Search

Purpose: Precision oncology requires biomarker testing from tumor tissue for clinical decision-making and selection of targeted therapies. We systematically evaluated the role of tissue biomarker testing within interventional clinical trials for locally advanced and metastatic urothelial carcinoma (UC). Methods: A systematic search within the publicly available ClinicalTrials.gov database was performed for the period 1995 to January 2020. We searched for all interventional studies on systemic treatments for advanced UC. Two investigators independently screened the records and extracted the data for statistical analyses. Results: We included 356 studies out of 827 initial records in the final analysis. The overall number of interventional trials in UC patients significantly increased during the past 25 years. Forty-three studies (12.1%) required specific biomarker testing as a prerequisite for inclusion. Of the remaining 313 trials, explorative biomarkers of interest were studied in 83 studies (23.3%). In trials with obligate biomarker testing as a precondition for study inclusion, only 3 studies (7%) required an actual fresh pretreatment biopsy, while the majority of studies did not state any tissue requirements (55.8%) or accepted archival tissue samples (37.3%). Among studies without biomarker prerequisites, freshly obtained tissue samples were required in 16.3% of studies evaluating immune checkpoint inhibition and 5.7% evaluating targeted therapy. The collection of archival tissue was allowed in 67.4% and 20% of studies evaluating immune checkpoint inhibitors and targeted therapies, respectively. Conclusion: There has been an increase in the number of studies using biomarker-guided interventions for the treatment of advanced UC over the past 25 years. Studies investigating druggable targets in actual UC biopsies immediately before treatment are still rare. Standardized criteria for tissue-based biomarker testing may further accelerate personalized treatment of patients with advanced UC.

Ureteral stenosis and urinary leakage are relevant problems after kidney transplantation. A standardized definition of ureterovesical anastomosis complications after kidney transplantation has not yet been established. This study was designed to demonstrate the predictive power of quantitative indocyanine green (ICG) fluorescence angiography. This bicentric historic cohort study, conducted between November 2015 and December 2019, included 196 kidney transplantations. The associations between quantitative perfusion parameters of near-infrared fluorescence angiography with ICG and the occurrence of different grades of ureterovesical anastomosis complications in the context of donor, recipient, periprocedural, and postoperative characteristics were evaluated. Post-transplant ureterovesical anastomosis complications occurred in 18%. Complications were defined and graded into three categories. They were associated with the time on dialysis (p = 0.0025), the type of donation (p = 0.0404), and the number of postoperative dialysis sessions (p = 0.0173). Median ICG ingress at the proximal ureteral third was 14.00 (5.00–33.00) AU in patients with and 23.50 (4.00–117.00) AU in patients without complications (p = 0.0001, cutoff: 16 AU, sensitivity 70%, specificity 70%, AUC = 0.725, p = 0.0011). The proposed definition and grading of post-transplant ureterovesical anastomosis complications is intended to enable valid comparisons between studies. ICG Fluorescence angiography allows intraoperative quantitative assessment of ureteral microperfusion during kidney transplantation and is able to predict the incidence of ureterovesical anastomosis complications. Registration number: NCT-02775838.

Oral antitumor therapeutics (OAT) bear a high risk for medication errors, e.g., due to drug–drug or drug–food interactions or incorrect drug intake. Advanced age, organ insufficiencies, and polymedication are putting uro-oncological patients at an even larger risk. This analysis sets out to (1) investigate the frequency and relevance of medication errors in patients with prostate cancer or renal cell carcinoma treated with OAT and (2) compile recommendations for clinical practice. This post-hoc subgroup analysis used data collected in the randomized AMBORA trial (2017–2020; DRKS00013271). Clinical pharmacologists/pharmacists conducted advanced medication reviews over 12 weeks after initiation of a new oral regimen and assessed the complete medication process for drug–related problems. Medication errors related to either the OAT, prescribed or prescription-free concomitant medication, or food were classified regarding cause and severity. We identified 67 medication errors in 38 patients within the complete medication within 12 weeks. Thereof, 55% were detected at therapy initiation, 27% were caused by the patients, and 25% were drug–drug or drug–food interactions. Problem-prone issues are summarized in a ‘medication safety table’ to provide recommendations for clinical practice in uro-oncology. Tailored strategies including intensified care by clinical pharmacologists/pharmacists should be implemented in clinical practice to improve medication safety.

Introduction: Ureteric implantation of the transplanted ureter into native urinary bladder tissue in kidney transplantation recipients is essential for post-operative kidney function. We aimed to determine the effects of Taguchi versus Lich-Grégoir extravesical ureteroneocystostomy in kidney transplantation. Methods: We searched multiple databases (MEDLINE, Cochrane Library, and Web of Science), trial registries, and conference proceedings until March 2021. We included prospective studies comparing Taguchi and Lich-Grégoir ureteroneocystostomy in kidney transplantation. Two review authors independently screened the identified records, extracted data, evaluated the risk of bias using ROBINS-I, and assessed the certainty of evidence according to GRADE. Results: We identified 3 prospective studies with serious or critical risk of bias, leading to low-certainty evidence. We downgraded the risk of bias due to study limitations. Assessment and/or reporting of baseline imbalances, co-interventions, and confounding factors was insufficient in all included studies. The effect of Taguchi ureteroneocystostomy remains unclear. Conclusion: Currently available evidence is not useful to determine the effect of Taguchi versus Lich-Grégoir ureteroneocystostomy in kidney transplantation. There is a need for methodologically better designed and executed studies, such as randomized controlled trials with long-term follow-up reporting baseline imbalances, co-interventions, and confounding factors.

Background Cancer patients often suffer from psychological distress. Psycho‐oncological services (POS) have been established in some health care systems in order to address such issues. This study aims to identify patient and center characteristics that elucidate the use of POS by patients in prostate cancer centers (PCCs). Methods Center‐reported certification and patient survey data from 3094 patients in 44 certified PCCs in Germany were gathered in the observational study (Prostate Cancer Outcomes). A multilevel analysis was conducted. Results Model 1 showed that utilization of POS in PCCs is associated with patients’ age (OR = 0.98; 95%‐CI = 0.96‐0.99; P, The paper identifies patient and center characteristics that account for the use of psycho‐oncological services by prostate cancer patients in certified prostate cancer centers in Germany. Multilevel analysis was conducted. The results indicate that the varying utilization of psycho‐oncological services in certified prostate cancer centers may be better explained by characteristics of the centers and the patients’ clinical characteristics, rather than by the patients’ sociodemographic features.

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.

