Impact of Male Patient Information on Quality of Urine Examination (PIQUE Study).

BACKGROUND: Urine examination has relevance for treatment, and reliability of positive urine culture (UC) is of importance. The technique of urine sampling (US), storage, and transportation is important. The objective of this study was to investigate if detailed patient information for the technique of US and hygiene reduces rates of contaminated UC in screened male patients, as this group was not investigated yet. METHODS: All patients independently of complaints were enrolled prospectively and consecutively in an outpatient setting in 2 groups - the first group did not receive detailed information and the second group did. We examined 372 consecutive patients in 2017, 190 not receiving (median age 69 years) and 182 receiving information (median age 70 years), with comparable numbers of patients and age. The result of UC and age was imposed. RESULTS: In all,74.2% of preclarification UC showed a contamination (n = 95) and 75.5% after clarification (n = 83), without significant differences (p = 0.827). This study is limited by the fact that adherence could not be checked. CONCLUSIONS: Similar to studies with females, no difference occurred in rates of contaminated UC, so detailed information regarding the US technique does not decrease rates of contaminated UC and vice versa does not increase the quality of midstream-sampled UC in male patients.

Final results of the PräVAC trial: prevention of wound complications following inguinal lymph node dissection in patients with penile cancer using epidermal vacuum-assisted wound closure.

PURPOSE: Inguinal lymphadenectomy in penile cancer is associated with a high rate of wound complications. The aim of this trial was to prospectively analyze the effect of an epidermal vacuum wound dressing on lymphorrhea, complications and reintervention in patients with inguinal lymphadenectomy for penile cancer. PATIENTS AND METHODS: Prospective, multicenter, randomized, investigator-initiated study in two German university hospitals (2013-2017). Thirty-one patients with penile cancer and indication for bilateral inguinal lymph node dissection were included and randomized to conventional wound care on one side (CONV) versus epidermal vacuum wound dressing (VAC) on the other side. RESULTS: A smaller cumulative drainage fluid volume until day 14 (CDF) compared to contralateral side was observed in 15 patients (CONV) vs. 16 patients (VAC), with a median CDF 230 ml (CONV) vs. 415 ml (VAC) and a median maximum daily fluid volume (MDFV) of 80 ml (CONV) vs. 110 ml (VAC). Median time of indwelling drainage: 7 days (CONV) vs. 8 days (VAC). All grade surgery-related complications were seen in 74% patients (CONV) vs. 74% patients (VAC); grade 3 complications in 3 patients (CONV) vs. 6 patients (VAC). Prolonged hospital stay occurred in 32% patients (CONV) vs. 48% patients (VAC); median hospital stay was 11.5 days. Reintervention due to complications occurred in 45% patients (CONV) vs. 42% patients (VAC). CONCLUSIONS: In this prospective, randomized trial we could not observe a significant difference between epidermal vacuum treatment and conventional wound care.

Radiation exposure during retrograde intrarenal surgery (RIRS): a prospective multicenter evaluation.

PURPOSE: Retrograde intrarenal surgery (RIRS) may require extensive X-ray usage. We evaluated the impact of preoperative surgeon briefing regarding the inclusion and evaluation of fluoroscopy time (FT) and dose area product (DAP) in a multicenter study on the applied X-ray usage. METHODS: A prospective multicenter study of 6 tertiary centers was performed. Each center recruited up to 25 prospective patients with renal stones of any size for RIRS. Prior to study´s onset, all surgeons were briefed about hazards of radiation and on strategies to avoid high doses in RIRS. Prospective procedures were compared to past procedures, as baseline data. FT was defined as the primary outcome. Secondary parameters were stone-free rate (SFR), complications according to the Clavien, SATAVA and postureteroscopic lesion scale. Results were analyzed using T test, chi-squared test, univariate analysis and confirmed in a multivariate regression model. RESULTS: 303 patients were included (145 retro- and 158 prospective). Mean FT and DAP were reduced from 130.8 s/565.8 to 77.4 s/357.8 (p < 0.05). SFR was improved from 85.5% to 93% (p < 0.05). Complications did not vary significantly. Neither stone position (p = 0.569), prestenting (p = 0.419), nor surgeons' experience (> 100 RIRS) had a significant impact on FT. Significant univariate parameters were confirmed in a multivariate model, revealing X-ray training to be radiation protective (OR - 44, p = 0.001). CONCLUSIONS: Increased surgeon awareness of X-ray exposure risks has a significant impact on FT and DAP. This "awareness effect" is a simple method to reduce radiation exposure for the patient and OR staff without the procedures´ outcome and safety being affected.

