Different patients, different preferences: A multicenter assessment of patients' personality traits and anxiety in shared decision making.

OBJECTIVE: Patient-centered care and shared decision making (SDM) are generally recognized as the gold standard for medical consultations, especially for preference-sensitive decisions. However, little is known about psychological patient characteristics that influence patient-reported preferences. We set out to explore the role of personality and anxiety for a preference-sensitive decision in bladder cancer patients (choice of urinary diversion, UD) and to determine if anxiety predicts patients' participation preferences. METHODS: We recruited a sample of bladder cancer patients (N = 180, primarily male, retired) who awaited a medical consultation on radical cystectomy and their choice of UD. We asked patients to fill in a set of self-report questionnaires before this consultation, including measures of treatment preference, personality (BFI-10), anxiety (STAI), and participation preference (API and API-Uro), as well as sociodemographic characteristics. RESULTS: Most patients (79%) indicated a clear preference for one of the treatment options (44% continent UD, 34% incontinent UD). Patients who reported more conscientiousness were more likely to prefer more complex methods (continent UD). The majority (62%) preferred to delegate decision making to healthcare professionals. A substantial number of patients reported elevated anxiety (32%), and more anxiety was predictive of higher participation preference, specifically for uro-oncological decisions (ß = 0.207, p < 0.01). CONCLUSIONS: Our findings provide insight into the role of psychological patient characteristics for SDM. Aspects of personality such as conscientiousness influence treatment preferences. Anxiety contributes to patients' motivation to be involved in pertinent decisions. Thus, personality and negative affect should be considered to improve SDM.

Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells.

Invasive urothelial carcinomas of the bladder (UCB) characteristically show a loss of differentiation markers. The transcription factor Grainyhead-like 3 (GRHL3) plays an important role in the development and differentiation of normal urothelium. The contribution to UCB progression is still elusive. Differential expression of GRHL3 was assessed in normal human urothelium and in non-invasive and invasive bladder cancer cell lines. The contribution of GRHL3 to cell proliferation, viability and invasion in UCB cell lines was determined by gain- and loss-of-function assays in vitro and in an organ culture model using de-epithelialized porcine bladders. GRHL3 expression was detectable in normal human urothelial cells and showed significantly higher mRNA and protein levels in well-differentiated, non-invasive RT4 urothelial carcinoma cells compared to moderately differentiated RT112 cells. GRHL3 expression was absent in anaplastic and invasive T24 cells. Ectopic de novo expression of GRHL3 in T24 cells significantly impaired their migration and invasion properties in vitro and in organ culture. Its downregulation improved the invasive capacity of RT4 cells. The results indicate that GRHL3 may play a role in progression and metastasis in UCB. In addition, this work demonstrates that de-epithelialized porcine bladder organ culture can be a useful, standardized tool to assess the invasive capacity of cancer cells.

POFUT1 mRNA expression as an independent prognostic parameter in muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is characterized by high recurrence and rapid progression. Progression is linked to changes in glycan structures and altered levels of glycosyltransferases. The relationship of mRNA expression by glycosyltransferase genes B4GALT1, EXT1, MGAT5B, and POFUT1 to the probability of surviving MIBC after radical cystectomy has not yet been investigated. mRNA expression was analyzed using qRT-PCR in formalin-fixed and paraffin-embedded tumor samples (n = 105; 74% male patients and 26% female patients; median age = 72 years), correlated with histopathological variables, and evaluated by means of multivariable Cox regression analysis regarding to overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Multivariable Cox regression analysis identified POFUT1 mRNA expression as superior prognostic marker, compared with currently used histological tumor stage methods, for CSS by MIBC patients following radical cystectomy. Thus, the patients with low POFUT1 mRNA were at a 4.9-fold greater risk for cancer-specific death according to the multivariable analysis (p = 0.0001). Low mRNA levels predicted poor survival according to the Kaplan-Meier analysis ((POFUT1:OS p = 0.0014; CSS p = 0.0007; DFS p = 0.0088); (EXT1:OS p = 0.0150; CSS p = 0.0130; DFS p = 0.0286); (B4GALT1:CSS p = 0.0134; DFS p = 0.0493)). A subgroup analysis of patients without lymph node metastasis (pN-; n = 73) indicated that low expression of POFUT1 predicted reduced OS (p = 0.0073), CSS (p = 0.0058,) and DSS (p = 0.0079). Low levels of POFUT1 mRNA are an independent prognostic indicator for OS and CSS in MIBC patients following radical cystectomy. This finding demonstrates the importance of altered glycosylation for the progress of MIBC.

