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A) Detection of a deletion event in LuCaP 86.2. This samples also displays signals of wildtype genomic DNA, displaying an AR-V567es positive sub-clone. B) Detection of an inversion event in LuCaP 136s2. Abbreviations: BPH, benign prostate hyperplasia

Purpose:Androgen receptor splice variants are known to facilitate resistance of prostate cancer cells toward antihormonal therapies. However, detection of the most prominent variant, AR-V7, on its own, is not sufficiently accurate for prediction of response. Thus, simultaneous detection of other variants might improve prediction. AR-V567es has been shown to be expressed in late stages of prostate cancer. Yet, there have been discrepant results regarding incidence of AR-V567es. We therefore aimed to perform a comprehensive comparison of different detection approaches for AR-V567es mRNA.Experimental Design:We compared a custom-made, probe-based PCR assay with 6 published AR-V567es detection PCR assays in distinct samples, that is, cancer cell lines, LuCaP xenografts, primary and metastatic tumor samples, and circulating tumor cells (CTC).Results:Using distinct approaches, we concordantly detected expression of AR-V567es in only three of 45 samples (LuCaP xenografts 86.2 and 136s2 as well as one CTC sample). We observed varying results in all other samples. Specificity analysis displayed nonspecific binding of 5 previously published PCR assays to AR full-length mRNA in the absence of AR-V567es.Conclusions:Validation of biomarker detection approaches is one of the most critical steps before transfer into clinical application. By performing comparative analysis of different detection approaches, we revealed eminent variability among previously described systems. Furthermore, we demonstrate an overestimation of AR-V567es in prostate cancer, presumably due to nonspecific detection of AR-FL mRNA. Therefore, any correlation between AR-V567es expression and clinical responses is highly doubtful and does not reflect the biological nature of the disease.

A) Genomic structure of the AR gene. B) Sequences of exon 4/8 spanning primers used in 6 different PCR assays (except PCR assay #4). C) PCR assay #4 (22) would lead to two distinct PCR products with the respective size, i.e. AR-V567es and AR-FL. Abbreviations: AR-FL, full length AR; bp, base pairs

Delta Ct values of AR-FL, AR-V3, AR-V7 and AR-V9 in LuCaP xenografts (Ct ARs - Ct RPL37A)

A) Expression of AR-FL in LuCaP xenografts displaying significantly lower expression of AR-FL in LuCaP xenograft 136s2. B/C/D) Expression of AR splice variants AR-V3 (C), AR-V7 (D) and AR-V9. Abbreviations: NTC, non-template control

Introduction and hypothesis This study analyzes the long-term results of supratrigonal cystectomy and augmentation cystoplasty in patients with severe ulcerative interstitial cystitis/bladder pain syndrome (IC/BPS) and reduced bladder capacity. Methods Outcome data were retrospectively and prospectively collected and analyzed in women who underwent supratrigonal cystectomy and augmentation cystoplasty for ulcerative IC/BPS at Muenster University Hospital between 1991 and 2006. We used cross-tabulation and Pearson’s Chi-squared test to examine how outcome is influenced by age, preoperative functional bladder volume, and choice of augmentation material. Results After a median 171-month follow-up, analysis could be done in 26 of 27 patients. Persistent pain necessitated early revision in 2 patients (7.7%). Mean postoperative O’Leary Sant IC Score was 12.7 in the prospectively questioned patients. Responses to Patient Global Impression of Improvement (PGI-I) were: “very much better” in 15 cases (65.2%) and “much better” in 7 (30.4%). Twelve patients (52.2%) emptied their augmented bladder voluntarily, whereas 7 (32%) needed intermittent self-catheterization (ISC). The rate of patients requiring ISC tended to be lower when detubularized ileocecal bowel was used. All 5 patients (19.2%) with late relapse of ulcerative IC/BPS needed ISC. Conclusions Severe ulcerative IC/BPS can be curatively treated in some patients by supratrigonal cystectomy and augmentation, which is associated with a high satisfaction rate and few long-term complications even over a very long follow-up. In our analysis, the need for ISC is a risk factor for late relapse, although ileocecal augmentation could increase the proportion of patients with sufficient voluntary micturition.

BACKGROUND: Temsirolimus is a mTOR inhibitor approved for the first-line treatment of advanced or metastatic renal cell carcinoma (a/mRCC) with poor prognosis. In treatment of a/mRCC several prognostic scoring systems are used. We assessed the prognostic value of these scores in a large temsirolimus treated cohort and compared the results with the physician’s prognosis. METHODS: A German multicenter registry (STAR-TOR) for a/mRCC patients (NCT00700258) was established to evaluate the efficacy and safety of temsirolimus 25 mg weekly in a routine clinical setting. These prospective data were systematically analyzed and followed-up by an independent clinical research organization to compare established prognostic scores (MSKCC, IMDC and Hudes) with the risk assessment by treating physicians based on their medical expertise and match them with survival outcomes. RESULTS: This interim analysis included 547 patients between 02/2008 and 05/2015 in 87 centers. Either prognostic tool resulted in significant and clinically meaningful differentiation between good, intermediate and poor prognosis. However, physician’s prognosis identified more patients with good prognosis (9.1% vs. 1.3%). In patients with good physician’s prognosis and intermediate prognosis by MSKCC, overall survival was nearly doubled compared to consensual intermediate prognosis (26.6 vs. 13.6 months), albeit without reaching statistical significance (P=0.09). For poor prognosis assessed by the physician, MSKCC performed statistically better for differentiation between poor and intermediate prognosis with a median overall survival of 10.3 vs. 5.5 months (P

