The Characterization of Non-oncologic Chronic Drug Therapy in Bladder Cancer Patients and the Impact on Recurrence-Free and Cancer-Specific Survival: A Prospective Study.

We aimed to characterize non-oncologic chronic drug therapy of bladder cancer (BC) patients and evaluate a possible impact on recurrence-free (RFS) and cancer-specific survival (CSS). Patients with a first diagnosis (FD) of BC or radical cystectomy (RC) were included in a prospective, monocentric, observational study. Drugs and medical data was assessed at start and three-monthly for 24 months. Drugs were classified by anatomical-therapeutic-chemical code (ATC). Endpoints for outcome analysis were RFS and CSS in univariate (Kaplan-Meier curves and log-rank test, Cox regression for Hazard Ratio (HR)) and multivariate (Cox regression models) analyses. Of 113 patients, 52 had FD and 78 RC. Median age was 74 and 72 years, 83% and 82% were male. Drugs of 114 ATC classes were taken by 48 (92%) FD patients (median number 4.5/IQR 2-7.5) and 73 (94%) of RC patients (median 5/IQR 2-9). In univariate analysis (log-rank test (p)/Cox regression (HR, 95% CI, p)), polypharmacy (p = 0.036/HR = 2.83, 95% CI = 1.02-7.90, p = 0.047), calcium channel blockers (p = 0.046/HR = 2.47, 95% CI = 0.97-6.27, p = 0.057) and proton pump inhibitors (p = 0.015/HR = 3.16, 95% CI = 1.18-8.41, p = 0.022) had a significant negative impact on RFS in RC patients, statins (p = 0.025/HR = 0.14, 95% CI = 0.02-1.06, p = 0.057) a positive effect on RFS in FD patients, angiotensin-converting enzyme inhibitors (p = 0.008/HR = 10.74, 95% CI = 1.20-96.17, p = 0.034) and magnesium (p = 0.042/HR = 5.28, 95% CI = 0.88-31.59, p = 0.067) a negative impact on CSS in FD patients. In multivariate analysis, the only significant drug effects were the negative impact of angiotensin-converting enzyme inhibitors (HR = 15.20, 95% CI = 1.30-177.67, p = 0.030) and magnesium (HR = 22.87, 95% CI = 1.57-333.81), p = 0.022) on CSS in FD patients, and the positive impact of statins (HR = 0.12, 95% CI = 0.01-0.97, p = 0.047) on RFS in FD patients. Impact of non-oncologic drugs on RFS and CSS was small in this prospective study. Thus, appropriate treatment of comorbidities is encouraged.

Macrophage-Derived Factors with the Potential to Contribute to Pathogenicity of HIV-1 and HIV-2: Role of CCL-2/MCP-1.

Human immunodeficiency virus type 2 (HIV-2) is known to be less pathogenic than HIV-1. However, the mechanism(s) underlying the decreased HIV-2 pathogenicity is not fully understood. Herein, we report that ß-chemokine CCL2 expression was increased in HIV-1-infected human monocyte-derived macrophages (MDM) but decreased in HIV-2-infected MDM when compared to uninfected MDM. Inhibition of CCL2 expression following HIV-2 infection occurred at both protein and mRNA levels. By microarray analysis, quantitative PCR, and Western blotting, we identified that Signal Transducer and Activator of Transcription 1 (STAT1), a critical transcription factor for inducing CCL2 gene expression, was also reduced in HIV-2-infected MDM. Blockade of STAT1 in HIV-infected MDM using a STAT1 inhibitor significantly reduced the production of CCL2. In contrast, transduction of STAT1-expressing pseudo-retrovirus restored CCL2 production in HIV-2-infected MDM. These findings support the concept that CCL2 inhibition in HIV-2-infected MDM is meditated by reduction of STAT1. Furthermore, we showed that STAT1 reduction in HIV-2-infected MDM was regulated by the CUL2/RBX1 ubiquitin E3 ligase complex-dependent proteasome pathway. Knockdown of CUL2 or RBX1 restored the expression of STAT1 and CCL2 in HIV-2-infected MDM. Taken together, our findings suggest that differential regulation of the STAT1-CCL2 axis may be one of the mechanisms underlying the different pathogenicity observed for HIV-1 and HIV-2.

Validation of a CE-IVD, urine exosomal RNA expression assay for risk assessment of prostate cancer prior to biopsy.

Improved risk stratification of patients suspected of prostate cancer prior to biopsy continues to be an unmet clinical need. ExoDx Prostate (IntelliScore) "EPI" is a non-invasive urine test utilizing RNA from exosomes to provide a risk score that correlates with the likelihood of finding high grade prostate cancer at biopsy. Here, we present the results from a prospective clinical validation study of EPI-CE, a CE-marked in-vitro diagnostic (IVD) assay, specifically developed for use in European clinical laboratories. The study (NCT04720599) enrolled patients with ≥ 50 years, PSA 2-10 ng/mL, prior to MRI, who were scheduled for initial biopsy. First catch urine samples were collected from participants without prior digital rectal examination or prostate massage. Exosomal RNA was isolated and expression levels of three biomarkers ERG, PCA3 and SPDEF were analyzed according to the EPI-CE Instructions For Use. In the study cohort of N = 109 patients, EPI-CE was validated to have a Negative Predictive Value of 89%, a Sensitivity of 92% and a superior performance to two commonly used multiparametric risk calculators (PCPT and ERSPC) in both Receiver Operating Characteristics with a higher Area Under the Curve for EPI-CE 0.67 (95% CI 0.56-0.77) versus PCPT 0.59 (95% CI 0.47-0.71) and ERSPC 0.60 (95% CI 0.49-0.72) and higher Net Benefits analysis across a wide range of risk acceptance levels. This is the first clinical study reporting on the performance of EPI-CE. We demonstrate that EPI-CE provides information beyond standard clinical parameters and provides a better risk assessment prior to MRI, of patients suspected of prostate cancer, than the commonly used multiparametric risk calculators.

Clinical Implication of Borderline CT-Morphological Metastatic Spread in Bladder Cancer: What You See Is Not Always What You Got.

INTRODUCTION: Palliative radical cystectomy (pRC) may be offered to selected bladder cancer (BC) patients with grievous local symptoms. However, there is only scarce information on perioperative complications and prognosis, especially in the case of metastatic spread. We intended to analyze morbidity and oncological outcome in this patient subgroup. MATERIALS: Patients undergoing pRC because of BC with radiologic evidence of metastases were included in this retrospective study. Perioperative adverse events (AEs) were graded by the Clavien-Dindo Classification system. All patients underwent CT-based surveillance, and questionnaires were sent for survival follow-up in predefined intervals. Oncological outcome and predictive markers were assessed in univariate and multivariate analyses, using log-rank tests and Cox-regression analyses. RESULTS: Between 2004 and 2016, 77 patients were identified. Median age at surgery was 70 years (IQR 66-77) and the median follow-up time was 12 months (IQR 4-44). Preoperative staging revealed pulmonary, hepatic, bone, peritoneal, and various other metastasis in 46/77 (60%), 14/77 (18%), 11/77 (14%), 5/77 (7%), and 11/77 (14%) cases, respectively. Most frequently observed symptoms at the time of pRC were severe gross hematuria (n = 41) and intense pain (n = 11). Most AEs were of minor grade (83%). The median length of stay was 20 days. Median CSS was 13 months with a 5-year CSS of 34%. Intriguingly and unsuspectedly, preoperatively suspicious lung lesions were confirmed during surveillance only in 33%, respectively. In multivariate analysis, intraoperative blood transfusions (HR = 2.25, 95% CI: 1.09-4.63, p = 0.028) were significantly associated with decreased CSS. The best outcome was observed in patients with only subpleural metastases (CSS 80 months, p = 0.039) and normal CRP- and Hb values. CONCLUSION: pRC can be performed with acceptable perioperative morbidity and mortality. Pulmonary lesions seem to have a risk of false-positive results and should be biopsied in all uncertain cases. Localization of lung metastases together with preoperative CRP- and Hb levels seem to play a prognostic role.

Computed-tomography based scoring system predicts outcome for clinical lymph node-positive patients undergoing radical cystectomy

ABSTRACT Purpose: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. Materials and Methods: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. Results: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p <0.001). Conclusion: In our study, solely LN size >15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

Computed-tomography based scoring system predicts outcome for clinical lymph node-positive patients undergoing radical cystectomy.

PURPOSE: Contrast-enhanced CT scan is the standard staging modality for patients with bladder cancer undergoing radical cystectomy (RC). Involvement of lymph nodes (LN) determines prognosis of patients with bladder cancer. The detection of LN metastasis by CT scan is still insufficient. Therefore, we investigated various CT scan characteristics to predict lymph node ratio (LNR) and its impact on survival. Also, pre-operative CT scan characteristics might hold potential to risk stratify cN+ patients. MATERIALS AND METHODS: We analyzed preoperative CT scans of patients undergoing RC in a tertiary high volume center. Retrospectively, local tumor stage and LN characteristics such as size, morphology (MLN) and number of loco-regional LN (NLN) were investigated and correlation to LNR and survival was analyzed. CT scan characteristics were used to develop a risk stratification using Kaplan-Maier and multivariate analysis. RESULTS: 764 cN0 and 166 cN+ patients with complete follow-up and imaging data were included in the study. Accuracy to detect LN metastasis and locally advanced tumor stage in CT scan was 72% and 62%. LN larger than 15mm in diameter were significantly associated with higher LNR (p=0.002). Increased NLN correlated with decreased CSS and OS (p=0.001: p=0.002). Furthermore, CT scan based scoring system precisely differentiates low-risk and high-risk profiles to predict oncological outcome (p < 0.001). CONCLUSION: In our study, solely LN size >15mm significantly correlated with higher LNR. Identification of increased loco-regional LN was associated with worse survival. For the first time, precise risk stratification based on computed-tomography findings was developed to predict oncological outcome for clinical lymph node-positive patients undergoing RC.

Retrospective evaluation of the impact of non-oncologic chronic drug therapy on the survival in patients with bladder cancer.

Background Chronic drug therapy may impact recurrence and survival of patients with bladder cancer and thus be of concern regarding drug choice and treatment decisions. Currently, data are conflicting for some drug classes and missing for others. Objective To analyze the impact of common non-oncologic chronic drug intake on survival in patients with bladder cancer and radical cystectomy. Setting. Patients with bladder cancer and radical cystectomy (2004-2018) at the University Hospital Munich. Method Data from an established internal database with patients with bladder cancer and radical cystectomy were included in a retrospective study. Drug therapy at the time of radical cystectomy and survival data were assessed and follow-up performed 3 months after radical cystectomy and yearly until death or present. Impact on survival was analyzed for antihypertensive, antidiabetic, anti-gout, antithrombotic drugs and statins, using the Kaplan-Meier method, log-rank test and Cox-regression models. Main outcome measure Recurrence free survival, cancer specific survival and overall survival for users versus non-users of predefined drug classes. Results Medication and survival data were available in 972 patients. Median follow-up time was 22 months (IQR 7-61). In the univariate analysis, a significant negative impact among users on recurrence free survival (n = 93; p = 0.038), cancer specific survival (n = 116; p < 0.001) and overall survival (n = 116; p < 0.001) was found for calcium-channel blockers, whereas angiotensin-receptor-blockers negatively influenced overall survival (n = 96; p = 0.020), but not recurrence free survival (n = 73; p = 0.696) and cancer specific survival (n = 96; p = 0.406). No effect of angiotensin-receptor-blockers and calcium-channel blockers was seen in the multivariate analysis. None of the other studied drugs had an impact on survival. Conclusion There was no impact on bladder cancer recurrence and survival for any of the analyzed drugs. Considering our results and the controverse findings in the literature, there is currently no evidence to withhold indicated drugs or choose specific drug classes among the evaluated non-oncologic chronic drug therapies. Thus, prospective studies are required for further insight. Trail registration This is part of the trial DRKS00017080, registered 11.10.2019.

Radical cystectomy for locally advanced urothelial carcinoma of the urinary bladder: Health-related quality of life, oncological outcomes and predictors for survival.