[The impact of radical cystectomy on health-related quality of life and potential for optimisation]. / Einfluss der radikalen Zystektomie auf die Lebensqualität und Strategien für deren Erhalt.

Radical cystectomy may have a major impact on the lives of affected patients. Older patients often have a reduced life expectancy after radical cystectomy. Therefore, aspects of health-related quality of life (HRQOL) have to be balanced against a solely tumour-directed therapy. In this narrative review, factors influencing the HRQOL of affected patients were identified and discussed by selective literature search.Besides strategies to minimise perioperative morbidity, these include a patient-oriented and individualised treatment plan taking into account factors such as age, comorbidities, choice of urinary diversion and age-specific conditions, in particular frailty. Patient-reported outcome measures (PROMs) are crucial instruments to assess HRQOL outcomes and should be further implemented into routine clinical use.

Correction: Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells.

The serine protease hepsin is frequently overexpressed in human prostate cancer (PCa) and is associated with matrix degradation and PCa progression in mice. Curiously, low expression of hepsin is associated with poor survival in different cancer types, and transgenic overexpression of hepsin leads to loss of viability in various cancer cell lines. Here, by comparing isogenic transfectants of the PCa cell line PC-3 providing inducible overexpression of wild-type hepsin (HPN) vs. the protease-deficient mutant HPNS353A, we were able to attribute hepsin-mediated tumor-adverse effects to its excess proteolytic activity. A stem-like expression signature of surface markers and adhesion molecules, Notch intracellular domain release, and increased pericellular protease activity were associated with low expression levels of wild-type hepsin, but were partially lost in response to overexpression. Instead, overexpression of wild-type hepsin, but not of HPNS353A, induced relocalization of the protein to the cytoplasm, and increased autophagic flux in vitro as well as LC3B punctae frequency in tumor xenografts. Confocal microscopy revealed colocalization of wild-type hepsin with both LC3B punctae as well as with the autophagy cargo receptor p62/SQSTM1. Overexpression of wild type, but not protease-deficient hepsin induced expression and nuclear presence of CHOP, indicating activation of the unfolded protein response and ER-associated protein degradation (ERAD). Whereas inhibitors of ER stress and secretory protein trafficking slightly increased viability, combined inhibition of the ubiquitin-proteasome degradation pathway (by bortezomib) with either ER stress (by salubrinal) or autophagy (by bafilomycin A1) revealed a significant decrease of viability during overexpression of wild-type hepsin in PC-3 cells. Our results demonstrate that a precise control of Hepsin proteolytic activity is critical for PCa cell fate and suggest, that the interference with ERAD could be a promising therapeutic option, leading to induction of proteotoxicity in hepsin-overexpressing tumors.

Systematic prostate biopsy still matters: A comprehensive analysis of MRI/TRUS-fusion targeted prostate biopsies across different indications.

OBJECTIVES: To assess if a multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TB) strategy is precise enough to replace systematic biopsies (SB) among men with different biopsy indications since an imaging-based pathway to guide indication and targeted prostate biopsy is currently under debate. MATERIALS AND METHODS: Retrospective analysis was performed of 594 patients with one or more lesions according to Prostate Imaging and Reporting Data System (PI-RADS) receiving a consecutive TB and SB for one of the 3 indications: primary cancer suspicion (51.7%), persistent cancer suspicion after prior negative biopsy (35.4%), or control of a confirmed cancer (12.9%). Detection rates for overall cancer (CaP) and clinically significant cancer (csCaP, Gleason Score ≥3+4) were compared between TB and SB and to a combined approach for all patients and within the subgroups. Characteristics of cancers missed by one biopsy strategy were analyzed. RESULTS: TB detected less CaP (302 vs. 366, P < 0.001) and csCaP (204 vs. 210 patients, P = 0.409) compared to SB except for men with prior negative biopsies (65 vs. 64 csCaP, P = 0.363). Cancer detection by TB or SB was independent of cancer localization and imaging characteristics. Combined TB and SB outperformed the single approaches for CaP and csCaP detection in each subgroup. CONCLUSIONS: A single mpMRI and TB approach leads to a substantial number of missed CaP and csCaP across biopsies with different indications. Ongoing improvements of imaging, reading standardization, and biopsy techniques are required before replacing SB.

