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Introduction and Objectives: We examined the impact of preoperative plasma potassium levels (PPLs) on outcomes in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB), hypothesizing that potassium imbalances might influence outcomes., Patients and Methods: In this retrospective study, 501 UCB patients undergoing RC from 2009 to 2017 at a tertiary center were analyzed. Blood samples collected a week prior to surgery defined normal and abnormal PPL based on institutional standards. We assessed overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), postoperative complications, 30-day mortality, and non-organ confined disease. Kaplan-Meier estimates, Cox proportional hazards, logistic regression, and decision curve analyses (DCA) were employed., Results: 63 (13%) patients had abnormal preoperative PPLs, with 50 (10%) elevated and 13 (2.5%) decreased. In a 59 months median follow-up, 152 (31%) had disease recurrence, 197 (39%) died from any cause, and 119 (24%) from UCB. Multivariable cox regression analyses adjusting for perioperative parameters demonstrated abnormal PPL was associated with worse OS (HR=1.9, P=0.009), CSS (HR=2.8, P<0.001) and RFS (HR=2.1; P=0.007). Elevated preoperative PPLs also demonstrated significant associations with adverse outcomes in OS, CSS, and RFS (all P<0.05). In multivariable logistic regression analyses, abnormal and elevated PPLs were not associated with 30-day mortality, major 30-day postoperative complications, positive nodal disease, pT3/4 stage, and non-organ confined disease (all P>0.05)., Conclusion: Abnormal and elevated preoperative PPLs correlate with adverse oncologic outcomes in UCB patients treated with RC. Pending external validation, preoperative PPLs might be a cost-effective, easily obtainable supplemental biomarker for enriching accuracy of outcome prediction in this highly variable maladie., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Limited data are available regarding the effect of enhanced recovery after surgery (ERAS) protocols on the long-term outcomes of radical cystectomy (RC) in bladder cancer patients. The aim of this study is to evaluate the oncological outcomes in patients who underwent RC with ERAS protocol., Methods: We reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to August 2022. The primary and secondary outcomes were recurrence-free (RFS) and overall survival (OS). Multivariable Cox regression analysis was performed to evaluate the effect of ERAS on oncological outcomes., Results: A total of 967 ERAS patients and 1144 non-ERAS patients were included in this study. The RFS rates at 1, 3, and 5 years after RC were 81%, 71.5%, and 69% in the ERAS cohort, respectively. This rate in the non-ERAS group was 81%, 71%, and 67% at 1, 3, and 5 years after RC, respectively (P = 0.50). However, ERAS patients had significantly better OS with 86%, 73%, and 67% survival rates at 1, 3, and 5 years compared to 84%, 68%, and 59.5% survival rates in the non-ERAS group, respectively (P = 0.002). In multivariable analysis adjusting for other relevant factors, ERAS was no longer independently associated with recurrence-free (HR = 0.96, 95% CI 0.76-1.22, P = 0.75) or overall survival (HR = 0.84, 95% CI 0.66-1.09, P = 0.28) following RC., Conclusion: ERAS protocols are associated with a shorter hospital stay, yet with no impact on long-term oncologic outcomes in patients undergoing RC for bladder cancer., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Examine patient, tumor, and treatment characteristics effect on the disparity between black and white patients with muscle-invasive bladder cancer (MIBC) who undergo radical cystectomy (RC)., Methods: 1,286 black patients in the 2004 to 2016 National Cancer Database fit inclusion criteria. A tapered match was performed from 17,374 white patients sequentially matched to the black cohort on demographics (age, gender, insurance, income, education, county, diagnosis year), presentation (demographic variables, stage, grade, tumor size, Charlson score), and treatment (demographic and presentation variables, lymph node count, hospital volume, neoadjuvant chemotherapy [NAC], treatment delay), creating 3 matched cohorts. Chi-square and Kruskal-Wallis tests were used to compare cohorts. Kaplan-Meier analysis was used to compare 5-year overall survival (OS)., Results: 5-year OS rate was 40.4% and 35.6% for unmatched white and black cohorts (P < 0.001), respectively. Following demographics and presentation match, 5-year OS rate for white patients decreased to 39.2% (P = 0.003) and 39.10% (P = 0.019), respectively. After treatment match, 5-year OS rate decreased to 36.7% for white patient (P = 0.32). Following presentation match, 7.2% of black patients vs. 5.8% of white patients had treatment delay, and 10.1% of black patients vs. 11.2% of white patients received NAC. The treatment match resulted in a 0.3% difference between groups for treatment delay and NAC., Conclusions: Our analysis demonstrates that disparity between black and white patients with muscle-invasive bladder cancer exists in demographic-, presentation-, and treatment-related variables. Treatment variables may be a large contributing factor to survival disparities. Further research is needed to identify social, biological, and organizational inputs that contribute to these