Transurethral en bloc submucosal hydrodissection vs conventional resection for resection of non-muscle-invasive bladder cancer (HYBRIDBLUE): a randomised, multicentre trial.

OBJECTIVE: To determine whether transurethral en bloc submucosal hydrodissection of bladder tumours (TUEB) improves the quality of the resection compared to conventional transurethral resection of bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A randomised, multicentre trial (HYBRIDBLUE) was conducted with a superiority design. Six German academic centres participated between September 2012 and August 2015. Based on literature analysis, a sample size for accurate histopathological assessment concerning muscle invasion was assumed to be feasible in 50% (P0 = 0.5) of TURBT and 80% of TUEB cases. After pre-screening of a total of 305 patients, participants were allocated to two study arms: Group I: hexaminolevulinate (HAL)-guided TUEB; Group II: conventional HAL-guided TURBT. The primary endpoint was the proportion of specimens that could be reliably evaluated pathologically concerning muscle invasiveness. Secondary endpoints included rates of histopathological completeness of the resection, muscularis propria content, recurrence, and complication rates. RESULTS: A total of 115 patients (TUEB 56; TURBT 59) were eligible for final analysis. Adequate histopathological assessment, which included muscularis propria content and tumour margins (R0 vs R1), was present in 48/56 (86%) TUEB patients compared to 37/59 (63%; P = 0.006) in the TURBT group. R0 was confirmed in 30/56 TUEB patients (57%) and five of 59 TURBT patients (9%; P < 0.001). No complications of Grade ≥III were observed in both arms. At 3 and 12 months, three and 19 patients recurred in the TUEB group vs seven and 11 patients in the TURBT group, respectively (P = 0.33 and P = 0.08). CONCLUSIONS: In this randomised study, TUEB was shown to be clinically safe regarding perioperative endpoints. An adequate histopathological assessment concerning muscle invasion was significantly better assessable in the TUEB arm compared to standard TURBT. This finding indicates the clinical potential for reducing the rate of early re-resections. Yet, a larger study with recurrence-free survival as the primary endpoint is needed to assess the oncological efficacy between both techniques.

Oncological long-term outcome of whole gland HIFU and open radical prostatectomy: a comparative analysis.

PURPOSE: To compare the oncological long-term efficacy of whole gland high-intensity focused ultrasound (HIFU) therapy and radical prostatectomy (RP) in patients with clinically localized prostate cancer. METHODS: 418 patients after open RP (1997-2004) were compared with 469 patients after whole gland HIFU (1997-2009) without preselection. Oncological follow-up focused on biochemical relapse, salvage treatment, life status and cause-specific mortality. The univariate log rank test was used to compare both treatment options regarding overall survival (OS), cancer-specific survival (CSS), biochemical failure-free survival (BFS) and salvage treatment-free survival (STS). To adjust the treatment effect for further prognostic baseline variables, a multivariable Cox proportional hazards regression model was calculated for each end point. RESULTS: Median follow-up was 13.3 years in the RP group and 6.5 years in the HIFU group. OS/CSS/BFS/STS rates at 10 years were 91/98/80/80% after RP and 76/94/70/71% after HIFU. HIFU therapy (reference RP) was a significant and independent predictor for an inferior OS, CSS and STS. In subgroup analysis, HIFU provided significantly reduced CSS for intermediate- (p = 0.010) and high-risk patients (p = 0.048); whereas no difference was observed in the low-risk group, intermediate-risk HIFU patients showed a significantly inferior STS (p = 0.040). CONCLUSIONS: While whole gland HIFU offers a comparable long-term efficacy for low-risk patients, sufficient cancer control for high-risk patients is more than doubtful. For the subgroup of intermediate-risk patients, CSS rates seem to be comparable up to 10 years suggesting that HIFU may be an alternative for older patients, although a higher risk of salvage treatment should be expected.