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

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

Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder.

Muscle-invasive urothelial carcinoma of the urinary bladder (UCB) often recurs following radical cystectomy (RC). An altered expression of sex-steroid hormone receptors has been associated with oncological outcomes of UCB and may represent therapeutic targets. Here the expression of different hormone receptors was measured on mRNA levels in patients treated by RC and associated with outcomes. Androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR) mRNA expression was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in RC samples of 87 patients with a median age of 66 (39-88) years. Univariate and multivariate analyses were performed to test associations with pathological and clinical characteristics as well as recurrence-free (RFS) and disease-specific survival (DSS). AR mRNA expression was lower in comparison with ESR1 and PGR expression (p < 0.0001). In univariate analysis, high expression levels of AR were associated with reduced RFS (HR 2.8, p = 0.015) and DSS (HR 2.8, p = 0.010). High AR mRNA expression and a positive lymph node status were independent predictors for reduced RFS (HR 2.5, p = 0.0049) and DSS (HR 3.4, p = 0.009). In patients with low AR mRNA expression, an increased ESR1 and PGR mRNA expression were associated with reduced RFS and DSS. High expression levels of AR are significantly associated with adverse outcome in patients with muscle-invasive UCB following RC. ESR1 and PGR expression status can further stratify patients with low AR expression into subgroups with significantly reduced RFS and DSS. Therapeutic targeting of AR may influence outcomes in patients with UCB.

Predictive value of lymphangiogenesis and proliferation markers on mRNA level in urothelial carcinoma of the bladder after radical cystectomy.

OBJECTIVE: To evaluate the mRNA expression of lymphangiogenesis and proliferation markers and to examine its association with histopathological characteristics and clinical outcome in patients with urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). PATIENTS AND METHODS: Gene expression analysis of the vascular endothelial growth -C and -D (VEGF-C/-D), its receptor VEGF receptor-3 (VEGFR-3), MKI67, and RACGAP1 was performed in 108 patients after radical cystectomy and their correlation with clinical-pathological parameters was investigated. Uni- and multivariate regression analyses were used to identify predictors for cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS) after RC. RESULTS: The expression of RACGAP1 and VEGFR-3 showed an association with a higher pT stage (P = 0.049; P = 0.009). MKI67 showed an association with a high-grade urothelial carcinoma of the bladder (P = 0.021). VEGFR-3 expression was significantly associated with the presence of lymphovascular invasion (LVI) (P = 0.016) and lymph node metastases (pN+) (P = 0.028). With the univariate analysis, overexpression of VEGFR-3 (P = 0.029) and the clinical-pathological parameters pT stage (P < 0.0001), pN+ (P = 0.0004), LVI (P < 0.0001) and female gender (P = 0.021) were significantly associated with a reduced CSS. Multivariate analysis identified a higher pT stage (P = 0.017) and LVI (P = 0.008) as independent predictors for reduced CSS. Independent predictors for reduced OS were a higher pT stage (P = 0.0007) and LVI (P = 0.0021), while overexpression of VEGF-D was associated with better OS (P < 0.0001). CONCLUSIONS: The mRNA expression of the investigated markers showed associations with common histopathological parameters. Increased expression of VEGF-D is independently associated with better overall survival.

Prostate cancer treatment by the latest focal HIFU device with MRI/TRUS-fusion control biopsies: A prospective evaluation.