disparities., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Robot-assisted radical cystectomy is being performed with increasing frequency, but it is unclear whether total intracorporeal surgery improves recovery compared with open radical cystectomy for bladder cancer., Objectives: To compare recovery and morbidity after robot-assisted radical cystectomy with intracorporeal reconstruction vs open radical cystectomy., Design, Setting, and Participants: Randomized clinical trial of patients with nonmetastatic bladder cancer recruited at 9 sites in the UK, from March 2017-March 2020. Follow-up was conducted at 90 days, 6 months, and 12 months, with final follow-up on September 23, 2021., Interventions: Participants were randomized to receive robot-assisted radical cystectomy with intracorporeal reconstruction (n = 169) or open radical cystectomy (n = 169)., Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital within 90 days of surgery. There were 20 secondary outcomes, including complications, quality of life, disability, stamina, activity levels, and survival. Analyses were adjusted for the type of diversion and center., Results: Among 338 randomized participants, 317 underwent radical cystectomy (mean age, 69 years; 67 women [21%]; 107 [34%] received neoadjuvant chemotherapy; 282 [89%] underwent ileal conduit reconstruction); the primary outcome was analyzed in 305 (96%). The median number of days alive and out of the hospital within 90 days of surgery was 82 (IQR, 76-84) for patients undergoing robotic surgery vs 80 (IQR, 72-83) for open surgery (adjusted difference, 2.2 days [95% CI, 0.50-3.85]; P = .01). Thromboembolic complications (1.9% vs 8.3%; difference, -6.5% [95% CI, -11.4% to -1.4%]) and wound complications (5.6% vs 16.0%; difference, -11.7% [95% CI, -18.6% to -4.6%]) were less common with robotic surgery than open surgery. Participants undergoing open surgery reported worse quality of life vs robotic surgery at 5 weeks (difference in mean European Quality of Life 5-Dimension, 5-Level instrument scores, -0.07 [95% CI, -0.11 to -0.03]; P = .003) and greater disability at 5 weeks (difference in World Health Organization Disability Assessment Schedule 2.0 scores, 0.48 [95% CI, 0.15-0.73]; P = .003) and at 12 weeks (difference in WHODAS 2.0 scores, 0.38 [95% CI, 0.09-0.68]; P = .01); the differences were not significant after 12 weeks. There were no statistically significant differences in cancer recurrence (29/161 [18%] vs 25/156 [16%] after robotic and open surgery, respectively) and overall mortality (23/161 [14.3%] vs 23/156 [14.7%]), respectively) at median follow-up of 18.4 months (IQR, 12.8-21.1)., Conclusions and Relevance: Among patients with nonmetastatic bladder cancer undergoing radical cystectomy, treatment with robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy resulted in a statistically significant increase in days alive and out of the hospital over 90 days. However, the clinical importance of these findings remains uncertain., Trial Registration: ISRCTN Identifier: ISRCTN13680280; ClinicalTrials.gov Identifier: NCT03049410.

Objective: To evaluate the perioperative outcomes of premenopausal women undergoing cystectomy or oophorectomy for ovarian endometriomas (OMAs) and other benign neoplasms., Design: Retrospective cohort study., Setting: Clinical database containing information from 580 US hospitals., Patient(s): Women 18 to 50 years old who underwent ovarian cystectomy or oophorectomy for benign indications between 2010 and 2020., Intervention(s): We compared procedure route, length of hospital stay, and complication rates by surgical indication (OMA vs. other benign neoplasms) and surgical procedure (cystectomy vs. oophorectomy)., Main Outcome Measure(s): Thirty-day perioperative adverse events following adnexal surgery, including conversion to laparotomy, blood transfusion, ileus, urinary tract injury, bowel injury, readmission, and death., Result(s): We identified 120,208 ovarian cystectomies (28,182 OMAs and 92,026 other indications) and 53,476 oophorectomies (8,622 OMAs and 44,854 other indications). During cystectomy, patients with OMAs more commonly experienced conversion to laparotomy (5.1% vs. 3.1%) and readmission (8.5% vs. 7.1%). For oophorectomies, patients with OMAs less frequently had minimally invasive surgery (55.8% vs. 64.8%) or outpatient procedures (33.8% vs. 41.8%). Urinary tract and bowel injuries were rare. Multivariable logistic regression demonstrated that the presence of OMA predicted composite complications during cystectomy (adjusted odds ratio [aOR] 1.23, 95% confidence interval [CI] 1.18-1.28) but not during oophorectomy (aOR 1.05, 95% CI 0.99-1.12). Patients with OMAs had 1.37 times the odds of a composite complication during oophorectomy than during cystectomy (95% CI 1.28-1.47)., Conclusion(s): Patients undergoing ovarian cystectomy for OMAs had higher rates of perioperative adverse events than patients undergoing ovarian cystectomy for other benign neoplasms. Laparotomies were performed more often during oophorectomies for OMAs than for other benign indications., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Context: Bladder cancer is one of the most common malignancies worldwide. Some studies noted sex differences in the prognosis of bladder cancer, but results are inconsistent., Subjects and Methods: In this study, we