Peri-operative allogeneic blood transfusion does not adversely affect oncological outcomes after radical cystectomy for urinary bladder cancer: a propensity score-weighted European multicentre study.

OBJECTIVES: To evaluate the effect of peri-operative blood transfusion (PBT) on recurrence-free survival, overall survival, cancer-specific mortality and other-cause mortality in patients undergoing radical cystectomy (RC), using a contemporary European multicentre cohort. PATIENTS AND METHODS: The Prospective Multicentre Radical Cystectomy Series (PROMETRICS) includes data on 679 patients who underwent RC at 18 European tertiary care centres in 2011. The association between PBT and oncological survival outcomes was assessed using Kaplan-Meier, Cox regression and competing-risks analyses. Imbalances in clinicopathological features between patients receiving PBT vs those not receiving PBT were mitigated using conventional multivariable adjusting as well as inverse probability of treatment weighting (IPTW). RESULTS: Overall, 611 patients had complete information on PBT, and 315 (51.6%) received PBT. The two groups (PBT vs no PBT) differed significantly with respect to most clinicopathological features, including peri-operative blood loss: median (interquartile range [IQR]) 1000 (600-1500) mL vs 500 (400-800) mL (P < 0.001). Independent predictors of receipt of PBT in multivariable logistic regression analysis were female gender (odds ratio [OR] 5.05, 95% confidence interval [CI] 2.62-9.71; P < 0.001), body mass index (OR 0.91, 95% CI 0.87-0.95; P < 0.001), type of urinary diversion (OR 0.38, 95% CI 0.18-0.82; P = 0.013), blood loss (OR 1.32, 95% CI 1.23-1.40; P < 0.001), neoadjuvant chemotherapy (OR 2.62, 95% CI 1.37-5.00; P = 0.004), and ≥pT3 tumours (OR 1.59, 95% CI 1.02-2.48; P = 0.041). In 531 patients with complete data on survival outcomes, unweighted and unadjusted survival analyses showed worse overall survival, cancer-specific mortality and other-cause mortality rates for patients receiving PBT(P < 0.001, P = 0.017 and P = 0.001, respectively). After IPTW adjustment, those differences no longer held true. PBT was not associated with recurrence-free survival (hazard ratio [HR] 0.92, 95% CI 0.53-1.58; P = 0.8), overall survival (HR 1.06, 95% CI 0.55-2.05; P = 0.9), cancer-specific mortality (sub-HR 1.09, 95% CI 0.62-1.92; P = 0.8) and other-cause mortality (sub-HR 1.00, 95% CI 0.26-3.85; P > 0.9) in IPTW-adjusted Cox regression and competing-risks analyses. The same held true in conventional multivariable Cox and competing-risks analyses, where PBT could not be confirmed as a predictor of any given endpoint (all P values >0.05). CONCLUSION: The present results did not show an adverse effect of PBT on oncological outcomes after adjusting for baseline differences in patient characteristics.

Sarcopenia predicts 90-day mortality and postoperative complications after radical cystectomy for bladder cancer.