OBJECTIVES: Magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion-guided focal high intensity focused ultrasound (HIFU) therapy of the prostate has recently been developed as a selective HIFU-therapy technique to enable targeted ablation of prostate cancer. Here we report a series of patients treated with focal HIFU therapy, discuss its potential pitfalls, and address controversies concerning the indications. MATERIALS AND METHODS: This single-center prospective study reports outcomes of patients treated from September 2014 to March 2016. Follow-up was a minimum of 12 months. MRI/TRUS-fusion-guided HIFU was performed under general anesthesia using the Focal One® device (EDAP, France). A control biopsy at 12 months was taken using the MRI/TRUS-fusion biopsy platform Artemis™ (Eigen, California) combining targeted and systematic cores. Prostate-specific antigen (PSA) changes from baseline, patient-reported outcome measures, and complications using the Clavien-Dindo classification system are also reported. RESULTS: Twenty-four patients (PSA < 10 ng/ml, n = 17 Gleason 3+3, n = 7 Gleason 3+4) with either unifocal or bifocal prostate imaging reporting and data system (PI-RADS) 3-5 lesions (n = 19) or without a PI-RADS lesion (n = 5) were treated. Nineteen patients underwent focal HIFU, five patients zonal HIFU. Of the 20 patients that had biopsies at 12 months, 8 patients had a positive biopsy within the ablation zone (overall cancer free rate: 60%). Using different definitions of clinically significant cancer, the cancer-free rate for the ablation zone varies between 75% and 95%. Four of the eight patients (all persistent Gleason 3+4 or upgrading to 4+3) underwent a radical whole gland salvage therapy. Patient-reported outcome measures showed no significant decrease in urinary continence (expanded prostate cancer index composite -26 urinary incontinence: P = 0.080), but there was a reduction in potency (International index of erectile function in preoperatively potent patients: median decrease of 2 points to a median of 19 points at 12 months; 95% confidence interval: 15.79-22.21; P = 0.044). Only one complication > grade II occurred. CONCLUSIONS: Targeted MRI/TRUS fusion-guided focal HIFU allows local tumor ablation, but is not free from limitations. The procedure has good functional outcomes and a quick recovery. Multicenter trials with more patients are required to determine the procedure´s role in the prostate cancer therapy algorithm.

Sarcopenia as a comorbidity-independent predictor of survival following radical cystectomy for bladder cancer.

BACKGROUND: A multicentre study was conducted to investigate the impact of sarcopenia as an independent predictor of oncological outcome after radical cystectomy for bladder cancer. METHODS: In total, 500 patients with available digital computed tomography scans of the abdomen obtained within 90 days before surgery were identified. The lumbar skeletal muscle index was measured using pre-operative computed tomography. Cancer-specific survival (CSS) and overall survival (OS) were estimated using Kaplan-Meier curves. Predictors of CSS and OS were analysed by univariable and multivariable Cox regression models. RESULTS: Based on skeletal muscle index, 189 patients (37.8%) were classified as sarcopenic. Patients with sarcopenia were older compared with their counterparts (P = 0.002), but both groups were comparable regarding to gender, comorbidity, tumor, node, metastasis (TNM) stage, and type of urinary diversion (all P > 0.05). In total, 234 (46.8%) patients died, and of these, 145 (29.0%) died because of urothelial carcinoma of the bladder. Sarcopenic patients had significantly worse 5 year OS (38.3% vs. 50.5%; P = 0.002) and 5 year CSS (49.5% vs. 62.3%; P = 0.016) rates compared with patients without sarcopenia. Moreover, sarcopenia was associated independently with both increased all-cause mortality (hazard ratio, 1.43; 95% confidence interval 1.09-1.87; P = 0.01) and increased cancer-specific mortality (hazard ratio, 1.42; 95% confidence interval, 1.00-2.02; P = 0.048). Our results are limited by the lack of prospective frailty assessment. CONCLUSIONS: Sarcopenia has been shown to be an independent predictor for OS and CSS in a large multicentre study with patients undergoing radical cystectomy for bladder cancer.

[Role of the human ErbB family receptors in urothelial carcinoma of the bladder: mRNA expression status and prognostic relevance]. / Bedeutung der ERBB-Rezeptorfamilie beim Urothelkarzinom der Harnblase: mRNA-Expression und prognostische Relevanz.

Background Altered expression of epidermal growth factor (EGF) family (ErbB) receptors in urothelial carcinoma of the urinary bladder (UCB) has been associated with adverse outcomes. Given the limited treatment options in UCB, EGFR and HER2 (ERBB2) represent established therapeutic targets in other entities. We assessed the expression of ErbB family receptors (ERBB1 - 4) on mRNA levels in correlation with histopathological and clinical parameters in patients treated with radical cystectomy (RC). Methods 94 patients (female = 22; male = 72; median age: 66.5 years [range 39 - 88]) with UCB (pT1 - 4) treated with RC were included. Median follow-up was 28.2 months (range 0.6 - 139). ErbB mRNA expression levels were determined after extraction from formalin-fixed, paraffin-embedded tissue. Univariate and multivariate Cox proportional hazard models were performed to assess recurrence-free survival (RFS) and cancer-specific survival (CSS). Results Overexpression was observed in 18 % (ERBB3), 39 % (EGFR), 34 % (HER2, ERBB2) and 30 % (ERBB4) of patients, respectively. Higher pathological stage (p = 0.012), a positive nodal status (p = 0.0002), high ERBB4 (p = 0.012) and high HER2 (ERBB2) levels (p = 0.014) were significantly associated with reduced RFS. A negative lymph node status (p = 0.0003) and low HER2 (ERBB2) (p = 0.042) levels had a favourable prognostic impact on CSS. In multivariate analysis, positive pN stage (p = 0.0011) and high ERBB4 (p = 0.0073) expression were independent predictors of reduced RFS. Higher pN stage (p = 0.0016) was an independent predictor of reduced CSS. Conclusions Higher HER2 (ERBB2) expression is associated with an unfavourable prognosis in patients with UCB. However, it is not an independent predictor when measured on mRNA levels. Further analyses need to clarify which patients may still benefit from HER2 (ERBB2) targeted drugs.