Introduction: The results of kidney transplants have improved dramatically in recent years, leading to reduced morbidity and mortality. Despite continuous improvements, urological complications occur at a rate of 2.6%–15%. Ureteral stenosis of graft ureters is the most common complication, with a probability of 0.5%–6.3%. This study aimed to determine the incidence of ureteral stenosis after kidney transplantation and identify risk factors that distinguish transplant patients with and without ureteral stenosis. Methods: This study retrospectively analyzed patients who had undergone kidney transplantation at the Department of Urology of the Friedrich-Alexander University Erlangen-Nuremberg between 2001 and 2015. Forty-seven patients developed ureteral stenosis during the operation. Most of the ureteral stenosis cases occurred in the first 4 months after transplantation. Kaplan-Meier analysis and the log-rank test were used to calculate the cumulative risk, and the Mann-Whitney U test was used nonparametrically. The significance level was set at p < 0.05. Results: Statistical analysis showed that residual diuresis (p = 0.008), cold ischemia time (CIT) (p = 0.040), the body mass index (p = 0.027), and donor serum creatinine value (p = 0.039) showed a significantly different distribution between recipients with or without ureteral stenosis after kidney transplantation. In multivariate Cox’s regression modeling, residual diuresis and the donor serum creatinine level were identified as the only independent predictors of patients’ stenosis-free survival. Conclusion: Urological complications not diagnosed and treated in time endanger the success of kidney transplantation. After evaluating the kidney transplantation data of the patients at the Transplant Center Erlangen-Nuremberg from 2001 to 2015, residual diuresis, CIT, the body mass index, and donor serum creatinine value were found to influence the development of ureteral stenosis.

Purpose Social service counseling (SSC) is an important instrument to support cancer patients, for example, regarding legal support, or rehabilitation. Several countries have established on-site SSC in routine care. Previous analyses have shown that SSC utilization varies across cancer centers. This analysis investigates patient and center-level predictors that explain variations in SSC utilization between centers. Methods Logistic multilevel analysis was performed with data from 19,865 prostate cancer patients from 102 prostate cancer centers in Germany and Switzerland. Data was collected within an observational study between July 2016 and June 2020 using survey (online and paper) and tumor documentation. Results The intraclass correlation coefficient for the null model implies that 51% of variance in SSC utilization is attributable to the center a patient is treated in. Patients aged 80 years and older, with higher education, private insurance, without comorbidities, localized intermediate risk, and undergoing androgen deprivation therapy before study inclusion were less likely to utilize SSC. Undergoing primary radiotherapy, active surveillance, or watchful waiting as compared to prostatectomy was associated with a lower likelihood of SSC utilization. Significant negative predictors at the center level were university hospital, center’s location in Switzerland, and a short period of certification. Conclusion The results show that patient and center characteristics contribute to explaining the variance in SSC utilization in prostate cancer centers to a large extent. The findings may indicate different organizational processes in the countries included and barriers in the sectoral structure of the healthcare system. In-depth analyses of processes within cancer centers may provide further insights into the reasons for variance in SSC utilization.

Molecular markers associated with breast cancer are assumed to be associated with outcome in non-muscle-invasive bladder cancer (NMIBC).We retrospectively investigated the association of the mRNA expression of estrogen receptor 1 (ESR1) and 2 (ESR2), progesterone receptor (PGR), MKI67, and HER2 (ERBB2) with recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS) in 80 patients with stage T1 NMIBC.High expression of ESR2 (P = 0.003), ERBB2 (P0.001), and MKI67 (P = 0.029) was associated with shorter RFS. Only high ERBB2 was an independent prognostic factor for reduced RFS (HR = 2.98; P = 0.009). When sub stratifying the cohort, high ESR2 was associated with reduced RFS (P0.001), CSS (P = 0.037) and OS (P = 0.006) in patients without instillation therapy. High ESR2 was associated with reduced CSS (P = 0.018) and OS (P = 0.029) in females and with shorter RFS in both sexes (males: P = 0.035; females: P = 0.010). Patients with high ERBB2 showed reduced CSS (P = 0.011) and OS (P = 0.042) in females and reduced CSS (P = 0.012) in those without instillation, while RFS was significantly reduced irrespective of sex or instillation.High mRNA expression of ERBB2 is an independent predictor of reduced RFS in patients with stage T1 NMIBC. High ERBB2 and ESR2 are associated with reduced outcomes, especially in females and patients without instillation therapy.

PURPOSE Oral anticancer drugs (eg, kinase inhibitors) play an important role in cancer therapy. However, considerable challenges regarding medication safety of oral anticancer drugs have been reported. Randomized, controlled, multicenter studies on the impact of intensified clinical pharmacological/pharmaceutical care on patient safety and patient treatment perception are lacking. METHODS Patients were eligible for the randomized, multicenter AMBORA study, if they were newly started on any of the oral anticancer drugs approved in 2001 or later without restriction to certain tumor entities. Patients were randomly assigned to receive either standard of care (control group) or an additional, intensified clinical pharmacological/pharmaceutical care, which included medication management and structured patient counseling, over a period of 12 weeks (intervention group). Primary end points were the number of antitumor drug–related problems (ie, side effects and unresolved medication errors) and patient treatment satisfaction with the oral anticancer therapy after 12 weeks measured with the Treatment Satisfaction Questionnaire for Medication, category convenience. RESULTS Two hundred two patients were included. Antitumor drug–related problems were significantly lower in the intervention compared with the control group (3.85 v 5.81 [mean], P < .001). Patient treatment satisfaction was higher in the intervention group (Treatment Satisfaction Questionnaire for Medication, convenience; 91.6 v 74.4 [mean], P < .001). The hazard ratio for the combined end point of severe side effects (Common Terminology Criteria for Adverse Events ≥ 3), treatment discontinuation, unscheduled hospital admission, and death was 0.48 (95% CI, 0.32 to 0.71, P < .001) in favor of the intervention group. CONCLUSION Treatment with oral anticancer drugs is associated with a broad range of medication errors and side effects. An intensified clinical pharmacological/pharmaceutical care has considerable, positive effects on the number of medication errors, patient treatment perception, and severe side effects.

Introduction: Older patients undergoing major urological tumor surgery are at severe risk of functional deterioration, complications, and mortality. We prospectively evaluated geriatric assessment tools and developed a novel easy-to-use assessment tool for clinical use. Methods: In 159 patients, geriatric assessment tools were used prior to cystectomy, prostatectomy, and renal tumor surgery, and their peri- and postoperative courses were recorded. Using all the tests, a short and easy-to-use assessment tool was developed, and nomograms were generated to predict functional outcomes and mortality. Results: Of all the patients, 13.8% underwent radical cystectomy, 37.7% underwent radical prostatectomy, and 48.4% underwent tumor surgery of the kidney at the age of 70 years or older. The average age was 75.6 years. Incomplete functional recovery at day 30 and day 180 was observed in 37.7% and 36.1% of the patients, respectively, and incomplete functional recovery was associated with impaired mobility, previous care dependency, frailty, comorbidities, and a high ASA score. The only predictor for high-grade complications was comorbidities, whereas mortality was associated with the geriatric screening tool scores, impaired mobility, preoperative care dependency, and comorbidities. The Erlangen Index (EI), a combination of the selected assessment tools, showed a good prediction of early (p = 0.002) and medium-term (p = 0.002) functional outcomes and mortality (p = 0.001). Conclusion: Our prospective evaluation confirms the high risk of incomplete functional recovery, high-grade complications, and mortality in older patients undergoing major urological tumor surgery. The EI is an easy-to-use preoperative assessment tool and therefore should be used in preoperative patient counseling.

