Quality-of-life outcomes of the ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial.

OBJECTIVES: To comprehensively compare quality-of-life (QoL) outcomes between open partial nephrectomy (OPN) and robot-assisted PN (RAPN) from the randomised ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non-existent, especially not from randomised controlled trials (RCTs). PATIENTS AND METHODS: The ROBOCOP II was a single-centre, open-label RCT between OPN and RAPN. The pre-planned analyses of QoL outcomes are presented. Data were analysed descriptively in a modified intention-to-treat population. RESULTS: A total of 50 patients underwent surgery. At postoperative Day 90 (POD90), there was no significant difference for the Kidney Disease Quality of Life-Short Form questionnaire score (mean [sd] OPN 72 [20] vs RAPN 76 [15], P = 0.850), while there were advantages for RAPN in the subdomains of 'Pain' (P = 0.006) and 'Physical functioning' (P = 0.011) immediately after surgery. For the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core there were overall advantages directly after surgery (mean [sd] score OPN 63 [20] vs RAPN 75 [17], P = 0.031), as well as for the subdomains 'Fatigue' (P = 0.026), 'Pain' (P = 0.002) and 'Constipation' (P = 0.045) but no differences at POD90. There were no differences for the EuroQoL five Dimensions five Levels questionnaire at POD90 (mean [sd] score OPN 70 [22] vs RAPN 72 [17], P = 1.0) or at any other time point. Finally, no significant differences were found for the overall Convalescence and Recovery Evaluation questionnaire score at POD90 (mean [sd] OPN 84 [13] vs RAPN 86 [10], P = 0.818) but less pain in the RAPN group (P = 0.017) directly after surgery. CONCLUSIONS: Pain and physical functioning as subdomains of QoL are improved after RAPN compared to OPN in the early postoperative course, while there are no differences anymore after 3 months.

Online decision aid for patients with prostate cancer evaluated by 11 290 patients and 91 urologists in Germany.

OBJECTIVE: To evaluate the nationwide online decision aid 'Entscheidungshilfe Prostatakrebs' (established in 2016, >11.000 users and 60 new users/week) for patients with non-metastatic prostate cancer (PCa), from the perspective of patients and urologists. PATIENTS AND METHODS: To provide personalised information, the tool collects most of the International Consortium for Health Outcomes Measurement standard set, personal preferences, psychological features, and a validated rating of the tool. To evaluate urologists' opinions, we developed a structured two-page questionnaire. All data were collected anonymously. RESULTS: From June 2016 to December 2020, 11 290 patients used the PCa decision aid. Their median (interquartile range [IQR]) age was 67 (61-72) years. The median (IQR) time from initial diagnosis to using the tool was 4 (3-7) weeks. In all, 87.7% of users reported high satisfaction. In a multivariable model, predictors for considering observation were higher knowledge, using the decision aid alone, lower oncological risk, normal erectile function, and respective personal preferences. Of 194 urologists, 91 (47%) had implemented the decision aid in their clinical practice. The urologists' mean (SD) satisfaction score (1 'very good'; 6 'unsatisfactory') with it was 1.45 (0.55), and 92% recommended it. Half of the urologists reported time savings. CONCLUSION: Patients and urologists report a very high level of acceptance and satisfaction with this online tool. It offers advantages in shared decision-making and time efficiency. The usage of the decision aid might improve the adoption of active surveillance and watchful waiting when indicated.

Pulse modulation in En-Bloc HoLEP: does it really matter? A propensity score matched analysis.

