Influence of Body Mass Index on Clinical Outcome Parameters, Complication Rate and Survival after Radical Cystectomy: Evidence from a Prospective European Multicentre Study.

Background/Aims/Objectives: To evaluate the influence of body mass index (BMI) on complications and oncological outcomes in patients undergoing radical cystectomy (RC). METHODS: Clinical and histopathological parameters of patients have been prospectively collected within the "PROspective MulticEnTer RadIcal Cystectomy Series 2011". BMI was categorized as normal weight (<25 kg/m2), overweight (≥25-29.9 kg/m2) and obesity (≥30 kg/m2). The association between BMI and clinical and histopathological endpoints was examined. Ordinal logistic regression models were applied to assess the influence of BMI on complication rate and survival. RESULTS: Data of 671 patients were eligible for final analysis. Of these patients, 26% (n = 175) showed obesity. No significant association of obesity on tumour stage, grade, lymph node metastasis, blood loss, type of urinary diversion and 90-day mortality rate was found. According to the -American Society of Anesthesiologists score, local lymph node (NT) stage and operative case load patients with higher BMI had significantly higher probabilities of severe complications 30 days after RC (p = 0.037). The overall survival rate of obese patients was superior to normal weight patients (p = 0.019). CONCLUSIONS: There is no evidence of correlation between obesity and worse oncological outcomes after RC. While obesity should not be a parameter to exclude patients from cystectomy, surgical settings need to be aware of higher short-term complication risks and obese patients should be counselled -accordingly.

Effectiveness of Adjuvant Chemotherapy After Radical Cystectomy for Locally Advanced and/or Pelvic Lymph Node-Positive Muscle-invasive Urothelial Carcinoma of the Bladder: A Propensity Score-Weighted Competing Risks Analysis.

BACKGROUND: The benefit of adjuvant chemotherapy (AC) for muscle-invasive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC) is controversial. OBJECTIVE: To assess the effectiveness of AC after RC for muscle-invasive UCB in contemporary European routine practice. DESIGN, SETTING, AND PARTICIPANTS: By using a prospectively collected European multicenter database, we compared survival outcomes between patients who received AC versus observation after RC for locally advanced (pT3/T4) and/or pelvic lymph node-positive (pN+) muscle-invasive UCB in 2011. INTERVENTION: AC versus observation after RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Inverse probability of treatment weighting (IPTW)-adjusted Cox regression and competing risks analyses were performed to compare overall survival (OS) as well as cancer-specific and other-cause mortality between patients who received AC versus observation. RESULTS AND LIMITATIONS: Overall, 224 patients who received AC (n = 84) versus observation (n = 140) were included. The rate of 3-yr OS in patients who received AC versus observation was 62.1% versus 40.9%, respectively (p = 0.014). In IPTW-adjusted Cox regression analysis, AC versus observation was associated with an OS benefit (hazard ratio: 0.47; 95% confidence interval [CI]: 0.25-0.86; p = 0.014). In IPTW-adjusted competing risks analysis, AC versus observation was associated with a decreased risk of cancer-specific mortality (subhazard ratio: 0.51; 95% CI: 0.26-0.98; p = 0.044) without any increased risk of other-cause mortality (subhazard ratio: 0.48; 95% CI: 0.14-1.60; p = 0.233). Limitations include the relatively small sample size as well as the potential presence of unmeasured confounders related to the observational study design. CONCLUSIONS: We found that AC versus observation was associated with a survival benefit after RC in patients with pT3/T4 and/or pN+ UCB. These results should encourage physicians to deliver AC and researchers to pursue prospective or large observational investigations. PATIENT SUMMARY: Overall survival and cancer-specific survival benefit was found in patients who received adjuvant chemotherapy relative to observation after radical cystectomy for locally advanced and/or pelvic lymph node-positive bladder cancer.

The EMPaCT Classifier: A Validated Tool to Predict Postoperative Prostate Cancer-related Death Using Competing-risk Analysis.