assessed whether women with bladder cancer exhibit a worse prognosis, after adjustment for disease stage, age, and body mass index (BMI), using clinical data from The Cancer Genome Atlas. We used a Student's t-test to compare age and BMI in groups with different sexes., Statistical Analysis Used: The Kaplan-Meier method with log-rank test was used to determine clinical prognosis., Results: The BMI (30.15 vs. 26.68, P = 0.0035) and age (67.54 years vs. 66.01 years, P = 0.045) of female patients with muscle-invasive bladder cancer (MIBC) were higher than those of male patients. The overall survival (OS) prognosis of female patients was worse than that of male patients. After grouping by disease characteristics, the disease-free survival (DFS) and OS prognoses of female patients under 60 years of age were worse than those of male patients. In the group with BMI >24, the OS prognosis of female patients was worse than that of male patients, but no difference was found in DFS prognosis. In the group with BMI ≤24, the DFS prognosis of female patients was worse than that of male patients, but no difference was found in OS prognosis. Compared to males, female patients with Stage III disease demonstrated a worse DFS prognosis and poorer OS prognosis, women with stage T3 demonstrated a worse DFS prognosis, and women with stage N0 demonstrated a poorer OS prognosis. No difference was found in prognosis between male and female patients in all other groups., Conclusions: In patients with MIBC, women tended to exhibit a worse prognosis than men. More specifically, we found a correlation between prognosis and sex after grouping patients by BMI., Competing Interests: None

Purpose: (I) To evaluate the clinical efficacy of three different BCG strains in patients with intermediate-/high-risk non-muscle-invasive bladder cancer (NMIBC). (II) To determine the importance of performing routine secondary resection (re-TUR) in the setting of BCG maintenance protocol for the three strains., Methods: NMIBCs who received an adjuvant induction followed by a maintenance schedule of intravesical immunotherapy with BCG Connaught, TICE and RIVM. Only BCG-naïve and those treated with the same strain over the course of follow-up were included. Cox proportional hazards model was developed according to prognostic factors by the Spanish Urological Oncology Group (CUETO) as well as by adjusting for the implementation of re-TUR., Results: n = 422 Ta-T1 patients (Connaught, n = 146; TICE, n = 112 and RIVM, n = 164) with a median (IQR) follow-up of 72 (60-85) were reviewed. Re-TUR was associated with improved recurrence and progression outcomes (HR RFS : 0.63; 95% CI 0.46-0.86; HR PFS : 0.55; 95% CI 0.31-0.86). Adjusting for CUETO risk factors and re-TUR, BGC TICE and RIVM provided longer RFS compared to Connaught (HR TICE : 0.58, 95% CI 0.39-0.86; HR RIVM : 0.61, 95% CI 0.42-0.87) while no differences were identified between strains for PFS and CSS. Sub-analysis of only re-TUR cases (n = 190, 45%) showed TICE the sole to achieve longer RFS compared to both Connaught and RIVM., Conclusion: Re-TUR was confirmed to ensure longer RFS and PFS in intermediate-/high-risk NMIBCs but did not influence the relative single BCG strain efficacy. When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to the other strains for RFS outcomes., (© 2021. The Author(s).)

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy., Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate., Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory., Conclusion: After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Purpose: To evaluate the safety and efficacy of gemcitabine and cisplatin in combination with the immune checkpoint inhibitor pembrolizumab as neoadjuvant therapy before radical cystectomy (RC) in muscle-invasive bladder cancer., Methods: Patients with clinical T2-4aN0/XM0 muscle-invasive bladder cancer eligible for RC were enrolled. The initial six patients received lead-in pembrolizumab 200 mg once 2 weeks prior to pembrolizumab 200 mg once on day 1, cisplatin 70 mg/m 2 once on day 1, and gemcitabine 1,000 mg/m 2 once on days 1 and 8 every 21 days for four cycles. This schedule was discontinued for toxicity and subsequent patients received cisplatin 35 mg/m 2 once on days 1 and 8 without lead-in pembrolizumab. The primary end point was pathologic downstaging (< pT2N0) with null and alternative hypothesis rates of 35% and 55%, respectively. Secondary end points were toxicity including patient-reported outcomes, complete pathologic response (pT0N0), event-free survival, and overall survival. Association of pathologic downstaging with programmed cell death ligand 1 staining was explored., Results: Thirty-nine patients were enrolled between June 2016 and March 2020 (72% cT2, 23% cT3, and 5% cT4a). Patients received a median of four cycles of therapy. All patients underwent RC except one who declined. Twenty-two of 39 patients (56% [95% CI, 40 to 72]) achieved < pT2N0 and 14 of 39 (36% [95% CI, 21 to 53]) achieved pT0N0. Most common adverse events (AEs) of any grade were thrombocytopenia (74%), anemia (69%), neutropenia (67%), and hypomagnesemia (67%). One patient had new-onset type 1 diabetes mellitus with ketoacidosis related to pembrolizumab and no patients required steroids for immune-related AEs. Clinicians consistently under-reported AEs when