate pedicle may be required to avoid positive surgical margins (PSMs) whereas preservation of neurovascular bundles requires resection close on the prostate. We studied Endo GIA™ stapling of prostate pedicle during RARP., Methods: Retrospectively the outcome of 55 men who underwent RARP with Endo GIA™ stapling (45-mm Echelon Ethicon; group A) of the pedicle were compared with 100 men where another method for prostate pedicle management (mono- and bipolar electrocautery, Hem-o-Lock clips or titanium 10-mm clips; group B) was used. Both groups were matched for age, prostate size, clinical T-stage, Gleason Score and fascia preservation (FP) score (as a measure of nerve sparing). Surgical, oncological, functional outcome factors and costs were compared., Results: The overall PSM rate was 33% in group A and 42% in group B (P=0.251). None of the cases had PSMs at the location of staples. PSMs with Endo GIA™ stapler at the periphery of the prostate were less frequent than in control group (4.1% vs. 11.5%; P=0.021). Median pedicle dissection time (7.8 [3.1-15.1] min vs. 10.5 [5.8-28.3] min; P=0.0001) and median operative time for RARP combined with lymphadenectomy (114 [70-129] min vs. 120 [67-200] min; P=0.043) tended to be shorter compared to group B. Erectile function and continence recovery at 12 months were comparable for both groups. Material costs for stapling (€730) were higher compared to variable costs in control group., Conclusions: Pedicle stapling during RARP reduced peripheral PSMs. It did not compromise functional results, provided a modest operation time gain for pedicle dissection, but is more expensive.

The European Association of Urology robotic training curriculum is a validated structured program to provide standardized training and to certify surgeons for specific urologic procedures., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: Urology is at the forefront of minimally invasive surgery to a great extent. These procedures produce additional learning challenges and possess a steep initial learning curve. Training and assessment methods in surgical specialties such as urology are known to lack clear structure and often rely on differing operative flow experienced by individuals and institutions., Objective: This article aims to assess current urology training modalities, to identify the role of simulation within urology, to define and identify the learning curves for various urologic procedures, and to discuss ways to decrease complications in the context of training., Evidence Acquisition: A narrative review of the literature was conducted through December 2015 using the PubMed/Medline, Embase, and Cochrane Library databases., Evidence Synthesis: Evidence of the validity of training methods in urology includes observation of a procedure, mentorship and fellowship, e-learning, and simulation-based training. Learning curves for various urologic procedures have been recommended based on the available literature. The importance of structured training pathways is highlighted, with integration of modular training to ensure patient safety., Conclusions: Valid training pathways are available in urology. The aim in urology training should be to combine all of the available evidence to produce procedure-specific curricula that utilise the vast array of training methods available to ensure that we continue to improve patient outcomes and reduce complications., Patient Summary: The current evidence for different training methods available in urology, including simulation-based training, was reviewed, and the learning curves for various urologic procedures were critically analysed. Based on the evidence, future pathways for urology curricula have been suggested to ensure that patient safety is improved., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To describe the progress being made in training for minimally invasive surgery (MIS) in urology., Methods: A group of experts in the field provided input to agree on recommendations for MIS training. A literature search was carried out to identify studies on MIS training, both in general and specifically for urological procedures., Results: The literature search showed the rapidly developing options for e-learning, box and virtual training, and suggested that box training is a relatively cheap and effective means of improving laparoscopic skills. Development of non-technical skills is an integral part of surgical skills training and should be included in training curricula. The application of modular training in surgical procedures showed more rapid skills acquisition. Training curricula for MIS in urology are being developed in both the USA and Europe., Conclusion: Training in MIS has shifted from 'see-one-do-one-teach-one' to a structured learning, from e-learning to skills laboratory and modular training settings., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Background: Use of robot-assisted radical prostatectomy (RARP) for prostate cancer is increasing. Structured surgical training and objective assessment are critical for outcomes., Objective: To develop and validate a modular training and assessment pathway via Healthcare Failure Mode and Effect Analysis (HFMEA) for trainees undertaking RARP and evaluate learning curves (LCs) for procedural steps., Design, Setting, and Participants: This multi-institutional (Europe, Australia, and United States) observational prospective study used HFMEA to identify the high-risk steps of RARP. A specialist focus group enabled validation. Fifteen trainees who underwent European Association of Urology robotic surgery curriculum training performed RARP and were assessed by mentors using the tool developed. Results produced LCs for each step. A plateau above score 4 indicated competence., Outcome Measurements and Statistical Analysis: We used a modular training and assessment tool (RARP Assessment Score) to evaluate technical skills. LCs were constructed. Multivariable