Risk factors for bladder neck contracture after transurethral resection of the prostate.

INTRODUCTION: Transurethral resection of the prostate (TURP) is the most frequently used treatment of benign prostate hyperplasia with a prostate volume of <80 mL. A long-term complication is bladder neck contracture (BNC). The aim of the present study was to identify the risk factors for BNC formation after TURP. METHODS: We conducted a retrospective analysis of all TURP primary procedures which were performed at one academic institution between 2013 and 2018. All patients were analyzed and compared with regard to postoperative formation of a BNC requiring further therapy. Uni- and multivariable logistic regression analyses (MVAs) were performed to identify possible risk factors for BNC development. RESULTS: We included 1368 patients in this analysis. Out of these, 88 patients (6.4%) developed BNC requiring further surgical therapy. The following factors showed a statistically significant association with BNC development: smaller preoperative prostate volume (p = 0.001), lower resected prostate weight (p = 0.004), lower preoperative levels of prostate-specific antigen (PSA, p < 0.001), shorter duration of the surgery (p = 0.027), secondary transurethral intervention (due to urinary retention or gross hematuria) during inpatient stay (p = 0.018), positive (≥100 CFU/mL) preoperative urine culture (p = 0.010), and urethral stricture (US) formation requiring direct visual internal urethrotomy (DVIU) postoperatively after TURP (p < 0.001), in particular membranous (p = 0.046) and bulbar (p < 0.001) strictures. Preoperative antibiotic treatment showed a protective effect (p = 0.042). Histopathological findings of prostate cancer (PCA) in the resected prostate tissue were more frequent among patients who did not develop BNC (p = 0.049). On MVA, smaller preoperative prostate volume (p = 0.046), positive preoperative urine culture (p = 0.021), and US requiring DVIU after TURP (p < 0.001) were identified as independent predictors for BNC development. CONCLUSION: BNC is a relevant long-term complication after TURP. In particular, patients with a smaller prostate should be thoroughly informed about this complication.

Short-Term and Long-Term Morbidity after Radical Cystectomy in Patients with NMIBC and Comparison with MIBC: Identifying Risk Factors for Severe Short-Term Complications.

INTRODUCTION: RC represents a viable treatment option for certain NMIBC patients. However, studies investigating morbidity in the context of RC for NMIBC are scarce. The goal of the current study was to assess and compare morbidity after RC performed in patients with NMIBC and patients with MIBC and to identify risk factors for severe short-term complications. METHODS: Medical records of 521 patients who underwent RC for bladder cancer were retrospectively reviewed. Patients were divided into patients with NMIBC and patients with MIBC. The groups were compared and risk factors for severe complications were identified. RESULTS: RC for NMIBC was performed in 123 patients (23.6%). Histological upstaging was seen in 47 NMIBC patients (38.2%) and in 231 MIBC patients (58%, p < 0.001). OS was 29.8% and CSS was 15.5%. Both endpoints were higher for RC for MIBC (p < 0.001). More complications affecting the urinary diversion were seen with RC for NMIBC (p = 0.033) and more continent urinary diversions (p = 0.040) were performed in those patients. Obesity (p = 0.008), a higher ASA score (p = 0.004), and preoperative medical drug anticoagulation (p = 0.025) were risk factors for severe short-term morbidity after both, RC for NMIBC and for MIBC. CONCLUSION: Patients who underwent RC for NMIBC are exposed to a comparably high perioperative risk than patients with MIBC. RC seems to be a viable treatment option for certain NMIBC patients with a significant histological upstaging in both groups. In patients with obesity, a high ASA score, and with medical drug anticoagulation, the indication for surgery should be confirmed especially strict and possible treatment alternatives should be considered particularly thorough.

A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14.

