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Background Although multiparametric magnetic resonance imaging (mpMRI) is recommended for primary risk stratification and follow-up in Active Surveillance (AS), it is not part of common AS inclusion criteria. The objective was to compare AS eligibility by systematic biopsy (SB) and combined MRI-targeted (MRI-TB) and SB within real-world data using current AS guidelines. Methods A retrospective multicenter study was conducted by a German prostate cancer (PCa) working group representing six tertiary referral centers and one outpatient practice. Men with PCa and at least one MRI-visible lesion according to Prostate Imaging Reporting and Data System (PI-RADS) v2 were included. Twenty different AS inclusion criteria of international guidelines were applied to calculate AS eligibility using either a SB or a combined MRI-TB and SB. Reasons for AS exclusion were assessed. Results Of 1941 patients with PCa, per guideline, 583–1112 patients with PCa in both MRI-TB and SB were available for analysis. Using SB, a median of 22.1% (range 6.4–72.4%) were eligible for AS. Using the combined approach, a median of 15% (range 1.7–68.3%) were eligible for AS. Addition of MRI-TB led to a 32.1% reduction of suitable patients. Besides Gleason Score upgrading, the maximum number of positive cores were the most frequent exclusion criterion. Variability in MRI and biopsy protocols potentially limit the results. Conclusions Only a moderate number of patients with PCa can be monitored by AS to defer active treatment using current guidelines for inclusion in a real-world setting. By an additional MRI-TB, this number is markedly reduced. These results underline the need for a contemporary adjustment of AS inclusion criteria.

Purpose EAU guidelines recommend multiparametric MRI of the prostate (mpMRI) prior to biopsy to increase accuracy and reduce biopsies. Whether biopsy can be avoided in case of negative mpMRI remains unclear. Aim of this study is to evaluate predictors of overall prostate cancer (PCa) in negative mpMRI. Methods A total of 216 patients from 2018 to 2020 with suspicion of PCa and negative mpMRI (PI-RADS ≤ 2) were interviewed by telephone about outcome and further follow-up. Clinically significant PCa (csPCa) was defined as ISUP ≥ 2. Patients with vs. without biopsy and with vs. without PCa were compared. Univariate and multivariate analyses were performed to evaluate predictors of PCa occurrence in patients with negative mpMRI. Results 15.7% and 5.1% of patients with PI-RADS ≤ 2 on mpMRI showed PCa and csPCa, respectively. PCa patients had higher PSAD (0.14 vs. 0.09 ng/ml2; p = 0.001) and lower prostate volume (50.5 vs. 74.0 ml; p = 0.003). Patients without biopsy (25%) after MRI were older (69 vs. 65.5 years; p = 0.027), showed lower PSA (5.7 vs. 6.73 ng/ml; p = 0.033) and lower PSA density (0.09 vs. 0.1 ng/ml2; p = 0.027). Multivariate analysis revealed age (OR 1.09 [1.02–1.16]; p = 0.011), prostate volume (OR 0.982 [0.065; 0.997]; p = 0.027), total PSA level (OR 1.22 [1.01–1.47], p = 0.033), free PSA (OR 0.431 [0.177; 0.927]; p = 0.049) and no PI-RADS lesion vs PI-RADS 1–2 lesion (OR 0.38 [0.15–0.91], p = 0.032.) as predictive factors for the endpoint presence of PCa. Conclusions Biopsy for selected patient groups (higher age, prostate volume and free PSA as well as lower PSA-Density) with negative mpMRI can be avoided, if sufficient follow-up care is guaranteed. Detailed counseling regarding residual risk for undetected prostate cancer should be mandatory.

Purpose: Focal therapy (FT) became a frequently discussed treatment strategy of localized prostate cancer (PCa), but the acceptance and evaluation of FT by practicing urologists are still unclear. ...

Since multiple oncological treatment options in metastatic castration-resistant prostate cancer (mCRPC) are available, optimal sequencing of therapies are under investigation. However, the efficacy of Cabazitaxel (CAB) in fourth and later lines of therapy is rarely investigated.Fifty three patients with mCRPC treated with CAB in fourth line or later were included in our retrospective study, which involved eight uro-oncology centers in Germany. Clinical and tumor characteristics, as well as PSA-response rates were analyzed. Kaplan-Meier plots addressed overall survival (OS) and progression-free survival (PFS). Logistic regression models predicted risk factors of overall mortality (OM).Of 53 patients, 79% (n=42), 19% (n=10) and 2% (n=1) received CAB in fourth, fifth and sixth line. A median of 4 cycles of CAB were administered. Median PSA at start of CAB was 199ng/ml (interquartile range (IQR) 70-869). In total, 89% had bone and 40% visceral metastases prior to the start of CAB. Moreover, 30% of patients received Docetaxel in first line therapy for mCRPC. Most frequent sequence of therapy was abiraterone followed by docetaxel and followed by enzalutamide. Overall, median PSA-response rate was -20% (IQR -80 to +10%). Patients with docetaxel in first line had a significantly better median PSA-response on CAB (-80 vs. 20%, P=0.03). Median OS, radiographic PFS and overall PFS were 14.8 (Confidence interval (CI): 11.0-20.8), 3.0 (CI: 2.9-4.0) and 2.9 (CI: 2.0-3.3) months, respectively. In multivariable analyses, visceral metastases, PSA100ng/ml, ISUP4+5 and later administration of Docetaxel were predictors of OM.Real-world experiences indicate that favorable oncologic outcomes can be achieved with CAB especially regarding PSA-response and OS even in the fourth line or later in patients with mCRPC.