BACKGROUND: Accurate prediction of survival after radical prostatectomy (RP) is important for making decisions regarding multimodal therapies. There is a lack of tools to predict prostate cancer-related death (PCRD) in patients with high-risk features. OBJECTIVE: To develop and validate a prognostic model that predicts PCRD combining pathologic features and using competing-risks analysis. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multi-institutional observational cohort study of 5876 patients affected by high-risk prostate cancer. Patients were treated using RP and pelvic lymph node dissection (PLND) in a multimodal setting, with median follow-up of 49 mo. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: For PCRD prediction, a multivariate model with correction for competing risks was constructed to evaluate pathologic high-risk features (pT3b-4, Gleason score ≥8, and pN1) as predictors of mortality. All possible associations of the predictors were combined, and then subgroups with similar risk of PCRD were collapsed to obtain a simplified model encoding subgroups with significantly differing risk. Eightfold cross-validation of the model was performed. RESULTS AND LIMITATIONS: After applying exclusion criteria, 2823 subjects were identified. pT3b-4, Gleason score ≥8, and pN1 were all independent predictors of PCRD. The simplified model included the following prognostic groups: good prognosis, pN0 with 0-1 additional predictors; intermediate prognosis, pN1 with 0-1 additional predictors; poor prognosis, any pN with two additional predictors. The cross-validation yielded excellent median model accuracy of 88%. The retrospective design and the short follow-up could limit our findings. CONCLUSIONS: We developed and validated a novel and easy-to-use prognostic instrument to predict PCRD after RP+PLND. This model may allow clinicians to correctly counsel patients regarding the intensity of follow-up and to tailor adjuvant treatments. PATIENT SUMMARY: Prediction of mortality after primary surgery for prostate cancer is important for subsequent treatment plans. We present an accurate postoperative model to predict cancer mortality after radical prostatectomy for high-risk prostate cancer.

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.

Impact of photodynamic diagnosis-assisted transurethral resection of bladder tumors on the prognostic outcome after radical cystectomy: results from PROMETRICS 2011.

PURPOSE: Results of a retrospective single-institution study recently suggested improved prognostic outcomes in patients undergoing photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT) prior to radical cystectomy (RC). We sought to validate the prognostic influence of PDD-assisted TURBT on survival after RC by relying on a multi-institutional dataset. METHODS: To provide a homogeneous study population, patients with organ metastasis at the time of RC and/or after neoadjuvant chemotherapy were excluded from analysis, which resulted in overall 549 bladder cancer (BC) patients from 18 centers of the Prospective Multicenter Radical Cystectomy Series 2011 (PROMETRICS 2011). To evaluate the influence of PDD conducted during primary or final TURBT on cancer-specific mortality (CSM) and overall mortality (OM) after RC, bootstrap-corrected multivariate Cox proportional-hazards regression models were applied (median follow-up: 25 months; IQR: 19-30). Sensitivity analyses were performed for both patients with pure urothelial carcinoma and patients undergoing one single TURBT only. RESULTS: In 88 (16.0 %) and 100 (18.2 %) patients, PDD was used in primary and final TURBTs, respectively. In 335 (61.0 %) patients, a single TURBT was performed prior to RC; in 194 patients (35.3 %), TURBT had been performed in a different center. CSM and OM rates at 3 years were 32 and 40 %, respectively. Use of PDD during primary or final TURBT was no independent predictor of CSM or OM. These results were internally valid and were confirmed in sensitivity analyses. CONCLUSIONS: PDD utilization during TURBT prior to RC does not independently impact the prognosis of BC patients after RC.

Optimised photodynamic diagnosis for transurethral resection of the bladder (TURB) in German clinical practice: results of the noninterventional study OPTIC III.

PURPOSE: White light cystoscopy (WLC) is the standard procedure for visualising non-muscle invasive bladder cancer (NMIBC). However, WLC can fail to detect all cancerous lesions, and outcomes with transurethral resection of the bladder differ between institutions, controlled trials, and possibly between trials and routine application. This noninterventional study assessed the benefit of hexaminolevulinate blue light cystoscopy (HALC; Hexvix®, Ipsen Pharma GmbH, Germany) plus WLC versus WLC alone in routine use. METHODS: From May 2013 to April 2014, 403 patients with suspected NMIBC were screened from 30 German centres to perform an unprecedented detailed assessment of the additional detection of cancer lesions with HALC versus WLC alone. RESULTS: Among the histological results for 929 biopsy samples, 94.3 % were obtained from suspected cancerous lesions under either WLC or HALC: 59.5 % were carcinoma tissue and 40.5 % were non-cancerous tissue. Of all cancer lesions, 62.2 % were staged as Ta, 20.1 % as T1, 9.3 % as T2, 7.3 % as carcinoma in situ (CIS), and 1.2 % were unknown. Additional cancer lesions (+6.8 %) and CIS lesions (+25 %, p < 0.0001) were detected by HALC plus WLC versus WLC alone. In 10.0 % of patients, ≥1 additional positive lesion was detected with HALC, and 2.2 % of NMIBC patients would have been missed with WLC alone. No adverse events were observed. CONCLUSIONS: The results of this study demonstrate that HALC significantly improves the detection of NMIBC versus WLC alone in routine clinical practice in Germany. While this benefit is statistically significant across all types of NMIBC, it seems most relevant in CIS.