Introduction: This analysis, based on pre- and postoperative urodynamic data, is the first to elucidate the influence of the Adjustable Transobturator Male System (ATOMS, A.M.I. GmbH, Feldkirch, Austria) on the lower urinary tract and disclose possible obstructive properties. Methods: A prospective study was performed in patients who had stress urinary incontinence and were scheduled for ATOMS implantation after radical prostatectomy. Apart from continence assessment (24-hour pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form [ICIQ-SF]), urodynamic testing was done with International Continence Society (ICS)-standardized pressure-flow analysis before and after ATOMS implantation/adjustment. The Wilcoxon signed-rank test was used for statistical analysis. Results: The analysis included 12 consecutive patients from two centers (mean age 69 years) with a mean followup of 246 days. Median urine leakage dropped from 240 (72-1250) to 70 (0-700) g/24 hours postoperatively, with a pad reduction of 4 to 0.9 pads/ day. Pressure-flow analysis revealed a significant change only in the bladder outlet obstruction index (BOOI). The bladder contractility index, intravesical pressure conditions, and uroflowmetry were not significantly affected. None of the patients showed de novo obstruction postoperatively in the ICS analysis. Conclusions: The ATOMS significantly increases the BOOI in conjunction with good continence results. However, no case reached pathological level according to the BOOI and thus there is no potential danger to the lower urinary tract or urethral integrity. Sin financiación 2.052 JCR (2021) Q4, 68/90 Urology & Nephrology 0.440 SJR (2021) Q3, 56/108 Urology No data IDR 2021 UEM

(1) Background: This study examined outcomes of second-line ATOMS implantation after failure of the fixed male sling (FMS) AdVance/AdVance XP. (2) Methods: A retrospective multicenter cohort analysis was carried out in men implanted with an ATOMS between 2011 and 2020 after failure of an AdVance/AdVance XP. Success was assessed on the basis of objective (dryness, 0–1 pad/24 h or >20 g/24 h pad test) and subjective results (PGI-I). We performed the Wilcoxon rank sum test, Fisher’s exact test, logistic regression, and multivariate analysis. (3) Results: The study included 88 patients from 9 centers with a mean age of 71.3 years. No Clavien–Dindo > II complications occurred within the first 3 months after ATOMS implantation. A total of 10 cases (9%) required revision in the ensuing clinical course. After a mean follow-up of 42.5 months, 76.1% achieved social continence, and 56.8% used no pads at all. Mean urine leakage/24 h dropped from 422 g (3.9 pads) to 38 g (0.69 pads) and the mean ICIQ-SF decreased from 16.25 to 5.3 (p < 0.0001). PROMs (patient-reported outcome measures) showed improvement in 98.9% of cases, and 63.6% gave a “very much better” PGI-I rating. Multivariate analysis identified a lower probability of achieving maximum satisfaction for the following factors: the AdVance XP as first-line therapy (OR 0.35), a lower ICIQ-SF question 1 (OR 0.26), status post-irradiation (OR 0.14), and more severe pain prior to ATOMS implantation (OR 0.51). (4) Conclusions: Implantation of an ATOMS is an effective and safe second-line treatment option for recurrent urinary incontinence after implantation of an AdVance/AdVance XP sling. High patient satisfaction was demonstrated in a long-term follow-up.

Purpose The aim was to study the correlation between cuff size and outcome after implantation of an AMS 800 artificial urinary sphincter. Methods A total of 473 male patients with an AMS 800 sphincter implanted between 2012 and 2014 were analyzed in a retrospective multicenter cohort study performed as part of the Central European Debates on Male Incontinence (DOMINO) Project. Results Single cuffs were implanted in 54.5% and double cuffs in 45.5% of the patients. The cuffs used had a median circumference of 4.5 cm. Within a median follow of 18 months, urethral erosion occurred in 12.8% of the cases and was associated significantly more often with small cuff sizes (P

ZusammenfassungDie Durchführung der radikalen Prostatektomie hat sich in den letzten 200 Jahren deutlich verändert; gerade in den letzten 50 Jahren entwickelte sich die Technik deutlich weiter. Als Meilensteine dürfen zum einen die Arbeiten von Walsh in den späten 70er und frühen 80er Jahren angesehen werden, welche zu einer signifikanten Reduktion der Morbidität des Eingriffes führten, zum anderen die Einführung (Roboter-assistierter) minimal-invasiver Operationstechniken. Den absoluten Goldstandard bzgl. des Zuganges gibt es bis heute nicht. Innovative Ansätze, z. B. die Zuhilfenahme der sog. „augmented reality“ werden aktuell bzgl. ihres Potentials evaluiert. Dieser Übersichtsartikel in der Jubiläumsausgabe des Urologen beschäftigt sich mit den Meilensteinen der Entwicklung dieses für die Urologie wichtigen Eingriffs.