Background Systemic androgen deprivation therapy (ADT), also referred to as hormone therapy,AÂ has long been the primary treatment for metastatic prostate cancer. Additional agents have been reserved for the castrate-resistant disease stage when ADT start becoming less effective. Abiraterone is an agent with an established role in that disease stage, which has only recently been evaluated in the hormone-sensitive setting. Objectives To assess the effects of early abiraterone acetate, in combination with systemic ADT, for newly diagnosed metastatic hormone-sensitive prostate cancer. Search methods We searched CENTRAL, MEDLINE, Embase, six other databases, two trials registries, grey literature, and conference proceedings, up to 15 May 2020. We applied no restrictions on publication language or status. Selection criteria We included randomized trials, in which men diagnosed with hormone-sensitive prostate cancer were administered abiraterone acetate and prednisolone with ADT or ADTAÂ alone. Data collection and analysis Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the quality of evidence according to the GRADE approach. Main results The search identified two randomized controlled trials (RCT), with 2201 men, who were assigned to receive either abiraterone acetate 1000 mg once daily and low dose prednisone (5mg) in addition to ADT, or ADT alone. In the LATITUDE trial, the median age and range of men in the intervention group was 68 (38 to 89) years, and 67 (33 to 92) years in the control group. Nearly all of the men in thisAÂ study (97.6%) had prostate cancer with a Gleason score of at least 8 (ISUP grade group 4). Primary outcomes The addition of abiraterone acetate to ADT reduces the probability of death from any cause compared to ADT alone (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56 to 0.73; 2 RCTs, 2201 men; high certainty of evidence); this corresponds to 163 fewer deaths per 1000 men with hormone-sensitive metastaticAÂ prostate cancerAÂ (210 fewer to 115 fewer) at five years. Abiraterone acetate in addition to ADT probably results in little to no differenceAÂ in quality of life compared to ADT alone, measured with the Functional Assessment of Cancer Therapy-prostate total score (FACT-P; range 0 to 156; higher values indicates better quality of life),AÂ at 12 months (mean difference [MD] 2.90 points, 95% CI 0.11 to 5.60; 1 RCT, 838 men; moderate certainty of evidence). Secondary outcomes Abiraterone plus ADT increases the risk of grades III to V adverse events compared to ADT alone (risk ratio [RR] 1.34, 95% CI 1.22 to 1.47; 1 RCT, 1199 men; high certainty of evidence); this corresponds to 162 more grade III to VAÂ events per 1000 men with hormone-sensitive metastaticAÂ prostate cancerAÂ (105 more to 224 more) at a median follow-up of 30AÂ months. Abiraterone acetate in addition to ADT probably reduces the probability of death due to prostate cancer compared to ADT alone (HR 0.58, 95% CI 0.50 to 0.68; 2 RCTs, 2201 men; moderate certainty of evidence). This corresponds to 120 fewer death from prostate cancer per 1000 men with hormone-sensitive metastaticAÂ prostate cancerAÂ (95% CI 145 fewer to 90 fewer) afterAÂ a median follow-up of 30 months. The addition of abiraterone acetate to ADT probably decreases the probability of disease progression compared to ADT alone (HR 0.35, 95%CI 0.26 to 0.49; 2 RCTs, 2097 men; moderate certainty of evidence). This corresponds to 369 fewer incidences of disease progression per 1000 men with hormone-sensitive metastaticAÂ prostate cancerAÂ (456 fewer to 256 fewer)AÂ after a median follow-up of 30 months. The addition of abiraterone acetate to ADT probably increases the risk of discontinuing treatment due to adverse events compared to ADT alone (RR 1.50, 95% CI 1.17 to 1.92; 1 RCT, 1199 men; moderate certainty of evidence). This corresponds to 51 more men (95% CI 17 more to 93 more) discontinuing treatment because of adverse events per 1000 men treated with abiraterone acetate and ADT compared to ADT alone afterAÂ a median follow-up of 30 months. Authors' conclusions The addition of abiraterone acetate to androgen deprivation therapy improves overall survival but probably not quality of life. ItAÂ probably also extends disease-specific survival, and delays disease progression compared to androgen deprivation therapy alone. However, the risk of grades III to V adverse events is increased, and probably, so is the risk of discontinuing treatment due to adverse events.

BACKGROUND: People with urothelial carcinoma of the bladder are at risk for recurrence and progression following transurethral resection of a bladder tumour (TURBT). Mitomycin C (MMC) and Bacillus Calmette‐Guérin (BCG) are commonly used, competing forms of intravesical therapy for intermediate‐ or high‐risk non‐muscle invasive (Ta and T1) urothelial bladder cancer but their relative merits are somewhat uncertain. OBJECTIVES: To assess the effects of BCG intravesical therapy compared to MMC intravesical therapy for treating intermediate‐ and high‐risk Ta and T1 bladder cancer in adults. SEARCH METHODS: We performed a systematic literature search in multiple databases (CENTRAL, MEDLINE, Embase, Web of Science, Scopus, LILACS), as well as in two clinical trial registries. We searched reference lists of relevant publications and abstract proceedings. We applied no language restrictions. The latest search was conducted in September 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared intravesical BCG with intravesical MMC therapy for non‐muscle invasive urothelial bladder cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, assessed risk of bias and rated the quality of evidence according to GRADE per outcome. In the meta‐analyses, we used the random‐effects model. MAIN RESULTS: We identified 12 RCTs comparing BCG versus MMC in participants with intermediate‐ and high‐risk non‐muscle invasive bladder tumours (published from 1995 to 2013). In total, 2932 participants were randomised. Time to death from any cause: BCG may make little or no difference on time to death from any cause compared to MMC (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.79 to 1.20; participants = 1132, studies = 5; 567 participants in the BCG arm and 565 in the MMC arm; low‐certainty evidence). This corresponds to 6 fewer deaths (40 fewer to 36 more) per 1000 participants treated with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Serious adverse effects: 12/577 participants treated with BCG experienced serious non‐fatal adverse effects compared to 4/447 participants in the MMC group. The pooled risk ratio (RR) is 2.31 (95% CI 0.82 to 6.52; participants = 1024, studies = 5; low‐certainty evidence). Therefore, BCG may increase the risk for serious adverse effects compared to MMC. This corresponds to nine more serious adverse effects (one fewer to 37 more) with BCG. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Time to recurrence: BCG may reduce the time to recurrence compared to MMC (HR 0.88, 95% CI 0.71 to 1.09; participants = 2616, studies = 11, 1273 participants in the BCG arm and 1343 in the MMC arm; low‐certainty evidence). This corresponds to 41 fewer recurrences (104 fewer to 29 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations, imprecision and inconsistency. Time to progression: BCG may make little or no difference on time to progression compared to MMC (HR 0.96, 95% CI 0.73 to 1.26; participants = 1622, studies = 6; 804 participants in the BCG arm and 818 in the MMC arm; low‐certainty evidence). This corresponds to four fewer progressions (29 fewer to 27 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Quality of life: we found very limited data for this outcomes and were unable to estimate an effect size. AUTHORS' CONCLUSIONS: Based on our findings, BCG may reduce the risk of recurrence over time although the Confidence Intervals include the possibility of no difference. It may have no effect on either the risk of progression or risk of death from any cause over time. BCG may cause more serious adverse events although the Confidence Intervals once again include the possibility of no difference. We were unable to determine the impact on quality of life. The certainty of the evidence was consistently low, due to concerns that include possible selection bias, performance bias, given the lack of blinding in these studies, and imprecision.