Kruskal-Wallis, Mann-Whitney U, and κ coefficient analyses were used., Results and Limitations: Five surgeons were observed for 42 console hours to map steps of RARP. HFMEA identified 84 failure modes and 46 potential causes with a hazard score ≥8. Content validation created the RARP Assessment Score: 17 stages and 41 steps. The RARP Assessment Score was acceptable (56.67%), feasible (96.67%), and had educational impact (100%). Fifteen robotic surgery trainees were assessed for 8 mo. In 426 RARP cases (range: 4-79), all procedural steps were attempted by trainees. Trainees were assessed with the RARP Assessment Score by their expert mentors, and LCs for individual steps were plotted. LCs demonstrated plateaus for anterior bladder neck transection (16 cases), posterior bladder neck transection (18 cases), posterior dissection (9 cases), dissection of prostatic pedicle and seminal vesicles (15 cases), and anastomosis (17 cases). Other steps did not plateau during data collection., Conclusions: The RARP Assessment Score based on HFMEA methodology identified critical steps for focused RARP training and assessed surgeons. LCs demonstrate the experience necessary to reach a level of competence in technical skills to protect patients., Patient Summary: We developed a safety and assessment tool to gauge the technical skills of surgeons performing robot-assisted radical prostatectomy. Improvement was monitored, and measures of progress can be used in future to guide mentors when training surgeons to operate safely., (Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The development of structured and validated training curricula is one of the current priorities in robot-assisted urological surgery., Objective: To establish the feasibility, acceptability, face validity, and educational impact of a structured training curriculum for robot-assisted radical prostatectomy (RARP), and to assess improvements in performance and ability to perform RARP after completion of the curriculum., Design, Setting, and Participants: A 12-wk training curriculum was developed based on an expert panel discussion and used to train ten fellows from major European teaching institutions. The curriculum included: (1) e-learning, (2) 1 wk of structured simulation-based training (virtual reality synthetic, animal, and cadaveric platforms), and (3) supervised modular training for RARP., Outcome Measurements and Statistical Analysis: The feasibility, acceptability, face validity, and educational impact were assessed using quantitative surveys. Improvement in the technical skills of participants over the training period was evaluated using the inbuilt validated assessment metrics on the da Vinci surgical simulator (dVSS). A final RARP performed by fellows on completion of their training was assessed using the Global Evaluative Assessment of Robotic Skills (GEARS) score and generic and procedure-specific scoring criteria., Results and Limitations: The median baseline experience of participants as console surgeon was 4 mo (interquartile range [IQR] 0-6.5 mo). All participants completed the curriculum and were involved in a median of 18 RARPs (IQR 14-36) during modular training. The overall score for dVSS tasks significantly increased over the training period (p<0.001-0.005). At the end of the curriculum, eight fellows (80%) were deemed able by their mentors to perform a RARP independently, safely, and effectively. At assessment of the final RARP, the participants achieved an average score ≥4 (scale 1-5) for all domains using the GEARS scale and an average score >10 (scale 4-16) for all procedural steps using a generic dedicated scoring tool. In performance comparison using this scoring tool, the experts significantly outperformed the fellows (mean score for all steps 13.6 vs 11)., Conclusions: The European robot-assisted urologic training curriculum is acceptable, valid, and effective for training in RARP., Patient Summary: This study shows that a 12-wk structured training program including simulation-based training and mentored training in the operating room allows surgeons with limited robotic experience to increase their robotic skills and their ability to perform the surgical steps of robot-assisted radical prostatectomy., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Low-risk prostate cancer is found in about half of newly diagnosed men subjected to PSA screening., Methods: To define the role of active surveillance and focal therapy in low- and intermediate-risk prostate cancers, an invited international panel of practicing physicians in the field of localized prostate cancer discussed the available literature in three consecutive meetings to come to a broad interpretation of the available data., Results: The panel ("new prostate cancer management group," npm) agreed on the following observations. In most men with a low-volume Gleason 6 tumor, initial conservative management is appropriate. In men with a larger unifocal Gleason score 6 or 3 + 4 lesion, focal therapy, although still considered an investigational approach, appears to be a suitable option in early non-randomized comparison studies. Furthermore, in patients with multifocal small satellite Gleason 6 lesions in the presence of a larger index lesion, focal therapy of the index lesion is an option. For patients with high-grade, large-volume disease, or in young men with evidence of high-volume multifocal low-grade prostate cancer, whole-gland treatment should be considered., Conclusion: Active surveillance is a preferred and safe option for low-risk prostate cancer. Focal therapy is still under investigation, but the available phase II data are promising. Clinical benefits must be shown in prospective trials. With improved imaging, focal therapy may be an option for patients not choosing active surveillance with low-risk disease, progression upon active surveillance or intermediate-risk cancers with a localizable lesion.