PURPOSE: A single-center study was conducted to investigate the impact of sarcopenia as a predictor for 90-day mortality (90 dM) and complications within 90 days after radical cystectomy for bladder cancer. METHODS: In total, 327 patients with preoperative available digital computed tomography (CT) scans of the abdomen and pelvis were identified. The lumbar skeletal muscle index was measured using preoperative abdominal CT to assess sarcopenia. Complications were recorded and graded according to Clavien-Dindo (CD). Predictors of 90 dM and complications within 90 days were analyzed by uni- and multivariable logistic regression. RESULTS: Of the 327 patients, 262 (80%) were male and 108 (33%) patients were classified as sarcopenic. Within 90 days, 28 (7.8%) patients died, of whom 15 patients were sarcopenic and 13 were not. In multivariable logistic regression analysis, sarcopenia (OR 2.59; 95% CI 1.13-5.95; p = 0.025), ASA 3-4 (OR 2.53; 95% CI 1.10-5.82; p = 0.029) and cM + (OR 7.43; 95% CI 2.34-23.64; p = 0.001) were independent predictors of 90-day mortality. Sarcopenic patients experienced significantly more complications, i.e., CD 4a-5 (p = 0.003), compared to non-sarcopenic patients. In multivariable logistic regression analysis, sarcopenia was independently associated with CD ≥ 3b complications corrected for age, BMI, ASA-Score and type of urinary diversion. CONCLUSIONS: We reported that sarcopenia proved an independent predictor for 90 dM and complications in patients undergoing RC for bladder cancer.

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.

Prospective Evaluation of Predictive Parameters for Urinary Tract Infection in Patients with Acute Renal Colic.

BACKGROUND: Acute renal colic (ARC) is an emergency that can mostly be treated conservatively, but can be life threatening in combination with urinary tract infection (UTI). Assessment for infection includes white blood cell (WBC) count and C-reactive protein (CRP), but these parameters are often unspecifically elevated and might lead to antibiotic over-therapy. In times of increasing antibiotic resistance, however, unnecessary antibiotic therapy should be avoided. OBJECTIVES: The goal of the study was to investigate the prevalence of UTI proven by urine culture (UC) in patients with ARC and to identify predictive factors in the emergency setting. PATIENTS AND METHODS: We prospectively enrolled 200 consecutive patients with ARC and evaluated blood test results, urinalysis, UC, symptoms suspicious for UTI, and time between symptom onset and admission, as well as body temperature. Logistic regression analyses were performed to identify predictive factors. RESULTS: There were 196 patients eligible for statistical analysis. UTI proven by positive UC was detected in 26 patients (13%). On multivariate logistic regression analysis, suspicious urinalysis (positive nitrite or bacteria > 20/high-power field [hpf] or WBC > 20/hpf), patient age ≥ 54 years and CRP ≥ 1.5 mg/dL (fivefold increase) were significant predictors for the presence of UTI. Neither elevated WBC count nor typical UTI symptoms were associated with UTI. CONCLUSIONS: Based on our results, a routine antibiotic prophylaxis in patients with ARC does not seem to be appropriate. Patient age and CRP can help to decide if antibiotic treatment might be indicated, even in case of a not clearly suspicious urinalysis.

The German linguistic validation of the Ureteral Stent Symptoms Questionnaire (USSQ).

PURPOSE: We developed and validated the German version of the Ureteral Stent Symptoms Questionnaire (USSQ) for male and female patients with indwelling ureteral stents. METHODS: The German version of the USSQ was developed following a well-established multistep process. A total of 101 patients with indwelling ureteral stents completed the German USSQ as well as the validated questionnaires International Prostate Symptom Score (IPSS) or International Consultation on Incontinence Questionnaire (ICIQ) and the Short Form Health Survey (SF-36). Patients completed questionnaires at 1 and 2-4 weeks after stent insertion and 4 weeks after stent removal. Statistical analyses were performed to assess the psychometric properties of the questionnaire. RESULTS: The German version of the USSQ showed good internal consistency (Cronbach's α = .72-.88) and test-retest reliability [intraclass correlation coefficient (ICC) = .81-.92]. Inter-domain associations within the USSQ showed substantial correlations between different USSQ domains, indicating a high conceptual relationship of the domains. Except from urinary symptoms and general quality of life, German USSQ showed good convergent validity with the corresponding validated questionnaires. All USSQ domains showed significant sensitivity to change (p ≤ .001). CONCLUSION: The new German version of the USSQ proved to be a reliable and robust instrument for the evaluation of ureteral stent-associated morbidity for both male and female patients. It is expected to be a valid outcome measure in the future stent research.