Objective To systematically evaluate evidence on prognostic factors for tumor recurrence in patients with clinical stage I seminoma undergoing surveillance. Methods Systematic literature search conducted of Medline, Web of Science, Cochrane Library, and the conference proceedings of the ASCO, AUA, and EAU meetings (last search: October 2016), according to our prospectively registered protocol (PROSPERO registration number CRD42014009434). Identified records were reviewed according to the Cochrane Method Group of Prognosis Reviews recommendations and the PRISMA reporting guideline. Study quality was appraised with the Quality in Prognosis Studies (QUIPS) tool. Results Nineteen studies reporting on 26 potential prognostic factors were included in our analysis. Among the most frequently reported factors, tumor size (continuous or dichotomized) was significantly associated with relapse in 10/14 studies with a hazard ratio (HR) ranging from 1.33 (95% confidence interval [CI]: 1.14–1.56) to 3.17 (95% CI: 1.08–9.26). Rete testis invasion was significantly associated with relapse in only 4/13 studies with a HR ranging from 1.18 (95% CI: 0.92–1.51) to 1.36 (95% CI: 0.81–2.28). Lymphovascular invasion, young age, and preoperative HCG level had no association with relapse. Our findings are limited by heterogeneity of study designs, potential reporting bias, and moderate-to-poor study quality. Conclusion In stage I seminoma, tumor size is the most valuable prognostic factor on which to base relapse risk and to counsel patients about adjuvant treatment. Large tumor size was defined quite inhomogenously among the included studies, so no distinct cutoff value for tumor size can be recommended. Other potential prognostic factors including rete testis invasion play a minor role in stage I seminoma.

Background B cell function and antibody production are crucial factors in host protection during inflammation. We aimed to synthesize the available evidence on the association between the reduction of circulating B cells and plasma immunoglobulin (IgM) levels and decreased survival during sepsis. Methods We performed a systematic search in PubMed, Embase, ISI Web of Knowledge, Cochrane Central Register of Controlled Trials, BioMed Central, and Science Direct. We selected studies with data on circulating B cells and plasma IgM levels within the initial 24 h after sepsis onset. Results In total nine studies (n = 992 patients) were identified. Circulating B cells were reduced in septic patients as compared to non-septic patients (mean difference [MD] −88.2 cells/μl; 95% confidence interval [CI] −148.6–−27.9). Sepsis non-survivors showed a significant reduction of circulating B cells and IgM levels compared to sepsis survivors (MD −77.1 cells/μl; 95% CI −111.4–−42.7 and MD −20.9 mg/dl; 95% CI −33.8–−8.0, respectively). Conclusions Our results suggest that a reduction of circulating B cells and IgM levels at sepsis onset are associated with decreased sepsis survival. However, due to methodological limitations and the risk of bias, we need further prospective studies to confirm this association. Registration The protocol was registered (PROSPERO 2016:CRD42016053184).

BACKGROUND Standard androgen suppression therapy (AST) using surgical or medical castration is considered a mainstay of advanced hormone-sensitive prostate cancer treatment. AST can be initiated early when disease is asymptomatic or deferred when patients suffer symptoms of disseminated prostate cancer. OBJECTIVES To assess the effects of early versus deferred standard AST for advanced hormone-sensitive prostate cancer. SEARCH METHODS For this Cochrane Review update, we performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Web of Science; last searched November 2018) and two clinical trial registers, with no restrictions on the language of publication or publication status. We also searched bibliographies of included studies and conference proceedings (last searched January 2019). SELECTION CRITERIA We included all randomised controlled trials (RCTs) with a direct comparison of early versus deferred standard AST. We excluded all other study designs. Participants included had advanced hormone-sensitive prostate cancer receiving surgical or medical castration. DATA COLLECTION AND ANALYSIS Two review authors independently classified studies and abstracted data. The primary outcomes were time to death of any cause and serious adverse events. Secondary outcomes were time to disease progression, time to death from prostate cancer, adverse events and quality of life. We performed statistical analyses using a random-effects model and assessed the certainty of evidence according to GRADE. We performed subgroup analyses for advanced but non-metastatic disease (T2-4/N+ M0), metastatic disease (M1), and prostate-specific antigen (PSA) relapse. MAIN RESULTS We identified seven new RCTs since publication of the original review in 2002. In total, we included 10 RCTs.Primary outcomesEarly AST probably reduces the risk of death from any cause over time (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75 to 0.90; moderate-certainty evidence; 4767 participants). This corresponds to 57 fewer deaths (95% CI 80 fewer to 31 fewer) per 1000 participants at 5 years for the moderate risk group and 23 fewer deaths (95% CI 32 fewer to 13 fewer) per 1000 participants at 5 years in the low risk group. We downgraded for study limitations. Early versus deferred AST may have little or no effect on serious adverse events (risk ratio (RR) 1.05, 95% CI 0.95 to 1.16; low-certainty evidence; 10,575 participants) which corresponds to 6 more serious adverse events (6 fewer to 18 more) per 1000 participants. We downgraded the certainty of evidence for study limitations and selective reporting.Secondary outcomesEarly AST probably reduces the risk of death from prostate cancer over time (HR 0.69, 95% CI 0.57 to 0.84; moderate-certainty evidence). This corresponds to 62 fewer prostate cancer deaths per 1000 (95% CI 87 fewer to 31 fewer) at 5 years for the moderate risk group and 24 fewer death from prostate cancer (95% CI 34 fewer to 12 fewer) per 1000 men at 5 years in the low risk group. We downgraded the certainty of evidence for study limitations.Early AST may decrease the rate of skeletal events (RR 0.37, 95% CI 0.17 to 0.80; low-certainty evidence) corresponding to 23 fewer skeletal events per 1000 (95% CI 31 fewer to 7 fewer). We downgraded for study limitations and imprecision. It may also increase fatigue (RR 1.41, 95% CI 1.23 to 1.62; low-certainty evidence), corresponding to 31 more men with this complaint per 1000 (95% CI 18 more to 48 more). We downgraded for study limitations and imprecision. It may increase the risk of heart failure (RR 1.90, 95% CI 1.09 to 3.33; low-certainty evidence) corresponding to 27 more events per 1000 (95% CI 3 more to 69 more). We downgraded the certainty of evidence for study limitations and imprecision.Global quality of life is probably similar after two years as assessed with the EORTC QLQ-C30 (version 3.0) questionnaire (mean difference -1.56, 95% CI -4.50 to 1.38; moderate-certainty evidence) with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. AUTHORS' CONCLUSIONS Early AST probably extends time to death of any cause and time to death from prostate cancer. It may slightly decrease the rate of skeletal events. Rates of serious adverse events and quality of life may be similar. It may increase fatigue and may increase the risk of heart failure. Better quality trials would be particularly important to better understand the outcomes related to possible treatment-related harm, for which we only found low-certainty evidence.