Impact of Lymph Node Burden on Survival of High-risk Prostate Cancer Patients Following Radical Prostatectomy and Pelvic Lymph Node Dissection.

AIM: To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP). MATERIAL AND METHODS: In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD. RESULTS: Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7% (n = 671). Final Gleason score (GS) was 2-6 in 12.7% (n = 158), 7 in 52% (n = 649), and 8-10 in 35.4% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3%) had 0-3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p < 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS. CONCLUSION: Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.

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.

Prediction of cancer-specific survival after radical cystectomy in pT4a urothelial carcinoma of the bladder: development of a tool for clinical decision-making.

OBJECTIVE: To externally validate the pT4a-specific risk model for cancer-specific survival (CSS) proposed by May et al. (Urol Oncol 2013; 31: 1141-1147) and to develop a new pT4a-specific nomogram predicting CSS in an international multicentre cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) PATIENTS AND METHODS: Data from 856 patients with pT4a UCB treated with RC at 21 centres in Europe and North-America were assessed. The risk model proposed by May et al., which includes female gender, presence of positive lymphovascular invasion (LVI) and lack of adjuvant chemotherapy administration as adverse predictors for CSS, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver-operating characteristic-derived area under the curve. A nomogram for predicting CSS in pT4a UCB after RC was developed after internal validation based on multivariable Cox proportional hazards regression analysis evaluating the impact of clinicopathological variables on CSS. Decision-curve analyses were applied to determine the net benefit derived from the two models. RESULTS: The estimated 5-year-CSS after RC was 34% in our cohort. The risk model devised by May et al. predicted individual 5-year-CSS with an accuracy of 60.1%. In multivariable Cox proportional hazards regression analysis, female gender (hazard ratio [HR] 1.45), LVI (HR 1.37), lymph node metastases (HR 2.54), positive soft tissue surgical margins (HR 1.39), neoadjuvant (HR 2.24) and lack of adjuvant chemotherapy (HR 1.67, all P < 0.05) were independent predictors of an adverse CSS rate and formed the features of our nomogram with a predictive accuracy of 67.1%. Decision-curve analyses showed higher net benefits for the use of the newly developed nomogram in our cohort over all thresholds. CONCLUSIONS: The risk model devised by May et al. was validated with moderate discrimination and was outperformed by our newly developed pT4a-specific nomogram in the present study population. Our nomogram might be particularly suitable for postoperative patient counselling in the heterogeneous cohort of patients with pT4a UCB.

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.

Optimizing outcome reporting after radical cystectomy for organ-confined urothelial carcinoma of the bladder using oncological trifecta and pentafecta.

UNLABELLED: Radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) is associated with heterogeneous functional and oncological outcomes. The aim of this study was to generate trifecta and pentafecta criteria to optimize outcome reporting after RC. METHODS: We interviewed 50 experts to consider a virtual group of patients (age ≤ 75 years, ASA score ≤ 3) undergoing RC for a cT2 UCB and a final histology of ≤pT3pN0M0. A ranking was generated for the three and five criteria with the highest sum score. The criteria were applied to the Prospective Multicenter Radical Cystectomy Series 2011. Multivariable binary logistic regression analyses were used to evaluate the impact of clinical and histopathological parameters on meeting the top selected criteria. RESULTS: The criteria with the highest sum score were negative soft tissue surgical margin, lymph node (LN) dissection of at least 16 LNs, no complications according to Clavien-Dindo grade 3-5 within 90 days after RC, treatment-free time between TUR-BT with detection of muscle-invasive UCB and RC <3 months and the absence of local UCB-recurrence in the pelvis ≤12 months. The first three criteria formed trifecta, and all five criteria pentafecta. A total of 334 patients qualified for final analysis, whereas 35.3 and 29 % met trifecta and pentafecta criteria, respectively. Multivariable analyses showed that the relative probability of meeting trifecta and pentafecta decreases with higher age (3.2 %, p = 0.043 and 3.3 %, p = 0.042) per year, respectively. CONCLUSIONS: Trifecta and pentafecta incorporate essential criteria in terms of outcome reporting and might be considered for the improvement of standardized quality assessment after RC for UCB.