compared with patients., Conclusion: Neoadjuvant gemcitabine and cisplatin plus pembrolizumab met its primary end point for improved pathologic downstaging and was generally safe. A global study of perioperative chemotherapy plus pembrolizumab or placebo is ongoing., Competing Interests: Tracy L. RoseResearch Funding: Roche/Genentech, GeneCentric, Bristol Myers Squibb, Merck, AstraZeneca Michael R. HarrisonConsulting or Advisory Role: Bayer, Exelixis, Genentech, Fujifilm, Janssen Oncology, AstraZeneca, Pfizer, Bristol Myers SquibbSpeakers' Bureau: Genentech, ExelixisResearch Funding: Bristol Myers Squibb, Genentech, Pfizer, Merck, Clovis Oncology, Acerta Pharma, AstraZeneca, Astellas Pharma, Bayer, Exelixis, Seattle Genetics Sundhar RamalingamHonoraria: Bayer Young E. WhangResearch Funding: Astellas Pharma, Clovis Oncology, Constellation Pharmaceuticals, Amgen, Regeneron, Arvinas Blaine BrowerConsulting or Advisory Role: Seattle Genetics/AstellasTravel, Accommodations, Expenses: Seattle Genetics/Astellas Marc A. BjurlinHonoraria: Intuitive Surgical Angela B. SmithConsulting or Advisory Role: Merck, Photocure, Urogen Pharma, Fergene, Ambu Matthew E. NielsenStock and Other Ownership Interests: Grand Rounds Health Eric WallenStock and Other Ownership Interests: MDxHealth Daniel GeorgeLeadership: Capio BioSciencesHonoraria: Sanofi, Bayer, Exelixis, EMD Serono, OncLive, Pfizer, UroToday, Acceleron Pharma, American Association for Cancer Research, Axess Oncology, Janssen Oncology, Millennium Medical PublishingConsulting or Advisory Role: Bayer, Exelixis, Pfizer, Sanofi, Astellas Pharma, Innocrin Pharma, Bristol Myers Squibb, Genentech, Janssen, Merck Sharp & Dohme, Myovant Sciences, AstraZeneca, Michael J. Hennessy Associates, Constellation Pharmaceuticals, Physicans' Education Resource, Propella Therapeutics, RevHealth LLCSpeakers' Bureau: Sanofi, Bayer, ExelixisResearch Funding: Exelixis, Janssen Oncology, Novartis, Pfizer, Astellas Pharma, Bristol Myers Squibb, Acerta Pharma, Bayer, Dendreon, Innocrin Pharma, Calithera Biosciences, Sanofi/AventisTravel, Accommodations, Expenses: Bayer, Exelixis, Merck, Pfizer, Sanofi, Janssen Oncology, UroToday Tian ZhangLeadership: Capio BioSciences, Archimmune TherapeuticsStock and Other Ownership Interests: Capio Biosciences, Archimmune Therapeutics, NanoroboticsHonoraria: Exelixis, Genentech/Roche, MJH Life Sciences, Pacific GenuityConsulting or Advisory Role: Janssen, Genentech/Roche, Sanofi, Exelixis, AstraZeneca, Pfizer, Bristol Myers Squibb, Foundation Medicine, Pharmacyclics, Amgen, Merck, Seattle Genetics, Dendreon, Calithera BiosciencesSpeakers' Bureau: Exelixis, Genentech/Roche, Genomic Health, Sanofi/AventisResearch Funding: Janssen, Acerta Pharma, Pfizer, Merrimack, Stem CentRx, Novartis, OmniSeq, Personal Genome Diagnostics, Regeneron, Merck, Mirati Therapeutics, Astellas PharmaPatents, Royalties, Other Intellectual Property: Circulating tumor cell novel capture by c-MET technology, Prochelators as Targeted Prodrugs for Prostate CancerTravel, Accommodations, Expenses: Acerta Pharma, Genomic Health, AstraZeneca Anthony DrierEmployment: Docs Global William Y. KimLeadership: Advanced Chemotherapy TechnologiesStock and Other Ownership Interests: Johnson & Johnson, Bristol Myers Squibb, Kura Oncology, BeiGene, FibroGen, Amgen, AbbVie, G1 Therapeutics, Spectrum Pharmaceuticals, Illumina, Arvinas, Fibrogen, NantWorks, Oramed, Natera, ZentalisHonoraria: Takeda, H3 BiomedicineConsulting or Advisory Role: GeneCentric, Foundation MedicineResearch Funding: Merck, GeneCentric, Foundation MedicinePatents, Royalties, Other Intellectual Property: BASE47 bladder cancer subtype classifier, PurIST (Purity Independent Subtyping of Tumors)Travel, Accommodations, Expenses: Takeda, H3 Biomedicine Matthew I. MilowskyResearch Funding: Merck, Roche/Genentech, Bristol Myers Squibb, Astellas Pharma, Clovis Oncology, Inovio Pharmaceuticals, Mirati Therapeutics, Constellation Pharmaceuticals, Syndax, Incyte, Amgen, Regeneron, Arvinas, Seagen, Pfizer, Johnson & Johnson/JanssenNo other potential conflicts of interest were reported.

This study aimed at systematically analyzing and evaluating the impact of perioperative blood transfusions (PBT) on oncologic outcomes of patients undergoing radical cystectomy for bladder cancer. This systematic review follows the recommendations of the Cochrane Handbook for Systematic Reviews and Interventions and was conducted in line with the PRISMA statement and the AMSTAR II criteria. A comprehensive database search was performed based on the PICO criteria. Two independent reviewers performed all screening steps and quality assessment. Risk of bias and certainty in evidence were assessed with the Newcastle Ottawa Scale for non-randomized trials and the GRADE approach. Of 1123 identified studies 20 were eligible for qualitative analysis and 15 for quantitative analysis reporting on 21,915 patients. Receiving a PBT was associated with an increased risk of all-cause mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.29 [1.18, 1.40]; p < 0.001), cancer-specific mortality (HR [CI]: 1.27 [1.15; 1.41]; p < 0.001) and disease recurrence (HR [CI]: 1.22 [1.12; 1.34]; p < 0.001). Subgroup analysis of transfusion timing revealed a significantly increased risk of mortality with intraoperative or combined intra- and postoperative transfusions compared to