Papillary renal cell carcinoma (PRCC) is currently divided in 2 subtypes. We reviewed a large cohort of PRCC and correlated subtype, morphological features and diagnostic marker expression with overall survival (OS) to uncover differences between the 2 subtypes. Three hundred seventy-six renal tumors initially diagnosed as PRCC with clinical and survival data were collected from the participating centers. Two hundred forty-six tumors were classified as PRCC1 (65.4%) and 130 as PRCC2 (34.6%) and graded according to the 2016 World Health Organization/International Society of Urological Pathology grading system. Morphological features (abundant cytoplasm, necrosis, fibrous stroma, foamy macrophages and psammoma bodies) were noted. Immunohistochemical stains (MIB1, p53, Racemase, EMA, CK7, CK20, E-Cadherin) were performed using tissue microarrays. χ2-Tests, log-rank tests and uni- and multivariate Cox regression analysis were performed. Both subtypes displayed different morphological features and immunohistochemical profiles: abundant cytoplasm was more frequent in PRCC2, while foamy macrophages were more common in PRCC1. Abundant cytoplasm and presence of psammoma bodies were associated with poorer OS. PRCC1 showed more frequent CK7 expression, PRCC2 more frequent E-Cadherin, p53 and higher MIB1 expression (>15%). Expression of Racemase and CK7 was associated with better OS, while high MIB1 (>15%) was associated with poorer OS. In multivariate analysis, the only independent predictors of OS were proliferation (MIB1), tumor stage, metastasis and age at surgery. Subtype was not an independent prognostic factor. Therefore, PRCC subtype on its own is not suitable for estimating survival. More data focusing on PRCC tumor biology is needed to define prognostic subgroups, especially in PRCC2.

Background In metastatic clear cell renal cell carcinoma (ccRCC), different combination therapies, each including anti-PD-1 immune checkpoint blockade (ICB), are applied as first-line treatment. Robust predictive biomarkers for rational upfront therapy decisions are lacking, although they are urgently needed. Recently, we showed that CTLA4 promoter methylation predicts response to ICB in melanoma. Here, we aimed to investigate CTLA4 methylation in ccRCC and its utility to serve as a predictive biomarker for anti-PD-1 based ICB in metastatic ccRCC. Methods CTLA4 methylation was analyzed with regard to transcriptional gene activity (mRNA expression), intratumoral immune cell composition, and clinical course in two ccRCC cohorts obtained from The Cancer Genome Atlas (TCGA cohort, n=533) and the University Hospital Bonn (UHB Non-ICB Cohort, n=116). In addition, CTLA4 methylation as well as CD8+ T cell infiltrates and PD-L1 expression were evaluated in pre-treatment samples from a multicenter cohort (RCC-ICB Cohort, n=71). Patients included in the RCC-ICB Cohort were treated with either first line anti-PD-1 based combination therapy (n=25) or monotherapy post–tyrosine kinase inhibition in second line or later. Analyses were performed with regard to treatment response according to RECIST, progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) following treatment initiation. Results CTLA4 promoter hypomethylation was significantly correlated with CTLA4 mRNA expression, lymphocyte infiltration, and poor OS in both primary ccRCC cohorts (TCGA: HR 0.30 (95% CI 0.18 to 0.49), p, publishedVersion

AIM To analyze the influence of implantation volume of artificial sphincters (AMS 800) on outcome in a large central European multicenter cohort study. METHODS As part of the DOMINO (Debates on Male Incontinence) project, the surgical procedures and outcomes were retrospectively analyzed in a total of 473 patients who received an artificial sphincter (AMS 800) between 2010 and 2012. Clinics that implanted at least 10 AMS 800 per year were defined as high-volume centers. RESULTS Sixteen centers had a mean rate of 9.54 AMS 800/y of which five clinics were identified as high-volume centers. They implanted significantly more double cuffs (55% vs 12.1%; P

BACKGROUND Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and 223Ra), most of these patients still succumb to prostate cancer. Recently, 177lutetium prostate-specific membrane antigen radioligand therapy (177Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy. OBJECTIVES Establishment of the current position of 177Lu-PSMA-RLT in mCRPC in 2017. MATERIALS AND METHODS Presentation of the therapy landscape in mCRPC and the current challenges within treatment and survey of the available data on 177Lu-PSMA-RLT after PubMed-based research. RESULTS In several larger retrospective studies, 177Lu-PSMA-RLT seems to be an encouraging new option with the potential to extend overall survival while displaying a favorable toxicity profile. CONCLUSIONS Prospective trials are urgently needed to confirm these encouraging results found in retrospective analyses with 177Lu-PSMA-RLT in the treatment of mCRPC.

// Yvonne Maertens 1 , Verena Humberg 1 , Franziska Erlmeier 2 , Sandra Steffens 1 , Julie Steinestel 1 , Martin Bogemann 1 , Andres Jan Schrader 1 and Christof Bernemann 1 1 Clinic for Urology, University Hospital Muenster, Muenster, Germany 2 Institute for Pathology and Pathological Anatomy, Technical University Munich, Munich, Germany Correspondence to: Christof Bernemann, email: christof.bernemann@ukmuenster.de Keywords: clear cell renal cell carcinoma, circulating tumor cells, biomarker, liquid biopsy, genitourinary cancer Received: June 15, 2017 Accepted: August 25, 2017 Published: September 23, 2017 ABSTRACT Background: Analysis of circulating tumor cells (CTCs) has progressed in several tumor entities. However, little is known about CTCs in clear cell renal cell carcinoma (ccRCC) patients. Aim of our studies was to build a stable in vitro fundament for isolation of CTCs in ccRCC. Methods: We compared the analytical performance of different CTC isolation methods with regard to yield and purity: EpCAM based enrichment, leukocyte depletion and size based enrichment. EpCAM and cytokeratin 8 (KRT8) as biomarker for CTCs expression were evaluated in ccRCC cell lines as well as clinical samples. Results: While the EpCAM based approach failed to successfully isolate tumor cells, CD45 based approaches showed intermediate recovery rates. The cell-size based Parsortix system showed highest recovery rates. EpCAM expression was low or absent in most cell lines as well as in clinical samples, whereas KRT8 was detected as a potential biomarker in ccRCC. Conclusion: EpCAM based approaches might miss a high number of CTCs due to low or absent expression of EpCAM in ccRCC, as shown in cell lines as well as in patient samples. We identified the cell-sized based, label independent Parsortix system to be the most effective recovery system for ccRCC CTCs.