Risk stratification for locoregional recurrence after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. METHODS: Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. RESULTS: After a median follow-up of 25 months (interquartile range 19-29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage ≥pT3 (HR 4.32, p < 0.001), positive STSM (HR 2.93, p = 0.005), lymphovascular invasion (HR 3.41, p < 0.001), the number of removed LNs <10 (HR 2.62, p < 0.001) and the administration of adjuvant chemotherapy (HR 0.40, p = 0.008) independently predicted the LR-rate. The resulting risk groups revealed significant differences in LR-rates after 24 months with 4.8 % for low-risk patients, 14.7 % for intermediate-risk patients and 38.9 % for high-risk patients (p < 0.001 for all), with a predictive accuracy of 85.6 %, respectively. CONCLUSIONS: The Christodouleas risk model has been successfully externally validated in the present prospective series. However, this analysis finds that overall model performance may be improved by incorporating lymphovascular invasion. After external validation of the newly proposed risk model, it may be used to identify patients who benefit from an adjuvant therapy and suit for inclusion in clinical trials.

Prognostic value of prior history of urothelial carcinoma of the bladder in patients with upper urinary tract urothelial carcinoma: results from a retrospective multicenter study.

BACKGROUND: Patients with urothelial carcinoma (UC) often develop multifocal metachronous tumors throughout the genitourinary tract. In the present study, we evaluated the prognostic value of prior history of UC of the bladder (UCB) in patients with upper tract urothelial carcinoma (UTUC) in an international multi-institutional cohort. PATIENTS AND METHODS: Data from 785 patients who underwent radical nephroureterectomy (RNU) with ipsilateral bladder cuff resection at nine academic institutions in Europe and the USA between 1987 and 2008 were reviewed. Log-rank tests and Cox proportional hazards regression models were used for univariable and multivariable analyses. RESULTS: The median follow-up of the whole cohort was 34 months (interquartile range 15-66 months). Five hundred and fifty-eight (72 %) patients had no UCB before the diagnosis of UTUC; a prior history of non-muscle-invasive and muscle-invasive UCB before the UTUC was found in 179 (23 %) and 36 (5 %), respectively. History of UCB before RNU was an independent predictor of both recurrence-free survival (p = 0.012; no UCB vs. non-muscle-invasive UCB: hazard ratio (HR) 1.4, p = 0.082; no UCB vs. muscle-invasive UCB: HR 2.1, p = 0.007) and cancer-specific survival (p = 0.008; no UCB vs. non-muscle-invasive UCB: HR 1.2, p = 0.279; no UCB vs. muscle-invasive UCB: HR 2.3, p = 0.008) on multivariable Cox regression analyses that included age, gender, surgical type, stage, grade, presence of concomitant carcinoma in situ, presence of lymphovascular invasion, and lymph node status. CONCLUSIONS: Prior history of muscle-invasive UCB was significantly associated with an increased risk of disease recurrence and cancer-specific death in patients with UTUC.

Evidence from the 'PROspective MulticEnTer RadIcal Cystectomy Series 2011 (PROMETRICS 2011)' study: how are preoperative patient characteristics associated with urinary diversion type after radical cystectomy for bladder cancer?

PURPOSE: The aim of this study was to examine preoperative patients' characteristics associated with the urinary diversion (UD) type (continent vs. incontinent) after radical cystectomy (RC) and UD-associated postoperative complications. MATERIALS: In 2011, 679 bladder cancer patients underwent RC at 18 European tertiary care centers. Data were prospectively collected within the 'PROspective MulticEnTer RadIcal Cystectomy Series 2011' (PROMETRICS 2011). Logistic regression models assessed the impact of preoperative characteristics on UD type and evaluated diversion-related complication rates. RESULTS: Of 570 eligible patients, 28.8, 2.6, 59.3, and 9.3% received orthotopic neobladders, continent cutaneous pouches, ileal conduits, and ureterocutaneostomies, respectively. In multivariable analyses, female sex (odds ratio [OR] 3.9; p = 0.002), American Society of Anesthesiologists score ≥3 (OR 2.3; p = 0.02), an age-adjusted Charlson Comorbidity Index ≥3 (OR 4.1; p < 0.001), and a positive biopsy of the prostatic urethra in the last transurethral resection of the bladder prior to RC (OR 4.9; p = 0.03) were independently associated with incontinent UD. There were no significant differences in 30- and/or 90-day complication rates between the UD types. Perioperative transfusion rates and 90-day mortality were significantly associated with incontinent UD (p < 0.001, respectively). Limitations included the small sample size and a certain level of heterogeneity in the application of clinical pathways between the different participating centers. CONCLUSIONS: Within this prospective contemporary cohort of European RC patients treated at tertiary care centers, the majority of patients received an incontinent UD. Female sex and pre-existing comorbidities were associated with receiving an incontinent UD. The risk of overall complications did not vary according to UD type.

Prognostic impact of infiltration of the vagina and/or uterus in women undergoing anterior pelvic exenteration for urothelial carcinoma of the bladder: results of a contemporary multicentre series.

PURPOSE: To evaluate for the first time the prognostic significance of female invasive patterns in stage pT4a urothelial carcinoma of the bladder in a large series of women undergoing anterior pelvic exenteration. PATIENTS AND METHODS: Our series comprised of 92 female patients in total of whom 87 with known invasion patterns were eligible for final analysis. Median follow-up for evaluation of cancer-specific mortality (CSM) was 38 months (interquartile ranges, 21-82 months). The impact on CSM was evaluated using multivariable Cox proportional-hazards regression analysis; predictive accuracy (PA) was assessed by receiver operating characteristic analysis. RESULTS: Vaginal invasion was noted in 33 patients (37.9 %; group VAG), uterine invasion in 20 patients (23 %; group UT), and infiltration of both vagina and uterus in 34 patients (39.1 %; group VAG + UT). Groups VAG and UT significantly differed from group VAG + UT with regard to the presence of positive soft tissue margins (STM) only. Five-year-cancer-specific survival probabilities in the groups VAG, UT, and VAG + UT were 21, 20, and 21 %, respectively (p = 0.955). On multivariable analysis, only STM status (HR = 2.02, p = 0.023) independently influenced CSM. C-indices of multivariable models for CSM with and without integration of invasive patterns were 0.570 and 0.567, respectively (PA gain 0.3 %, p = 0.526). CONCLUSIONS: Infiltration of the vagina, the uterus or both is associated with poor 5-year survival rates. With regard to CSM, no difference was detectable between patients with different invasion patterns, thus justifying further collectively including these invasive patterns as stage pT4a.

Concomitant seminal vesicle invasion in pT4a urothelial carcinoma of the bladder with contiguous prostatic infiltration is an adverse prognosticator for cancer-specific survival after radical cystectomy.

PURPOSE: To evaluate the prognostic value of concomitant seminal vesicle invasion (cSVI) in patients with urothelial carcinoma of the bladder (UCB) and contiguous prostatic stromal infiltration in a large cystectomy series. METHODS: A total of 385 patients with UCB and contiguous prostatic infiltration comprised our study. Patients were divided in two groups according to cSVI. Median follow-up was 36 months (interquartile range 11-74); the primary end point was cancer-specific mortality. The prognostic impact of cSVI was evaluated using multivariable Cox regression analysis. The predictive accuracy was assessed by a receiver operating characteristic analysis. RESULTS: A total of 229 patients (59.5 %) without cSVI comprised group A, and 156 patients (40.5 %) with cSVI comprised group B. Positive lymph nodes (63 vs. 44 %, p < 0.001) and positive surgical margins (34 % vs. 14 %, p < 0.001) were more common in patients with cSVI. The 5- and 10-year cancer-specific survival rates were 41 % and 32 % (group A) and 21 and 17 % (group B) (p < 0.001). In multivariable analysis, pathological nodal stage (hazard ratio [HR] 2.19, p < 0.001), soft tissue surgical margin (HR 1.57, p = 0.010), clinical tumor stage (HR 1.46, p = 0.010), adjuvant chemotherapy (HR 0.40, p < 0.001), and cSVI (HR 1.69, p < 0.001) independently impacted cancer-specific mortality. The c-indices of the multivariable models with and without inclusion of cSVI were 0.658 (95 % confidence interval 0.60-0.71) and 0.635 (95 % confidence interval 0.58-0.69), respectively, resulting in a predictive accuracy gain of 2.3 % (p = 0.002). CONCLUSIONS: In patients with UCB and prostatic stromal invasion, cSVI adversely affected cancer-specific survival compared to patients without cSVI. The inclusion of cSVI significantly improved the predictive accuracy of our multivariable model regarding survival.

Prediction of 90-day mortality after radical cystectomy for bladder cancer in a prospective European multicenter cohort.

BACKGROUND: Despite recent improvements, radical cystectomy (RC) is still associated with adverse rates for 90-d mortality. OBJECTIVE: To validate the performance of the Isbarn nomogram incorporating age and postoperative tumor characteristics for predicting 90-d RC mortality in a multicenter series and to generate a new nomogram based strictly on preoperative parameters. DESIGN, SETTING, AND PARTICIPANTS: Data of 679 bladder cancer (BCa) patients treated with RC at 18 institutions in 2011 were prospectively collected, from which 597 patients were eligible for final analysis. INTERVENTION: RC for BCa. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: An established prediction tool, the Isbarn nomogram, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver operating characteristics-derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities. Univariable and multivariable logistic regression models were fitted to assess the impact of preoperative characteristics on 90-d mortality. RESULTS AND LIMITATIONS: The 30-, 60-, and 90-d mortality rates in the development cohort (n=597) were 2.7%, 6.7%, and 9.0%, respectively. The Isbarn nomogram predicted individual 90-d mortality with an accuracy of 68.6%. Our preoperative multivariable model identified age (odds ratio [OR]:1.052), American Society of Anesthesiologists score (OR: 2.274), hospital volume (OR: 0.982), clinically lymphatic metastases (OR: 4.111), and clinically distant metastases (OR: 7.788) (all p<0.05) as independent predictors of 90-d mortality (predictive accuracy: 78.8%). Our conclusions are limited by the lack of an external validation of the preoperative model. CONCLUSIONS: The Isbarn nomogram was validated with moderate discrimination. Our newly developed model consisting of preoperative characteristics might outperform existing models. Our model might be particularly suitable for preoperative patient counseling. PATIENT SUMMARY: The current report validated an established nomogram predicting 90-d mortality in patients with bladder cancer after radical cystectomy (RC). We developed a new prediction tool consisting of strictly preoperative parameters, thus allowing clinicians an optimal consultation for RC candidates.

EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013.

CONTEXT: The most recent summary of the European Association of Urology (EAU) guidelines on prostate cancer (PCa) was published in 2011. OBJECTIVE: To present a summary of the 2013 version of the EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined PCa. EVIDENCE ACQUISITION: A literature review of the new data emerging from 2011 to 2013 has been performed by the EAU PCa guideline group. The guidelines have been updated, and levels of evidence and grades of recommendation have been added to the text based on a systematic review of the literature, which included a search of online databases and bibliographic reviews. EVIDENCE SYNTHESIS: A full version of the guidelines is available at the EAU office or online (www.uroweb.org). Current evidence is insufficient to warrant widespread population-based screening by prostate-specific antigen (PSA) for PCa. Systematic prostate biopsies under ultrasound guidance and local anesthesia are the preferred diagnostic method. Active surveillance represents a viable option in men with low-risk PCa and a long life expectancy. A biopsy progression indicates the need for active intervention, whereas the role of PSA doubling time is controversial. In men with locally advanced PCa for whom local therapy is not mandatory, watchful waiting (WW) is a treatment alternative to androgen-deprivation therapy (ADT), with equivalent oncologic efficacy. Active treatment is recommended mostly for patients with localized disease and a long life expectancy, with radical prostatectomy (RP) shown to be superior to WW in prospective randomized trials. Nerve-sparing RP is the approach of choice in organ-confined disease, while neoadjuvant ADT provides no improvement in outcome variables. Radiation therapy should be performed with ≥ 74 Gy in low-risk PCa and 78 Gy in intermediate- or high-risk PCa. For locally advanced disease, adjuvant ADT for 3 yr results in superior rates for disease-specific and overall survival and is the treatment of choice. Follow-up after local therapy is largely based on PSA and a disease-specific history, with imaging indicated only when symptoms occur. CONCLUSIONS: Knowledge in the field of PCa is rapidly changing. These EAU guidelines on PCa summarize the most recent findings and put them into clinical practice. PATIENT SUMMARY: A summary is presented of the 2013 EAU guidelines on screening, diagnosis, and local treatment with curative intent of clinically organ-confined prostate cancer (PCa). Screening continues to be done on an individual basis, in consultation with a physician. Diagnosis is by prostate biopsy. Active surveillance is an option in low-risk PCa and watchful waiting is an alternative to androgen-deprivation therapy in locally advanced PCa not requiring immediate local treatment. Radical prostatectomy is the only surgical option. Radiation therapy can be external or delivered by way of prostate implants. Treatment follow-up is based on the PSA level.

EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer.

OBJECTIVE: To present a summary of the 2013 version of the European Association of Urology (EAU) guidelines on the treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC). EVIDENCE ACQUISITION: The working panel performed a literature review of the new data (2011-2013). The guidelines were updated, and levels of evidence and/or grades of recommendation were added to the text based on a systematic review of the literature that included a search of online databases and bibliographic reviews. EVIDENCE SYNTHESIS: Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they may be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy (RT). Therapy for PSA relapse after RP includes salvage RT (SRT) at PSA levels <0.5 ng/ml and SRP or cryosurgical ablation of the prostate in radiation failures. Endorectal magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel at 75mg/m(2) every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications. CONCLUSIONS: The knowledge in the field of advanced, metastatic, and castration-resistant PCa is rapidly changing. These EAU guidelines on PCa summarise the most recent findings and put them into clinical practice. A full version is available at the EAU office or at www.uroweb.org. PATIENT SUMMARY: We present a summary of the 2013 version of the European Association of Urology guidelines on treatment of advanced, relapsing, and castration-resistant prostate cancer (CRPC). Luteinising hormone-releasing hormone (LHRH) agonists are the standard of care in metastatic prostate cancer (PCa). LHRH antagonists decrease testosterone without any testosterone surge, and they might be associated with an oncologic benefit compared with LHRH analogues. Complete androgen blockade has a small survival benefit of about 5%. Intermittent androgen deprivation results in noninferior oncologic efficacy when compared with continuous androgen-deprivation therapy (ADT) in well-selected populations. In locally advanced and metastatic PCa, early ADT does not result in a significant survival advantage when compared with delayed ADT. Relapse after local therapy is defined by prostate-specific antigen (PSA) values >0.2 ng/ml following radical prostatectomy (RP) and >2 ng/ml above the nadir and after radiation therapy. Therapy for PSA relapse after RP includes salvage radiation therapy at PSA levels <0.5 ng/ml and salvage RP or cryosurgical ablation of the prostate in radiation failures. Multiparametric magnetic resonance imaging and 11C-choline positron emission tomography/computed tomography (PET/CT) are of limited importance if the PSA is <1.0 ng/ml; bone scans, and CT can be omitted unless PSA is >20 ng/ml. Follow-up after ADT should include analysis of PSA and testosterone levels, and screening for cardiovascular disease and metabolic syndrome. Treatment of castration-resistant CRPC includes sipuleucel-T, abiraterone acetate plus prednisone (AA/P), or chemotherapy with docetaxel 75 mg/m(2) every 3 wk. Cabazitaxel, AA/P, enzalutamide, and radium-223 are available for second-line treatment of CRPC following docetaxel. Zoledronic acid and denosumab can be used in men with CRPC and osseous metastases to prevent skeletal-related complications. The guidelines reported should be adhered to in daily routine to improve the quality of care in PCa patients. As we have shown recently, guideline compliance is only in the area of 30-40%.