postoperative transfusion only for all three outcomes (p < 0.001). Leukocyte-depletion was associated with increased all-cause mortality, but not cancer-specific mortality. The administration of PBT negatively impacts oncological outcomes after radical cystectomy. Therefore, careful treatment indication and strict adherence to transfusion guidelines is encouraged in order to avoid adverse effects during the perioperative course., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: To investigate treatment patterns of partial cystectomy (PC), neoadjuvant chemotherapy (NAC), lymph node dissection (LND), and treatment delays, and the associations with overall survival (OS) among patients with muscle-invasive bladder cancer., Patients and Methods: We identified patients with cT2-4cN0cM0 urothelial carcinoma of the bladder in the National Cancer Database who underwent PC from 2007 through 2015. We performed descriptive statistics and assessed temporal trends using the Cochrane-Armitage test. Our outcomes of interest were NAC, LND, and treatment delay defined as ≥8 or ≥12 weeks for patients who underwent NAC or upfront surgery, respectively. We used logistic regression and multivariable Cox proportional hazards models to evaluate predictors and associations with OS, respectively., Results: A total of 9,199 patients met inclusion criteria. Over the study period, PC utilization decreased from 9% to 7% (P = 0.06). Compared with patients who underwent radical cystectomy, patients treated with PC less frequently received NAC (7% vs. 17%, P < 0.01) and LND (57% vs. 91%, P < 0.01), but were less likely to experience treatment delays (25% vs. 31%, P < 0.01). Only 4.1% (27/655) of patients treated with PC received the combination of NAC, LND, and no treatment delay. In a Cox model, adequacy of LND was associated with improved OS (<10 nodes: HR 0.62, 95% CI 0.48-0.81 and ≥10 nodes: HR 0.48, 95% Cl 0.32-0.72)., Conclusion: PC is uncommon and associated with poorer utilization of NAC and LND, but fewer treatment delays. The adequacy of LND was associated with improved OS while NAC and treatment delay were not., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The cell surface interleukin 22 (IL-22) receptor complex is mainly expressed in epithelial and tissue cells like pancreatitis cells. Recent studies described that IL-22R was overexpressed in malignant diseases and was associated with a poor overall survival (OS). The role of IL-22RA1 gene expression in muscle invasive bladder cancer (MIBC) has not been investigated, yet., Objectives: The aim of this study was to analyze the role of IL-22RA1 gene expression in patients with MIBC., Methods: In a cohort of 114 patients with MIBC who underwent radical cystectomy, IL-22RA1 gene expression was analyzed with qRT-PCR and correlated with clinical parameters. Furthermore, Kaplan-Meier and Cox regression analysis were performed. For validation, an in silico dataset (TCGA 2017, n=407) was reanalyzed., Results: IL-22RA1 gene expression was independent of clinicopathological parameters like age (P=0.2681), T stage (P=0.2130), nodal status (P=0.3238) and lymph vascular invasion (LVI, P=0.5860) in patients with MIBC. A high expression of IL-22RA1 was associated with a shorter OS (P=0.0040) and disease-specific survival (P=0.0385). Furthermore, a shorter disease-free survival (DFS) was also associated with a high expression of IL-22RA1 (P=0.0102). In the multivariable analysis, IL-22RA1 expression was an independent prognostic predictors regarding OS (P=0.0096, HR=0.48). In the TCGA cohort, IL-22RA1 expression was independent regarding to OS and DFS., Conclusion: A high IL-22RA1 gene expression was associated with worse outcome. Furthermore, IL-22RA1 represented an independent predictor regarding OS in our cohort and therefore might be used for risk stratification in patients with MIBC., Competing Interests: Conflict of interest All authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Perioperative blood transfusion (PBT) has been associated with worse outcomes across tumor types, including bladder cancer. We report our institutional experience with PBT utilization in the setting of radical cystectomy (RC) for patients with bladder cancer, exploring whether timing of PBT receipt influences perioperative and oncologic outcomes., Methods: Consecutive patients with bladder cancer treated with RC were identified. PBT was defined as red blood cell transfusion during RC or the postoperative admission. Clinicopathologic and peri and/or postoperative parameters were extracted and compared between patients who did and did not receive PBT using Mann Whitney U Test, chi-square, and log-rank test. Overall (OS) and recurrence-free survival (RFS) were estimated with the Kaplan Meier method. Univariate/multivariate logistic and Cox proportional hazards regression were used to identify variables associated with postoperative and oncologic outcomes, respectively., Results: The cohort consisted of 747 patients (77% men; median age 67 years). Median follow-up was 61.5 months (95% CI 55.8-67.2) At least one postoperative complication (90-day morbidity) occurred in 394 (53%) patients. Median OS and RFS were 91.8 months (95% CI: 76.0-107.6) and 66.0 months (95% CI: 48.3-83.7), respectively. On multivariate analysis, intraoperative, but not postoperative, BT was independently associated