Background: Several reports have shown that patients who undergo minimally invasive radical prostatectomy have a lower chance of undergoing pelvic lymph node dissection (PLND), irrespective of the disease characteristics., Objective: We evaluated the rate and extension of PLND in patients who underwent robot-assisted radical prostatectomy (RARP). We tested the adherence of the indication for PLND to the European Association of Urology (EAU) guidelines., Design, Setting, and Participants: Our study was a multi-institutional retrospective analysis of prospectively collected data on 2985 consecutive patients who underwent RARP at five high-volume European institutions. Patients were stratified according to preoperative cancer risk group., Intervention: RARP., Outcome Measurements and Statistical Analysis: The rate and extent of PLND across different institutions were analyzed. Univariable and multivariable logistic regression models evaluated the association between preoperative variables and the probability of receiving PLND, as well as the presence of lymph node invasion (LNI). Finally, the probability of LNI was calculated for each patient, and the indication for PLND was compared with the EAU guidelines' indications., Results and Limitations: A lymph node dissection was performed in 1777 patients (59.7%; 34.5% of low-risk patients, 64.9% of intermediate-risk patients, and 91.2% of high-risk patients). These rates were different across institutions: 5.0-41.4% in low-risk patients (p<0.001), 31.3-81.4% in intermediate-risk patients (p<0.001), and 84.6-96.4% in high-risk patients (p=0.06). The mean and median number of nodes removed was 10.8, and 122 patients (4.1%) had nodal metastases. At multivariable analysis, the institution represented an independent predictor of PLND (p<0.001). Of patients with current indication for PLND (EAU guidelines), 77.8% actually received the procedure. Limitations were the retrospective study design with different pathologic assessment and lack of follow-up data., Conclusions: PLND is performed in a high proportion of patients undergoing RARP in high-volume centers in Europe for whom the procedure is indicated by the EAU guidelines, but significant differences exist among institutions. An effort toward a more rigorous standardization of PLND is advocated., Patient Summary: In this paper, we investigated the indication for and extension of pelvic lymph node dissection (PLND) in different institutions in Europe. Despite PLND being widely performed, significant variations with regard to PLND do exist among different institutions. Therefore, a thrust toward more rigorous attention to PLND is advocated., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Social media use is becoming common in medical practice. Although primarily used in this context to connect physicians, social media allows users share information, to create an online profile, to learn and keep knowledge up to date, to facilitate virtual attendance at medical conferences, and to measure impact within a field. However, shared content should be considered permanent and beyond the control of its author, and typical boundaries, such as the patient-physician interaction, become blurred, putting both parties at risk. The European Association of Urology brought together a committee of stakeholders to create guidance on the good practice and standards of use of social media. These encompass guidance about defining an online profile; managing accounts; protecting the reputations of yourself and your organization; protecting patient confidentiality; and creating honest, responsible content that reflects your standing as a physician and your membership within this profession., (Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Context: The Second International Consultation on Bladder Cancer recommendations on urothelial carcinoma (UC) of the prostate were presented at the 2011 European Association of Urology Congress in Vienna, Austria, on March 18, 