Introduction Immune checkpoint inhibition gained significant impact in therapeutic handling of advanced bladder cancer. PD-L1 testing is currently required for first-line immune therapy in platinum-ineligible patients and bases on complex scoring algorithms. We aimed to decipher the composition of distinct scoring algorithms and their associations with immune biological determinants. Methods 193 consecutively collected MIBC patients were assessed with four approved PD-L1 assays for all currently established scoring algorithms (IC-Score [companion drug: atezolizumab], CPS [companion drug: pembrolizumab], ICarea/TC-score [companion drug: Durvalumab]). Results were correlated with a combined immune infiltration and immune checkpoint signature consisting of multiple immune cell populations (CD3, CD8, FOXP3, GZMB, CD56, CD68) and other immune checkpoint proteins (LAG3, CTLA4, PD-1). Findings were correlated with clinico-pathological data to elucidate the biological implications of different PD-L1 scoring algorithms. Results Of the three scoring algorithms exclusively the IC-score identified patient subsets with different survival rates between PD-L1 negative and positive subgroups (improved survival for PD-L1 positive subset; HR=0.44, P=0.0004) which predominantly detects patients with high PD-L1 expression on immune cells, while the CPS predominantly covers PD-L1 tumor cell positive cases. The ICarea/TC score equally identified both populations. Deeper analysis of the underlying immune biology revelead that high aberrant PD-L1 tumor cell expression associated with worse survival while PD-L1 immune cell expression is highly associated with improved survival. Compared to predominantly PD-L1 tumor cell positive tumors, general immune infiltration is higher in cases with strong PD-L1 expression on immune cells (P=0.0037). Conclusions PD-L1 scoring algorithms identify different patient populations with either predominant immune cell (IC-Score [atezolizumab]) or tumor cell expression (CPS [pembrolizumab]), while the ICarea/TC-score (durvalumab) sufficiently covers both populations. High expression of PD-L1 on tumor cells associated with worse survival indicating high predictive potential for PD-L1 inhibition while high expression on immune cells is a baseline characteristic for improved patient survival (positive prognostic value).

Die Behandlung von Knochenmetastasen urologischer Tumoren stellt – bis auf die Resektion solitarer Metastasen von Nierenzellkarzinomen – eine palliative Therapieform dar. Aufgrund der hohen Inzidenz von Wirbelkorpermetastasen konnen fur den Patienten hierbei klinisch bedeutende Symptome und mogliche Komplikationen wie Schmerzen, eine Instabilitat der Wirbelsaule oder eine Spinalkanalkompression mit entsprechenden neurologischen Ausfallserscheinungen resultieren. Durch gezielte Diagnostik und Einleitung strahlentherapeutischer und/oder chirurgischer Therapien kann bei einem Grosteil der Patienten eine unmittelbare Schmerzreduktion, sowie eine fruhzeitige Mobilisierung und teils auch eine Regredienz bestehender neurologischer Ausfallserscheinungen und somit eine bessere Lebensqualitat erreicht werden.

Computer-aided diagnosis (CADx) approaches could help to objectify reporting on prostate mpMRI, but their use in many cases is hampered due to common-built algorithms that are not publicly available. The aim of this study was to develop an open-access CADx algorithm with high accuracy for classification of suspicious lesions in mpMRI of the prostate. This retrospective study was approved by the local ethics commission, with waiver of informed consent. A total of 124 patients with 195 reported lesions were included. All patients received mpMRI of the prostate between 2014 and 2017, and transrectal ultrasound (TRUS)-guided and targeted biopsy within a time period of 30 days. Histopathology of the biopsy cores served as a standard of reference. Acquired imaging parameters included the size of the lesion, signal intensity (T2w images), diffusion restriction, prostate volume, and several dynamic parameters along with the clinical parameters patient age and serum PSA level. Inter-reader agreement of the imaging parameters was assessed by calculating intraclass correlation coefficients. The dataset was stratified into a train set and test set (156 and 39 lesions in 100 and 24 patients, respectively). Using the above parameters, a CADx based on an Extreme Gradient Boosting algorithm was developed on the train set, and tested on the test set. Performance optimization was focused on maximizing the area under the Receiver Operating Characteristic curve (ROCAUC). The algorithm was made publicly available on the internet. The CADx reached an ROCAUC of 0.908 during training, and 0.913 during testing (p = 0.93). Additionally, established rule-in and rule-out criteria allowed classifying 35.8% of the malignant and 49.4% of the benign lesions with error rates of &lt, 2%. All imaging parameters featured excellent inter-reader agreement. This study presents an open-access CADx for classification of suspicious lesions in mpMRI of the prostate with high accuracy. Applying the provided rule-in and rule-out criteria might facilitate to further stratify the management of patients at risk.

Standard androgen deprivation therapy (ADT) can be initiated early at the time of diagnosis in asymptomatic castration-sensitive advanced prostate cancer. This definition has recently been expanded to also include an early combined treatment with standard ADT and new antihormonal drugs. We aimed to present the best available evidence for the timing of initiation of ADT monotherapy and combined treatments in castration-sensitive/-resistant prostate cancer. For this narrative review, we searched Cochrane reviews in the Cochrane Library, systematic reviews and randomized controlled trials in MEDLINE, phase III and ongoing trials in ClinicalTrials.gov and screened the reference lists to extract articles of interest. One author screened the references which were finally included after assessing their relevance through discussion with other experts in the field. The identified references were grouped by medication (standard ADT, androgen biosynthesis inhibitor, androgen receptor antagonists or combined therapies) and tumor stage (castration sensitive or resistant). The evidence was narratively summarized and discussed in the context of the current therapeutic landscape. Early standard ADT can reduce symptoms of disease progression and may extend progression-free and overall survival. The patient should be well informed about the higher rates of treatment-related side effects. Deferring standard ADT might be indicated only for well-informed or unfit patients. Early standard ADT is increasingly combined with new antihormonal drugs in castration-sensitive metastatic prostate cancer to gain additional survival and quality of life benefits. Combined treatment at the time of development of castration-resistant disease is well established.