BACKGROUND: VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation. OBJECTIVE: To report on the efficacy, safety, tolerability and quality of life of intravesical VPM1002BC for the treatment of non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We designed a phase 1/2 single-arm trial (NCT02371447). Patients with recurrent NMIBC after BCG induction ± BCG maintenance therapy and intermediate to high risk for cancer progression were eligible. INTERVENTION: Patients were scheduled for standard treatment of six weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was defined as the recurrence-free rate (RFR) in the bladder 60 wk after trial registration. The sample size was calculated based on the assumption that ≥30% of the patients would be without recurrence at 60 wk after registration. RESULTS AND LIMITATIONS: After exclusion of two ineligible patients, 40 patients remained in the full analysis set. All treated tumours were of high grade and 27 patients (67.5%) presented with carcinoma in situ. The recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial registration. At the same time, progression to muscle-invasive disease had occurred in three patients and metastatic disease in four patients. Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 54.8%, and 4.8% of the patients, respectively. No grade ≥4 AEs occurred. Two of the 42 patients did not tolerate five or more instillations during induction. Limitations include the single-arm trial design and the low number of patients for subgroup analysis. CONCLUSIONS: At 1 yr after treatment start, almost half of the patients remained recurrence-free after therapy with VPM100BC. The primary endpoint of the study was met and the therapy is safe and well tolerated. PATIENT SUMMARY: We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (BCG) strain for treatment of bladder cancer not invading the bladder muscle. At 1 year after the start of treatment, almost half of the patients with a recurrence after previous conventional BCG were free from non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and VPM1002BC merits further evaluation in randomised studies for patients with NMIBC.

Oncological Long-term Outcome After Whole-gland High-intensity Focused Ultrasound for Prostate Cancer-21-yr Follow-up.

BACKGROUND: Owing to the morbidity of established radical treatment options for prostate cancer, alternative whole-gland and focal treatment strategies have emerged. High-intensity focused ultrasound (HIFU) is one of the most studied sources for tissue ablation and has been used since the 1990s. OBJECTIVE: To provide 21-yr oncological long-term follow-up data of an unselected series of patients who underwent whole-gland HIFU for nonmetastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: A total of 674 patients were treated between November 1997 and November 2012 in one university center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The oncological outcome was assessed by biopsy failure-free survival (BFFS), salvage treatment-free survival (STFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Multivariable Cox proportional hazard regression analyses were performed to estimate the prognostic relevance of clinical variables. RESULTS AND LIMITATIONS: In total, 560 patients were included into the evaluation and the median follow-up was 15.1 yr, with a range up to 21.4 yr. At 15 yr, CSS rates for low-, intermediate-, and high-risk patients were 95%, 89%, and 65%, respectively; MFS, STFS-1 (salvage treatment other than HIFU), STFS-2 (salvage treatment including repeat HIFU), and BFFS rates were 91%, 85%, and 58%; 77%, 63%, and 29%; 67%, 52%, and 28%; and 82%, 73%, and 47%, respectively. Preoperative high-risk category was an independent predictor of inferior OS, CSS, MFS, STFS, and BFFS. CONCLUSIONS: Although whole-gland HIFU achieved good long-term cancer control in low- and intermediate-risk patients, high-risk patients should not be treated routinely by HIFU. Intermediate-risk patients achieve high CSS and MFS rates, but a relevant salvage treatment rate has to be reckoned with. Long-term data after whole-gland therapy might help derive implications for focal treatment sources and patient selection. PATIENT SUMMARY: Long-term data after whole-gland high-intensity focused ultrasound (HIFU) therapy are crucial to prove its oncological efficacy, and may help derive implications for focal treatment strategies and patient selection. In this context, whole-gland HIFU achieved good long-term cancer control up to 21 yr in low- and intermediate-risk prostate cancer (PCa) patients. Owing to considerably inferior long-term cancer control, it should not routinely be used in high-risk PCa patients.

The Effect of Low-intensity Shockwave Therapy on Non-neurogenic Lower Urinary Tract Symptoms: A Systematic Review and Meta-analysis of Preclinical and Clinical Studies.