2011., Objective: Our aim is to summarize the Second International Consultation on Bladder Cancer recommendations on UC of the prostate to help clinicians assess the current evidence-based management., Evidence Acquisition: The committee performed a thorough review of new data and updated previous recommendations. Levels of evidence and grades of recommendation were assigned based on a systematic review of the literature that included a search of online databases and review articles., Evidence Synthesis: Once a non-muscle-invasive high-grade tumor or carcinoma in situ (CIS) of the bladder has been diagnosed, careful follow-up of the prostatic urethra is necessary. Noninvasive UC including CIS of the prostate should be treated with intravesical bacillus Calmette-Guérin (BCG) following endoscopic resection. A transurethral resection of the prostate may improve contact of BCG with the prostatic urethra, and it appears that response rates to BCG are increased (level of evidence: 3). Transurethral biopsy of the prostatic urethra is effective in identifying prostatic involvement but may not accurately reveal the extent of involvement, particularly with stromal invasion. Stromal invasion by UC of the prostate carries a poor prognosis. Radical cystoprostatectomy is the treatment of choice for locoregional control in patients with prostatic stromal invasion., Conclusions: These recommendations contain updated information on the diagnosis and treatment of UC of the prostate. However, prospective trials are needed to further elucidate the best management of these patients., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Although the initial robot-assisted radical prostatectomy (RARP) series showed 12-mo potency rates ranging from 70% to 80%, the few available comparative studies did not permit any definitive conclusion about the superiority of this technique when compared with retropubic radical prostatectomy (RRP) and laparoscopic radical prostatectomy (LRP)., Objectives: The aims of this systematic review were (1) to evaluate the current prevalence and the potential risk factors of erectile dysfunction after RARP, (2) to identify surgical techniques able to improve the rate of potency recovery after RARP, and (3) to perform a cumulative analysis of all available studies comparing RARP versus RRP or LRP., Evidence Acquisition: A literature search was performed in August 2011 using the Medline, Embase, and Web of Science databases. Only comparative studies or clinical series including >100 cases reporting potency recovery outcomes were included in this review. Cumulative analysis was conducted using Review Manager v.4.2 software designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK)., Evidence Synthesis: We analyzed 15 case series, 6 studies comparing different techniques in the context of RARP, 6 studies comparing RARP with RRP, and 4 studies comparing RARP with LRP. The 12- and 24-mo potency rates ranged from 54% to 90% and from 63% to 94%, respectively. Age, baseline potency status, comorbidities index, and extension of the nerve-sparing procedure represent the most relevant preoperative and intraoperative predictors of potency recovery after RARP. Available data seem to support the use of cautery-free dissection or the use of pinpointed low-energy cauterization. Cumulative analyses showed better 12-mo potency rates after RARP in comparison with RRP (odds ratio [OR]: 2.84; 95% confidence interval [CI]: 1.46-5.43; p=0.002). Only a nonstatistically significant trend in favor of RARP was reported after comparison with LRP (OR: 1.89; p=0.21)., Conclusions: The incidence of potency recovery after RARP is influenced by numerous factors. Data coming from the present systematic review support the use of a cautery-free technique. This update of previous systematic reviews of the literature showed, for the first time, a significant advantage in favor of RARP in comparison with RRP in terms of 12-mo potency rates., (Copyright © 2012. Published by Elsevier B.V.)