Radical cystectomy (RC) has a high morbidity and leads to a significant socio-economic burden. We aimed to investigate pre-, intra-, and post-operative variables to create a novel score predicting both post-operative clinical (complications) and economic (length of hospital stay) outcome after RC. We retrospectively evaluated clinical and histopathological data of 317 patients after RC. We performed univariate and multivariate logistic regression analyses to identify variables associated with post-operative clinical (30-day morbidity according to Clavien–Dindo complications) and economic (length of hospital stay) outcome. In multivariate analysis, a high number of intraoperative transfusions (T) of packed red blood cells predicted major complications (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.10–2.58, p = 0.017), preoperative potassium (P) level predicted three or more complications (OR for high preoperative potassium 0.71, 95% CI 0.52–0.98, p = 0.037), and high drain (D) loss on post-operative day 1 predicted a longer hospital stay ≥ 22 days (OR 1.57, 95% CI 1.04–2.35, p = 0.003). The PT2D-Score was able to predict three or more complications (area under the curve: 0.70, 95% CI 0.61–0.78, p

The extent of variation in urinary and sexual functional outcomes after radical prostatectomy (RPE) between prostate cancer (PC) operating sites remains unknown. Therefore, this analysis aims to compare casemix-adjusted functional outcomes (EPIC-26 scores incontinence, irritative/obstructive function and sexual function) between operating sites 12 months after RPE.Analysis of a cohort of 7065 men treated with RPE at 88 operating sites (prostate cancer centers, "PCCs") between 2016 and 2019. Patients completed EPIC-26 and sociodemographic information surveys at baseline and 12 months after RPE. Survey data were linked to clinical data. EPIC-26 domain scores at 12 months after RPE were adjusted for relevant confounders (including baseline domain score, clinical and sociodemographic information) using regression analysis. Differences between sites were described using minimal important differences (MIDs) and interquartile ranges (IQR). The effects of casemix adjustment on the score results were described using Cohen's d and MIDs.Adjusted domain scores at 12 months varied between sites, with IQRs of 66-78 (incontinence), 89-92 (irritative/obstructive function), and 20-29 (sexual function). Changes in domain scores after casemix adjustment for sites ≥ 1 MID were noted for the incontinence domain (six sites). Cohen's d ranged between - 0.07 (incontinence) and - 0.2 (sexual function), indicating a small to medium effect of casemix adjustment.Variation between sites was greatest in the incontinence and sexual function domains for RPE patients. Future research will need to identify the factors contributing to this variation.The study is registered at the German Clinical Trial Registry ( https://www.drks.de/drks_web/ ) with the following ID: DRKS00010774.

Background: The aim of the present study is to analyze the efficacy of 68Gallium (Ga)-PSMA-11 PET/CT for detecting and localizing recurrent prostate carcinoma (PC) in patients with different prostate-specific antigen (PSA), PSA velocity (PSAvel) and doubling time (PSAdt). Results: The PR of 68Ga-PSMA-11 PET/CT showed a positive relationship with PSA levels. Even at restaging PSA-values (PSAV) of lower than 0.2 ng/ml, PR was 41%. For PSAV of 0.2-5 ng/ml/y. No significant association was found for PSAdt. Methods: PET/CT scans of 660 patients with biochemical recurrence (BCR) after primary therapy of PC were included in the analysis. We correlated serum PSA levels, measured at the time of imaging with PSMA PET/CT-positivity rates (PR) as well as PSAvel (in 225 patients) and PSAdt (660 patients). Additionally we compared the incidence of localized disease to metastases as related to these PSA-biomarkers. Conclusion: We have shown, in a large cohort of patients, that 68Ga-PSMA-11 PET/CT is a sensitive tool for restaging PC and has a high detection efficacy, even in patients with very low PSA levels (

Purpose Open simple prostatectomy (OSP) is a standard surgical technique for patients with benign prostatic hyperplasia with prostate size larger than 80 ml. As a minimally invasive approach, robot-assisted simple prostatectomy (RASP) emerged as a feasible surgical alternative. Currently, there are no definite recommendations for the standard use of RASP. Therefore, we aimed at investigating various clinical outcomes comparing RASP with OSP. Methods In this retrospective single-center study, we evaluated clinical data from 103 RASP and 31 OSP patients. Both cohorts were compared regarding different clinical characteristics with and without propensity score matching. To detect independent predictive factors for clinical outcomes, multivariate logistic regression analysis was performed. Results Robot-assisted simple prostatectomy patients demonstrated a lower estimated blood loss and need for postoperative blood transfusions as well as less postoperative complications. OSP had a shorter operative time (125 min vs. 182 min) longer hospital stay (11 days vs. 9 days) and longer time to catheter removal (8 days vs. 6 days). In the multivariate analysis, RASP was identified as an independent predictor for longer operative time, lower estimated blood loss, shorter length of hospital stay, shorter time to catheter removal, less postoperative complications and blood transfusions. Conclusion Robot-assisted simple prostatectomy is a safe alternative to OSP with less perioperative and postoperative morbidity. Whether OSP (shorter operative time) or RASP (shorter length of hospital stay) has a more favorable economic impact depends on the particular conditions of different health care systems. Further prospective comparative research is warranted to define the value of RASP in the current surgical management of benign prostatic hyperplasia.