CONTEXT: Low-intensity shockwave therapy (LiST) has emerged as an effective treatment for pain in patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and it has been postulated that LiST may also be effective in patients with lower urinary tract symptoms (LUTS). OBJECTIVE: To perform a systematic review and meta-analysis of experimental and clinical studies exploring the effect of LiST on LUTS in an attempt to provide clinical implications for future research. EVIDENCE ACQUISITION: We systematically searched PubMed, Cochrane Library, and Scopus databases from inception to March 2021 for relevant studies. We provided a qualitative synthesis regarding the role of LiST in LUTS and performed a single-arm, random-effect meta-analysis to assess the absolute effect of LiST on LUTS only in patients with CP/CPPS (PROSPERO: CRD42021238281). EVIDENCE SYNTHESIS: We included 23 studies (11 experimental studies, seven nonrandomized controlled trials [non-RCTs], and five RCTs) in the systematic review and seven in the meta-analysis. All experimental studies were performed on rats with LUTS, and the clinical studies recruited a total of 539 participants. In patients with CP/CPPS, the absolute effect of LiST on maximum flow rate and postvoid residual was clinically insignificant. However, the available studies suggest that LiST is effective for the management of pain in patients with either CP/CPPS or interstitial cystitis/bladder pain syndrome. Additionally, LiST after intravesical instillation of botulinum neurotoxin type A may enhance its absorption and substitute botulinum neurotoxin type A injections in patients with overactive bladder. Furthermore, the available evidence is inconclusive about the role of LiST in patients with benign prostatic obstruction, stress urinary incontinence, or underactive bladder/detrusor hypoactivity. CONCLUSIONS: LiST may be effective for some disorders causing LUTS. Still, further studies on the matter are necessary, since the available evidence is scarce. PATIENT SUMMARY: Low-intensity shockwave therapy represents a safe, easily applied, indolent, and repeatable on an outpatient basis treatment modality that may improve lower urinary tract symptoms.

Tumor budding correlates with tumor invasiveness and predicts worse survival in pT1 non-muscle-invasive bladder cancer.

Tumor budding is defined as a single cell or a cluster of up to 5 tumor cells at the invasion front. Due to the difficulty of identifying patients at high risk for pT1 non-muscle-invasive bladder cancer (NMIBC) and the difficulties in T1 substaging, tumor budding was evaluated as a potential alternative and prognostic parameter in these patients. Tumor budding as well as growth pattern, invasion pattern and lamina propria infiltration were retrospectively evaluated in transurethral resection of the bladder (TURB) specimens from 92 patients with stage pT1 NMIBC. The presence of tumor budding correlated with multifocal tumors (p = 0.003), discontinuous invasion pattern (p = 0.039), discohesive growth pattern (p < 0.001) and extensive lamina propria invasion (p < 0.001). In Kaplan-Meier analysis, tumor budding was associated with significantly worse RFS (p = 0.005), PFS (p = 0.017) and CSS (p = 0.002). In patients who received BCG instillation therapy (n = 65), the absence of tumor budding was associated with improved RFS (p = 0.012), PFS (p = 0.011) and CSS (p = 0.022), with none of the patients suffering from progression or dying from the disease. Tumor budding is associated with a more aggressive and invasive stage of pT1 NMIBC and a worse outcome. This easy-to-assess parameter could help stratify patients into BCG therapy or early cystectomy treatment groups.

Epidemiology and therapy of symptomatic lymphoceles after robot-assisted radical prostatectomy (RARP).

BACKGROUND: Lymphoceles are a common postoperative complication after radical prostatectomy with pelvic lymphadenectomy. Therapeutic options include cannulation and drainage (CD), drainage and instillation (DI), or laparoscopic fenestration (LF). The aim of this study was to investigate the epidemiology of symptomatic lymphoceles (SLC) and evaluate the treatment options. METHODS: We retrospectively analysed all patients who underwent robot-assisted radical prostatectomy (RARP) at our clinic from January 1, 2014 to December 31, 2018. All documented lymphoceles of these patients were recorded and analysed with regard to symptoms, possible infection and the treatment option (or options) chosen. RESULTS: We were able to include all 1,029 patients who underwent RARP in the aforementioned period of time. Of these, 18.1% were diagnosed with a lymphocele either when discharged or when readmitted and 6.9% experienced an SLC requiring treatment. Thirteen-point-seven percent of patients readmitted with SLC showed an accompanying thrombosis. Due to recurring or bilateral SLCs receiving different treatment options for each side, there was a total of 115 SLCs treated. CD was carried out in 102 cases. Twenty-point-six percent of patients were sufficiently treated this way, the rest required further treatment or experienced recurrences not requiring further treatment. DI was carried out in 56 cases. Of those patients, 46.4% were sufficiently treated. LF was carried out in 54 cases (either after CD, or after DI, or primarily). Of those patients, 98.1% were treated sufficiently. LF had a statistically significant higher success rate compared to CD and DI (P<0.001 respectively). CONCLUSIONS: The study confirmed the significance of SLC as a common complication after RARP. LF turned out to be the most effective treatment option for SLC, while CD as well as DI have not been proven effective.

The comprehensive complication index is associated with a significant increase in complication severity between 30 and 90 days after radical cystectomy for bladder cancer.

OBJECTIVE: To assess the true cumulative morbidity after RC by implementing the Comprehensive Complication Index (CCI) over a 90-day period, since recent evidence suggests underreporting of the cumulative morbidity after radical cystectomy (RC) with inconsistent complication rates when reported with conventional reporting systems. PATIENTS AND METHODS: Medical records of 433 patients with bladder cancer who underwent RC were retrospectively reviewed over a 90-day period. Clinical variables were assessed and complications were graded by the Clavien-Dindo Classification (CDC). The resulting 30- and 90-day CCI-scores were calculated and compared for each patient. Multivariable regression models for developing at least one severe (≥CDC IIIb) complication were designed. RESULTS: Overall, 848 complications were recorded in 371 patients (85.7%). Severe complications occurred in 130 patients (30%) and the cumulative morbidity corresponded to the level of a severe complication in 159 patients (36.7%), meaning an upgrade in 6.7% of patients compared to the CDC. The 90-day CCI (24.2 (median, IQR 20.9-39.7)) was higher than the 30-day CCI (22.6 (median, IQR 8.7-39.7)), (p < 0.001). Comorbidity indices (ASA, ACE 27), BMI, and incontinent urinary diversions were independent risk factors for suffering a severe complication within 90 days post-surgery. CONCLUSION: The cumulative morbidity (CCI) after RC seems to be higher than previously reported with CDC, especially over a 90-day period. The CCI is an appropriate assessment-tool with an upgrade in morbidity in a significant proportion of patients when compared to the CDC. BMI, several comorbidity indices, and incontinent urinary diversions are independent risk factors for suffering a severe complication after RC.

Prognostic Role of mRNA-Expression of Aquaporins (AQP) 3, 4, 7 and 9 in Stage pT1 Non-Muscle-Invasive Bladder Cancer.

BACKGROUND: AQP proteins show a variety of functions in human cell metabolism. The role of different AQP subtypes in tumor metabolism and prognosis are subject of ongoing research. OBJECTIVE: To investigate the mRNA expression of Aquaporin (AQP) 3, 4, 7 and 9 in pT1 non-muscle-invasive bladder cancer (NMIBC) and its prognostic value in therapeutic decision making. METHODS: Formalin-fixed-paraffin-embedded (FFPE) tissues from transurethral resection of the bladder (TURB) from 112 patients with initial diagnosis of stage pT1 NMIBC were analyzed retrospectively together with clinical data and therapeutic approaches. mRNA expression of AQP3, 4, 7 and 9 was measured and quantified using RT-qPCR. RESULTS: Of the 112 patients (83.9%male, median age 72 years), 40 had a recurrence (35.7%), 16 a progression (14.3%) and 14 patients (12.5%) died tumor-related. mRNA expression for AQP3 was detected in 99.1%, AQP4 in 46.4%, AQP7 in 86.6%and AQP9 in 97.3%. Spearman analysis revealed statistically significant correlations between AQP3, AQP7 and AQP9 mRNA expression with adverse clinical and histopathological parameters (WHO1973 grade 3, concomitant Cis or multifocality). High AQP9 mRNA expression was associated with worse PFS in the total cohort (p = 0.034) and in Grade 3 tumors (p = 0.003) in Kaplan-Meier analysis. In patients with bladder sparing approach, high AQP3 mRNA expression was significantly associated with worse CSS in patients receiving BCG therapy (p = 0.029). CONCLUSIONS: mRNA expression of AQP3, 7 and 9 correlates with adverse clinical and pathological parameters. AQP3 and 9 may help to identify a subgroup of highest risk patients who may be considered for early cystectomy.