BACKGROUND Taxen-based chemotherapy has been established as an effective treatment option in castration-resistant metastatic prostate cancer (mCRPC). Randomized phase III studies, however, have shown that even in the hormone-naive metastatic state, the early use of chemotherapy in addition to the classical androgen deprivation therapy (ADT) approach leads to a significant increase in median overall survival. OBJECTIVE This position paper aims to provide current data and orientation in the evidence-based treatment of mPC patients in daily clinical practice. MATERIALS AND METHODS A German group of clinical experts analyzed the current data and developed criteria for the treatment of mPC patients in daily clinical practice. RESULTS In the current treatment of hormone-naive mPC, a beneficial effect of chemotherapy in addition to ADT has become evident. Provided patients are in an appropriate condition, those with a high metastatic load should receive chemotherapy in addition to ADT. Especially in high-risk mCRPC patients (PSA >114 ng/ml, visceral metastasis, ADT response

Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with 177Lu-PSMA-617. Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66–76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee. The 59 patients were treated with a total of 159 cycles (median 3 cycles, range 1–7) of 177Lu-PSMA-617 (median dose 6.11 GBq, IQR 5.9–6.3 GBq). The median follow-up was 24 weeks (IQR 15–36 weeks). Follow-up data for at least 12 weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32 weeks. An initial alkaline phosphatase (ALP) level

// Thomas J. Schnoeller 1 , Florian Jentzmik 1, 2 , Andres J. Schrader 3 and Julie Steinestel 3 1 Department of Urology, Ulm University Medical Center, Ulm, Germany 2 Department of Urology, St. Elisabeth Hospital, Ravensburg, Germany 3 Department of Urology, Muenster University Medical Center, Muenster, Germany Correspondence to: Julie Steinestel, email: Julie.steinestel@ukmuenster.com Keywords: prostate cancer, tumor biology, biomarker, cholesterol, statin therapy Received: February 13, 2017 Accepted: March 14, 2017 Published: April 07, 2017 ABSTRACT Both cholesterol levels and the use of statins have been described to influence the development and prognosis of prostate cancer (PC). In this retrospective, cross-sectional analysis of consecutive cases from a tertiary referral center we evaluated an association between hypercholesterolemia (≥5.0mmol/l), the use of statins, and advanced/aggressive PC in 767 men with histologically confirmed, clinically localized PC awaiting radical prostatectomy. We found that patients with HCE (n=287, 37.4%) had a significantly higher incidence of poorly differentiated PC (Gleason score ≥7b, 81.1% vs. 4.9%), advanced local tumor stage (≥pT3, 57.7% vs. 22.2%), and nodal involvement (19.8% vs. 1.6%). Multivariate logistic regression analysis identified hypercholesterolemia as a risk factor for aggressive and/or advanced PC (OR 2.01, p

Die S3-Leitlinie (Version Oktober 2014) gibt Empfehlungen zur Prostatakrebsfruherkennung. Wir untersuchten ihre Umsetzung in niedergelassenen urologischen Praxen im Regierungsbezirk Munster. Zur Datenerhebung wurde ausgehend von der COREQ-Checkliste („consolidated criteria for reporting qualitative research“) fur Fokusgruppen eine teilstandardisierte, qualitative Befragung mit 22 niedergelassenen Urologen aus dem Regierungsbezirk Munster in vier Fokusgruppen mit je 5–6 Befragten durchgefuhrt. Zu 12 Aussagen der Leitlinie im Abschnitt „Fruherkennung und Biopsie“ wurden 23 Fragen gestellt. Bei den Aussagen handelt es sich um 9 „starke Empfehlungen“, eine „offene Empfehlung“ und 2 „Statements“. Nach dem Mixed-methods-Design wurde mittels Haufigkeitsanalysen und Berechnung von Lage- und Streumasen ein Summenscore gebildet, um die Adharenz zur Leitlinie zu ermitteln. Die qualitative Inhaltsanalyse nach Mayring wurde zur qualitativen Auswertung genutzt. Die befragten Urologen befolgen 6 der 9 „starken Empfehlungen“, in 3 weichen sie ab. Inhaltlich beziehen sich diese Abweichungen auf: Aufklarung uber die Vor- und Nachteile der Fruherkennungsmasnahmen, Empfehlung einer Prostatabiopsie bei kontrolliertem PSA-Wert ≥4 ng/ml, Indikation zur Wiederholungsbiopsie. Weitere Abweichungen ergeben sich fur die „offene Empfehlung“ und die beiden „Statements“. Dem Grosteil der „starken Empfehlungen“ wird von den befragten Urologen im Regierungsbezirk Munster Folge geleistet. Inhaltlich relevante Abweichungen werden begrundet, so z. B. die nur bedingte Ubertragbarkeit des PSA-Grenzwertes von 4 ng/ml aus populationsbezogenen Reihenuntersuchungen asymptomatischer Manner auf die Klientel einer urologischen Praxis.

We evaluated the diagnostic value and accuracy of prostate-specific membrane antigen (PSMA) PET for the intraprostatic delineation of prostate cancer before prostatectomy. Methods: We identified 6 patients with biopsy-proven high-risk prostate cancer who were referred for 68Ga-PSMA PET/CT before radical prostatectomy to rule out metastasis. After prostatectomy, a histologic map of the prostate was reconstructed. The histologic extent and Gleason score of each segment of the prostate were compared with 68Ga-PSMA PET images resliced to the histologic axis. Sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratios were calculated. The SUV of each segment was measured, and median values were compared. Results: Of the 132 segments, 112 were eligible for analysis. The correlation of histologic results with 68Ga-PSMA PET images showed a specificity and sensitivity of 92%. The positive and negative likelihood ratio and the positive and negative predictive value for detection of prostate cancer on 68Ga-PSMA PET were 11.5, 0.09, 96%, and 85%, respectively. The median SUVmax of true-positive prostate segments was significantly higher than that of true-negative segments (11.0 ± 7.8 vs. 2.7 ± 0.9, P

Prostate Cancer (PCa) is an important age-related disease being the most common cancer malignancy and the second leading cause of cancer mortality in men in Western countries. Initially, PCa progression is androgen receptor (AR)- and androgen-dependent. Eventually advanced PCa reaches the stage of Castration-Resistant Prostate Cancer (CRPC), but remains dependent on AR, which indicates the importance of AR activity also for CRPC. Here, we discuss various pathways that influence the AR activity in CRPC, which indicates an adaptation of the AR signaling in PCa to overcome the treatment of PCa. The adaptation pathways include interferences of the normal regulation of the AR protein level, the expression of AR variants, the crosstalk of the AR with cytokine tyrosine kinases, the Src-Akt-, the MAPK-signaling pathways and AR corepressors. Furthermore, we summarize the current treatment options with regard to the underlying molecular basis of the common adaptation processes of AR signaling that may arise after the treatment with AR antagonists, androgen deprivation therapy (ADT) as well as for CRPC, and point towards novel therapeutic strategies. The understanding of individualized adaptation processes in PCa will lead to individualized treatment options in the future.

Programmed death-1 receptor (PD-1) and programmed death-1 receptor-ligand (PD-L1) have been suggested to play a role as prognostic markers in clear cell renal cell carcinoma (ccRCC). The association between PD-L1 and prognosis seems to be more robust than for PD-1. Further, preliminary analyses suggest that neither PD-1 nor its ligands play a role as prognostic markers in non-clear cell RCC, while the prognostic role of PD-L2 in ccRCC as well as in non-clear cell RCC remains unclear.

In the context of cancer immunotherapy, PD-1 as well as PD-L1 has been widely studied in renal cell carcinoma (RCC). PD-1 and PD-L1 play a significant role as prognostic markers in clear cell renal cell carcinoma. In contrast, little is known about PD-L2 expression patterns in RCC, especially in rarer subtypes. The aim of this study was to evaluate the prevalence, distribution and prognostic impact of PD-L2 expression in chromophobe (ch)RCC. Eighty-one patients who underwent renal surgery due to chRCC were retrospectively evaluated. Tumor specimens were analyzed for PD-L2 expression by immunohistochemistry. Expression data were associated with clinicopathological parameters and overall survival (OS). Twenty-three (28.4%) patients showed a PD-L2 > median (PD-L2 high) staining intensity. No significant association between clinicopathological parameters and PD-L2 expression was identified. A significant difference between 5- and 10-year OS in dependence of PD-L2 expression was found (PD-L2 low 96.4 and 87.7% vs. PD-L2 high 87.1 and 56%; log rank, p = 0.029). However, in multivariate analysis PD-L2 expression failed to be proofed as an independent prognostic factor. In conclusion, to our knowledge this is the first study evaluating the prognostic impact of PD-L2 in a considerably large cohort of chRCC. Our results showed a significant diminished OS in dependence of PD-L2 expression. This implicates that PD-L2 might play a role as prognostic marker in chRCC demanding further evaluation.

The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR) and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR 5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months) (HR: 1.6 (95%CI:0.9–2.8); p = 0.11). After multivariate adjustment (MVA), ECOG > 0–1, baseline LDH>upper limit of normal (UNL) and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months) (HR: 2.3 (95%CI:1.3–4.0); p < 0.01). In MVA, ECOG > 0–1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to 5, NLR-change to

Chromophobe renal cell carcinoma (chRCC) is the third most common subtype of RCC, after clear cell (ccRCC) and papillary RCC. Its lower incidence and frequent exclusion from clinical trials might be why chRCC characteristics have not been extensively studied. The aim of our study was to examine tumor characteristics and long-term prognosis of chRCC compared to ccRCC. We collected 4,210 evaluable patients subjected to surgery for chRCC (n = 176) or ccRCC (n = 4,034) at five centers in Germany (University Hospitals of Hannover, Homburg/Saar, Mainz, Ulm, and Marburg) between 1990 and 2010. Patients with chRCC were significantly younger (mean, 60.1 vs. 62.1 years) and tended to be more frequently female (43.8 vs. 36.5 %). Although Fuhrman grade and median tumor diameter were not significantly different, significantly fewer patients with chRCC than with ccRCC presented with high tumor stage or metastasis at diagnosis (18.5 vs. 43.8 %). Moreover, significantly more chRCC patients were treated with partial nephrectomy (41.5 vs. 26.2 %). Accordingly, 5-year cancer-specific survival (CSS) rates were 83.2 % for chRCC against 75.8 % for ccRCC patients (p = 0.014, log rank). However, in multivariate analysis, chromophobe subtype was not confirmed as a significant positive prognostic factor for RCC (HR 0.88, 95 % CI 0.63-1.24; p = 0.48 Cox regression). This is one of the largest studies to date showing that chRCC is associated with a significantly lower risk of locally invasive tumor growth and metastatic disease than ccRCC. We conclude that the clinical behavior of chRCC is less aggressive than that of ccRCC, independent of Fuhrman grade or tumor size.

Hintergrund Die Therapie maligner Hodentumore ist seit jeher durch ein hohes Mas an Radikalitat gekennzeichnet. Dank zahlreicher medizinischer Fortschritte haben sich die Heilungschancen von Hodentumorpatienten in den letzten Jahrzehnten deutlich verbessert. Mittlerweile liegen die Bestrebungen vornehmlich in einer Therapiereduktion, wodurch auch die Semikastratio als bislang einzig adaquate Therapie des Primartumors zunehmend zur Diskussion steht.

Die Urolithiasis stellt bei weltweit steigender Inzidenz eine zunehmende Belastung der Gesundheitssysteme dar. Die Ureterorenoskopie (URS) zur Steinextraktion gehort zu den Standardtherapieverfahren bei Harnleitersteinen. Um die Erfolgsrate der URS zu erhohen und die Zahl an Komplikationen zu reduzieren, wurde bereits in der Vergangenheit die praoperative Harnleiterschienung („Prestenting“) als adaquates Mittel beschrieben. Die Datenlage hierzu ist jedoch nach wie vor uneinheitlich. Die vorliegende Arbeit beschreibt monozentrisch den Einfluss des Prestenting auf Erfolgs- und Komplikationsraten der ureterorenoskopischen Steintherapie. Retrospektive Untersuchung anhand von 442 Patienten, bei denen in der Zeit von 2010–2011 im Klinikum Wolfsburg eine Steinextraktion mittels starrer URS erfolgte. Die statistische Analyse der erhobenen Daten erfolge mit Hilfe des exakten Tests nach Fisher, des χ2- und des Mann-Whitney-U-Tests. Obwohl jene Patientengruppe, die ein Prestenting erhalten hatte, signifikant grosere Steine aufwies und diese zudem haufiger proximal lokalisiert waren, war die Notwendigkeit intra-/postoperativer Harnleiterschienung sowie die Rate an perioperativen Komplikationen signifikant niedriger als in der Patientengruppe, die kein Prestenting erhalten hatte (p 5 mm aufwiesen. Entsprechend dieser retrospektiv erhobenen Daten ist Prestenting vor URS mit einer signifikant niedrigen Komplikationsrate und einer hoheren Steinfreiheitsrate assoziiert und fuhrte dazu, dass seltener die Indikation zu einer intra-/postoperativen Harnleiterschienung gestellt wurde bzw. werden musste.

Goldstandard zur Diagnosestellung und Therapie eines Harnblasentumors ist die transurethrale Resektion (TURB) mit konsekutiver histopathologischer Begutachtung. Ziel der Studie war es zu uberprufen, inwieweit der operierende Urologe den Befund bzgl. Dignitat und Stadium per Blickdiagnose richtig pradizieren kann. Dies ist u. a. entscheidend fur die mogliche Indikation einer Mitomycin-Fruhinstillationstherapie. Im Rahmen dieser prospektiven Untersuchung haben Urologen aus 5 deutschen Kliniken ihre Einschatzung zur Dignitat, dem Tumorstadium und der Tumordifferenzierung in 311 Fallen unmittelbar nach der TURB anhand eines einheitlichen Fragebogens dokumentiert. Die Sensitivitat der Einschatzung, dass es sich bei dem resezierten Befund um ein Malignom handelte, betrug 97 %, wohingegen die Spezifitat nur bei 41 % lag. Der positive (PPV) bzw. negative Vorhersagewert (NPV) betrugen 76 bzw. 88 %. Es wurden ebenfalls haufiger muskelinvasive Tumoren vermutet als histopathologisch bestatigt (PPV 52 %). Wurde eine Muskelinvasivitat nach makroskopischem Eindruck ausgeschlossen, so stimmte dies in der uberwiegenden Mehrzahl der Falle (NPV 95 %). Das Ausbildungsstadium der Operateure wirkte sich interessanterweise nicht auf den Vorhersagewert der Blickdiagnose aus. Insgesamt wird deutlich, dass makroskopisch im Rahmen einer TURB tumorsuspekte Urothelveranderungen durch den operierenden Urologen, unabhangig von seinem Ausbildungsstand, nicht sicher beurteilt werden konnen. Der Urologe bleibt zur weiteren Therapieplanung auf das sichere Urteil des Uropathologen angewiesen.

In 2006, the German Testicular Cancer Study Group initiated an extensive evidence-based national second-opinion network to improve the care of testicular cancer patients. The primary aims were to reflect the current state of testicular cancer treatment in Germany and to analyze the project’s effect on the quality of care delivered to testicular cancer patients. A freely available internet-based platform was developed for the exchange of data between the urologists seeking advice and the 31 second-opinion givers. After providing all data relevant to the primary treatment decision, urologists received a second opinion on their therapy plan within

Modern diagnostic ultrasound and cross-sectional imaging has enabled the detection of increasing numbers of renal tumours. The aim of this study was to investigate the tumour- and patient-specific characteristics and prognosis of small renal cell carcinomas (RCCs) after surgical resection.The study included 2197 patients who underwent surgical resection of histologically confirmed RCC ⩽ 4 cm between 1990 and 2011. Median (mean) follow-up was 56.2 (65.5) months.At the time of surgery, tumours were staged as pT ⩾ 3a in 175 (8.0%) cases, 134 (6.2%) were poorly differentiated and 75 (3.5%) were metastasised. The larger the tumour size, the higher was the risk of presenting with stage pT ⩾ 3a (p0.001), poor tumour differentiation (p = 0.004), microscopic vascular involvement (p = 0.001) and collecting system invasion (p = 0.03). The 5-year cancer-specific survival (CSS) rate was 93.8% for stage pT1a versus 79.4% for stage pT ⩾ 3a (p0.001), and it was 93.7% for G1-2 versus 76.8% for G3-4 differentiation (p0.001). Multivariate analysis identified age in years (hazard ratio (HR) 1.04, p0.001), metastatic disease (HR 12.5, p0.001), tumour differentiation (HR 2.8, p0.001) and non-clear cell histology (HR 0.51, p = 0.02) as independent prognosticators for CSS in patients with small RCC. Interestingly, the 5-year cancer-specific mortality rate for pT1a N/M0 patients was 5.8%.This large multicenter study has clearly shown that, though most small RCC have a low pathological stage and a good prognosis, there is also a small but significant subgroup of these tumours that are already locally advanced or poorly differentiated.

1494 Objectives: Striatal dopamine transporter (DAT) deficiency and abnormal expression of Parkinson’s disease (PD) related pattern (PDRP) have been observed in patients with idiopathic REM sleep behavior disorder (IRBD). But the relationship between the two distinct measures remains unclear. This study aimed to investigate the correlations between dopaminergic dysfunction and abnormal metabolic network activity in IRBD patients with comparison to PD using a dual tracer imaging design. Methods: A total of 37 IRBD patients, 86 PD patients (mild, HY moderate, HY advanced, H&Y4-5, 15 patients) and 15 control subjects matched in age underwent concurrent PET scans with 11C-CFT to quantify dopaminergic dysfunction and 18F-FDG to quantify PDRP expression. To perform the investigations further on a hemispheric basis, some scans (both 11C-CFT and 18F-FDG) were flipped so that all hemispheres more affected appeared on the right side of the brain. Differences in regional DAT binding and PDPR values among patient groups and normal controls were assessed by using one-way ANOVA with post hoc Bonferroni tests. The effect of the hemispheres and hemisphere × group interaction was evaluated by two-way ANOVA using a general linear model with repeated measures. Correlations between regional 11C-CFT uptake, network expression and UPDRS motor ratings (PD only) were evaluated using Pearson correlation coefficients. All analyses were performed using SPSS software and considered significant at p Results: IRBD patients were divided into two subgroups: those with relatively normal (IRBD-RN) or abnormal (IRBD-AB) striatal DAT binding. Significantly decreased striatal DAT binding and increased PDRP scores were present in all patient groups, except for IRBD-RN, relative to the controls. There was a significant effect of hemisphere and hemisphere × group interaction for striatal DAT binding but not for PDRP expression. Significant correlations were observed between DAT binding and PDRP expression in the IRBD-AB and PD groups but not in the IRBD-RN group. Conclusions: IRBD patients present with an intermediate state in striatal DAT distribution and PDRP activity between PD and normal controls. The modest correlations between the two measures in both IRBD and PD suggest differences in network activity that cannot be fully explained by nigrostriatal dopaminergic denervation.

Das Zweitmeinungsprojekt testikulare Keimzelltumoren ist eine internetbasierte Plattorm, welche sich an Primarbehandler von Hodentumorpatienten richtet. Sie ermoglicht die Einholung einer Zweitmeinung vor der weiteren Therapiefestlegung nach Orchiektomie und Durchfuhrung der Ausbreitungsdiagnostik. Die Plattform wurde mittlerweile mehr als 3 000 Mal in Anspruch genommen. Die zahlreichen Diskrepanzen von Erst- und Zweitmeinung in mehr als 30% der Falle sprechen fur ein bestehendes Defizit bei der Umsetzung von publizierten Therapieleitlinien. Die Zweitmeinungsplattform ist nach der aktuellen Zwischenbilanz in der Lage, Ubertherapie bei Hodentumorpatienten zu reduzieren. Die hohe Akzeptanz des Projektes und die ermutigenden Daten der Zwischenbilanz geben Anlass zu Uberlegungen, das Zweitmeinungsnetzwerk-Modell auch auf andere Erkrankungen, w. z. B. das Peniskarzinom, zu ubertragen.

Hintergrund Die Therapie des Seminoms im klinischen Stadium I ist einem steten Wandel unterworfen. Wurden Surveillance, adjuvante Strahlentherapie und adjuvante Chemotherapie bis vor wenigen Jahren als weitgehend gleichberechtigte Therapiealternativen angesehen, machen aktuell publizierte Studien eine differenziertere Betrachtungsweise notwendig.

Hintergrund Ubergewicht stellt ein wachsendes Problem in unserer Gesellschaft dar. Folglich steigt auch das Interesse, den Einfluss von Adipositas auf urologische Tumorerkrankungen zu verstehen.

A number of very interesting studies presented this year at the ASCO (American Society of Clinical Oncology) Annual Meeting, the ASCO-GU (ASCO Genitourinary Cancers) Spring Meeting, and the ESMO (European Society for Medical Oncology) Annual Congress could strongly influence or even revolutionize the systemic treatment of advanced renal cell carcinoma (RCC). The aim of this article is to identify, summarize and discuss some outstanding studies of direct or indirect clinical relevance for systemic therapy.

Die moderne Palliativmedizin geht in ihren Grundzugen auf die englische Krankenschwester und spatere Arztin Dame Cicely Mary Strode Saunders zuruck. Unter Palliativmedizin versteht man die multimodaltherapeutische Begleitung eines Patienten, bei dem eine kurative Behandlung nicht sinnvoll erscheint oder nicht zum gewunschten Erfolg gefuhrt hat. In diesem Artikel wird ein Uberblick uber die Palliativmedizin im Allgemeinen und die erweiterte medikamentose Therapie im Speziellen, insbesondere in der Sterbephase, geben.

Hintergrund Aufgrund geringerer Raten an postoperativer Niereninsuffizienz, Diabetes, kardiovaskularer Folgeerkrankungen und damit einem langeren Gesamtuberleben bei gleich langem tumorspezifischem Uberleben stellt die partielle Nephrektomie heute den Goldstandard in der Therapie des renalen Neoplasmas dar, inzwischen auch fur Tumore ≥ 4 cm. Die Hauptkomplikationen der nierenerhaltenden Chirurgie, insbesondere bei groseren und zentral liegenden Tumoren, sind die Nachblutung aus dem Parenchym sowie das Auftreten von Urinfisteln nach intraoperativer Eroffnung des Nierenbeckenkelchsystems (NBKS).

The purpose of this study was to evaluate the prognostic ability of early changes of total prostate specific antigen (tPSA), free PSA (fPSA), [−2]proPSA and the Prostate Health Index (PHI) following initiation of Abiraterone-therapy in men with castration resistant prostate cancer (mCRPC). In 25 patients, PSA-subforms were analyzed before and at 8–12 weeks under therapy as prognosticators of progression-free-survival (PFS) and overall survival (OS). Comparing patients with a PFS < vs. ≥12 months by using Mann–Whitney–Wilcoxon Tests, the relative-median-change of tPSA (−0.1% vs. −86.8%; p = 0.02), fPSA (12.1% vs. −55.3%; p = 0.03) and [−2]proPSA (8.1% vs. −59.3%; p = 0.05) differed significantly. For men with ≤ vs. >15 months of OS there was a non-significant trend for a difference in the relative-median-change of fPSA (17.0% vs. −46.3%; p = 0.06). In Kaplan–Meier analyses, declining fPSA and [−2]proPSA were associated with a longer median PFS (13 months, 95% confidence interval (CI): 9.6–16.4 vs. 10 months, 95% CI: 3.5–16.5; p = 0.11), respectively. Correspondingly, decreasing fPSA and [−2]proPSA values indicated an OS of 32 months (95% CI: not reached (NR)) compared to 21 months in men with rising values (95% CI: 7.7–34.3; p = 0.14), respectively. We concluded that the addition of fPSA- and [−2]proPSA-changes to tPSA-information might be further studied as potential markers of early Abiraterone response in mCRPC patients.

Objective Even though the exact mechanism is largely unknown until now, statins are supposed to improve survival outcomes in various malignancies. For prostate cancer however, statins are known to compete with dehydroepiandrosterone (DHEAS) for the transport into the cytosol both using the cell by the Solute Carrier Transporter and thus diminish the cellular uptake of DHEAS as a precursor of androgens. Abiraterone inhibits CYP17A1 and thus effectively decreases the production of all relevant androgens including DHEAS. In this study we examined whether statins still affect survival outcome in patients with metastatic castration resistant prostate cancer (mCRPC) when treated with Abiraterone. Patients and Methods 108 men with mCRPC treated with Abiraterone from 02/2010 to 07/2015 with (n = 21) or without (n = 87) concomitant treatment with statins were investigated. Progression free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier-estimates and univariate Cox-regression analysis. The influence on best clinical benefit under Abiraterone treatment was analyzed with bivariate and multivariate logistic regression analysis. Results PSA-decline ≥ 50% was not significantly different in both groups (57 vs. 53%; p = 0.73). The median PFS (9 vs. 10 months; p = 0.97) and OS (14 vs. 18 months; p = 0.77) did not differ significantly between those men treated with and without concomitant statin therapy, respectively. Accordingly, there was no improvement for best clinical benefit in patients using statins (odds ratio: 1.2 (CI: 0.4–4.2); p = 0.76). Conclusion Use of statins as concomitant medication did not improve survival outcomes or best clinical benefit in men with mCRPC treated with Abiraterone.