The high incidence of bone metastases of urologic neoplasms and their morbidity, especially of vertebral metastases, requires exact diagnosis and consequent therapy. Conventional radiography plays an important role in the diagnosis of symptomatic bone lesions. Computed tomography can evaluate the stability of metastatic lesions and is indispensable for therapy planning. MRI and PET-CT have the highest diagnostic accuracy for the detection of bone metastases and MRI can evaluate their intra- and extraosseus components. PET-CT, PET-MRI, or SPECT-CT in combination with specific tracers - due to their high specificity and sensitivity - have the potential to replace conventional methods in the future. Conservative treatment basically consists of analgesic therapy, the administration of calcium and vitamin D3 and bisphosphonates or inhibitors of RANKL (denosumab). Moreover radium-223-dichloride can improve overall survival and the time to the first symptomatic skeletal event in castration-resistant prostate cancer patients with bone metastases.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of pembrolizumab monotherapy versus chemotherapy for the second‐line treatment of advanced urothelial carcinoma.

BACKGROUND: Despite local therapies, commonly transurethral resection (TUR) followed by adjuvant treatments, non‐muscle‐invasive bladder cancer (NMIBC) has a high rate of recurrence and progression. Intravesical Bacillus Calmette‐Guérin (BCG) has been shown to reduce recurrence and progression in people with NMIBC following TUR, however many people do not respond to treatment, have recurrence shortly after, or cannot tolerate standard‐dose therapy. The potential for synergistic antitumour activity of interferon (IFN)‐alpha (α) and BCG provides some rationale for combination therapy for people who do not tolerate or respond to standard‐dose BCG therapy. OBJECTIVES: To assess the effects of intravesically administered BCG plus IFN‐α compared with BCG alone for treating non‐muscle‐invasive bladder cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 8, 2016), MEDLINE (OvidSP) (1946 to 2016), Embase (OvidSP) (1974 to 2016), ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) as well as reference lists of retrieved articles and handsearched abstract proceedings of relevant conferences for the past three years. We applied no language restrictions. The date of last search of all databases was 25 August 2016. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and pseudo‐randomised trials assessing intravesically administered BCG plus IFN‐α versus BCG alone in adults of either gender with histologically confirmed Ta and T1 superficial bladder cancer, with or without carcinoma in situ, treated with TUR. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data, and assessed the risk of bias of included studies. We used Review Manager 5 for data synthesis and employed the random‐effects model for meta‐analyses. For prespecified outcomes, where we were unable to derive time‐to‐event information (e.g. time‐to‐recurrence), we assessed dichotomous outcomes (e.g. recurrence) instead. We assessed the quality of the evidence for the main comparisons using the GRADE approach. MAIN RESULTS: We included five RCTs involving a total of 1231 participants with NMIBC in this review. Due to poor reporting, the risk of bias in the included studies was often unclear. We assessed the studies under two main comparisons: intravesical BCG plus IFN‐α versus intravesical BCG alone (four RCTs), and intravesical BCG alternating with IFN‐α versus intravesical BCG alone (one RCT). Intravesical BCG plus IFN‐α versus intravesical BCG alone (four RCTs): We observed no clear difference between BCG plus IFN‐α and BCG alone for recurrence (average risk ratio (RR) 0.76, 95% confidence interval (CI) 0.44 to 1.32; 4 RCTs; 925 participants; very low‐quality evidence) or progression (average RR 0.26, 95% CI 0.04 to 1.87; 2 RCTs; 219 participants; low‐quality evidence). The included RCTs did not report on the other primary outcome of this review, discontinuation of therapy due to adverse events. Regarding secondary outcomes, we observed no clear difference for disease‐specific mortality (RR 0.38, 95% CI 0.05 to 3.05; 1 RCT; 99 participants; very low‐quality evidence). Two RCTs reporting contradictory findings for adverse events could not be pooled due to variation in definitions. There were no data from the included RCTs on time‐to‐death or disease‐specific quality of life. Intravesical BCG alternating with IFN‐α versus intravesical BCG alone (one RCT): We observed shorter time‐to‐recurrence for participants in the BCG alternating with IFN‐α group compared with the BCG alone group (hazard ratio (HR) 2.86, 95% CI 1.98 to 4.13; 1 RCT; 205 participants; low‐quality evidence), but no clear differences in time‐to‐progression (HR 2.39, 95% CI 0.92 to 6.21; 1 RCT; 205 participants; low‐quality evidence) and discontinuation of therapy due to adverse events (RR 2.97, 95% CI 0.31 to 28.09; 1 RCT; 205 participants; low‐quality evidence). Regarding secondary outcomes, there were no clear differences between the BCG alternating with IFN‐α and BCG alone groups for disease‐specific mortality (HR 2.74, 95% CI 0.73 to 10.28; 1 RCT; 205 participants; low‐quality evidence), time‐to‐death (overall survival) (HR 1.00, 95% CI 0.68 to 1.47; 1 RCT; 205 participants; low‐quality evidence), or systemic or local adverse events (RR 1.65, 95% CI 0.41 to 6.73; 1 RCT; 205 participants; low‐quality evidence). There were no data on disease‐specific quality of life. AUTHORS' CONCLUSIONS: We found low‐ to very low‐quality evidence suggesting no clear differences in recurrence or progression with BCG plus IFN‐α compared with BCG alone for people with NMIBC; there was no information to determine the effect on discontinuation of therapy due to adverse events. Low‐quality evidence suggests BCG alternating with IFN‐α compared with BCG alone may increase time‐to‐recurrence, however low‐quality evidence also suggests no clear differences for time‐to‐progression or discontinuation of therapy due to adverse events. Additional high‐quality, adequately powered trials using standardised instillation regimens and doses of both BCG and IFN‐α, reporting outcomes in subgroups stratified by patient and tumour characteristics, and on long‐term outcomes related not only to recurrence but also to progression, discontinuation due to adverse events, and mortality may help to clarify the ideal treatment strategy and provide a more definitive result.