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) is an established option in the surgical treatment of benign prostatic hyperplasia. Pulse modulation, such as MOSES® technology, has recently been introduced and may offer potential advantages in HoLEP. METHODS: Perioperative data from 117 patients who underwent MOSES® laser enucleation of the prostate (MoLEP) were collected. Propensity score matching using prostate volume, age, body mass index (BMI), and anticoagulant intake was performed using a database of 237 patients treated with HoLEP. In total, 234 patients were included in the analysis. RESULTS: Prostate volume (104 vs. 102 ml), age (70 vs. 71 years), BMI (27 vs. 27), and anticoagulant intake (34 vs. 35%) did not differ significantly between the groups. There were no significant differences in operation time (61.5 vs. 58.1 min, p = 0.42), enucleation efficiency (2.5 vs. 2.6 g/min, p = 0.74), hemostasis time (7.8 vs. 8 min, p = 0.75) and hemoglobin drop (0.9 vs. 0.7 mg/dl, p = 0.48). The complication rates were low in both groups (16.2% for HoLEP and 17.1% for MoLEP). No differences were noted in the Clavien-Dindo Classification (p = 0.63) and the Comprehensive Complication Index (p = 0.24). The rate of complications > CDC IIIa was 0.9% for HoLEP (endoscopic coagulation) and 1.7% for MoLEP (2 cases of endoscopic coagulation). No transfusions were administered. CONCLUSION: Overall, the enucleation efficiency was high in both groups and the procedure time was short. HoLEP is an efficient and safe treatment option in experienced hands, regardless of the use of pulse modulation technology.

Perioperative Antibiotic Prophylaxis in Radical Prostatectomy: "Single-Shot" versus Multiday Regimen.

INTRODUCTION: Perioperative antibiotic prophylaxis (AP) is common in radical prostatectomy (RP). Yet there is no standard recommendation in international guidelines due to poor evidence. It is of great importance that these perioperative AP are sufficiently checked and systemically validated. The objective of this study was to determine whether a "single-shot" (single-use) perioperative AP yields equivalent results compared to a multiday prophylaxis in RP regarding postoperative wound infections and urinary tract infections. METHODS: 376 patients treated by RP at the University Medical Centre Mannheim, from 2014 to 2016, were included in this retrospective study. RP was performed either in a robotic-assisted or open manner. One group received an intravenous dose of perioperative AP with either ciprofloxacin or levofloxacin, continued by an oral dose of AP with ciprofloxacin or levofloxacin until catheter removal, while the other group received a single-shot intravenous perioperative AP with either ciprofloxacin or cefuroxime. RESULTS: There was no significant difference regarding the occurrence of postoperative infections between both AP regimes (p = 0.5). Age, body mass index, and ASA classification did not differ significantly between both groups (p > 0.25). Except for surgery time (p < 0.05), perioperative parameters, such as the preoperative presence of germ-free urine culture, length of hospital stay, catheter time, drain lay time, Gleason score, and TNM stadium, did not differ significantly. CONCLUSION: The present study shows that perioperative single-shot AP does not entail any disadvantage compared to the multiday AP in terms of postoperative infections after RP.

Prospective, Randomized Comparative Evaluation of a Novel Hands-On Endourology Training Curriculum.

INTRODUCTION: The aim of this randomised prospective trial was to evaluate a novel hands-on endourological training programme (HTP) and compare it to the standard endourological colloquium (SC). METHODS: A new HTP was created based on a sequence of theoretical, video-based, and practical elements emphasising contemporary teaching methods. An existing SC in which live endourological operations were attended served as a comparison. Medical students were enrolled in a ratio of 1:2 (SC:HTP). Objective knowledge questionnaires (5 questions, open answers) and subjective Likert-type questionnaires (rating 1-3 vs. 4-5) were used for evaluation. Primary endpoint was urological knowledge transfer; secondary endpoints were learning effects, progression, and urological interest. RESULTS: 167 students (SC n = 52, HTP n = 115) were included. The knowledge assessment showed a significant increase in knowledge transfer benefitting the HTP on all 5 surveyed items (mean: n = 4/5/4/3/2 vs. n = 2/3/1/1, p < 0.0001). Interest and duration of the course were rated significantly more positively by HTP students (100.0/95.0% vs. 85.0/70.0%, p < 0.0001). The HTP students were significantly more confident in performing a cystoscopy independently (HTP 43.5% vs. SC 11.5%, p < 0.0001) and significantly claimed more often to have gained interdisciplinary and urological skills during the course (HTP 90.0/96.5% vs. SC 23.1/82.7%, p < 0.0001/p = 0.003). HTP students were also more likely to take the course again (HTP 98.2% vs. SC 59.6%, p < 0.0001). CONCLUSION: Modifying endourological teaching towards hands-on teaching resulted in stronger course interest, greater confidence regarding endourologic procedures, and significantly increased urologic knowledge transfer.