Context: Robot-assisted radical prostatectomy (RARP) was proposed to improve functional outcomes in comparison with retropubic radical prostatectomy (RRP) or laparoscopic radical prostatectomy (LRP). In the initial RARP series, 12-mo urinary continence recovery rates ranged from 84% to 97%. However, the few available studies comparing RARP with RRP or LRP published before 2008 did not permit any definitive conclusions about the superiority of any one of these techniques in terms of urinary continence recovery., Objective: The aims of this systematic review were (1) to evaluate the prevalence and risk factors for urinary incontinence after RARP, (2) to identify surgical techniques able to improve urinary continence recovery after RARP, and (3) to perform a cumulative analysis of all available studies comparing RARP versus RRP or LRP in terms of the urinary continence recovery rate., Evidence Acquisition: A literature search was performed in August 2011 using the Medline, Embase, and Web of Science databases. The Medline search included only a free-text protocol using the term radical prostatectomy across the title and abstract fields of the records. The following limits were used: humans; gender (male); and publication date from January 1, 2008. Searches of the Embase and Web of Science databases used the same free-text protocol, keywords, and search period. Only comparative studies or clinical series including >100 cases reporting urinary continence outcomes were included in this review. Cumulative analysis was conducted using the Review Manager v.4.2 software designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK)., Evidence Synthesis: We analyzed 51 articles reporting urinary continence rates after RARP: 17 case series, 17 studies comparing different techniques in the context of RARP, 9 studies comparing RARP with RRP, and 8 studies comparing RARP with LRP. The 12-mo urinary incontinence rates ranged from 4% to 31%, with a mean value of 16% using a no pad definition. Considering a no pad or safety pad definition, the incidence ranged from 8% to 11%, with a mean value of 9%. Age, body mass index, comorbidity index, lower urinary tract symptoms, and prostate volume were the most relevant preoperative predictors of urinary incontinence after RARP. Only a few comparative studies evaluated the impact of different surgical techniques on urinary continence recovery after RARP. Posterior musculofascial reconstruction with or without anterior reconstruction was associated with a small advantage in urinary continence recovery 1 mo after RARP. Only complete reconstruction was associated with a significant advantage in urinary continence 3 mo after RARP (odds ratio [OR]: 0.76; p=0.04). Cumulative analyses showed a better 12-mo urinary continence recovery after RARP in comparison with RRP (OR: 1.53; p=0.03) or LRP (OR: 2.39; p=0.006)., Conclusions: The prevalence of urinary incontinence after RARP is influenced by preoperative patient characteristics, surgeon experience, surgical technique, and methods used to collect and report data. Posterior musculofascial reconstruction seems to offer a slight advantage in terms of 1-mo urinary continence recovery. Update of a previous systematic review of literature shows, for the first time, a statistically significant advantage in favor of RARP in comparison with both RRP and LRP in terms of 12-mo urinary continence recovery., (Copyright © 2012. Published by Elsevier B.V.)

Context: Radical retropubic prostatectomy (RRP) has long been the most common surgical technique used to treat clinically localized prostate cancer (PCa). More recently, robot-assisted radical prostatectomy (RARP) has been gaining increasing acceptance among patients and urologists, and it has become the dominant technique in the United States despite a paucity of prospective studies or randomized trials supporting its superiority over RRP., Objective: A 2-d consensus conference of 17 world leaders in prostate cancer and radical prostatectomy was organized in Pasadena, California, and at the City of Hope Cancer Center, Duarte, California, under the auspices of the European Association of Urology Robotic Urology Section to systematically review the currently available data on RARP, to critically assess current surgical techniques, and to generate best practice recommendations to guide clinicians and related medical personnel. No commercial support was obtained for the conference., Evidence Acquisition: A systematic review of the literature was performed in agreement with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement., Evidence Synthesis: The results of the systematic literature review were reviewed, discussed, and refined over the 2-d conference. Key recommendations were generated using a Delphi consensus approach. RARP is associated with less blood loss and transfusion rates compared with RRP, and there appear to be minimal differences between the two approaches in terms of overall postoperative complications. Positive surgical margin rates are at least equivalent with RARP, but firm conclusions about biochemical recurrence and other oncologic end points are difficult to draw because the follow-up in existing studies is relatively short and the overall experience with RARP in locally advanced PCa is still limited. RARP may offer advantages in postoperative recovery of urinary continence and erectile function, although there are methodological limitations in most studies to date and a need for well-controlled comparative outcomes studies of radical prostatectomy surgery following best practice guidelines. Surgeon experience and institutional volume of procedures strongly predict better outcomes in all relevant domains., Conclusions: Available evidence suggests that RARP is a valuable therapeutic option for clinically localized PCa. Further research is needed to clarify the actual role of RARP in patients with locally advanced disease., (Copyright © 2012. Published by Elsevier B.V.)

Prostate cancer (PCa) is a major lethal malignancy in men, but the molecular events and their interplay underlying prostate carcinogenesis remain poorly understood. Epigenetic events and the upregulation of polycomb group silencing proteins including Bmi1 have been described to occur during PCa progression. Here, we found that conditional overexpression of Bmi1 in mice induced prostatic intraepithelial neoplasia, and elicited invasive adenocarcinoma when combined with PTEN haploinsufficiency. In addition, Bmi1 and the PI3K/Akt pathway were coactivated in a substantial fraction of human high-grade tumors. We found that Akt mediated Bmi1 phosphorylation, enhancing its oncogenic potential in an Ink4a/Arf-independent manner. This process also modulated the DNA damage response and affected genomic stability. Together, our findings demonstrate the etiological role of Bmi1 in PCa, unravel an oncogenic collaboration between Bmi1 and the PI3K/Akt pathway, and provide mechanistic insights into the modulation of Bmi1 function by phosphorylation during prostate carcinogenesis.

Context: Although oncologic results remain the main outcome assessment for radical prostatectomy (RP), there is a need to include both urinary continence and potency recovery in the assessment of success for this procedure. Unfortunately, the widely used trifecta system does not weigh these outcomes differently. Moreover, the trifecta system-and even more so, the recently described pentafecta system-is only applicable in preoperatively continent and potent patients who receive bilateral nerve-sparing RP, and thus it is not an appropriate reporting tool for the majority of patients undergoing RP., Objective: Perform a systematic review to evaluate critically the trifecta and pentafecta models and describe a novel system that can be used to report the most relevant intermediate- and long-term outcomes after RP. This system has increased generalizability by being applicable to all patients undergoing RP., Evidence Acquisition: A literature search was performed in March 2011 using the Medline, Embase, and Web of Science databases. The Medline search included only a free-text protocol using the terms radical prostatectomy, trifecta, and pentafecta across the Title and Abstract fields of the records. Subsequently, the following limits were used: humans, gender (male), and language (English). The searches of the Embase and Web of Science databases used the same free-text protocol and the same keywords, applying no limits., Evidence Synthesis: Eleven original articles reported trifecta outcomes, and only one original article used the pentafecta model. These systems were correctly applied in only 28-62% of treated patients. A mean of 57% (range: 20-83%) of patients achieved continence and potency without prostate-specific antigen failure after RP. All the original articles were surgical series (level 4 evidence). The new proposed system categorizes the three outcomes using the letter S for biochemical disease-free survival, the letter C for urinary continence, and the letter P for potency recovery. This SCP system can be applied to all patients who undergo RP and is thus analogous to the use of the TNM system for classifying disease stage. Moreover, the SCP system allows us to distinguish four different clinical scenarios: (1) oncologic and functional success, (2) oncologic success and functional failure, (3) oncologic failure and functional success, and (4) oncologic and functional failure., Conclusions: The proposed novel SCP system offers the opportunity to appropriately classify all patients who undergo RP according to the oncologic and functional outcomes of relevance to them on an individual basis. We contend that this system's greater generalizability may make it more useful than the currently used trifecta and pentafecta systems, though its validation remains to be performed., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: To assess the risk of second primary cancer (SPC) after [(125)I]iodine prostate cancer brachytherapy compared with prostatectomy and the general population., Patients and Methods: In a cohort consisting of 1,888 patients with prostate cancer who received monotherapy with brachytherapy (n = 1,187; 63%) or prostatectomy (n = 701; 37%), SPC incidences were retrieved by linkage with the Dutch Cancer Registry. Standardized incidence rates (SIRs) and absolute excess risks (AERs) were calculated for comparison., Results: A total of 223 patients were diagnosed with SPC, 136 (11%) after brachytherapy and 87 (12%) after prostatectomy, with a median follow-up of 7.5 years. The SIR for all malignancies, bladder cancer, and rectal cancer were 0.94 (95% CI, 0.78 to 1.12), 1.69 (95% CI, 0.98 to 2.70), and 0.90 (95% CI, 0.41 to 1.72) for brachytherapy and 1.04 (95% CI, 0.83 to 2.28), 1.82 (95% CI, 0.87 to 3.35), and 1.50 (95% CI, 0.68 to 2.85) for prostatectomy, respectively. Bladder SPC risk was significantly increased after brachytherapy for patients age 60 years or younger (SIR, 5.84; 95% CI, 2.14 to 12.71; AER, 24.03) and in the first 4 years of follow-up (SIR, 2.14; 95% CI, 1.03 to 3.94; AER, 12.24). Adjusted for age, the hazard ratio (brachytherapy v prostatectomy) for all SPCs combined was 0.87 (95% CI, 0.64 to 1.18)., Conclusion: Overall, we found no difference in SPC incidence between patients with prostate cancer treated with prostatectomy or brachytherapy. Furthermore, no increased tumor incidence was found compared with the general population. We observed a higher than expected incidence of bladder SPC after brachytherapy in the first 4 years of follow-up, probably resulting from lead time or screening bias. Because of power limitations, a small increased SPC risk cannot be formally excluded.