Introduction & Objectives: In this study, we investigated the safety of robotic surgery during the pandemic period concerning new-acquired COVID-19 infections for both patients, assessed by follow-up telephone interview, and healthcare workers, assessed by swab tests on SARS-CoV-2. Materials & Methods: We performed a retrospective single-centre cohort study of patients undergoing robotic surgery in the initial 2-months period of COVID-19 focusing on safety. Patients’ COVID-19 infection status was assessed by telephone follow-up at a minimum of 14 days (median: 48) after robotic surgery. All healthcare workers involved in robotic surgery including console surgeons, bedside surgeons, anesthetists, scrub nurses and anesthesia nurses were investigated for presence of SARS-CoV-2 in nasopharyngeal swabs at three different time points during the study period from 12 March to 11 May 2020. Results: After 61 robotic surgeries, 1 patient (1.6%) had a COVID-19 infection. 60 healthcare workers (4 console surgeons, 8 bedside surgeons, 21 anesthetists, 13 scrub nurses and 14 anesthesia nurses) that were cumulatively exposed to 1,187 hours of robotic surgery had no COVID-19 infection. One patient with proof of SARS-CoV-2 on postoperative day two after radical prostatectomy had complete recovery without need for ventilation. After this potentially contagious robotic surgery, 8 healthcare workers with direct patient contact had no COVID-19 infection after 2 weeks and follow-up with each 3 nasopharyngeal swabs. Conclusions: Early clinical experience of robotic surgery during COVID-19 pandemic on 61 patients shows that robotic surgery can be safely performed for both patients and healthcare workers. In particular, there was no COVID-19 infection among 8 healthcare workers with direct contact during potentially contagious robotic surgery on a patient for whom COVID-19 infection was proven two days after surgery.

Introduction Overdiagnosis and overtherapy in prostate cancer (PCa) treatment should be avoided, which has led to an awareness of the need to decrease treatment in cases of low-risk PCa with radical prostatectomy (RP). Simultaneously, prostate-specific antigen testing has become less popular in the last few years, which has resulted in higher cancer grade and stage at diagnosis. We evaluated stage and grade migration in the disease of patients treated with RP in a large German cohort. Patients and Methods Overall, 4842 patients undergoing RP between 2000 and 2019 were included. Age, prostate-specific antigen level, biopsy, and pathologic Gleason score as well as clinical and pathologic stage were collected. D’Amico risk groups and Gleason score were evaluated over different time points. Results We detected a significant grade migration toward higher grade. The proportion of biopsy Gleason sum ≤ 6 dropped from 45.8% to 20.6% between ≤ 2010 and 2017-2019. Further, the proportion of patients with low D’Amico risk scores also decreased by almost 50% (20.8% vs 12.2%). Finally, the proportion of non–organ-confined PCa increased over time, and the proportion of postoperative Gleason sum ≤ 6 decreased from 20% to 10% over time. Conclusion Taken together, data indicate a significant preoperative grade and stage migration toward disease of higher grade in RP-treated PCa. Between the years 2000 and 2019, the proportion of biopsy Gleason sum ≤ 6 and the proportions of D’Amico low risk disease decreased by approximately 50% (respectively, 45% to 20% and 20.8% to 12.2%). This might indicate better patient selection for RP, but might also be a telltale sign of the rising mortality and morbidity of PCa.

Focal therapy (FT) with its favorable side-effect profile represents an option between active surveillance and traditional whole-gland treatment in localized prostate cancer (PCa). Consensus statements recommend eligibility criteria based on magnetic resonance imaging (MRI)-targeted and systematic combination biopsy.To estimate the future potential of FT by analyzing the number of men eligible for FT among all men with biopsy-proven PCa and to judge the potential of different energy sources.Consensus criteria on FT were analyzed. Patients with biopsy-proven PCa from six tertiary referral hospitals and one outpatient practice in Germany had received a software-based combination biopsy. Men with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 lesions based on PI-RADS v2 were included.Patients were analyzed for potential treatment by FT and hemiablation. MRI lesions were mapped according to prostatic zones.In total, 2371 patients were analyzed. According to consensus criteria (biopsy-proven unifocal lesion of International Society of Urological Pathology [ISUP] grade group ≤2, prostate-specific antigen [PSA] ≤15ng/mL, and life expectancy10yr), 303 patients (12.8%; ISUP 1: n=148 [6.2%]; ISUP 2: n=155 [6.5%]) were potential candidates for FT. A maximum PSA level of10ng/mL would exclude further 60 (2.5%) of these men. The eligibility for hemiablation is slightly higher (16.2%). Unifocal lesions (n=288) were equally distributed within the prostate (anteriorly [31%], apically [29%], and dorsally [36%]).With adherence to consensus statements, only a minority of PCa patients present as potential candidates for FT. Distribution of tumor localization suggests the need for different energy modalities to warrant an optimal FT treatment.We analyzed how many men who receive a magnetic resonance imaging-targeted and systematic prostate biopsy are candidates for the experimental focal therapy of the prostate. When following expert recommendations, only a small number of men are potential candidates for this alternative treatment.

Objectives While the coronavirus disease 2019 (COVID-19) pandemic captures healthcare resources worldwide, data on the impact of prioritization strategies in urology during pandemic are absent. We aimed to quantitatively assess the global change in surgical and oncological clinical practice in the early COVID-19 pandemic. Methods In this cross-sectional observational study, we designed a 12-item online survey on the global effects of the COVID-19 pandemic on clinical practice in urology. Demographic survey data, change of clinical practice, current performance of procedures, and current commencement of treatment for 5 conditions in medical urological oncology were evaluated. Results 235 urologists from 44 countries responded. Out of them, 93% indicated a change of clinical practice due to COVID-19. In a 4-tiered surgery down-escalation scheme, 44% reported to make first cancellations, 23% secondary cancellations, 20% last cancellations and 13% emergency cases only. Oncological surgeries had low cancellation rates (%): transurethral resection of bladder tumor (27%), radical cystectomy (21–24%), nephroureterectomy (21%), radical nephrectomy (18%), and radical orchiectomy (8%). (Neo)adjuvant/palliative treatment is currently not started by more than half of the urologists. COVID-19 high-risk-countries had higher total cancellation rates for non-oncological procedures (78% vs. 68%, p = 0.01) and were performing oncological treatment for metastatic diseases at a lower rate (35% vs. 48%, p = 0.02). Conclusion The COVID-19 pandemic has affected clinical practice of 93% of urologists worldwide. The impact of implementing surgical prioritization protocols with moderate cancellation rates for oncological surgeries and delay or reduction in (neo)adjuvant/palliative treatment will have to be evaluated after the pandemic.

The current coronavirus disease 2019 (COVID-19) pandemic has placed considerable strain on hospital resources. We explored whether telemedicine (defined as a videoconference) might help. We undertook prospective structured phone interviews of urological patients (n = 399). We evaluated their suitability for telemedicine (judged by a panel of four physicians) and their risks from COVID-19 (10 factors for a poor outcome), and collected willingness for telemedicine and demographic data. Risk factors for an adverse outcome from COVID-19 infection were common (94.5% had one or more) and most patients (63.2%) were judged suitable for telemedicine. When asked, 84.7% of patients wished for a telemedical rather than a face-to-face consultation. Those favouring telemedicine were younger (68 [58-75] vs 76 [70-79.2] yr, p < 0.001). There was no difference in preference with oncological (mean 86%) or benign diagnoses (mean 85%), or with COVID-19 risks factors. In subgroup analysis, men with prostate cancer preferred telemedicine (odds ratio: 2.93 [1.07-8.03], p = 0.037). We concluded that many urological patients have risk factors for a poor outcome from COVID-19 and most preferred telemedicine consultations at this time. This appears to be a solution to offer contact-free continuity of care. PATIENT SUMMARY: Risk factors for a severe course of coronavirus disease 2019 are common (94.5%) in urology patients. Most patients wished for a telemedical consultation (84.7%). This appears to be a solution to offer contact-free continuity of care.

INTRODUCTION Prostate cancer is the most common urological tumour disease in men. In the localized tumour stage in combination with radiotherapy and especially in advanced metastastic disease, classical androgen deprivation remains an essential therapy. During the last 10 years, our knowledge of the cardiovascular risk of this therapy has rapidly increased. MATERIAL AND METHODS This non-systematic review highlights the current data on cardiovascular risk in the use of androgen deprivation therapy in prostate cancer. RESULTS Essential publications about the cardiovascular risk of antihormonal therapy are summarised in detail. In particular, the current data on the potential cardiovascular benefit when using GnRH antagonists in androgen deprivation are discussed. The article further highlights the problem of today's antihormonal overtreatment, despite the lack of scientific evidence and points out that patient selection should be improved in the future. CONCLUSION The multicentre prospective PRONOUNCE study has been designed to answer the question in more detail, as to whether GnRH antagonist therapy provides benefit with respect to the cardiovascular risk as compared to classical LHRH analogue androgen deprivation therapy.

The purpose of this study is to analyze clinical outcomes and costs of single-use flexible ureterorenoscopes in comparison with reusable flexible ureterorenoscopes in a tertiary referral center. Prospectively, 68 flexible ureterorenoscopies utilizing reusable (Flex-X2S, Flex-XC, Karl Storz) and 68 applying single-use flexible ureterorenoscopes (LithoVue, Boston Scientific) were collected. Clinical outcome parameters such as overall success rate, complication rates according to Clavien-Dindo, operation time and radiation exposure time were measured. Cost analysis was based on purchase costs and recurrent costs for repair and reprocessing divided by number of procedures. In each group 68 procedures were available for evaluation. In 91% of reusable and 88% of single-use ureterorenoscopies stone disease was treated with a mean stone burden of 101 ± 226 and 90 ± 244 mm2 and lower pole involvement in 47 and 41%, respectively (p > 0.05). Comparing clinical outcomes of reusable vs. single-use instruments revealed no significant difference for overall success rates (81 vs. 87%), stone-free rates (82 vs. 85%), operation time (76.2 ± 46.8 vs. 76.8 ± 40.2 min), radiation exposure time (3.83 ± 3.15 vs. 3.93 ± 4.43 min) and complication rates (7 vs. 17%) (p > 0.05). A wide range of repair and purchase costs resulted in total to $1212-$1743 per procedure for reusable ureterorenoscopy whereas price of single-use ureterorenoscopy was $1300-$3180 per procedure. The current work provided evidence for equal clinical effectiveness of reusable and single-use flexible ureterorenoscopes. Partially overlapping ranges of costs for single-use and reusable scopes stress the importance to precisely know the expenses and caseload when negotiating purchase prices, repair prices and warranty conditions.

Introduction Treatment strategy for inoperable and metastatic urothelial carcinoma (mUC) has been revolutionized by the introduction of programmed cell death protein 1 (PD-1) and programmed cell death protein ligand (PD-L1) antibodies. During the last 3 decades treatment options were limited to chemotherapy, making further treatment of patients whose disease progressed under ongoing therapy or who were ineligible to receive cytotoxic therapy in the first place, nearly impossible. Evidence acquisition Five antibodies including pembrolizumab (PD-L1 antibody), atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab (PD-L1 antibodies) have been approved in the treatment of advanced urothelial carcinoma in first- and second-line treatment setting. The objective of this review was to examine and compare the different cohorts and to discuss the quality of the respective studies in order to set up selection criteria for clinical decision making. Evidence synthesis So far pembrolizumab and atezolizumab have demonstrated overall survival (OS) benefit in phase II studies and have shown superiority over standard chemotherapy in phase III studies which has granted them approval in first and second-line treatment setting. Improved OS and durable responses were also seen in phase Ib/II non-randomized, single-arm trials conducted with nivolumab, avelumab and durvalumab and granting accelerated approval for second-line treatment. The huge advantage of immunotherapy and one of the reasons for its overall recognition is its good tolerability profile especially in comparison to chemotherapy. Conclusions Pembrolizumab has to be recommended in second-line therapy due to reporting in a phase III trial and OS survival benefit compared to chemotherapy control group. In cisplatin-eligible and treatment-naive patients with visceral or liver metastases data also slightly favors pembrolizumab rather than atezolizumab.

To compare toxicity and response of docetaxel chemotherapy between metastatic hormone-sensitive prostate cancer (mHSPC) and castration-resistant metastatic prostate cancer (mCRPC) patients of the same therapeutic era for assessing of upfront docetaxel against the benchmark of docetaxel in the castrate resistant stage in the setting outside of clinical trials.A prospectively collected database of real-world prostate cancer patients receiving docetaxel was divided in mHSPC and mCRPC cases and retrospectively analyzed. Principal objectives were toxicity measured by the common criteria of adverse events terminology and response characterized by Prostate specific antigen decline and radiographic progression-free disease at restaging. The prognostic value of suspected variables for grade 3 to 5 toxicity and response was investigated by logistic regression analysis.Of 72 patients 34 (47%) were treated for mHSPC and 38 (53%) for mCRPC. Patients with mCRPC were older and had worse performance status (P0.01). In mHSPC total number of grade 3 to 5 adverse events (24, median 0, interquartile range 0-1) was significantly less than in mCRPC (46, median 1, interquartile range 1-2) (P = 0.01). Multivariable analysis revealed age as independent predictive variable for grade 3 to 5 toxicity (P = 0.03) but not disease stage, Prostate specific antigen predocetaxel, volume of disease, and Eastern Cooperative Oncology Group performance status (P0.05). Objective response was significantly higher in mHSPC compared to mCRPC patients (P0.01). Multivariable analysis confirmed mHSPC stage as independent prognostic factor for radiographic progression free disease at restaging (P0.01).The association of age with toxicity and of mHSPC stage with response resulted in significantly fewer grade 3 to 5 adverse events but higher response rates for upfront docetaxel in mHSPC compared with docetaxel in the later mCRPC stage.

Introduction/Background Currently, 7 agents are approved for the first- and second-line therapy for metastatic renal cell carcinoma. In contrast, data supporting their use beyond second line are limited. Here we summarize our experience in patients treated with more than 4 lines of therapy. Methods We retrospectively assessed the outcome of 24 patients treated at our institution with at least 4 lines of therapy. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates. Results Median OS from the initiation of first-line therapy for the whole cohort is 64.7 months. Up to 96% of the patients received a tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor (mTOR-I) within the first 3 lines of treatment. In the fourth or following lines, patients were treated with TKI, mTOR-I, bevacizumab/interferon, or experimental drugs. Seven patients continued treatment with a sixth-line agent; one has been treated up to the ninth line. Sixteen percent of the patients receiving fourth-line therapy and 13% receiving fifth-line therapy experienced a partial remission, which was independent from response to previous therapies. Median OS from fourth and fifth line was 30.8 and 26.2 months, respectively. Median PFS for fourth-line therapy was 5.8 months. No significant difference in PFS was observed for patients with disease that responded or did not respond to first-line therapy. Conclusion Despite the limitations of a retrospective analysis, our study suggests that selected patients benefit from multiple lines of treatment, independent of response to first-line therapy. However, the optimal sequence of treatment with regard to later lines remains to be determined.

For rare cancers such as neuroendocrine bladder cancer treatment options are limited due partly to the lack of preclinical models. Techniques to amplify rare primary neuroendocrine bladder cancer cells could provide novel tools for the discovery of drug and diagnostic targets. We developed preclinical experimental models for neuroendocrine bladder cancer.Fresh tumor tissue from 2 patients with neuroendocrine bladder cancer was used to establish in vitro and in vivo models. We analyzed additional archived tissues in the National Center of Tumor Diseases tissue bank from patients with neuroendocrine bladder cancer. Primary tumor samples were collected during radical cystectomy. PHA-665752 was used to inhibit MET in animal models and cell cultures. The expression of markers and drug targets in neuroendocrine bladder cancer was determined by flow cytometry. The growth of neuroendocrine bladder cancer in vitro was determined by counting live cells. Tumor growth in mice was assessed by measuring tumor volume. Groups were compared using the nonparametric Kruskal-Wallis test.Xenograft models and serum-free cultures of neuroendocrine bladder cancer cells allowed screening for cell surface markers and drug targets. We found expression of the HGF receptor MET in neuroendocrine bladder cancer cultures, xenograft models and primary patient sections. The growth of neuroendocrine bladder cancer spheroids in vitro depended critically on HGF. Treatment of neuroendocrine bladder cancer bearing mice with a MET inhibitor significantly decreased tumor growth compared to that in control treated mice.Neuroendocrine bladder cancer xenografts and serum-free cultures provided suitable models in which to identify diagnostic markers and therapeutic targets. Using the models, we noted HGF dependent growth of human neuroendocrine bladder cancer and identified MET as a new treatment target for neuroendocrine bladder cancer.