Perioperative Outcome of Thulium Laser Enucleation of the Prostate versus Robot-Assisted Simple Prostatectomy: A Propensity Score-Matched Analysis.

INTRODUCTION: The aim of this study was to investigate and compare clinical safety and efficiency of Thulium laser enucleation of the prostate (ThuLEP) and robot-assisted simple prostatectomy (RASP) for the treatment of large gland benign prostatic hyperplasia in a tertiary care center. METHODS: Perioperative data of 39 patients who underwent RASP in our institution from 2015 to 2021 was collected. Propensity score matching using prostate volume, patient age, and body mass index (BMI) was performed from a database of 1,100 Patients treated by ThuLEP from 2009 to 2021. A total of 76 patients were matched. Preoperative parameters such as BMI, age, and prostate volume, as well as intra- and postoperative parameters such as operation time, resection weight, transfusion rate, postoperative catheterization time, length of hospital stay (LoS), hemoglobin drop, postoperative urinary retention (PUR), Clavien-Dindo Classification (CDC), and the Combined Complication Index (CCI), were evaluated. RESULTS: There was no difference in mean hemoglobin drop (2.2 vs. 1.9 g/dL, p = 0.34), yet endoscopic surgery showed superiority in mean operation time (109 vs. 154 min, p < 0.001), mean postoperative catheterization time (3.3 vs. 7.2 days, p < 0.001), and mean LOS (5.4 vs. 8.4 days, p < 0.001). Complication rates evaluated by CDC (p = 0.11) and CCI (p = 0.89) were similar in both groups. Within the documented complications, transfusion rate (0 vs. 3, p = 0.08) and the occurrence of PUR (1 vs. 2, p = 0.5) showed no significant difference. CONCLUSION: ThuLEP and RASP show similar perioperative efficacy and a low rate of complications. ThuLEP had shorter operation times, shorter catheterization time, and a shorter LoS.

A prospective study on inter-operator variability in semi-robotic software-based MRI/TRUS-fusion targeted prostate biopsies.

PURPOSE: Magnetic resonance imaging (MRI)/ultrasound-fusion prostate biopsy (FB) comprises multiple steps each of which can cause alterations in targeted biopsy (TB) accuracy leading to false-negative results. The aim was to assess the inter-operator variability of software-based fusion TB by targeting the same MRI-lesions by different urologists. METHODS: In this prospective study, 142 patients eligible for analysis underwent software-based FB. TB of all lesions (n = 172) were carried out by two different urologists per patient (n = 31 urologists). We analyzed the number of mismatches [overall prostate cancer (PCa), clinically significant PCa (csPCa) and non-significant PCa (nsPCa)] between both performed TB per patient. In addition we evaluated factors contributing to inter-operator variability by uni- and multivariable analyses. RESULTS: In 11.6% of all MRI-lesions (10.6% of all patients) there was a mismatch between TB1 and TB2 in terms of overall prostate cancer (PCa detection. Regarding csPCa, patient-based mismatch occurred in 14.8% (n = 21). Overall PCa and csPCa detection rate of TB1 and TB2 did not differ significantly on a per-patient and per-lesion level. Analyses revealed a smaller lesion size as predictive for mismatches (OR 9.19, 95% CI 2.02-41.83, p < 0.001). CONCLUSION: Reproducibility and precision of targeting particularly small lesions is still limited although using software-based FB. Further improvements in image-fusion, segmentation, needle-guidance, and automatization are necessary.

Upper Tract Urinary Cancer Recurrence after Radical Cystectomy: Risk Assessment of Intraoperative Frozen Section.