[Systematic review on conservative treatment options in non-muscle-invasive bladder cancer patients refractory to Bacillus Calmette-Guérin instillation therapy]. / Konservative Therapieoptionen beim nicht-muskelinvasiven Urothelkarzinom der Harnblase nach BCG-Versagen: Systematische Übersichtsarbeit.

Background Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). However, a significant proportion of patients fail treatment, and radical cystectomy (RC) is the subsequent gold standard. On the other hand, there is an unmet need for conservative alternatives for patients who are unfit or unwilling to undergo surgery. This study aimed to identify conservative treatment options in NMIBC patients after BCG failure. Material and Methods We performed a systematic search in the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, including all randomised controlled trials (RCTs), quasi-RCTs and single-arm studies, in which patients with NMIBC were treated with second-line intravesical or systemic therapy after BCG failure. A minimum of eight patients were included in each treatment arm. Full papers were restricted to English language. Literature research and data analysis were assessed independently by two reviewers. Data on treatment response, recurrence, time to recurrence, progression and rate of cystectomy were collected and analysed. Results This systematic review included 42 publications with a total of 3521 patients (2371 BCG failures). Valrubicin, taxanes, gemcitabine, combination chemotherapy, thermochemotherapy, photodynamic therapy, combination of BCG and interferon and immunotherapies or targeted therapies were identified as conservative treatment options. For taxanes, gemcitabine and thermochemotherapy there is the highest evidence for a clinical meaningful response with minor toxicities. Conclusions Despite some promising response rates for taxanes, gemcitabine or thermochemotherapy, an evidence-based recommendation for treatment options superior to RC in patients failing BCG therapy cannot be made. The definition of BCG failure is still inconsistent and heterogeneous outcomes in patients with BCG failure have been reported. In order to identify effective conservative therapy options in patients failing BCG therapy, prospective trials with a standardised trial design are needed.

Effect of Hospital and Surgeon Case Volume on Perioperative Quality of Care and Short-term Outcomes After Radical Cystectomy for Muscle-invasive Bladder Cancer: Results From a European Tertiary Care Center Cohort.

BACKGROUND: Case volume has been suggested to affect surgical outcomes in different arrays of procedures. We aimed to delineate the relationship between case volume and surgical outcomes and quality of care criteria of radical cystectomy (RC) in a prospectively collected multicenter cohort. PATIENTS AND METHODS: This was a retrospective analysis of a prospectively collected European cohort of patients with bladder cancer treated with RC in 2011. We relied on 479 and 459 eligible patients with available information on hospital case volume and surgeon case volume, respectively. Hospital case volume was divided into tertiles, and surgeon volume was dichotomized according to the median annual number of surgeries performed. Binomial generalized estimating equations controlling for potential known confounders and inter-hospital clustering assessed the independent association of case volume with short-term complications and mortality, as well as the fulfillment of quality of care criteria. RESULTS: The high-volume threshold for hospitals was 45 RCs and, for high-volume surgeons, was > 15 cases annually. In adjusted analyses, high hospital volume remained an independent predictor of fewer 30-day (odds ratio, 0.34; P = .002) and 60- to 90-day (odds ratio, 0.41; P = .03) major complications but not of fulfilling quality of care criteria or mortality. No difference between surgeon volume groups was noted for complications, quality of care criteria, or mortality after adjustments. CONCLUSION: The coordination of care at high-volume hospitals might confer a similar important factor in postoperative outcomes as surgeon case volume in RC. This points to organizational elements in high-volume hospitals that enable them to react more appropriately to adverse events after surgery.