Background Partial nephrectomy and radical nephrectomy are the relevant surgical therapy options for localised renal cell carcinoma. However, debate regarding the effects of these surgical approaches continues and it is important to identify and summarise high-quality studies to make surgical treatment recommendations. Objectives To assess the effects of partial nephrectomy compared with radical nephrectomy for clinically localised renal cell carcinoma. Search methods We searched CENTRAL, MEDLINE, PubMed, Embase, Web of Science, BIOSIS, LILACS, Scopus, two trial registries and abstracts from three major conferences to 24 February 2017, together with reference lists; and contacted selected experts in the field. Selection criteria We included a randomised controlled trial comparing partial and radical nephrectomy for participants with small renal masses. Data collection and analysis One review author screened all of the titles and abstracts; only citations that were clearly irrelevant were excluded at this stage. Next, two review authors independently assessed full-text reports, identified relevant studies, evaluated the eligibility of the studies for inclusion, assessed trial quality and extracted data. The update of the literature search was performed by two independent review authors. We used Review Manager 5 for data synthesis and data analyses. Main results We identified one randomised controlled trial including 541 participants that compared partial nephrectomy to radical nephrectomy. The median follow-up was 9.3 years. Based on low quality evidence, we found that time-to-death of any cause was decreased using partial nephrectomy (HR 1.50, 95% CI 1.03 to 2.18). This corresponds to 79 more deaths (5 more to 173 more) per 1000. Also based on low quality evidence, we found no difference in serious adverse events (RR 2.04, 95% CI 0.19 to 22.34). Findings are consistent with 4 more surgery-related deaths (3 fewer to 78 more) per 1000. Based on low quality evidence, we found no difference in time-to-recurrence (HR 1.37, 95% CI 0.58 to 3.24). This corresponds to 12 more recurrences (14 fewer to 70 more) per 1000. Due to the nature of reporting, we were unable to analyse overall rates for immediate and long-term adverse events. We found no evidence on haemodialysis or quality of life. Reasons for downgrading related to study limitations (lack of blinding, cross-over), imprecision and indirectness (a substantial proportion of patients were ultimately found not to have a malignant tumour). Based on the finding of a single trial, we were unable to conduct any subgroup or sensitivity analyses. Authors' conclusions Partial nephrectomy may be associated with a decreased time-to-death of any cause. With regards to surgery-related mortality, cancer-specific survival and time-to-recurrence, partial nephrectomy appears to result in little to no difference.

Background Degarelix is a gonadotropin-releasing hormone antagonist that leads to medical castration used to treat men with advanced or metastatic prostate cancer, or both. It is unclear how its effects compare to standard androgen suppression therapy. Objectives To assess the effects of degree compared with standard androgen suppression therapy for men with advanced hormone-sensitive prostate cancer. Search methods We searched multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science, LILACS until September 2020), trial registries (until October 2020), and conference proceedings (until December 2020). We identified other potentially eligible trials by reference checking, citation searching, and contacting study authors. Selection criteria We included randomized controlled trials comparing degarelix with standard androgen suppression therapy for men with advanced prostate cancer. Data collection and analysis Three review authors independently classified studies and abstracted data from the included studies. The primary outcomes were overall survival and serious adverse events. Secondary outcomes were quality of life, cancer-specific survival, clinical progression, other adverse events, and biochemical progression. We used a random-effects model for meta-analyses and assessed the certainty of evidence for the main outcomes according to GRADE. Main results We included 11 studies with a follow-up of between three and 14 months. We also identified five ongoing trials. Primary outcomes Data to evaluate overall survival were not available. Degarelix may result in little to no difference in serious adverse events compared to standard androgen suppression therapy (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.62 to 1.05; low-certainty evidence; 2750 participants). Based on 114 serious adverse events in the standard androgen suppression group, this corresponds to 23 fewer serious adverse events per 1000 participants (43 fewer to 6 more). We downgraded the certainty of evidence for study limitations and imprecision. Secondary outcomes Degarelix likely results in little to no difference in quality of life assessed with a variety of validated questionnaires (standardized mean difference 0.06 higher, 95% CI 0.05 lower to 0.18 higher; moderate-certainty evidence; 2887 participants), with higher scores reflecting better quality of life. We downgraded the certainty of evidence for study limitations. Data to evaluate cancer-specific survival were not available. The effects of degarelix on cardiovascular events are very uncertain (RR 0.15, 95% CI 0.04 to 0.61; very low-certainty evidence; 80 participants). We downgraded the certainty of evidence for study limitations, imprecision, and indirectness as this trial was conducted in a unique group of high-risk participants with pre-existing cardiovascular morbidities. Degarelix likely results in an increase in injection site pain (RR 15.68, 95% CI 7.41 to 33.17; moderate-certainty evidence; 2670 participants). Based on 30 participants per 1000 with injection site pain with standard androgen suppression therapy, this corresponds to 440 more injection site pains per 1000 participants (192 more to 965 more). We downgraded the certainty of evidence for study limitations. We did not identify any relevant subgroup differences for different degarelix maintenance doses. Authors' conclusions We did not find trial evidence for overall survival or cancer-specific survival comparing degarelix to standard androgen suppression, but serious adverse events and quality of life may be similar between groups. The effects of degarelix on cardiovascular events are very uncertain as the only eligible study had limitations, was small with few events, and was conducted in a high-risk population. Degarelix likely results in an increase in injection site pain compared to standard androgen suppression therapy. Maximum follow-up of included studies was 14 months, which is short. There is a need for methodologically better designed and executed studies with long-term follow-up evaluating men with metastatic prostate cancer.

Summary Objective To compare the efficacy and safety of different pivmecillinam (PIV) regimes for uncomplicated lower urinary tract infections (UTIs). Methods The MEDLINE, Embase, and Cochrane Library databases were searched. Randomized controlled clinical trials (RCTs) involving adults or children with symptoms suggestive of uncomplicated UTI and that compared different PIV regimes or PIV versus other antibiotics were included. Meta-analyses were conducted to obtain direct and indirect efficacy estimates. PIV regimes were categorized into high total dosage, moderate total dosage, and low total dosage. The risk of bias was evaluated using the Cochrane tool. Results Twenty-four RCTs were identified. No difference in clinical cure was found for the high vs. moderate (short-term: risk ratio (RR) 1.01, p =0.813; long term: RR 1.09, p =0.174) or high vs. low dosage comparisons (mean difference 0, 95% confidence interval −0.44 to 0.45, p =1). For bacteriological cure, comparisons of high vs. moderate dosage (short term: RR 1.05, p =0.056; long term: RR 1.05, p =0.131) and high vs. low dosage (short term: RR 1.02, p =0.759; long term: RR 1.13, p =0.247) showed a trend in favor of the high dosage treatment. Results for relapse, re-infection, and failure were inconclusive and not statistically significant. Patients treated with high dosages were 40% ( p =0.062) and 44% ( p =0.293) more likely to report mild to moderate adverse events. Conclusions There is insufficient evidence to support the use of an optimal combination of dosage, frequency, and duration of PIV therapy for the treatment of uncomplicated lower UTI. Evidence is limited due to the high risk of bias, poor reporting, and heterogeneous study data.