INTRODUCTION: Upper tract urinary cancer recurrence (UTUCR) after radical cystectomy (RC) is outcome-limiting. Surgical recommendations on intraoperative performance of frozen section analysis (FSA) and management of positive ureteral margin (PUM) are lacking. METHODS: 634 RC cases were identified (2010-2018). In patients with PUM, sequential ureteral resections up to a negative margin were performed. We investigated the accuracy of FSA, significance of PUM, and identified risk factors (RFs) to stratify patients for UTUCR. RESULTS: FSA was performed in 355 patients, including a total of 693 ureters. FSA sensitivity was 0.93 and specificity 0.99. PUM conversion was possible in 52 (91.2%) cases. UTUCR occurred in 17 (4.8%) patients. Identified UTUCR RFs are non-muscle invasive bladder carcinoma (NMIBC) (OR 3.8, 95% confidence intervals [CI] 1.4-10.2, p = 0.008), multifocal bladder cancer in cystectomy specimen (OR 4.7, CI 1.1-20.8, p = 0.042), and recurrent NMIBC (OR 4.1, CI 1.5-10.9, p = 0.006). Risk-group stratification showed a six-fold increase in UTUCR risk (low-to high-risk). CONCLUSION: FSA is a sensitive and specific method to identify PUM. UTUCR occurs significantly more often in patients with recurrent, multifocal NMIBC at the time of RC. Patients can be risk stratified for UTUCR. In case of NMIBC-PUM, surgeons can safely opt for a kidney preserving strategy.

Treatment decision satisfaction and regret after focal HIFU for localized prostate cancer.

PURPOSE: Focal therapies (FTs) are investigated within prospective studies on selected patients treated for localized prostate cancer (PCa). Benefits are preservation of genitourinary function and reduced complications, but follow-up is elaborate and is associated with uncertainty as cancer-free survival appears to be lower compared to standard radical treatments. The aim of this study was to analyse patient-reported acceptance of FT and evaluate factors associated with treatment decision regret. METHODS: 52 patients who received focal high-intensity focused ultrasound for low- to intermediate-risk PCa between 2014 and 2019 within two prospective trials were eligible for a survey regarding PCa-related treatment regret and quality-of-life (Clark's scale) and the following potential predictors: sociodemographic variables, Charlson Comorbidity Index, subjective aging (AARC-10 SF), and general health-related quality-of-life (SF-12). Cancer persistence/recurrence (multiparametric MRI and fusion biopsy after 12 months) and functional outcomes (EPIC-26 UI/UIO/S) data were also included in this study. RESULTS: The overall survey response rate was 92.3% (48/52 patients). Median follow-up was 38 months (interquartile range = 25-50 months). In total, ten patients (20.8%) reported treatment decision regret. In univariable analyses, a clinically meaningful increase in urinary incontinence showed a significant association (OR 4.43; 95% CI 0.99-20.53; p = 0.049) with regret. Cancer recurrence (OR 12.31; 95% CI 1.78-159.26; p = 0.023) and general health worry as a domain of Clark's scale (OR 1.07; 95% CI 1.03-1.14; p < 0.01) were predictors of regret in a multivariable logistic regression model (AUC = 0.892). CONCLUSION: Acceptance of FT is comparable to standard treatments. Extensive follow-up including regular PSA testing does not cause additional regret but careful patient selection and information before FT is crucial.

Robotic-Assisted Versus Conventional Open Partial Nephrectomy (Robocop): A Propensity Score-Matched Analysis of 249 Patients.

OBJECTIVES: The objective of this study was to compare open partial nephrectomy (OPN) and robotic-assisted PN (RAPN) based on a propensity score-matched sample and to test the Comprehensive Complication Index (CCI) as an end point for complications. METHODS: Patients undergoing PN from 2010 to 2018 at a university care center were included. OPN and RAPN cases were matched in a 2:1 ratio using propensity score-matching with age, gender, BMI, RENAL score, and tumor size as confounders. The primary end point was complications measured with the CCI as continuous score (0-100, 100 indicating death). RESULTS: Data of 570 patients were available. After matching, both cohorts (OPN = 166; RAPN = 83) showed no baseline differences. For the primary end point, CCI, RAPN was superior (RAPN 2.6 ± 7.9 vs. OPN 8.7 ± 13.9; p < 0.001). Additionally, RAPN was superior for length of stay (RAPN 6.5 ± 4.0 vs. OPN 7.4 ± 3.5 days; p < 0.001), hemoglobin drop (RAPN 2.8 ± 1.4 vs. OPN 3.8 ± 1.6 g/dL; p < 0.001), and drop of glomerular filtration rate (RAPN 11.4 ± 14.2 vs. OPN 19.5 ± 14.3 mL/min; p < 0.001). OPN had shorter operating times (RAPN 157 ± 43 vs. OPN 143 ± 45 min; p = 0.014) and less ischemia (RAPN 13% vs. OPN 28%; p = 0.016). CONCLUSIONS: RAPN provides superior short-term results regarding overall complications without compromising renal function for small and less complex tumors. However, OPN remains an important option for more complex and larger tumors.