with shorter OS (HR: 1.74, 95% CI: 1.32-2.29) and RFS (HR: 1.55, 95%CI: 1.20-2.01), after adjusting for relevant clinicopathologic variables. PBT (intra- or post- operative) was significantly associated with prolonged postoperative hospitalization ≥10 days., Conclusions: Intraoperative BT was associated with inferior OS and RFS, and PBT overall was associated with prolonged hospitalization following RC. Further studies are needed to validate this finding and explore potential causes for this observation., Competing Interests: Conflict of interest Leonidas N. Diamantopoulos: no conflicts to disclose;Rishi R. Sekar: no conflicts to disclose; Sarah K. Holt: no conflicts to disclose; Ali R. Khaki: no conflicts to disclose; Natalie J Miller: no conflicts to disclose; Adam Gadzinski: no conflicts to disclose; Yaw A. Nyame: no conflicts to disclose; Brian R. Winters: no conflicts to disclose; Funda Vakar-Lopez: no conflicts to disclose; Maria S. Tretiakova: no conflicts to disclose; Sarah P. Psutka: Honoraria - Prime; Education; Travel, Accommodations, Expenses - Prime Education. John L. Gore: Research Grant funding from Ferring Pharmaceuticals.Daniel W. Lin: DSMB for the POTOMAC study with AstraZeneca; Consulting or Advisory Role – Astellas Pharma, Clovis Oncology, Dendreon; Research Funding – GenomeDx; Genomic Health; MDxHealth. George R. Schade: Patents, Royalties, Other Intellectual Property - Global Cancer Technology. Andrew C. Hsieh: Honoraria - Hotspot Therapeutics; Research Funding - eFFECTOR Inc; Patents, Royalties, Other Intellectual Property - MTOR modulators and uses thereof Patent number: 9629843; Use Of Translational Profiling To Identify Target Molecules For Therapeutic Treatment, Publication number: 20140288097. John K. Lee: Research Funding - Immunomedics; Todd Yezefski: no conflicts to disclose; Michael T. Schweizer: Paid consultant to  Resverlogix. He has received research funding to his institution from Immunomedics, Janssen, AstraZeneca, Pfizer, Madison Vaccines, Tmunity and Hoffmann-La Roche. Heather H. Cheng: Research Funding - Astellas Medivation, Clovis Oncology, Color Foundation, Janssen, Sanofi. Consulting for AstraZeneca. Royalties – UpToDate. Evan Y. Yu: consulting for Abbvie, Advanced Accelerator Applications, Amgen, AstraZeneca, Bayer, Clovis, Dendreon, Incyte, Janssen, Merck, Pharmacyclics, QED, Sanofi, and Seattle Genetics; institutional research support from Bayer, Blue Earth, Daiichi-Sankyo, Dendreon, Merck, Pharmacyclics, Taiho, and Seattle Genetics (all unrelated in last 3 years).Lawrence D. True: Stock and Other Ownership Interests – Lightspeed Micro Research Funding, Ventana Medical Systems; Patents, Royalties, Other Intellectual Property – Lens on an open-top lightsheet microscope. Robert B. Montgomery: Research Funding – AstraZeneca, ESSA, Ferring, Janssen Oncology. Petros Grivas (all unrelated in the last 3 years): consulting for AstraZeneca, Bayer, Bristol-Myers Squibb, Clovis Oncology, Dyania Health, Driver, EMD Serono, Exelixis, Foundation Medicine, GlaxoSmithKline, Genentech, Genzyme, Heron Therapeutics, Immunomedics, Janssen, Merck, Mirati Therapeutics, Pfizer, Roche, Seattle Genetics, QED Therapeutics; institutional research funding from AstraZeneca, Bavarian Nordic, Bayer, Bristol-Myers Squibb, Clovis Oncology, Debiopharm, Genentech, GlaxoSmithKline, Immunomedics, Kure It Cancer Research, Merck, Mirati Therapeutics, Oncogenex, Pfizer, QED Therapeutics. Jonathan L. Wright: Royalties – UpToDate; Clinical Trials - Movember Foundation, Merck, Nucleix, Altor Biosciences; Consulting – Sanofi Genzyme., (Published by Elsevier Inc.)

Background: Radical cystectomy (RC) remains the standard approach to treating muscle invasive bladder cancer. Despite improvements in surgical and anaesthetic care, morbidity and mortality remain high. In the United Kingdom, centralisation has improved outcomes following RC. However, in New Zealand no centralisation or mandatory reporting of outcomes exists., Methods: A retrospective review of all patients who underwent RC at Christchurch Hospital, New Zealand, between January 2007 and January 2018 was undertaken. Data on demographic, opera-tive and post-operative variables were collected. Thirty- and 90-day mortality rates were assessed along with five-year survival. Multivariate logistic regression was used to assess factors associated with survival., Results: During the 11-year period, 135 patients underwent RC. There were low rates of neo-adjuvant (11%) and adjuvant (5%) chemotherapy use. The median length of stay was 10 days (6-44 days) and 23 patients (17%) had a Clavien-Dindo grade 3 or above complication. Thirty- and 90-day mortality was 2.2% and 4.4% respectively. Five-year overall and disease-specific survival rates were 49.7% and 59.3% respectively. American Joint Committee on Cancer (AJCC) stage was a positive predictor of overall survival, with the risk of death increasing incrementally for each progression of stage. Age, sex and comorbidity status were not significant predictors of either overall or disease-specific survival., Conclusion: Our study is the first to report radical cystectomy outcomes in New Zealand. Alt-hough the perioperative outcomes were comparable to other published series, the subsequent development of metastatic disease remains a problem, with poor five-year survival rates., Competing Interests: Nil.