Context: Newly discovered biomarkers ideally should prove clinical usefulness, provide additional detection, staging, and prognosis information to improve individual risk assessment, and potentially permit targeted cancer therapy., Objective: To review, display, and evaluate the current evidence regarding the biologic and analytic approach of urinary prostate cancer gene 3 (PCA3) in prostate cancer (PCa) detection, staging, and prognosis, and its therapeutic potential., Evidence Acquisition: A systematic and comprehensive Medline search was performed using the Medical Subject Headings search terms PCA3, DD3, UPM3, prostate cancer, cell-lines, prostate tissue, prostate biopsy, detection, diagnosis, radical prostatectomy, staging, grading, progression, and gene therapy. Results were restricted to English-language papers published within the period 1999-2011., Evidence Synthesis: The PCA3 gene is highly overexpressed in specific PCa cell lines and prostatic tumours. In 2006, a simple and robust urine test (Progensa) became commercially available. Despite its costs, prostate cancer antigen 3 (PCA3) is superior to prostate-specific antigen (PSA) and percent free PSA in the early detection of PCa. PCA3 improves the diagnostic accuracy of externally validated nomograms among men with an elevated PSA undergoing biopsy. PCA3 independently predicts low-volume disease and pathologically insignificant PCa but is not associated with locally advanced disease and is limited in the prediction of aggressive cancer. Preliminary data demonstrate that combining PCA3 with other new biomarkers further improves diagnostic and prognostic accuracy. Finally, findings of the first PCA3-Gene-ViroTherapy study suggest therapeutic potential by exploiting PCA3 overexpression., Conclusions: PCA3, integrated in novel biopsy nomograms or risk stratification tools, can be used to counsel or confirm biopsy indications. If confirmed in further studies, using PCA3 together with established staging risk factors could assist clinicians in specific pretreatment decision making. So far no evidence for the usefulness of PCA3 in active surveillance programs has been presented., (Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

We present whole genome profiling (WGP), a novel next-generation sequencing-based physical mapping technology for construction of bacterial artificial chromosome (BAC) contigs of complex genomes, using Arabidopsis thaliana as an example. WGP leverages short read sequences derived from restriction fragments of two-dimensionally pooled BAC clones to generate sequence tags. These sequence tags are assigned to individual BAC clones, followed by assembly of BAC contigs based on shared regions containing identical sequence tags. Following in silico analysis of WGP sequence tags and simulation of a map of Arabidopsis chromosome 4 and maize, a WGP map of Arabidopsis thaliana ecotype Columbia was constructed de novo using a six-genome equivalent BAC library. Validation of the WGP map using the Columbia reference sequence confirmed that 350 BAC contigs (98%) were assembled correctly, spanning 97% of the 102-Mb calculated genome coverage. We demonstrate that WGP maps can also be generated for more complex plant genomes and will serve as excellent scaffolds to anchor genetic linkage maps and integrate whole genome sequence data.

Choline is an essential amino acid, which is needed for the synthesis of membrane phospholipids. The choline uptake pathway is increasingly applied for molecular imaging of proliferating tumors. We describe a patient in whom we encountered an unexpected finding when he was referred for a routine [18F]-methylcholine PET/computed tomography scan to restage his prostate carcinoma. There was only visualization of circulating [18F]-methylcholine and no active uptake in any relevant organ. Owing to this abnormal biological behavior the scan was deemed uninterpretable. On checking his comorbidity and medication, the patient was found to take colchicine on a daily basis for his gout. After discontinuation of colchicine, the biodistribution of [18F]-methylcholine normalized. We present a possible explanation for these findings, with an impact on molecular imaging of the choline pathway and possibly reaching beyond colchicine alone.