Bladder cancer (UCB) staged pT4a show heterogeneous outcome after radical cystectomy (RC). No risk model has been established to date. Despite gender-specific differences, no comparative studies exist for this tumor stage.Cancer-specific survival (CSS) of 245 UCB patients without neoadjuvant chemotherapy staged pT4a, pN0-2, M0 after RC were analyzed in a retrospective multi-center study. Seventeen patients were excluded from further analysis due to carcinoma in situ (CIS) of the prostatic urethra and/or positive surgical margins. Average follow-up period was 30 months (IQR: 14-45). The influence of different clinical and histopathologic variables on CSS was determined through uni- and multivariate Cox regression analyses. Two risk groups were generated using factors with independent effect in multivariate models. Internal validity of the prediction model was evaluated by bootstrapping.Eighty-four percent of the patients (n = 192) were male; 72% (n = 165) showed lymphovascular invasion (LVI). The 5-year CSS rate was 31%, and significantly different between male and female (35% vs. 15%, P = 0.003). Multivariate Cox regression modeling, female gender (HR = 1.83, P = 0.008), LVI (HR = 1.92, P = 0.005), and absence of adjuvant chemotherapy (HR = 0.61, P = 0.020) significantly worsened CSS. Two risk groups were generated using these 3 criteria, which differed significantly between each other in CSS (5-year-CSS: 46% vs. 12%, P0.001). The c-index value of the risk model was 0.61 (95% CI: 0.53-0.68, P0.001).Prognosis in UCB staged pT4a is heterogeneous. Female gender and LVI are adverse factors. Adjuvant chemotherapy seems to improve outcome. The present analysis establishes the first risk model for this demanding tumor stage.

Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.

Objective To describe the prevalence of incidental prostate cancer in patients undergoing radical cystoprostatectomy for bladder malignancy; to quantify the association between incidental prostate cancer and mortality in these patients; and to quantify the association between incidental prostate cancer and age in radical cystoprostatectomy specimens. Methods Consecutive patients undergoing radical cystoprostatectomy for bladder malignancy at six academic institutions were assessed. End-points were the histological diagnosis of prostate cancer in the radical cystoprostatectomy specimens and mortality. The association between incidental prostate cancer and mortality was calculated by multivariable Cox regression, and the association between age and the occurrence of prostate cancer was calculated by logistic regression. Results A total of 1122 patients (aged 65.6 ± 10 years) were included in this analysis. Prostate cancer was detected in 17.8% (n = 200) of the cystoprostatectomy specimens. After multivariable adjustment, prostate cancer was significantly associated with mortality (hazard ratio 1.27, 95% confidence interval 1.03–1.56). There was a significant association between age and the presence of prostate cancer in the cystoprostatectomy specimen. The odds ratio for the presence of prostate cancer was 1.028 (95% confidence interval 1.011–1.045; P

OBJECTIVE •To evaluate the characteristics and long-term outcome of patients with pT0 stage after radical cystectomy (RC) for urothelial carcinoma of the urinary bladder (UCB). PATIENTS AND METHODS •Clinical and pathological records of 2403 patients treated with RC for UCB were collected in a multi-institutional database. •The patients met the following criteria: clinical tumour stage cTa-cT2, cN0, cM0, no neoadjuvant chemotherapy or radiotherapy. •Overall (OS) and cancer-specific survival rates (CSS) were calculated for the various clinical tumour stages in relation to their corresponding pathological tumour stage in the RC sample. •Further to this, a multivariable prediction model was developed based on the available clinical data to estimate the probability of tumour stage pT0. RESULTS •The mean follow-up was 53 months and 132 patients (5.5%) were stage pT0. •Patients with stage cT2-pT0 had a 5-year CSS of 87% vs 69% for cT2-pT2 (P= 0.012) and 57% for cT2-pT+ (P < 0.001). •In a multivariable Cox-model, stage pT0 led to a significant reduction of cancer-specific mortality (hazard ratio0.27; 95% confidence interval 0.12-0.61). •A logistical regression model identified clinical tumour stage (advantage for non-invasive stages) and transurethral resection of the urinary bladder (TURB) time frame (advantage for more recent surgery) as independent predictors for stage pT0. CONCLUSIONS •In muscle-invasive clinical tumour stages, patients with pathological tumour stage pT0 form a subgroup showing a significantly better CSS. •A radical TURB is, assumedly, not causative of this improved survival rate, but rather it is that individual tumour characteristics allow for complete tumour eradication through the TURB procedure. •A TURB with R0 resection is, as such, only a sign of a better tumour prognosis.

Der therapeutische Goldstandard bei muskelinvasiven Karzinomen stellt die radikale Zystektomie (RZE) dar, wobei widerspruchliche Daten bezuglich der therapieassoziierten Mortalitat und des onkologischen Nutzens bei alteren Patienten vorliegen. Das Ziel unserer Studie bildete der Vergleich des Gesamtuberlebens und des karzinomspezifischen Uberlebens zwischen Patienten ≥75 und

To investigate prostate-specific antigen density as a predictor for pathologic upstaging in patients initially thought to have unilateral prostate cancer.We analyzed 438 patients with unilateral prostate cancer in prostate biopsy samples that were treated with radical prostatectomy. Bilateral or extracapsular growth in the final surgical specimens was defined as upstaging. Using Kaplan-Meier curves and a multivariate Cox proportional hazard model, we evaluated the oncologic effect of pathologic upstaging on biochemical recurrence-free survival. Prostate-specific antigen density was evaluated as a diagnostic tool to predict upstaging using ROC-curve analysis.Of the patients, 30.8% had bilateral prostate cancer or extracapsular extension in the surgical specimen. Prostate-specific antigen density was a diagnostic predictor for pathologic upstaging in patients initially thought to have unilateral prostate cancer (AUC 0.62, P0.001). Using a lower cutoff value of PSA density0.056 ng/ml/cm3, upstaging could be excluded in patients with a sensitivity of98%.A considerable amount of patients that are initially diagnosed with unilateral prostate cancer on biopsy are underdiagnosed and are upstaged in the radical prostatectomy specimen. In general, AUC of PSA density is too low to use PSA density as diagnostic tool to predict pathologic upstaging in all patients. Nonetheless, PSA density could be used for hemiablative focal therapy decision making using a lower cutoff value of0.056 ng/ml/cm3.

Study Type – Prognosis (inception cohort) Level of Evidence 1b OBJECTIVES To validate the association of lymphovascular invasion (LVI) with disease recurrence and cancer-specific survival (CSS) in a multicentre cohort of patients treated with radical cystectomy (RC) for urothelial bladder cancer (UBC). PATIENTS AND METHODS We collected pathological and clinical data on 1099 lymph node-negative patients treated with RC at six German institutions. LVI was defined as the presence of tumour cells within an unequivocal endothelium-lined space in haematoxylin and eosin-stained sections. RESULTS LVI was present in 295 (26.8%) patients; the presence of LVI correlated significantly with increasing tumour stage, i.e. pT1, 65 (29.4%); pT2, 88 (31.5%); pT3 110 (31.8%); and pT4 32 (38.1%) (P= 0.002) and grade (P 75 vs ≥75 years; P= 0.018) and LVI (P < 0.001) were identified as independent predictors of CSS. CONCLUSIONS Our large multicentre study confirms the independent prognostic value of LVI in patients with node-negative UBC. LVI can be regarded as a surrogate variable for lymphatic micrometastasis in node-negative UBC. Assessment of LVI might improve the selection of patients who are likely to benefit from adjuvant therapy after RC. The identification of factors involved in the process of LVI could reveal new therapeutic targets for UBC.

To report the outcome and course of disease in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel followed by abiraterone acetate in a single center.In this retrospective observational study, we reviewed the course of disease of all applicable patients with mCRPC treated with docetaxel followed by abiraterone at our center. We analyzed progression-free survival (PFS) of docetaxel and abiraterone treatments. We further searched for predictive factors for the duration of treatment response.Median PFS between initiation of androgen deprivation therapy and the diagnosis of mCRPC was 32 months. Median PFS on docetaxel treatment was 9 months. Median PFS on abiraterone treatment was 11 months. Patients with higher Gleason scores (GS) (8-10) at initial diagnosis had a significantly longer median PFS on docetaxel as compared to patients with GS 6-7, p = 0.01. We demonstrate a significant correlation between the PFS on docetaxel and PFS on abiraterone in the post-docetaxel setting (Kendall tau r = 0.32, p = 0.019) as well as a significant negative correlation between the PSA nadir under abiraterone treatment and the time to progression under abiraterone (Kendall tau r = -0.43, p = 0.007).High Gleason score appears to be predictive of duration of response to docetaxel. Interestingly, progression-free survival with abiraterone appears to be correlated with the duration of response with docetaxel, whereas PSA decline and low nadir appear to be predictive of response to abiraterone.

Familial Mediterranean fever (FMF) can present cutaneous symptoms. In the reported case, infiltrating perineal and scrotal inflammation were attributed to FMF and treated by systemic medication with colchicine. The poor outcome of this conservative approach and pathognomonic axillary dermatological findings allowed the diagnosis of acne inversa to be made. Knowledge of this clinical picture possibly including genital manifestations is crucial, as early excision of all affected regions is the therapy of choice that enables healing.

Objectives To evaluate CD24/CD44/CD47 cancer stem cell marker expressions in bladder cancer (BCa) and provide data on their prognostic significance for clinical outcome in patients undergoing radical cystectomy (RC). Material and methods Primary BCa tissue was used for xenograft studies. A tissue microarray was prepared using specimens from a cohort of 132 patients. All patients underwent RC for urothelial BCa between 2001 and 2010. Expression of CD24, CD44, and CD47 was examined in primary samples and xenografts by fluorescence-activated cell sorting. Populations of CD24low- and CD24high- expressing cells were sorted and evaluated for tumorigenicity in vivo. Tissue microarray was analyzed for CD24/CD44 staining intensity and tumor-specific vs. stromal cell staining. Associations with BCa survival, BCa stage, and lymph node status were evaluated by univariate and multivariate analyses. Results CD24 and CD44/CD47 expressions mark distinct cell populations within the normal urothelium as well as in BCa. CD24high/low expression was not sufficient to characterize CD24 as a BCa-initiating marker in in vivo primary xenotransplants. CD24 and CD44 expressions correlated with lower cancer-specific survival in patients. However, multivariate analyses of CD24 or CD44 did not demonstrate significantly increased hazards for cancer-specific death if analyzed together with stage, grade, and nodal status of patients. Conclusions Cancer stem cell markers CD24/CD44/CD47 are differentially expressed in cells of urothelial BCa in patients undergoing RC and influence cancer-specific survival of patients. Further evaluation of CD24/CD44/CD47 protein expression could be of high therapeutic value in BCa. However, both CD24 and CD44 expressions cannot be regarded as independent prognostic parameters for patients undergoing RC.