The Use of Neoadjuvant Chemotherapy in Patients With Urothelial Carcinoma of the Bladder: Current Practice Among Clinicians.

INTRODUCTION: Guidelines recommend neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in patients with urothelial carcinoma of the bladder in clinical stages T2-T4a, cN0M0. We examined the frequency and current practice of NAC and sought to identify predictors for the use of NAC in a prospective contemporary cohort. MATERIALS AND METHODS: We analyzed prospective data from 679 patients in the PROMETRICS (PROspective MulticEnTer RadIcal Cystectomy Series 2011) database. All patients underwent RC in 2011. Uni- and multivariable regression analyses identified predictors of NAC application. Furthermore, a questionnaire was used to evaluate the practice patterns of NAC at the PROMETRICS centers. RESULTS: A total of 235 patients (35%) were included in the analysis. Only 15 patients (2.2%) received NAC before RC. Younger age (< 70 years; P = .035), lower case volume of the center (< 30 RC/year; P < .001), and advanced tumor stage (≥ cT3; P = .038) were identified as predictors for NAC. Of the 200 urologists who replied to the questionnaire, 69% (n = 125) declared tumor stage cT3-4 a/o N1M0 to be the best indication for NAC application, although 45% of the urologists stated that they would not perform NAC despite recommendations. The decision for NAC was made by the individual urologist in 69% of cases, and only 29% reported that all cases were discussed in an interdisciplinary tumor board. CONCLUSION: NAC was rarely applied in the present cohort. We observed a discrepancy between guideline recommendations and practice patterns, despite medical indication and pre-therapeutic interdisciplinary discussion. The potential benefit of NAC within a multimodal approach seems to be neglected by many urologists.

Comparative analysis of the effect of prostatic invasion patterns on cancer-specific mortality after radical cystectomy in pT4a urothelial carcinoma of the bladder.

PURPOSE: To evaluate the prognostic relevance of different prostatic invasion patterns in pT4a urothelial carcinoma of the bladder (UCB) after radical cystectomy. MATERIALS AND METHODS: Our study comprised a total of 358 men with pT4a UCB. Patients were divided in 2 groups-group A with stromal infiltration of the prostate via the prostatic urethra with additional muscle-invasive UCB (n = 121, 33.8%) and group B with continuous infiltration of the prostate through the entire bladder wall (n = 237, 66.2%). The effect of age, tumor grade, carcinoma in situ, lymphovascular invasion, soft tissue surgical margin, lymph node metastases, administration of adjuvant chemotherapy, and prostatic invasion patterns on cancer-specific mortality (CSM) was evaluated using competing-risk regression analysis. Decision curve analysis was used to evaluate the net benefit of including the variable invasion pattern within our model. RESULTS: The estimated 5-year CSM-rates for group A and B were 50.1% and 66.0%, respectively. In multivariable competing-risk analysis, lymph node metastases (hazard ratio [HR] = 1.73, P<0.001), lymphovascular invasion (HR = 1.62, P = 0.0023), soft tissue surgical margin (HR = 1.49, P = 0.026), absence of adjuvant chemotherapy (HR = 2.11, P<0.001), and tumor infiltration of the prostate by continuous infiltration of the entire bladder wall (HR = 1.37, P = 0.044) were significantly associated with a higher risk for CSM. Decision curve analysis showed a net benefit of our model including the variable invasion pattern. CONCLUSIONS: Continuous infiltration of the prostate through the entire bladder wall showed an adverse effect on CSM. Besides including these patients into clinical trials for an adjuvant therapy, we recommend including prostatic invasion patterns in predictive models in pT4a UCB in men.

Malignant Perivascular Epithelioid Cell Neoplasm (PEComa) of the Pelvis: A Case Report.

Perivascular epithelioid cell neoplasms (PEComa) are rare mesenchymal tumors that can occur in any part of the body and have unpredictable pathological behavior. They are usually benign, but may be malignant. We present a case of malignant PEComa of the pelvic retroperitoneum treated with radical surgery.

Prediction of Locally Advanced Urothelial Carcinoma of the Bladder Using Clinical Parameters before Radical Cystectomy--A Prospective Multicenter Study.

INTRODUCTION: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. MATERIALS AND METHODS: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. RESULTS: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p < 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p < 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p < 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. CONCLUSION: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters.