[Early cystectomy-patient selection and technique]. / Indikationen und Technik der Frühzystektomie.

Early radical cystectomy (RC) is a therapeutic option for non-muscle invasive bladder cancer (NMIBC). The 15-year overall survival after early RC in NMIBC patients is about 70%. Nevertheless, RC is associated with significant morbidity and mortality and therefore requires careful patient selection. The aim of the following review is to assess the selection process for early RC in NMIBC. Especially, the new European Association of Urology (EAU) risk calculator identifying NMIBC patients with very high risk for disease progression is described in detail. Furthermore, the technical aspects of the procedure are evaluated. A review of the current literature (PubMed) and national and international guideline recommendations was also conducted.

[Quality assessment of radical cystectomy-opportunities, risks, challenges]. / Qualitätsparameter bei der radikalen Zystektomie ­ Chancen, Risiken, Herausforderungen.

Radical cystectomy (RC) is the standard treatment for nonmetastatic muscle-invasive urothelial carcinoma of the urinary bladder. It is associated with relevant morbidity and mortality. After RC, the 5­year overall survival rate is approximately 60%. In the context of the present work, quality parameters of RC divided into oncological/functional criteria and freedom from complications are identified and summarized. A PubMed search was performed. In addition to early criteria such as negative surgical margins, performance of pelvic lymphadenectomy, creation of a continent urinary diversion or preservation of sexual function, long-term criteria were identified such as the absence of higher-grade postoperative complications, recurrence-free survival and the preservation of health-related quality of life. The early criteria are suitable for individualized therapy planning, whereas the long-term criteria can be used for quality monitoring.

The role of device-assisted therapies in the management of non-muscle invasive bladder cancer: A systematic review.

OBJECTIVE: Despite optimal treatment, patients affected by non-muscle invasive bladder cancer (NMIBC) suffer from high risk of recurrence and progression. Intravescical device assisted therapies such as radiofrequency induced thermochemotherapeutic effect (RITE) and electromotive drug administration (EMDA) have shown promising effect in enhancing the effect of intravescical chemotherapies. The aim of the study was to assess clinical outcomes of these two devices in non-muscle invasive bladder cancer. METHODS: A systematic literature review was performed in December 2019 using the Medline, Embase, and Web of Science databases. Only articles published in the last 10 years were considered (2009-2019). The articles were selected using the following keywords association: "bladder cancer" AND "EMDA' AND "synergo" AND "hyperchemotherapy" AND "electromotive drug administration", AND "radiofrequency induced thermochemotherapeutic" AND "RITE". RESULTS: We found 16 studies published in the last ten years regarding the efficacy of RITE (12 studies) and EMDA (4 studies) in the treatment of NMIBC. Both RITE and EMDA showed promising results in the treatment of intermediate and high risk NMIBC as well as in patients affected by recurrent BCa after BCG failure. In high-risk BCG naïve NMIBC patients treated with EMDA recurrence and progression rates were 68% and 95%, respectively. Considering RITE, recurrence and progression range rates were 43%-88% and 62%-97%, respectively. Discordance results were reported regarding its effect on patients with carcinoma in situ. However, only few studies could be compared since differences exist regarding inclusion criteria with high patients' heterogeneity. Considering recurrence after BCG, recurrence and progression range rates were 29%-29.2% and 62%-83% for RITE and 25% and 75% for EMDA, respectively. CONCLUSION: Delivery of intravescical hyperthermia seems to enhance the normal effect of intravescical chemotherapy instillation. Although prospective trials supported its effect on both BCG naïve and BCG failure patients, data are urgently required to validate these findings and to understand its effect on patients with carcinoma in situ. LEVEL OF PROOF: 3.

Early recovery after surgery for radical cystectomy: comprehensive assessment and meta-analysis of existing protocols.

PURPOSE: Different enhanced recovery after surgery (ERAS) protocols (EP) for radical cystectomy (RC) have been published. Protocols highly differ in number of included items and specific measures. MATERIALS AND METHODS: A systematic review and meta-analysis on EPs in RC were performed using the databases MedLine, Cochrane Library, Web of science, and Google Scholar. The specific ERAS measures of the protocols were extracted, analyzed, and compared. Pooling of available outcome data was performed for length of stay, complications, readmission rate, and time to defecation. RESULTS: The search yielded a total of 860 studies of which 25 studies were included in qualitative and 22 in quantitative analysis. Oral bowel preparation (BP) was omitted in 24/25 (96%) EPs, optimized fluid management was administered in 22/25 (88%) EPs and early mobilization (postoperative day 1) in 21/25 (84%). Gum chewing (n = 12, 46%), metoclopramide (n = 11, 44%), and alvimopan (n = 6, 24%) were the most common measures to prevent postoperative ileus. Our meta-analysis revealed a significant benefit in favor of EPs for the outcome parameters length of stay [mean difference (MD) - 3.46 d, 95% confidence interval (CI) - 4.94 to - 1.98, p < 0.01], complications [Odds ratio (OR) = 0.76, 95% CI 0.61-0.94, p = 0.01] and time to defecation (MD - 1.37 d, 95% CI - 2.06 to - 0.69, p < 0.01). Readmission rate did not show a significant difference (OR = 0.73, 95% CI 0.52-1.03, p = 0.07). CONCLUSION: Current EPs focus on omitting oral BP, early mobilization, and optimized fluid management while they differ in methods preventing postoperative ileus. Our meta-analysis revealed a benefit in introducing these protocols into clinical practice.

[Modern networks : Topics in the working group "Bladder cancer research" of the GeSRU Academics]. / Modernes Netzwerken : Thematische Ausrichtungen in der Arbeitsgruppe "Blasenkarzinom Experimentell" der GeSRU Academics.

In January 2015, the research group "bladder cancer research" was founded as part of the GeSRU Academics research initiative. A general challenge to work successfully in a novel network structure is to identify common scientific topics and technical expertise in the group. Thus, one of the first tasks was to learn about current research projects from members within the group in order to address a project that suits the group's expertise. The following review summarizes three different directions that are key projects in Urologic Departments at German Universities that will be the basis to start fruitful collaborations.

[Complications after ileal conduit: Urinary diversion-associated complications after radical cystectomy]. / Komplikationen nach Ileumconduitanlage : Harnableitungsspezifische Komplikationen nach radikaler Zystektomie.

BACKGROUND: We analyzed complications associated with urinary diversion after radical cystectomy (RC) and ileal conduit (IC) for bladder cancer (BCa). PATIENTS AND METHODS: A total of 305 BCa patients after RC with IC were included in the study (June 2003-December 2010). IC complications (peristomal hernia, IC stenosis, stenosis of the ureteral anastomosis, IC bleeding, urolithiasis, urinary infections, and renal insufficiency) were identified according to the Clavien-Dindo classification (CDC). Kaplan-Meier plots were generated. Uni- and multivariable Cox regression analyses with backward selection for prediction of high-grade complications (CDC ≥ III) and IC revision surgery were conducted; covariates included age, previous abdominal/pelvic radiation, body mass index (BMI), previous abdominal/pelvic surgery, comorbidities, and advanced tumor stage. RESULTS: An IC complication (CDC ≥ I) or a high-grade IC complication (CDC ≥ III) was experienced by 32.7 and 13.4 % of our cohort: 14.8 %, 4.3 %, 4.6 % developed a peristomal hernia, IC stenosis, stenosis of the ureteral anastomosis, respectively. IC revision was required by 10.5 % of patients (median follow-up 19.5 months, IQR 7-47 months). The estimated rate of IC complications at 5 years was 52 % (CDC ≥ I) and 22 % (CDC ≥ III). The final model of the multivariable analysis showed that patients with a history of previous radiation (HR 4.33), a BMI ≥ 30 (HR 2.24), or longer duration of surgery (HR 1.01; all p < 0.05) were at higher risk for IC revision surgery. A BMI ≥ 30 (HR 2.49, p = 0.011) was a risk factor for high-grade complications. CONCLUSION: The risk of experiencing a high-grade IC complication is moderate. Previous radiation, obesity, and comorbidities represent risk factors for IC revision surgery. Moreover, obesity is a risk factor for high-grade complications.

[Clinical and histopathological parameters of prostate cancer: influence of anthropometric indices]. / Klinische und histopathologische Parameter des Prostatakarzinoms : Einfluss anthropometrischer Indizes.

BACKGROUND: Adipose tissue is increasingly considered as an endocrinal active organ and may have an influence on the development and progression of prostate cancer. Adverse body fat distribution, considered a risk factor for cardiovascular disease, is not reflected by the body mass index (BMI). OBJECTIVE: The purpose of this work was to assess anthropometric indices which provide a better estimate of body fat distribution and to evaluate their association with clinical and histopathological parameters of prostate cancer. PATIENTS AND METHODS: In patients scheduled for radical prostatectomy between March 2011 and March 2013, height, weight, waist circumference (WC) and hip circumference were measured, then the BMI, waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were calculated. The relationships between anthropometric measures and indices and clinical and histopathological features of PCA were evaluated with uni- and multivariate analyses. RESULTS: In 668 patients available for evaluation, obesity rates were 22.8 %, 50.6% and 30.2 % as defined by BMI ≥ 30, WHR ≥ 1 and WHtR ≥ 0.6, respectively. On univariate analysis, WC and WHtR ≥ 0.6 correlated with tumor volume (TV) > 2.1 cm(2) (p < 0.05), respectively. WC and WHtR were independent predictors of a TV ≥ 2.1 cm(2) (p < 0.05) and a WHtR ≥ 0.6 was an independent predictor of a TV ≥ 2.1 cm(2) (p < 0.018, risk ratio 1.506, 95 % confidence interval 1.072-2.115). CONCLUSION: In general a higher degree of adiposity seems to correlate with a higher tumor volume. Whether anthropometric indices have prognostic impact needs to be clarified during follow-up.

Fusion of Magnetic Resonance Imaging and Real-Time Elastography to Visualize Prostate Cancer: A Prospective Analysis using Whole Mount Sections after Radical Prostatectomy.

PURPOSE: To determine whether the fusion of multiparametric magnetic resonance imaging (MRI) with transrectal real-time elastography (RTE) improves the visualization of PCa lesions compared to MRI alone. MATERIALS AND METHODS: In a prospective setting, 45 patients with biopsy-proven PCa received prostate MRI prior to radical prostatectomy (RP). T2 and diffusion-weighted imaging (T2WI/DW-MRI) and, if applicable, dynamic contrast-enhanced sequences (T2WI/DW/DCE-MRI) were used to perform MRI/RTE fusion. The probability of PCa on MRI was graded according to the PI-RADS score for 12 different prostate sectors per patient. MRI images were fused with RTE to stratify suspicious from non-suspicious sectors. Imaging results were compared to whole mount sections using nonparametrical receiver operating characteristic curves and the area under these curves (AUC). RESULTS: 41 of 45 patients were eligible for final analyses. Histopathology confirmed PCa in 261 (53%) of 492 prostate sectors. MRI alone provided an AUC of 0.62 (T2WI/DW-MRI) and 0.65 (T2WI/DW/DCE-MRI) to predict PCa and was meaningfully enhanced to 0.75 (T2WI/DW-MRI) and 0.74 (T2WI/DW/DCE-MRI) using MRI/RTE fusion. Sole MRI showed a sensitivity and specificity of 57.9% and 61% with the best results for ventral prostate sectors whereas RTE was superior in dorsal and apical sectors. MRI/RTE fusion improved sensitivity and specificity to 65.9% and 75.3%, respectively. Additional use of DCE sequences showed a sensitivity and specificity of 65% and 55.7% for MRI and 72.1% and 66% for MRI/RTE fusion. CONCLUSION: MRI/RTE fusion provides improved PCa visualization by combining the strength of both imaging techniques in regard to prostate zonal anatomy and thereby might improve future biopsy-guided PCa detection.

The effect of age at diagnosis on prostate cancer mortality: a grade-for-grade and stage-for-stage analysis.

OBJECTIVE: To evaluate the effect of advancing age on cancer-specific mortality (CSM) after radical prostatectomy (RP). MATERIALS AND METHODS: Overall, 205,551 patients with PCa diagnosed between 1988 and 2009 within the Surveillance Epidemiology and End Results (SEER) database were included in the study. Patients were stratified according to age at diagnosis: ≤ 50, 51-60, 61-70, and ≥ 71 years. The 15-year cumulative incidence CSM rates were computed. Competing-risks regression models were performed to test the effect of age on CSM in the entire cohort, and for each grade (Gleason score 2-4, 5-7, and 8-10) and stage (pT2, pT3a, and pT3b) sub-cohorts. RESULTS: Advancing age was associated with higher 15-year CSM rates (2.3 vs. 3.4 vs. 4.6 vs. 6.3% for patients aged ≤ 50 vs. 51-60 vs. 61-70 vs. ≥ 71 years, respectively; P < 0.001). In multivariable analyses, age at diagnosis was a significant predictor of CSM. This relationship was also observed in sub-analyses focusing on patients with Gleason score 5-7, and/or pT2 disease (all P ≤ 0.05). Conversely, age failed to reach the independent predictor status in men with Gleason score 2-4, 8-10, pT3a, and/or pT3b disease. CONCLUSIONS: Advancing age increases the risk of CSM. However, when considering patients affected by more aggressive disease, age was not significantly associated with higher risk of dying from PCa. In high-risk patients, tumor characteristics rather than age should be considered when making treatment decisions.

The impact of robot-assisted radical prostatectomy on the use and extent of pelvic lymph node dissection in the "post-dissemination" period.

INTRODUCTION: Previous series during the dissemination era of minimally invasive techniques for treatment of prostate cancer (PCa) showed a declining use of pelvic lymph node dissection (PLND). The aim of our study was to re-assess the impact of robot-assisted radical prostatectomy (RARP) on the utilization rate of PLND and its extent in the post-dissemination period. METHODS: Relying on the Surveillance Epidemiology and End Results (SEER) Medicare-linked database, 5804 patients with non-metastatic PCa undergoing open radical prostatectomy (ORP) or RARP between years 2008 and 2009 were identified. Uni- and multivariable logistic regression analyses tested the relationship between surgical approach (RARP vs. ORP) and: 1 - the rate of PLND (pNx vs. pN0-1); and 2 - the extent of PLND (limited vs. extended). RESULTS: Overall, 3357 (57.8%) patients underwent a PLND. The proportion of patients treated with PLND was significantly higher among ORP vs. RARP patients: 71.2 vs. 48.6%, respectively (P < 0.001). In addition, the median number of lymph nodes removed was significantly higher for patients treated with ORP vs. RARP: 5 vs. 4, respectively (P < 0.001). In multivariable analyses, ORP was associated with 2.7- and 1.3-fold higher odds of undergoing PLND and of receiving an extended PLND compared to RARP, respectively (both P ≤ 0.001). Stratified analyses according to disease risk classifications revealed similar trends. CONCLUSIONS: In the post-dissemination era, RARP remains associated with a decreased use of PLND and suboptimum extent. Efforts should be made to improve guideline adherence in performing a PLND whenever indicated according to tumor aggressiveness, despite surgical approach.

Long-term survival in patients with germ cell testicular cancer: a population-based competing-risks regression analysis.

BACKGROUNDS: Incidence of secondary malignancies and cardiovascular diseases among testicular germ cell tumor (TGCT) survivors is higher compared to the general population. We sought to describe the rates of other-cancer (OCM), non-cancer related (NCRM), and cancer-specific mortality (CSM) among men with TGCT. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, 31,330 patients with a primary diagnosis of TGCT between 1973 and 2009 were identified. The primary endpoints comprised of 15-year CSM, OCM, and NCRM rates. Survival rates were stratified according to histology (seminoma vs. non-seminoma), median age (<34 vs. ≥34 years old), and disease stage (localized vs. regional vs. distant). Competing-risks Poisson regression methodologies were performed. RESULTS: For seminoma patients, the rates of CSM at 15 years increased with advancing stage (0.4-12.6%; P < 0.001), but varies little with age. In contrast, the rates of OCM (0.4-7.9%) and NCRM (2.9-8.9%) at 15 years increased with advancing stage and age (all P < 0.001). For non-seminoma patients, the 15-year CSM rates increased with advancing stage and age (1.9-24.4%; all P < 0.001). For the same time point, the rates of OCM (0.3-11.4%) and NCRM (2.4-8.0%) also increased with age and stage (all P ≤ 0.001). CONCLUSIONS: The risk of dying from secondary malignancies or other causes significantly increases with advancing stage and age at diagnosis among TGCT survivors. Such information can help provide patients and physicians with better screening strategies, follow-up protocols, and mental preparedness for such undesirable effects.

[Value of real-time elastography to guide the systematic prostate biopsy in men with normal digital rectal exam]. / Stellenwert der Real-Time Elastografie zur Steuerung der systematischen Prostatabiopsie bei Männern mit unauffälligem digital-rektalen Tastbefund.

The aim of this study was to evaluate whether real-time elastography-guided biopsy in comparison to grey-scale ultrasound improves prostate cancer detection in patients with an unremarkable digital rectal exam.A total of 231 patients suspicious for prostate cancer were prospectively randomised to transrectal real-time elastography- (126) or grey-scale ultrasound (105)-guided biopsy. The peripheral zone was divided into 6 sectors from base, mid-gland to apex. Lesions with reduced elasticity during real-time elastography and hypoechoic areas during grey-scale ultrasound were defined as suspicious for prostate cancer. Prostate biopsy was guided by real-time elastography (RTE) or grey-scale ultrasound (GSU) using a systematic 10-core approach. Suspicious lesions on RTE or GSU in the corresponding randomised group were targeted within each sector. Accuracy of cancer prediction and histopathological cancer detection rates were evaluated and compared between the 2 imaging modalitiesBaseline characteristics of patients undergoing real-time elastography and grey-scale ultrasound, including age, prostate-specific antigen and prostate volume were not significantly different statistically (p>0.05). Overall, prostate cancer was detected in 76 of 231 cases (32.9%). The cancer detection rate was significantly higher (p=0.007) in patients who underwent a biopsy using real-time elastography (40.5%) compared to the grey-scale-guided group of men (23.8%). Sensitivity and specificity to detect prostate cancer in 1 386 prostate sectors was 53.5% and 70.5% for real-time elastography vs. 11.7% and 93.7% for grey-scale ultrasound, respectively.Compared to conventional grey-scale ultrasound, accuracy to detect prostate cancer using a systematic 10-core biopsy approach was significantly improved under the guidance of real-time elastography.

[Cystectomy in elderly patients: analysis of complications using the Clavien-Dindo classification]. / Die Zystektomie im Alter : Komplikationsanalyse unter Anwendung der Clavien-Dindo-Klassifikation.

Radical cystectomy (RC) represents the gold standard in the treatment of muscle invasive urothelial cancer of the bladder. Due to improvements in operation techniques and perioperative care it has become a good and safe procedure even in elderly patients. In recent years the Clavien-Dindo classification has been frequently used for complication assessment in urological research. The Charlson comorbidity index without age correction can be used in treatment planning for RC to identify patients at risk.