To evaluate the influence of type 2 diabetes on cancer-specific outcome in patients undergoing surgery for localized renal cell carcinoma (RCC).A total of 1,140 patients with localized RCC undergoing radical or partial nephrectomy were enrolled into this retrospective case-control study. Primary outcome was the cancer-specific survival comparing patients with and without type 2 diabetes at the time of surgery. Secondary outcomes were recurrence-free survival and metastases-free survival comparing the same groups. Additionally, the influence of accompanying factors on cancer-specific survival and overall survival of patients was evaluated in a multivariate analysis. Among 1,140 patients included in the analyses, 202 had diabetes at the time of surgery and 938 patients without diabetes served as control.The univariate comparisons between patients with and without diabetes regarding recurrence-free, metastases-free, and cancer-specific survival revealed no significant differences. Multivariate results demonstrate that age, BMI, and diabetes had no significant effect on cancer-specific hazard among participants. After adjustment of the factors in terms of overall survival, however, increased age, increased BMI, and type 2 diabetes at the time of surgery were independent risk factors for the occurrence of the event death.Type 2 diabetes and obesity at the time of surgery have no significant impact on cancer-specific and recurrence-free survival in patients with localized renal cancer.

and ChIP test whether AIB1 is necessary for glycolytic genes transcription. The independent statistics analysis of microarray was employed to identify the correlation between AIB1 and glycolytic genes. RESULTS: Our results demonstrated knockdown of AIB1 in bladder cancer cells induced G1 arrest and Our results demonstrated knockdown of AIB1 in bladder cancer cells induced G1 arrest and apoptosis, inhibited colony formation and tumorigenesis in vivo. Cell cycle inhibitor, p27, was up-regulated and survival protein BCL2 was reduced in AIB1 knockdown cells independence of cell type. Depletion of AIB1 by RNA interference and pharmacologic inhibition reduced glucose consumption, lactate and ATP production in T24 cancer cells under hypoxia. By interacting with HIF1 , AIB1 was required for HIF1 transcriptional activity and its glycolytic target gene expression, through direct recruitment onto promoters of HIF1 target genes. AIB1expression level showed positive correlation with glycolytic genes in clinic UCB specimen. CONCLUSIONS: Together, oveexpression of AIB1 is required for glycolysis in bladder cancer cells through HIF1 , eventually to facilitate tumorigenesis. Targeting AIB1 by gossypol may be an intriguing approach for bladder cancer therapy.

Aim The outcome of patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) shows remarkable variability. We evaluated the ability of artificial neural networks (ANN) to perform risk stratification in UCB patients based on common parameters available at the time of RC. Methods Data from 2111 UCB patients that underwent RC in eight centers were analysed; the median follow-up was 30 months (IQR: 12–60). Age, gender, tumour stage and grade (TURB/RC), carcinoma in situ (TURB/RC), lymph node status, and lymphovascular invasion were used as input data for the ANN. Endpoints were tumour recurrence, cancer-specific mortality (CSM) and all-cause death (ACD). Additionally, the predictive accuracies (PA) of the ANNs were compared with the PA of Cox proportional hazards regression models. Results The recurrence-, CSM-, and ACD- rates after 5 years were 36%, 33%, and 46%, respectively. The best ANN had 74%, 76% and 69% accuracy for tumour recurrence, CSM and ACD, respectively. Lymph node status was one of the most important factors for the network's decision. The PA of the ANNs for recurrence, CSM and ACD were improved by 1.6% ( p = 0.247), 4.7% ( p p = 0.007), respectively, in comparison to the Cox models. Conclusions ANN predicted tumour recurrence, CSM, and ACD in UCB patients after RC with reasonable accuracy. In this study, ANN significantly outperformed the Cox models regarding prediction of CSM and ACD using the same patients and variables. ANNs are a promising approach for individual risk stratification and may optimize individual treatment planning.

Patrick J. Bastian*, Munchen, Germany; Matthias May, Straubing, Germany; Hans-Martin Fritsche, Regensburg, Germany; Alexander Buchner, Munchen, Germany; Sabine Brookman-May, Regensburg, Germany; Christian Bolenz, Mannheim, Germany; Edwin Hermann, Munster, Germany; Maximillian Burger, Regensburg, Germany; Thomas Hofner, Heidelberg, Germany; Jorg Elliger, Bonn, Germany; Derya Tilki, Munchen, Germany; Lutz Trojan, Mannheim, Germany; Christian Wulfing, Munster, Germany; Axel Haferkamp, Frankfurt, Germany; Christian Gilfrich, Straubing, Germany; Markus Hohenfellner, Heidelberg, Germany; Wolf F. Wieland, Regensburg, Germany; Stefan C. Muller, Bonn, Germany; Philipp Nuhn, Munchen, Germany

Purpose To perform the first external validation of a recently identified association between disease-free survival at two years (DFS2) or three years (DFS3) and overall survival at five years (OS5) in patients after radical cystectomy (RC) for muscle-invasive urothelial carcinoma of the bladder (UCB). Methods and Methods Records of 2483 patients who underwent RC for UCB at eight European centers between 1989 and 2008 were reviewed. The cohort included 1738 patients with pT2-4a tumors and negative soft tissue surgical margins (STSM) according to the selection criteria of the previous study (study group (SG)). In addition, 745 patients with positive STSM or other tumor stages (pT0-T1, pT4b) that were excluded from the previous study (excluded patient group (EPG)) were evaluated. Kappa statistic was used to measure the agreement between DFS2 or DFS3 and OS5. Results The overall agreement between DFS2 and OS5 was 86.5% (EPG: 88.7%) and 90.1% (EPG: 92.1%) between DFS3 and OS5. The kappa values for comparison of DFS2 or DFS3 with OS5 were 0.73 (SE: 0.016) and 0.80 (SE: 0.014) respectively for the SG, and 0.67 (SE: 0.033) and 0.78 (SE: 0.027) for the EPG (all p -values Conclusions We externally validated a correlation between DFS2 or DFS3 and OS5 for patients with pT2-4a UCB with negative STSM that underwent RC. Furthermore, this correlation was found in patients with other tumor stages regardless of STSM status. These findings indicate DFS2 and DFS3 as valid surrogate markers for survival outcome with RC.