Strong Expression of Cancertestis Antigens CTAG1B and MAGEA3 Is Correlated with Unfavourable Histopathological Features and MAGEA3 Is Associated with Worse Progression-Free Survival in Urothelial Bladder Cancer.

BACKGROUND: Cancer/testis antigens (CTA) are expressed in urothelial bladder cancer (UBC). Their therapeutical and prognostic relevance remains unclear. We studied the correlation of MAGEA3 and CTAG1B with histopathological factors in UBC and their prognostic value. METHODS: Retrospective analysis of 93 patients who underwent treatment for UBC was conducted. Besides clinical and histopathological parameters, the expression of MAGEA3 and CTAG1B was assessed by immunohistochemistry. RESULTS: Median follow-up was 75 months. Fifteen per cent of patients showed strong positive reaction to MAGEA3 staining. These tumours were statistically and significantly more often correlated with unfavourable World Health Organization (WHO) grading (G1: 0%, G2: 10.3%, G3: 23.4%, p = 0.048; low grade 0%, high grade 18.4%, p = 0.046 respectively). Correlation of CTAG1B with WHO grading was impressive with strong expression in no G1, 31.1% of G2 and 51.1% of G3 tumours (low grade 0%, high grade 43.4%, p = 0.001, respectively). Concomitant carcinoma in situ (Cis) was associated with strong CTAG1B expression (54.2% in concomitant Cis vs. 29% without concomitant Cis, p = 0.026). Kaplan-Meier analysis revealed statistically and significantly worse 5 years progression-free survival (PFS) associated with a strong expression of MAGEA3 (59 vs. 84%, p = 0.032). CONCLUSIONS: Strong CTA expression was correlated with unfavourable histopathological features. A strong expression of MAGEA3 was statistically and significantly associated with worse PFS across all stages of UBC.

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.

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.

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

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

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.

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.

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.

[Clinical and pathological prognostic factors for the long-term survival of patients with pT1 renal cell carcinoma]. / Klinische und pathologische Prognosefaktoren für das Langzeitüberleben von Patienten mit pT1 Nierenzellkarzinom.

Introduction The incidence of renal cell carcinoma (RCC) has been increasing over the past few decades. Simultaneously, due to improved imaging, small renal masses at stage pT1 have been diagnosed more frequently. However, it is known that even small RCCs may recur and metastasize at a late point of time. This study aimed to identify easy-to-assess clinical and histopathological prognostic markers for long-term survival. Patients/Methods We performed a retrospective analysis of patients who underwent surgical treatment of a pT1 RCC in a single centre between 1993 and 2007. The prognostic impact of clinical and histopathological parameters was investigated regarding recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). Univariate Kaplan-Meier analysis and multivariate Cox regression analysis were performed using SPSS 23. Results Overall, 571 patients were included with a median follow-up of 111 months. Univariate analysis revealed that higher grading (p = 0.031) and stage pT1b (p < 0.001) were statistically significantly associated with worse RFS. Likewise, stage pT1b (p = 0.001) and grading G2/3 (p = 0.019) were significantly associated with shorter CSS. Multivariate analysis revealed that stage pT1b was the only predictor for reduced RFS (p = 0.001) and CSS (p = 0.009). Total nephrectomy (p = 0.024), and diabetes (p < 0.001) were significantly associated with reduced OS. Multivariate analysis revealed that multifocal tumours (p = 0.041) and diabetes (p < 0.001) were the best predictive factors for OS.  Conclusion The identified prognostic parameters may help to provide a risk-adapted after follow-up for patients with small renal tumours.

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.

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

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

Epithelial-mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma.

PURPOSE: To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer. METHODS: We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan-Meier analysis and uni- and multivariate Cox regression analysis. RESULTS: Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan-Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS. CONCLUSION: Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.