PURPOSE: While survival outcomes of locally advanced bladder cancer patients undergoing radical cystectomy are known to be poor, less is known regarding patient-reported outcomes and predictive features for survival in this patient subgroup. METHODS: One hundred and eighteen consecutive patients with pT4a cM0 urothelial carcinoma of the bladder were included. Based on pathological review, patients were stratified into 3 subgroups based on existence of additional lesions and invasion depth of the respective lesions. Cancer-specific survival and overall survival (OS) was determined using Kaplan-Meier-analyses and multivariate Cox regression models (P <0.05). Health-related quality of life was assessed using the validated EORTC-QLQ-C30 questionnaire pre- and postoperatively. RESULTS: Seventy-two (61.0%) patients were ineligible for neoadjuvant chemotherapy. Median follow-up based on censored patients was 12 months. Twelve month OS rate was 56.1%, 24 months OS rate was 21.1%. A total of 44.4% of the patients stated good general health-related quality of life. In multivariate analysis, we found significantly adverse OS outcomes for female patients (hazard ratio 2.35, 95% confidence interval 1.09-5.08, P = 0.030). Patients with at least 1 additional locally advanced tumor had significantly worse OS outcomes compared to patients who had no additional lesions in multivariate Cox regression analysis (hazard Ratio 3.37, 95% confidence interval 1.29-8.78, P = 0.013). CONCLUSION: Existence of multiple locally advanced lesions and female gender is an independent predictor of worse survival outcomes in patients with pT4a urothelial carcinoma undergoing radical cystectomy.

The natural course of urinalysis after urinary diversion.

OBJECTIVE: To evaluate the impact of urinary diversion on regular features of urinalysis and to screen for risk factors of infection-related complications. METHODS: We conducted a retrospective, single-centre study of 429 patients who underwent open radical cystectomy. Patients were followed for 12 months and data of the complete urinalyses were analysed at three pre-defined time points. RESULTS: Two weeks after surgery, dipstick testing with positive reactions for leukocyte esterase and haemoglobin were confirmed in 80.7% and 80% after ileal conduit (IC) and orthotopic ileal neobladder (NB), respectively. Every patient was positive for these parameters 12 months after surgery. Correspondingly, the microscopic examination detected leukocytes (84% vs. 85.4%), erythrocytes (82.8% vs. 83.8%) and bacteria (94.3% vs. 96.8%) following IC and NB reconstruction. After 12 months, all parameters were positive irrespective of the type of urinary diversion. Two weeks after surgery positive urine cultures were obtained in more than 50% of cases after IC (52.5%) and NB (60.5%) (p > 0.05). All urine cultures were positive after 12 months with significantly more poly-microbial results found after NB (81.3%) compared with IC (67.2%) (p = 0.018). In univariate and multivariate logistic regression analysis the presence of hydronephrosis was independently associated with the occurrence of infectious complications (OR 4.2; CI 95% 1.525-11.569; p = 0.006). CONCLUSION: A positive urinalysis is a common finding after urinary diversion. Hydronephrosis is a serious risk factor with respect to infection-related complications. The simple fact of a positive urinalysis does not warrant antimicrobial treatment.

EGFR activity addiction facilitates anti-ERBB based combination treatment of squamous bladder cancer.

Recent findings suggested a benefit of anti-EGFR therapy for basal-like muscle-invasive bladder cancer (MIBC). However, the impact on bladder cancer with substantial squamous differentiation (Sq-BLCA) and especially pure squamous cell carcinoma (SCC) remains unknown. Therefore, we comprehensively characterized pure and mixed Sq-BLCA (n = 125) on genetic and protein expression level, and performed functional pathway and drug-response analyses with cell line models and isolated primary SCC (p-SCC) cells of the human urinary bladder. We identified abundant EGFR expression in 95% of Sq-BLCA without evidence for activating EGFR mutations. Both SCaBER and p-SCC cells were sensitive to EGFR tyrosine kinase inhibitors (TKIs: erlotinib and gefitinib). Combined treatment with anti-EGFR TKIs and varying chemotherapeutics led to a concentration-dependent synergism in SCC cells according to the Chou-Talalay method. In addition, the siRNA knockdown of EGFR impaired SCaBER viability suggesting a putative "Achilles heel" of Sq-BLCA. The observed effects seem Sq-BLCA-specific since non-basal urothelial cancer cells were characterized by poor TKI sensitivity associated with a short-term feedback response potentially attenuating anti-tumor activity. Hence, our findings give further insights into a crucial, Sq-BLCA-specific role of the ERBB signaling pathway proposing improved effectiveness of anti-EGFR based regimens in combination with chemotherapeutics in squamous bladder cancers with wild-type EGFR-overexpression.

Is It Safe to Offer Radical Cystectomy to Patients above 85 Years of Age? A Long-Term Follow-Up in a Single-Center Institution.

PURPOSE: With a median age at diagnosis of 73 years, bladder cancer has the highest median age of all cancers. Age alone seems to be an independent risk factor for developing the disease with peak age advancing into the range of 85 years. As demographic changes will lead to an ever more aging population in western countries, incidence of advanced age malignancies will rise. We, therefore, analyzed a contemporary radical cystectomy (RC) series at a single high-volume center on patients undergoing RC for urothelial carcinoma of the bladder (UCB). We aim to evaluate the feasibility of RC in the oldest-old patient cohort by assessing perioperative complications and long-term outcome. MATERIALS AND METHODS: We retrospectively analyzed data of 1,278 consecutive patients who underwent RC for UCB at our tertiary referral center between 2004 and 2019. A total of 408 patients were aged 75-97 years at the time of RC and were further divided into 2 groups: 75-84 years of age (group 1) and ≥85 years of age (group 2). Median follow-up was 23 months. Outcome was analyzed using the χ2 test, Mann-Whitney U test, Kaplan-Meier method, and log-rank test. RESULTS: Perioperative Clavien-Dindo grade ≥III complications were seen in 25.1% (92/366) of group 1 patients and 35.7% (15/42) of group 2 patients (p = 0.073). Thirty- and 90-day mortality was 3.3 and 8.7% in group 1 and 4.8 and 14.3% in group 2 (p = 0.617 and p = 0.242, respectively). Three-year overall survival was 54.6% in group 1 and 31.3% in group 2 (p = 0.03). Three-year cancer-specific survival was 64.8% in group 1 and 38.8% in group 2 (p = 0.037). Recurrence-free survival was 105 months in group 1 and 12 months in group 2 (p = 0.039). CONCLUSION: In light of increasing life expectancy in western nations, we sought to evaluate the impact of age in a large series of elderly patients undergoing RC for UCB. We found that RC offers acceptable perioperative complication rates in the oldest-old patient cohort (≥85 years). Therefore, RC for UCB can be offered as a viable treatment option even in the oldest patients.

Impact of Routine Laboratory Parameters in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: A Long-Term Follow-Up.

OBJECTIVES: Patients' oncological outcome after radical cystectomy (RC) due to urothelial carcinoma of the urinary bladder (UCB) is always up for debate. There is accumulating evidence on the influence of routine blood parameters. We aimed to identify reasonable and easy-to-detect biomarkers, such as preoperative C-reactive protein (CRP) and hemoglobin (Hb) levels, as predictors of overall survival (OS) and cancer-specific survival (CSS) in patients undergoing RC for UCB. MATERIALS AND METHODS: This is a large single-center study in which both preoperative CRP and Hb levels were available in 1,043 patients undergoing RC for UCB from 2004 to 2018 with a median follow-up time of 22 months (mean 38, max. 170). We used the Kaplan-Meier method, log-rank test, and Cox regression models for assessment of OS and CSS. Using our data, we validated an existing outcome prediction score (TNR-C). RESULTS: Median CRP level was 0.5 mg/dL (IQR 0.2-1.4), and median Hb level was 13.4 g/dL (IQR 11.9-14.7). We found that patients with CRP values above the median reached a significantly lower median survival than those with CRP values below the median (23 vs. 83 months, p < 0.001). The TNR-C score was successfully validated, and we discriminated between 3 risk groups (5-year CSS: 76, 40, and 16% for low, intermediate, and high risk, respectively). We observed a similar outcome for patients with a Hb level below the median: CSS was significantly poorer than with Hb levels above the median (median CSS 27 vs. 91 months, p < 0.001). Multivariant analysis showed CRP and Hb levels to be independent prognostic parameters for CSS and OS. CONCLUSIONS: We found elevated preoperative CRP levels and decreased Hb levels to be independent prognostic factors indicating an unfavorable outcome in patients undergoing RC for UCB and were able to validate the TNR-C score in a large patient cohort. We propose using these routine biomarkers for individual risk stratification and optimization of therapeutic strategies in patients undergoing RC for UCB.