RNA Expression of DNA Damage Response Genes in Muscle-Invasive Bladder Cancer: Influence on Outcome and Response to Adjuvant Cisplatin-Based Chemotherapy.

BACKGROUND: Perioperative cisplatin-based chemotherapy (CBC) can improve the outcome of patients with muscle-invasive bladder cancer (MIBC), but it is still to be defined which patients benefit. Mutations in DNA damage response genes (DDRG) can predict the response to CBC. The value of DDRG expression as a marker of CBC treatment effect remains unclear. MATERIAL AND METHODS: RNA expression of the nine key DDRG (BCL2, BRCA1, BRCA2, ERCC2, ERCC6, FOXM1, RAD50, RAD51, and RAD52) was assessed by qRT-PCR in a cohort of 61 MICB patients (median age 66 y, 48 males, 13 females) who underwent radical cystectomy in a tertiary care center. The results were validated in the The Cancer Genome Atlas (TCGA) cohort of MIBC (n = 383). Gene expression was correlated with disease-free survival (DFS) and overall survival (OS). Subgroup analyses were performed in patients who received adjuvant cisplatin-based chemotherapy (ACBC) (Mannheim n = 20 and TCGA n = 75). RESULTS: Low expression of RAD52 was associated with low DFS in both the Mannheim and the TCGA cohorts (Mannheim: p = 0.039; TCGA: p = 0.017). This was especially apparent in subgroups treated with ACBC (Mannheim: p = 0.0059; TCGA: p = 0.012). Several other genes showed an influence on DFS in the Mannheim cohort (BRCA2, ERCC2, FOXM1) where low expression was associated with poor DFS (p < 0.05 for all). This finding was not fully supported by the data in the TCGA cohort, where high expression of FOXM1 and BRCA2 correlated with poor DFS. CONCLUSION: Low expression of RAD52 correlated with decreased DFS in the Mannheim and the TCGA cohort. This effect was especially pronounced in the subset of patients who received ACBC, making it a promising indicator for response to ACBC on the level of gene expression.

Prospective Feasibility Study of Single-Shot Antibiotic Prophylaxis in Transrectal Focal Ablation of Prostate Cancer.

INTRODUCTION: Urinary tract infections (UTI) represent the most frequent complications after transrectal focal ablation of prostate cancer. Single-shot antibiotic prophylaxis for prevention has not yet been described. METHODS: In this cohort study of patients who received a high-intensity focused ultrasound (HIFU) ablation of prostate cancer within a registered prospective single-arm trial, we analyzed posttreatment UTI (≤30 days after HIFU) related to perioperative antibiotic management in an exploratory analysis: single-shot prophylaxis or targeted treatment for bacteriuria. Potential risk factors associated with UTI were evaluated by uni- and multivariate regression analyses. RESULTS: In total, 55 patients were eligible for analysis. Of these, 76.4% received antibiotic single-shot prophylaxis. UTI occurred in 10.7% of all patients, 5.4% developed fever, 3.6% required hospitalization. An antibiotic single-shot prophylaxis helped to protect 90.5% of men from infectious complications. Estimated effects indicate that a longer posttreatment catheterization (OR 3.38, 95% CI 0.47-27.08) and larger ablation volume (OR 4.85, 95% CI 0.61-107.49) might be associated with the highest risk for UTI after treatment. CONCLUSION: Single-shot antibiotic prophylaxis compared to a targeted antibiotic treatment showed a similar effectivity to prevent patients from infectious complications and should be considered as an element of antibiotic stewardship. Further research on risk factors and antibiotic strategies is required.

Phosphodiesterase SMPDL3B Gene Expression as Independent Outcome Prediction Marker in Localized Prostate Cancer.