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.

Epidemiology, diagnosis, preoperative evaluation and prognostic assessment of upper-tract urothelial carcinoma (UTUC).

PURPOSE: Upper-tract urothelial carcinoma (UTUC) is a relatively uncommon disease with limited available evidence on specific topics. The purpose of this article was to review the previous literature to summarize the current knowledge about UTUC epidemiology, diagnosis, preoperative evaluation and prognostic assessment. METHODS: Using MEDLINE, a non-systematic review was performed including articles between January 2000 and February 2016. English language original articles, reviews and editorials were selected based on their clinical relevance. RESULTS: UTUC accounts for 5-10 % of all urothelial cancers, with an increasing incidence. UTUC and bladder cancer share some common risk factors, even if they are two different entities regarding practical, biological and clinical characteristics. Aristolochic acid plays an important role in UTUC pathogenesis in certain regions. It is further estimated that approximately 10 % of UTUC are part of the hereditary non-polyposis colorectal cancer spectrum disease. UTUC diagnosis remains mainly based on imaging and endoscopy, but development of new technologies is rapidly changing the diagnosis algorithm. To help the decision-making process regarding surgical treatment, extent of lymphadenectomy and selection of neoadjuvant systemic therapies, predictive tools based on preoperative patient and tumor characteristics have been developed. CONCLUSIONS: Awareness regarding epidemiology, diagnosis, preoperative evaluation and prognostic assessment changes is essential to correctly diagnose and manage UTUC patients, thereby potentially improving their outcomes.

[Do General Surgeons Feel Adequately Prepared for the Complex Questions Associated with the Handling of Multi-Resistant Pathogens? - Results of the MR2 Survey]. / Fühlen sich Chirurgen gerüstet für die komplexen Fragestellungen im Umgang mit multiresistenten Erregern? ­ Ergebnisse der Fragebogenstudie MR2.

Background At the present time, there is no evidence available as to the knowledge of general surgeons regarding multi-resistant pathogens (MRP) and the rational use of antibiotic medication (antibiotic stewardship/ABS) compared with physicians from other disciplines. Methods As part of the MR2 survey (Multiinstitutional Reconnaissance of practice with MultiResistant bacteria - a survey focussing on German hospitals), a questionnaire comprising 4 + 35 items was distributed to urologists, internists, gynaecologists and general surgeons in 18 hospitals. Multivariate regression models were applied to assess the impact of each discipline affiliation on predefined endpoints. Results 456 evaluable surveys were analysed. The response rate of surgeons (156/330; 47%) and physicians from other disciplines (300/731; 41%) did not differ significantly. Based on their self-assessment, surgeons indicated a significantly lower certainty regarding the correct choice of dose, frequency and duration of antibiotic treatment (p = 0.005), the decision between intravenous or oral application (p = 0.005), as well as the accurate interpretation of microbiological reports (p = 0.023). Both surgeons and doctors from other disciplines rated their knowledge of ABS as limited. An insignificant difference was found between surgeons and non-surgeons regarding the knowledge of E. coli resistance against Ciprofloxacin in their own hospital (27.6 vs. 35.3% estimated the correct category; p = 0.114), with 64% of surgeons underestimating the local resistance rates. Both physician groups assumed that the frequent use of broad-spectrum antibiotics is substantially responsible for the increase in MRP. However, in the given case study of a highly symptomatic female patient with uncomplicated urinary tract infection, both physician groups were almost equally likely to propose treatment with a broad-spectrum antibiotic (34.0 vs. 29.3%; p = 0.331). Based on the results of the multivariate models, there were no significant differences between surgeons and non-surgeons with regard to both the attendance of training courses related to MRP/ABS over the past 12 months and the quality of discharge summaries in their hospitals regarding the correct listing of MRP. Conclusion In due consideration of the results of the MR2 survey, mandatory ABS programs should be implemented in hospitals, including regular training of physicians regardless of their discipline.

Oncologic Outcomes of Kidney Sparing Surgery versus Radical Nephroureterectomy for the Elective Treatment of Clinically Organ Confined Upper Tract Urothelial Carcinoma of the Distal Ureter.

PURPOSE: We compared the oncologic outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery for elective treatment of clinically organ confined upper tract urothelial carcinoma of the distal ureter. MATERIALS AND METHODS: From a multi-institutional collaborative database we identified 304 patients with unifocal, clinically organ confined urothelial carcinoma of the distal ureter and bilateral functional kidneys. Rates of overall, cancer specific, local recurrence-free and intravesical recurrence-free survival according to surgery type were compared using Kaplan-Meier statistics. Univariable and multivariable Cox regression analyses were performed to assess the adjusted outcomes of radical nephroureterectomy, distal ureterectomy and endoscopic surgery. RESULTS: Overall 128 (42.1%), 134 (44.1%) and 42 patients (13.8%) were treated with radical nephroureterectomy, distal ureterectomy and endoscopic surgery, respectively. Although rates of overall, cancer specific and intravesical recurrence-free survival were equivalent among the 3 surgical procedures, 5-year local recurrence-free survival was lower for endoscopic surgery (35.7%) than for nephroureterectomy (95.0%, p <0.001) or ureterectomy (85.5%, p = 0.01) with no significant difference between nephroureterectomy and distal ureterectomy. On multivariable analyses only endoscopic surgery was an independent predictor of decreased local recurrence-free survival compared to nephroureterectomy (HR 1.27, p = 0.001) or distal ureterectomy (HR 1.14, p = 0.01). Distal ureterectomy and endoscopic surgery did not significantly correlate to cancer specific or intravesical recurrence-free survival. However, when adjustment was made for ASA(®) (American Society of Anesthesiologists(®)) score, distal ureterectomy (HR 0.80, p = 0.01) and endoscopic surgery (HR 0.84, p = 0.02) were independent predictors of increased overall survival, although no significant difference was found between them. CONCLUSIONS: Because of better oncologic outcomes, distal ureterectomy could be considered the elective first line treatment of clinically organ confined urothelial carcinoma of the distal ureter.

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.

Prognostic factors and outcomes in primary urethral cancer: results from the international collaboration on primary urethral carcinoma.

PURPOSE: To evaluate risk factors for survival in a large international cohort of patients with primary urethral cancer (PUC). METHODS: A series of 154 patients (109 men, 45 women) were diagnosed with PUC in ten referral centers between 1993 and 2012. Kaplan-Meier analysis with log-rank test was used to investigate various potential prognostic factors for recurrence-free (RFS) and overall survival (OS). Multivariate models were constructed to evaluate independent risk factors for recurrence and death. RESULTS: Median age at definitive treatment was 66 years (IQR 58-76). Histology was urothelial carcinoma in 72 (47 %), squamous cell carcinoma in 46 (30 %), adenocarcinoma in 17 (11 %), and mixed and other histology in 11 (7 %) and nine (6 %), respectively. A high degree of concordance between clinical and pathologic nodal staging (cN+/cN0 vs. pN+/pN0; p < 0.001) was noted. For clinical nodal staging, the corresponding sensitivity, specificity, and overall accuracy for predicting pathologic nodal stage were 92.8, 92.3, and 92.4 %, respectively. In multivariable Cox-regression analysis for patients staged cM0 at initial diagnosis, RFS was significantly associated with clinical nodal stage (p < 0.001), tumor location (p < 0.001), and age (p = 0.001), whereas clinical nodal stage was the only independent predictor for OS (p = 0.026). CONCLUSIONS: These data suggest that clinical nodal stage is a critical parameter for outcomes in PUC.

Prognostic Significance of Incidental Prostate Cancer at Radical Cystoprostatectomy for Bladder Cancer.

OBJECTIVE: The aim of the study was to evaluate the impact of the clinical significance of incidental prostate cancer (PC) on overall survival (OS) after radical cystoprostatectomy (RC) for bladder cancer (BC). METHODS: A total of 822 consecutive men underwent RC in 3 academic centers between 1996 and 2011. The clinical significance of incidental PC was determined according to the Epstein criteria. The Kaplan-Meier analysis with log-rank was used to investigate the impact of PC on OS and univariate and multivariate Cox regression analyses for risk factors of OS. The median follow-up was 36 months (interquartile range 10-49). RESULTS: Of the 822 men, 117 (14.2%) had clinically significant, 243 (29.6%) insignificant and 462 (56.2) no PC at RC. Men with PC were at higher risk for lymphovascular invasion (LVI) of BC compared to men without PC (p < 0.001). The 5-year OS for men with clinically significant, insignificant and no PC was 33.3, 51.3 and 51.5%, respectively (p = 0.050). In the subgroup of pN0 patients (n = 601), clinically significant PC was significantly associated with inferior OS (p = 0.044) but not in multivariable analysis (p = 0.46). CONCLUSIONS: We did not find the clinical significance of incidental PC to be an independent predictor. However, the positive correlation between incidental PC and LVI of BC deserves further investigation.

Oncological Outcomes of Patients with Concomitant Bladder and Urethral Carcinoma.

INTRODUCTION: The study aimed to investigate oncological outcomes of patients with concomitant bladder cancer (BC) and urethral carcinoma. METHODS: This is a multicenter series of 110 patients (74 men, 36 women) diagnosed with urethral carcinoma at 10 referral centers between 1993 and 2012. Kaplan-Meier analysis was used to investigate the impact of BC on survival, and Cox regression multivariable analysis was performed to identify predictors of recurrence. RESULTS: Synchronous BC was diagnosed in 13 (12%) patients, and the median follow-up was 21 months (interquartile range 4-48). Urethral cancers were of higher grade in patients with synchronous BC compared to patients with non-synchronous BC (p = 0.020). Patients with synchronous BC exhibited significantly inferior 3-year recurrence-free survival (RFS) compared to patients with non-synchronous BC (63.2 vs. 34.4%; p = 0.026). In multivariable analysis, inferior RFS was associated with clinically advanced nodal stage (p < 0.001), proximal tumor location (p < 0.001) and synchronous BC (p = 0.020). CONCLUSION: The synchronous presence of BC in patients diagnosed with urethral carcinoma has a significant adverse impact on RFS and should be an impetus for a multimodal approach.

Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients.

OBJECTIVE: To compare outcomes of patients with lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) treated with or without cisplatin-based combined adjuvant chemotherapy (AC) after radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed 1523 patients with LN-positive UCB, who underwent RC with bilateral pelvic LN dissection. All patients had no evidence of disease after RC. AC was administered within 3 months. Competing-risks models were applied to compare UCB-related mortality. RESULTS: Of the 1523 patients, 874 (57.4%) received AC. The cumulative 1-, 2- and 5-year UCB-related mortality rates for all patients were 16%, 36% and 56%, respectively. Administration of AC was associated with an 18% relative reduction in the risk of UCB-related death (subhazard ratio 0.82, P = 0.005). The absolute reduction in mortality was 3.5% at 5 years. The positive effect of AC was detectable in patients aged ≤70 years, in women, in pT3-4 disease, and in those with a higher LN density and lymphovascular invasion. This study is limited by its retrospective and non-randomised design, selection bias, the absence of central pathological review and lack in standardisation of LN dissection and cisplatin-based protocols. CONCLUSION: AC seems to reduce UCB-related mortality in patients with LN-positive UCB after RC. Younger patients, women and those with high-risk features such as pT3-4 disease, a higher LN density and lymphovascular invasion appear to benefit most. Appropriately powered prospective randomised trials are necessary to confirm these findings.

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.