Bladder Cancer Stage Development, 2004-2014 in Europe Compared With the United States: Analysis of European Population-based Cancer Registries, the United States SEER Database, and a Large Tertiary Institutional Cohort.

BACKGROUND: The purpose of this study was to analyze trends of bladder cancer (BC) stages and incidence in Europe and the United States (US). MATERIALS AND METHODS: Tumor stages after radical cystectomy were assessed in a monocentric cohort from 2006 to 2016. BC incidence was assessed between 2004 and 2014 based on the German Center for Cancer Registry Data dataset at the Robert Koch Institute (n = 111,002), the Netherland Cancer Registry (n = 64,226), cancer registration statistics of England (n = 179,883), and the pooled data from the Scandinavian cancer registries, NORDCAN (n = 77,585) and the SEER (Surveillance, Epidemiology, and End Results) database (n = 184,519) for the complete populations and gender-specific subgroups. The average annual percent changes (AAPC) were used for statistical evaluation. RESULTS: Non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC) did not change in the institutional cohort at the point of radical cystectomy. The incidence of total BC (AAPC, -0.3), NMIBC (AAPC, -0.1), and non-metastasized MIBC (AAPC, 0.1) did not change in Germany during the time period under survey. BC total incidence in the Netherlands did not change significantly. In England and the Nordic countries, the incidence of total BC increased (AAPC, 0.8 and 0.5, respectively). In contrast, both the incidence of total BC (AAPC, -1.4), NMIBC (AAPC, -1.6), and non-metastasized MIBC (AAPC, -1.6) significantly decreased in the US. CONCLUSIONS: Between 2004 and 2014 the incidence of BC was significantly sinking in the US, was stable in Germany and the Netherlands, and increased in England and the Nordic countries. Predominantly, differences in the smoking prevalence within the last decades but also gender-specific factors might be responsible for this discrepancy.

Midterm Health-related Quality of Life After Radical Cystectomy: A Propensity Score-matched Analysis.

BACKGROUND: Radical cystectomy (RC) and urinary diversion affect various dimensions of patents' health-related quality of life (HRQOL). Knowledge regarding patient-reported HRQOL following RC is mainly based on retrospective findings of cross-sectional studies. OBJECTIVE: To provide data from a large prospective propensity score-matched cohort with a systematic follow-up of up to 2 yr. DESIGN, SETTING, AND PARTICIPANTS: A total of 134 consecutive patients who underwent RC and ileal conduit (IC) or orthotopic ileal neobladder (ONB) urinary diversion in a tertiary care centre were prospectively enrolled, and a propensity score matching analysis based on American Society of Anesthesiologists score, age, and tumour stage was performed. Exclusion criteria encompassed age <30 yr and RC due to benign diseases. HRQOL was addressed with the validated European Organization for Research and TREATMENT: of Cancer QLQ-C30 questionnaire. HRQOL was assessed preoperatively, and at 3, 12, and 24 mo postoperatively. Of the nondeceased patients, 85.1% (IC) and 78.2% (ONB) completed the study. INTERVENTION: RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was good general HRQOL based on previously published cut-off values. Secondary endpoints encompassed the respective HRQOL domains. Univariate and multivariate analyses were performed using binary logistic regression models. RESULTS AND LIMITATIONS: In the longitudinal analysis of RC patients, functioning and symptoms scores show a similar natural HRQOL course for IC and ONB patients. After 24 mo, general HRQOL was significantly higher in the ONB subcohort (60.5 vs 73.6, p=0.013). Good general HRQOL was reached by 32.4 (IC) versus 61.1% (ONB; p=0.019). In the multivariable analysis, ONB was not an independent predictor of good HRQOL (odds ratio 2.211, 95% confidence interval 0.684-7.150, p=0.185). Limitations include the nonbladder specificity of the QLQ-C30 questionnaire and the small sample size. CONCLUSIONS: The current study provides prospective data from a unique propensity score-matched contemporary patient cohort. We display the natural history of general HRQOL and its subdomains without observing significantly higher midterm postoperative HRQOL in patients undergoing continent urinary diversion in the multivariable analysis. PATIENT SUMMARY: We analyse the health-related quality of life (HRQOL) of European patients who underwent radical cystectomy due to bladder cancer and found that HRQOL was slightly better for orthotopic ileal neobladder than for ileal conduit urinary diversion after 24 mo.

Preoperative Thrombocytosis in Patients Undergoing Radical Cystectomy for Urothelial Cancer of the Bladder: An Independent Prognostic Parameter for an Impaired Oncological Outcome.

BACKGROUND: Preoperative thrombocytosis (PTC) is frequently observed in various solid malignancies and often associated with an unfavourable oncological outcome. OBJECTIVES: The aim of this study was to investigate the influence of PTC in patients undergoing radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder on the oncological prognosis and additionally on perioperative blood transfusions (PBT). METHOD: A retrospective analysis of 866 patients undergoing RC in a tertiary care centre was performed. PTC was defined as a platelet count >400 G/L. A chi-square test and Mann-Whitney test were used to investigate the association of PTC with categorical clinicopathological variables. A logrank test and multivariable Cox regression analyses were used to assess the association of PTC with cancer-specific survival. RESULTS: PTC was detected in 8% (n = 67) of the patients and was significantly associated with muscle invasion (p = 0.004), advanced tumour stages (p = 0.003) and nodal metastases (p < 0.001) and with a higher rate of PBT (p< 0.001). In the multivariate analysis, PTC was significantly related to poor oncological survival (hazard ratio 2.23, 95% CI 1.51-3.30, p < 0.001). CONCLUSION: PTC is significantly associated with an impaired oncological outcome in patients undergoing RC for UC. PTC therefore represents an independent and easy to determine prognostic parameter for patients' oncological outcome. Intriguingly, PTC is significantly associated with an increased rate of PBT.

Benefits and Limitations of Transurethral Resection of the Prostate Training With a Novel Virtual Reality Simulator.

PURPOSE: Profound endourological skills are required for optimal postoperative outcome parameters after transurethral resection of the prostate (TURP). We investigated the Karl Storz (Tuttlingen, Germany) UroTrainer for virtual simulation training of the TURP. MATERIALS AND METHODS: Twenty urologists underwent a virtual reality (VR) TURP training. After a needs analysis, performance scores and self-rated surgical skills were compared before and after the curriculum, the realism of the simulator was assessed, and the optimal level of experience for VR training was evaluated. Statistical testing was done with SPSS 25. RESULTS: Forty percent of participants indicated frequent intraoperative overload during real-life TURP and 80% indicated that VR training might be beneficial for endourological skills development, underlining the need to advance classical endourological training. For the complete cohort, overall VR performance scores (P = 0.022) and completeness of resection (P < 0.001) significantly improved. Self-rated parameters including identification of anatomical structures (P = 0.046), sparing the sphincter (P = 0.002), and handling of the resectoscope (P = 0.033) became significantly better during the VR curriculum. Participants indicated progress regarding handling of the resectoscope (70%), bleeding control (55%), and finding the correct resection depth (50%). Although overall realism and handling of the resectoscope was good, virtual bleeding control and correct tissue feedback should be improved in future VR simulators. Seventy percent of participants indicated 10 to 50 virtual TURP cases to be optimal and 80% junior residents to be the key target group for VR TURP training. CONCLUSIONS: There is a need to improve training the TURP and VR simulators might be a valuable supplement, especially for urologists beginning with the endourological desobstruction of the prostate.

Long-Term Follow-Up and Oncological Outcome of Patients Undergoing Radical Cystectomy for Bladder Cancer following an Enhanced Recovery after Surgery (ERAS) Protocol: Results of a Large Randomized, Prospective, Single-Center Study.

INTRODUCTION: Enhanced recovery after surgery (ERAS) concepts are implemented in various surgical disciplines. For patients undergoing radical cystectomy, prospective data are still rare. In the year 2014, our group could prove significant benefits of ERAS for these patients in a prospective randomized study compared to a conservative regimen. OBJECTIVE: To evaluate long-term follow-up results of ERAS concepts in patients undergoing radical cystectomy for bladder cancer. METHODS: Of the 101 patients who had initially prospectively been randomized to ERAS or a conservative regimen, 35 patients could be included in the study. Median follow-up time was 83 months. Primary end point assessed quality of life. Secondary end points were cancer-specific survival and overall survival. RESULTS: Five to seven years after the initial inclusion to the study, no significant difference regarding quality of life parameters was detected (p values range between 0.112 and 0.970). Continence status in patients with neobladder showed no significant differences between ERAS and conservative regimens (p = 0.785). Cancer-specific survival in the ERAS group did not differ significantly from that in the conservative group (49 vs. 58%, p = 0.725). CONCLUSIONS: While ERAS represents an excellent way to improve postoperative reconvalescence and quality of life in the short-term follow-up, our data do not support the idea that there is also a long-term effect in terms of quality of life issues.

Benefits and Complications during the Stay at an Early Rehabilitation Facility after Radical Cystectomy and Orthotopic Ileum Neobladder Reconstruction.

PURPOSE: Early rehabilitation (ER) after radical cystectomy (RC) seems to be crucial for quality of life, education and prevention of complications after hospital discharge. We investigated an inpatient ER setting for bladder cancer (BC) patients. METHODS: In total, 103 BC patients who underwent ileum neobladder reconstruction were included. The major issues from the patients' point of view, functional outcome parameters and complications during ER were analysed. A Wilcoxon signed rank test was used to compare body mass index (BMI) and diurnal as well as nocturnal use of urinary pads before and after ER. RESULTS: At the beginning of ER, the median Karnovsky performance scale score was 70% (interquartile range [IQR] 70-90%) and the mean BMI was 25.8 kg/m2 (IQR 21.9-27.9). The 4 most common complaints were urinary incontinence (80.6%), general weakness (73.8%), urinary mucus (49.5%) and mental distress (44.7%). During the programme, 28.2% of patients had a urinary tract infection requiring antibiotics and 15.5% presented a symptomatic acidosis. Median diurnal use of urinary pads significantly decreased during ER (4 vs. 3; p < 0.001). At the end of the ER programme, 76.0, 54.8 and 30.8% of the patients indicated an improvement of their physical capacity, incontinence and psychological distress respectively. CONCLUSIONS: Our study demonstrates the need for postoperative rehabilitation after RC. Further investigations should compare outcome parameters to ambulatory and outpatient ER models.

Prognostic value and association with epithelial-mesenchymal transition and molecular subtypes of the proteoglycan biglycan in advanced bladder cancer.

OBJECTIVE: Dysregulation of the extracellular matrix molecule biglycan (BGN) predicts poor survival in several cancer entities. Our study investigated the prognostic impact of BGN in bladder cancer (BC) in 2 independent cohorts and assessed its role in epithelial-mesenchymal transition (EMT) and association with molecular BC subtypes. METHODS: BGN protein expression was correlated with the oncological outcome of 162 patients with BC undergoing radical cystectomy (RC) in a single center and furthermore on gene expression level in the TCGA database. Cut-off values for BGN protein and RNA expression were tested with receiver operating characteristic (ROC) curves. BGN gene expression was correlated with established EMT and BC gene signatures in the TCGA database using gene set enrichment analysis (GSEA). Key EMT and basal/luminal molecular BC subtype markers were correlated with BGN expression and data were shown in a heat map. RESULTS: BGN upregulation in BC cells on the protein level predicted poor oncological survival in the institutional cohort for both univariate (P = 0.007) and multivariate (P = 0.040) analyses. BGN expression was not associated with other clinicopathological parameters. The prognostic value of BGN was validated on the mRNA level in the BC TCGA database (P = 0.002). Both EMT and BC core gene signatures (P < 0.001) correlated with BGN expression in GSEA. BGN gene expression was associated with key indicators of EMT. BGN was associated positively with the molecular basal BC subtype and negatively with the BC luminal subtype. CONCLUSION: BGN is an independent prognosticator for poor survival in BC patients. BGN is associated with the basal molecular BC subtype. EMT might be a key player for BGN driven oncogenesis, as BGN expression correlates with EMT gene signatures.