Current outcome prediction markers for localized prostate cancer (PCa) are insufficient. The impact of the lipid-modifying Sphingomyelin Phosphodiesterase Acid Like 3B (SMPDL3B) in PCa is unknown. Two cohorts of patients with PCa who underwent radical prostatectomy (n = 40, n = 56) and benign prostate hyperplasia (BPH) controls (n = 8, n = 11) were profiled for SMPDL3B expression with qRT-PCR. Publicly available PCa cohorts (Memorial Sloane Kettering Cancer Centre (MSKCC; n = 131, n = 29 controls) and The Cancer Genome Atlas (TCGA; n = 497, n = 53 controls)) served for validation. SMPDL3B's impact on proliferation and migration was analyzed in PC3 cells by siRNA knockdown. In both cohorts, a Gleason score and T stage independent significant overexpression of SMPDL3B was seen in PCa compared to BPH (p < 0.001 each). A lower expression of SMPDL3B was associated with a shorter overall survival (OS) (p = 0.005) in long term follow-up. A SMPDL3B overexpression in PCa tissue was confirmed in the validation cohorts (p < 0.001 each). In the TCGA patients with low SMPDL3B expression, biochemical recurrence-free survival (p = 0.011) and progression-free interval (p < 0.001) were shorter. Knockdown of SMPDL3B impaired PC3 cell migration but not proliferation (p = 0.0081). In summary, SMPLD3B is highly overexpressed in PCa tissue, is inversely associated with localized PCa prognosis, and impairs PCa cell migration.

Association of training level and outcome of software-based image fusion-guided targeted prostate biopsies.

PURPOSE: The aim of this study was to assess the impact of experience on the outcome of image fusion-guided prostate biopsies performed by urologists working at a high-volume medical center. METHODS: The first 210 consecutive fusion biopsies were analyzed following installation of the software-based biopsy platform Artemis™ (Eigen, USA). The impact of training was measured in terms of changes in prostate cancer detection rates and biopsy duration over time. We sought to identify a threshold of experience for urologists, which predicts higher detection rates of targeted biopsies. The influence of various factors on prostate cancer detection rates was evaluated using bi- and multivariate analysis. RESULTS: Twenty-two urologists (n = 9 senior urologists, n = 13 urological residents) performed targeted biopsies followed by systematic 12-core biopsies. Overall, targeted biopsies yielded a positive result in 39.6% of 260 suspicious MRI lesions. A subgroup analysis of the six urologists who performed more than ten biopsies was then conducted, and their level of experience (i.e., performance of more than eight biopsies) was found to be associated with higher detection rates than those with less experience (49.0% and 23.0%, respectively; p < 0.001) in the targeted biopsies. Experience was likewise a significant and independent predictor of a cancer-positive targeted biopsy (p = 0.002). Experienced senior physicians did not outperform residents in their targeted biopsy results. Further, biopsy duration correlated negatively (r = - 0.5931, p < 0.001) with the total number of biopsies performed for all subgroups during the period of assessment. CONCLUSIONS: Experience is an important predictor of the rate of detection in targeted biopsies using software-based biopsy platforms with semi-robotic assistance. Moreover, the performance of just a few procedures appears sufficient to increase biopsy effectiveness significantly. Lastly, supervision by experts is recommended during the training phase.

Defining the target prior to prostate fusion biopsy: the effect of MRI reporting on cancer detection.

PURPOSE: Definition of targets in multiparametric MRI (mpMRI) prior to MRI/TRUS fusion prostate biopsy either by urologist or radiologist, as a prose report or by illustration is crucial for accurate targeted biopsies (TB). The objective was to analyze the effect of MRI reporting on target definition and cancer detection. METHODS: 202 patients underwent MRI/TRUS fusion biopsy with Artemis™ (Eigen, USA). mpMRI results were submitted in written form to urologists, who marked the targets in the proprietary software. An expert uroradiologist reviewed and marked mpMRI targets blinded to biopsy data. We compared number, localization and volume of targets between the observers and analyzed whether variations impaired TB results by bivariate and logistic regression models. RESULTS: Interobserver variability was moderate regarding number and low regarding localization of targets. Urologists overestimated target volumes significantly compared to radiologists (p = 0.045) and matching target volume between both observers was only 43.9%. Overall cancer detection rate was 69.8 and 52.0% by TB. A higher matching target volume was a significant predictor of cancer in TB (p < 0.001). Logistic regression revealed prostate volume and PI-RADS as independent predictors. Defining targets in incorrect T2w slices in the cranio-caudal axis are one presumable reason for missing cancer in TB. CONCLUSIONS: A high concordance of the target definition between radiologist and urologist is mandatory for accurate TB. Optimized ROI definition is recommended to improve TB results, preferably as contouring in MRI sequences by the radiologist or, if not feasible, by precise MRI reports including specific localization in sequence and slice as well as an illustration. High prostate volume and low PI-RADS score have to be considered as limiting factors for target definition.

Database-augmented Mass Spectrometry Analysis of Exosomes Identifies Claudin 3 as a Putative Prostate Cancer Biomarker.

In prostate cancer and other malignancies sensitive and robust biomarkers are lacking or have relevant limitations. Prostate specific antigen (PSA), the only biomarker widely used in prostate cancer, is suffering from low specificity. Exosomes offer new perspectives in the discovery of blood-based biomarkers. Here we present a proof-of principle study for a proteomics-based identification pipeline, implementing existing data sources, to exemplarily identify exosome-based biomarker candidates in prostate cancer.Exosomes from malignant PC3 and benign PNT1A cells and from FBS-containing medium were isolated using sequential ultracentrifugation. Exosome and control samples were analyzed on an LTQ-Orbitrap XL mass spectrometer. Proteomic data is available via ProteomeXchange with identifier PXD003651. We developed a scoring scheme to rank 64 proteins exclusively found in PC3 exosomes, integrating data from four public databases and published mass spectrometry data sets. Among the top candidates, we focused on the tight junction protein claudin 3. Retests under serum-free conditions using immunoblotting and immunogold labeling confirmed the presence of claudin 3 on PC3 exosomes. Claudin 3 levels were determined in the blood plasma of patients with localized (n = 58; 42 with Gleason score 6-7, 16 with Gleason score ≥8) and metastatic prostate cancer (n = 11) compared with patients with benign prostatic hyperplasia (n = 15) and healthy individuals (n = 15) using ELISA, without prior laborious exosome isolation. ANOVA showed different CLDN3 plasma levels in these groups (p = 0.004). CLDN3 levels were higher in patients with Gleason ≥8 tumors compared with patients with benign prostatic hyperplasia (p = 0.012) and Gleason 6-7 tumors (p = 0.029). In patients with localized tumors CLDN3 levels predicted a Gleason score ≥ 8 (AUC = 0.705; p = 0.016) and did not correlate with serum PSA.By using the described workflow claudin 3 was identified and validated as a potential blood-based biomarker in prostate cancer. Furthermore this workflow could serve as a template to be used in other cancer entities.

Complete and Durable Remission of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Urothelial Carcinoma Following Third-Line Treatment with Trastuzumab and Gemcitabine.

Urothelial carcinoma (UC) is one of the most common cancers and survival rates are low in metastatic disease with currently established first-line platinum-based chemotherapies. Unlike in many other cancers, no clinically established molecular targeted therapies exist for the treatment of this malignancy. Here we present a case of complete tumor remission following third-line treatment with trastuzumab and gemcitabine in a patient with human epidermal growth factor receptor 2 (HER2)-positive UC after progression under cisplatin and vinflunine chemotherapies. This case shows the potential significance of anti-HER2 therapy in selected patients with molecularly characterized UC. Clinical trials so far show inconclusive outcomes of anti-HER2 therapies in UC, indicating further need for both basic research and clinical studies for the identification of resistance factors and improved patient selection.

The EEF1A2 gene expression as risk predictor in localized prostate cancer.