Introduction: With increasing life expectancy, curative treatment of octogenarians with urothelial carcinoma of the bladder (UCB) becomes more important. Materials and Methods: The treatment modalities of 276 octogenarians with UCB who were treated at the University Hospital of Erlangen between 1982 and 2011 were assessed retrospectively. Results: One hundred forty-six patients had non-muscle invasive bladder cancer (NMIBC) while 71 had muscle invasive bladder cancer (MIBC). No data was available for 59 patients. Eighty-five (58.2%) of the 146 patients with NMIBC received transurethral resection of the bladder tumor (TURBT) only, another 38 patients (26%) underwent additional intravesical therapy; and 8.9% were treated with radiochemotherapy (RCT), 4.1% with radiotherapy (RT), 1.4% with systemic chemotherapy and 1.4% with radical cystectomy (RC). Of the 71 patients suffering from MIBC, 39 (54.9%) received TURBT alone. A potentially curative therapy was performed on 31 of the 71 patients with MIBC (43.7%). Of these, 16 patients (51.6%) received RCT, 9 patients (29.0%) RT and 6 patients (19.4%) RC. In Kaplan-Meier analysis, patients with MIBC had better median overall survival with curative treatment compared to TURBT alone (28 vs. 9 months; p < 0.001, log-rank test). Conclusions: By offering a wide range of treatment options, over 43% of octogenarians with MIBC received a curative therapy at a maximum care hospital.

Objectives To describe genomic imbalances in plasmacytoid urothelial carcinoma (PUC), which is a rare and aggressive variant of urothelial carcinoma (UC). Methods and materials In total, 25 formalin-fixed paraffin-embedded PUCs were analyzed by metaphase comparative genomic hybridization. Genomic imbalances were considered to be characteristic if they were detected in≥20% of the cases. Chromosome regions deviating by≥3 standard deviations from the average chromosome profile were scored as chromosomal gains or losses. Copy-number variations (CNVs) of CDH1 (16q 22.1), SNAI1 (20q 13.1), CCND1 (11q13.3), ERBB2 (17q12), and FOXO3 (6q21) were validated using quantitative polymerase chain reaction. Results Chromosomal aberrations were detected in every PUC analyzed, and the average number of aberrations was 10.24 (ranging from 1–15). Characteristic aberrations were gains on 1q (48%), 3p (20%), 6p (32%), 11q (72%), 15q (36%), 16q (44%), 17p (76%), 17q (88%), and 20q (88%) and losses on 2q (24%) 4p (36%), 4q (84%), 5q (44%), 6q (68%), 13q (20%), and Xq (52%). polymerase chain reaction-based analysis of CNV for CCND1 (11q13) showed a deletion in 73% of the cases. CDH1 (16q22) was deleted in 72% and amplified in 5%. ERBB2 (17q12) displayed remarkably few copy-number alterations, with only 14% showing an amplification. SNAI1 (20q13) showed reduced gene copy numbers in 59.1% of the cases, whereas no copy-number gains were detected. FOXO3 (6q21) exhibited the lowest number of copy-number alterations, with 9% of all cases showing an amplification. Conclusions In PUCs, the frequency of aneuploidy and the complexity of genomic changes per tumor are greater than those described in conventional UC. The aberrations described in PUC involve the same regions that are associated with aggressive biological behavior in conventional UC. Gains on 11q, 17q, 17p, and 20q and losses on 4q and 6q affect most PUCs and seem to harbor important chromosomal regions for PUC carcinogenesis. Large-scale deletions on chromosome 9 were not detected. CNV analysis indicates heterozygous deletion of CDH1 as one underlying mechanism of loss of membranous E-cadherin in PUC. Loss of CCND1 and SNAI1 is a common molecular feature and could contribute to the aggressive biological behavior of PUC.

To introduce a simplified technique for MRI-guided core biopsies (MRGB) of the prostate in the supine position using large-bore magnet systems. Fifty men with a history of negative transrectal ultrasound-guided biopsies underwent MRGB in either a 1.5-T (13/50) or 3.0-T (37/50) wide-bore MRI unit. MRGBs were conducted with the patients in a supine position using a dedicated MR-compatible biopsy device. We developed a dedicated positioning device for the supine position. Using this device, the biopsies were performed successfully in all patients. Apart from minor rectal bleeding, only one patient developed a major side effect (urosepsis). Histology revealed prostate cancer in 25/50 (50 %) patients. The new technique appears feasible. Its major advantage is the more comfortable and patient-friendly supine position during the biopsy without the need to modify the MRI system’s patient table. • A novel positioning device for MRI-guided prostate biopsies has been developed. • Biopsies can be performed in the patient-friendly supine position. • The positioning device can be utilised without modifying the MRI’s patient table.

Introduction: Renal cell carcinoma (RCC) is characterized by intense angiogenesis with hyperexpression of proangiogenic factors. This study explored the potential of dynamic tissue perfusion measurement (DTPM) to detect differences in tissue perfusion between kidneys with RCC and corresponding healthy kidneys. Patients and Methods: 30 patients with unilateral, histologically confirmed RCC underwent DTPM by color Doppler ultrasound. Before scheduled surgery, Doppler ultrasound data were acquired from four transverse areas of the affected kidney and the contralateral healthy kidney. Doppler ultrasound data were recorded over a 10-second period and characteristic tissue perfusion parameters were determined. Results: The kidneys with RCC displayed characteristic changes in perfusion parameters. A significant increase in signal intensity and a significant decrease in flow resistance were noted. A combination of several DTPM parameters was used to distinguish correctly between kidneys bearing RCC or healthy kidneys with up to 75% accuracy. There was no association between the perfusion parameters and the pathological characteristics of the respective tumors. Conclusions: DTPM is a promising tool for the evaluation of whole-organ tissue perfusion. This study demonstrates the feasibility of performing DTPM measurements in kidneys bearing RCC lesions. In tumors that are characterized by extensive neovascularization, this method has the potential to be a valuable diagnostic tool.

Loss of E-cadherin represents a hallmark of plasmacytoid differentiation. We analyzed the effect of membranous E-cadherin loss and its nuclear accumulation in patients with locally advanced conventional urothelial carcinoma (UC) who were treated with radical cystectomy and adjuvant chemotherapy. A total of 247 formalin-fixed, paraffin-embedded tumor samples were reviewed to detect histological variants of UC. Immunohistochemical staining of E-cadherin was performed and analyzed for membranous and nuclear expression. The correlation between E-cadherin expression and histology was assessed, and overall survival (OS) was analyzed with univariate and multivariate Cox regression and Kaplan–Meier analyses. Correlation of nuclear E-cadherin to tumor stage (pT), lymph node metastasis (pN), histologic subtype, and chemotherapy was performed by Fisher’s exact test. Membranous and nuclear E-cadherin expression was strongly correlated to plasmacytoid urothelial carcinoma (PUC) (p