BACKGROUND: Besides clinical stage and Gleason score, risk-stratification of prostate cancer in the pretherapeutic setting mainly relies on the serum PSA level. Yet, this is associated with many uncertainties. With regard to therapy decision-making, additional markers are needed to allow an exact risk prediction. Eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) was previously suggested as driver of tumor progression and potential biomarker. In the present study its functional and prognostic relevance in prostate cancer was investigated. METHODS: EEF1A2 expression was analyzed in two cohorts of patients (n = 40 and n = 59) with localized PCa. Additionally data from two large expression dataset (MSKCC, Cell, 2010 with n = 131 localized, n = 19 metastatic PCa and TCGA provisional data, n = 499) of PCa patients were reanalyzed. The expression of EEF1A2 was correlated with histopathology features and biochemical recurrence (BCR). To evaluate the influence of EEF1A2 on proliferation and migration of metastatic PC3 cells, siRNA interference was used. Statistical significance was tested with t-test, Mann-Whitney-test, Pearson correlation and log-rank test. RESULTS: qRT-PCR revealed EEF1A2 to be significantly overexpressed in PCa tissue, with an increase according to tumor stage in one cohort (p = 0.0443). In silico analyses in the MSKCC cohort confirmed the overexpression of EEF1A2 in localized PCa with high Gleason score (p = 0.0142) and in metastatic lesions (p = 0.0038). Patients with EEF1A2 overexpression had a significantly shorter BCR-free survival (p = 0.0028). EEF1A2 expression was not correlated with serum PSA levels. Similar results were seen in the TCGA cohort, where EEF1A2 overexpression only occurred in tumors with Gleason 7 or higher. Patients with elevated EEF1A2 expression had a significantly shorter BCR-free survival (p = 0.043). EEF1A2 knockdown significantly impaired the migration, but not the proliferation of metastatic PC3 cells. CONCLUSION: The overexpression of EEF1A2 is a frequent event in localized PCa and is associated with histopathology features and a shorter biochemical recurrence-free survival. Due to its independence from serum PSA levels, EEF1A2 could serve as valuable biomarker in risk-stratification of localized PCa.

Development of a standardised training curriculum for robotic surgery: a consensus statement from an international multidisciplinary group of experts.

OBJECTIVES: To explore the views of experts about the development and validation of a robotic surgery training curriculum, and how this should be implemented. MATERIALS AND METHODS: An international expert panel was invited to a structured session for discussion. The study was of a mixed design, including qualitative and quantitative components based on focus group interviews during the European Association of Urology (EAU) Robotic Urology Section (ERUS) (2012), EAU (2013) and ERUS (2013) meetings. After introduction to the aims, principles and current status of the curriculum development, group responses were elicited. After content analysis of recorded interviews generated themes were discussed at the second meeting, where consensus was achieved on each theme. This discussion also underwent content analysis, and was used to draft a curriculum proposal. At the third meeting, a quantitative questionnaire about this curriculum was disseminated to attendees to assess the level of agreement with the key points. RESULTS: In all, 150 min (19 pages) of the focus group discussion was transcribed (21 316 words). Themes were agreed by two raters (median agreement κ 0.89) and they included: need for a training curriculum (inter-rater agreement κ 0.85); identification of learning needs (κ 0.83); development of the curriculum contents (κ 0.81); an overview of available curricula (κ 0.79); settings for robotic surgery training ((κ 0.89); assessment and training of trainers (κ 0.92); requirements for certification and patient safety (κ 0.83); and need for a universally standardised curriculum (κ 0.78). A training curriculum was proposed based on the above discussions. CONCLUSION: This group proposes a multi-step curriculum for robotic training. Studies are in process to validate the effectiveness of the curriculum and to assess transfer of skills to the operating room.

ZIRK-Technique: Zero Ischemia Resection in the Kidney for High-Risk Renal Masses: Perioperative Outcome.

OBJECTIVES: This study evaluates the feasibility and safety of open-partial nephrectomies in the ZIRK-technique (Zero Ischemia Resection in the Kidney) for renal masses with high-risk anatomical features--objectified by the PADUA score. METHODS: We identified 40 consecutive cases of partial nephrectomies performed without clamping of the renal artery in our department of urology. Retrospective analysis of the preoperative CT or MRI scans showed 27 cases with a PADUA score ≥8, of which 15 cases had a score ≥10. Cases were in particular assessed regarding operation time (ORT), estimated blood loss (EBL), surgical margins and postoperative complications using the Clavien classification. RESULTS: The mean age of the study population was 67.6 years with an average BMI of 26.8 kg/m2. The mean ORT was 1:46 with an average EBL of 521 ml. Clavien grade II complications were observed seven times, while 3 patients had a grade IIIa complication. Despite complex and adverse location of the tumors, nephron-sparing surgery without ischemia could be performed with negative surgical margins for all cases. EBL, transfusion rate and complication were considerably more frequent in high-risk tumors. CONCLUSION: Highly complex renal tumors, PADUA ≥10, can be resected in ZIRK-technique with good operative outcome and a low complication rate.