Introduction: In surgical series of muscle-invasive bladder cancer (MIBC), women have higher recurrence rates, disease progression, and mortality following radical cystectomy than men. Similar reports of oncologic differences between men and women following trimodality therapy (TMT) are rare. Our hypothesis was that there would be no difference in overall survival (OS) between sexes receiving TMT., Methods: We queried the National Cancer Database (NCDB) for patients diagnosed with clinical stage T2-T4aN0 M0 MIBC between 2004-2016. We considered patients to have received TMT if they received 55 Gy in 20 fractions or 59.4-70.2 Gy of radiotherapy with concurrent chemotherapy following a transurethral resection of bladder tumor (TURBT). We used multivariable Cox proportional hazard models to determine whether sex was associated with risk of mortality. In addition to OS, we calculated relative survival (RS) to adjust for the fact that females generally survive longer than males., Results: Of the patients, 1960 underwent TMT and had survival data. Less than one quarter were female. In the first year following treatment, women had worse OS and RS than men (p = 0.093 and p = 0.030, respectively). However, overall and relative survival differences between sexes were not statistically significantly different in Years 2 and later. Unlike with OS, the RS between sexes remained significant at 9 years; in multivariable analysis based on RS, women were 43% more likely to die than men (p < 0.001)., Conclusions: Women had a higher initial risk of death than men in the first year following TMT. However, long-term survival between sexes was similar. TMT is an important treatment option in both men and women seeking bladder preservation., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Immediate single instillation of chemotherapy following transurethral resection of bladder tumor (TURBT) is suggested for non-muscle invasive bladder cancer (NMIBC) patients. However, no study has evaluated molecular marker that was involved in intravesical recurrence (IVR) after single instillation of chemotherapy. Therefore, this study aimed to evaluate whether P-glycoprotein, multidrug resistance protein 1 (MRP1), Annexin A2 (ANXA2) or nucleophosmin (NPM) expression predicts IVR after initial TURBT and immediate single intravesical adriamycin instillation., Methods: We retrospectively reviewed consecutive 443 patients who underwent TURBT. Of these, 54 patients who underwent initial TURBT and single instillation of adriamycin for NMIBC were included. The expressions of P-glycoprotein, MRP1, ANXA2 and NPM were evaluated immunohistochemically and were divided into 2 groups (low or high) according to the staining intensity and/or proportion of positive cells. IVR was assessed by Kaplan-Meier method. Cox`s multivaritate analyses were performed to identify independent predictors for IVR., Results: Nineteen patients (35.1%) had IVR. High P-glycoprotein expression was significantly correlated with multiplicity, pT stage and high grade. High ANXA2 expression was significantly correlated with high grade. MRP1 and NPM were not correlated with any clinicopathological variables. MRP1 expression and ANXA2 expression were significantly correlated with P-glycoprotein expression. Patients with high P-glycoprotein expression had significantly worse IVR-free survival (IVRFS) than those with low P-glycoprotein expression (P =0.015). The difference in IVRFS rates between patients with high ANXA2 expression and those with low ANXA2 expression was nearly significant (P =0.057). Univariate analyses indicated multiplicity, high grade and high P-glycoprotein expression were significant predictors for IVR. Multivariate analysis indicated high grade was an independent predictor for IVR., Conclusions: High P-glycoprotein expression was associated with IVR. Further study was needed to determine significance of P-glycoprotein expression in IVR after single intravesical adriamycin instillation.

Objectives: To evaluate the postoperative complication and mortality rate following laparoscopic radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) in octogenarians., Patients and Methods: We conducted a retrospective analysis comparing postoperative complication and mortality rates depending on age in a consecutive series of 1890 patients who underwent RARC with ICUD for bladder cancer between 2004 and 2018 in 10 European centres. Outcomes of patients aged <80 years and those aged ≥80 years were compared with regard to postoperative complications (Clavien-Dindo grading) and mortality rate. Cancer-specific mortality (CSM) and other-cause mortality (OCM) after surgery were calculated using the non-parametric Aalen-Johansen estimator., Results: A total of 1726 patients aged <80 years and 164 aged ≥80 years were included in the analysis. The 30- and 90-day rate for high-grade (Clavien-Dindo grades III-V) complications were 15% and 21% for patients aged <80 years compared to 11% and 13% for patients aged ≥80 years (P = 0.2 and P = 0.03), respectively. In a multivariable logistic regression analysis adjusting for pre- and postoperative variables, age ≥80 years was not an independent predictor of high-grade complications (odds ratio 0.6, 95% confidence interval 0.3-1.1; P = 0.12). The non-cancer-related 90-day mortality was 2.3% for patients aged ≥80 years and 1.8% for those aged <80 years, respectively (P = 0.7). The estimated 12-month CSM and OCM rates for those aged <80 years were 8% and 3%, and for those aged ≥80 years, 15% and 8%, respectively (P = 0.009 and P < 0.001)., Conclusions: The minimally invasive approach to RARC with ICUD for bladder cancer in well-selected elderly patients (aged ≥80 years) achieved a tolerable high-grade complication rate; the 90-day postoperative mortality rate was driven by cancer progression and the non-cancer-related rate was equivalent to that of patients aged <80 years. However, an increased OCM rate in this elderly group after the first year should be taken into account. These results will support clinicians and patients when balancing cancer-related vs treatment-related risks and benefits., (© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: To determine the effect of a previously unassessed measure of quality-preventable hospitalization rate-on mortality after oncologic surgery for 4 procedures with established volume-outcome relationships. We hypothesize that hospitals with higher preventable hospitalization rates (indicating poor quality of primary care) have increased hospital mortality. Additionally, patients having surgery at hospitals with higher preventable hospitalization rates have increased mortality., Summary Background Data: Although different factors have been used to measure healthcare quality, most have not resulted in long-term hospital-based improvements in patient outcomes., Methods: We retrieved data from Taiwan's National Health Insurance database for patients who underwent surgery during 2001 to 2014 for esophagectomy, pancreatectomy, lung resection, or cystectomy. Preventable hospitalization rates assess hospitalizations for 11 chronic conditions that are deemed to be preventable with effective primary care. The outcome was 30-day surgical mortality. Identifiable factors potentially related to surgical mortality, including surgeon and hospital volume, were controlled for in the models., Results: Our dataset contained 35,081 patients who had surgery for one of the procedures. For all procedures, hospitals with high preventable hospitalization rates were associated with higher mortality rates (all P < 0.01). For esophagectomy, lung resection, and cystectomy, the adjusted odds of individual mortality increased by 8% to 10% (P < 0.01) for every 1% increase in the preventable hospitalization rate. For pancreatectomy, the adjusted odds of individual mortality increased by 21% for every 1% increase in preventable hospitalization rate when the rate was ≥8% (P < 0.01)., Conclusions: Preventable hospitalization rates could serve as warning signs of low quality of care and be a publically-reported quality measure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To perform an external validation of the Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival (CSS) after radical cystectomy (RC) in a large bi-institutional cohort of patients., Patients and Methods: Patients treated with RC and lymph node dissection (LND) between May 1996 and July 2017 were retrieved from the RC databases of Leuven and Turin. Collected variables were age at RC, tumour stage, lymph node (LN) density, neoadjuvant chemotherapy, the extent of LND, and nodal stage. The primary outcome was CSS visualised using Kaplan-Meier plots. Cox proportional hazard models were used to assess the impact of variables on CSS. We performed a pairwise comparison between the COBRA score levels using a log-rank test corrected by Bonferroni, and developed a simplified COBRA score with three risk categories. To compare models, we assessed concordance indices (C-indices), receiver operating characteristic curves with area under the curve (AUC), calibration plots, and decision curve analysis (DCA). Finally, we compared both COBRA and simplified COBRA models with the established American Joint Committee on Cancer (AJCC) model., Results: A total of 812 patients were included. All COBRA score variables had a significant impact on CSS in a Cox proportional hazard model. However, pairwise comparison of the COBRA subscores could not differentiate significantly between all COBRA score levels. Based on these findings, we developed a simplified COBRA score by introducing three categories within the following COBRA score ranges: low- (0-1) vs intermediate- (2-4) vs high-risk (5-7). A pairwise comparison could discriminate significantly between all COBRA risk categories. When finally comparing COBRA and simplified COBRA models with the AJCC model, AJCC performed better than both. C-indices, AUCs, calibration plots and DCA for AJCC were all better compared with the original and simplified COBRA models., Conclusion: We performed an external validation of the COBRA score in a large bi-institutional cohort. We observed that several risk groups had overlapping CSS, demonstrating suboptimal performance of the COBRA score. Therefore, we constructed a simplified model with three COBRA score risk categories. This model resulted in demarcated risk groups with non-overlapping CSS and good predictive accuracy. However, both COBRA score models were outperformed by the AJCC staging system. Therefore, we conclude that the AJCC staging system should remain the current standard for stratifying patients after RC for CSS., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

The reported results of trimodal treatment (TMT) in muscle-invasive bladder cancer vary widely. We attempted to characterize the profile of ideal candidates for this approach. Between 2000 and 2019, 105 patients (median age 78 years) with T2-4aN0M0 bladder cancer were treated with TMT and analyzed retrospectively. Mean radiotherapy dose was 62 Gy (SD 8.4). Ten pretreatment prognostic parameters were evaluated including tumor diameter on pre-TURBT CT. Multivariate analyses was performed and combination of parameters was studied. After a median follow-up of 29 months, 53 patients (50.5%) developed recurrence and 70 patients (67.7%) died. Death was disease-specific in 46 patients (65.7%). Tumor diameter was the most significant prognostic parameter with p < 0.0001 for overall, disease-specific and recurrence-free survivals. For every 1 cm increase in tumor diameter, the risk of disease-specific mortality increased by 1.57. Age, cisplatin eligibility and the Charlson Comorbidity Index were significant predictors of overall survival but not of disease-specific or recurrence-free survival. Patients who were cisplatin-eligible with a tumor diameter ≤3 cm had a 5-year disease-specific survival rate of 79.2% as opposed to 33.9% in patients without one of these features (p < 0.001). When tumor diameter exceeded 5 cm (irrelevant of all other parameters), 5-year disease-specific survival rate was only 28.2%. Patient profiles can accurately predict response to TMT. In cisplatin-eligible patients with a tumor diameter ≤3 cm, TMT provides an excellent disease-specific survival rate. In patients with a tumor diameter >5 cm TMT renders unacceptably poor treatment outcomes., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Black individuals with muscle-invasive bladder cancer (MIBC) experienced 21% lower odds of guideline-based treatment (GBT) and differences in treatment explain 35% of observed Black-White differences in survival. Yet little is known of how interactions between race/ethnicity and receipt of GBT drive within- and between-race survival differences., Methods: Black, White, and Latino individuals diagnosed with nonmetastatic, locally advanced MIBC from 2004 to 2013 within the National Cancer Database were included. Guideline-based treatment was defined as the receipt including one or more of the following treatment modalities: radical cystectomy (RC), neoadjuvant chemotherapy with RC, RC with adjuvant chemotherapy, and/or chemoradiation based on American Urological Association guidelines. Cox proportional hazards model of mortality estimated effects of GBT status, race/ethnicity, and the GBT-by-race/ethnicity interaction, adjusting for covariates., Results: Of the 54 910 MIBC individuals with 125 821 person-years of posttreatment observation (max = 11 years), 6.9% were Black, and 3.0% were Latino. Overall, 51.4%, 45.3%, and 48.5% of White, Black, and Latino individuals received GBT. Latino individuals had lower hazard of death compared to Black (HR 0.81, 95% CI 0.75-0.87) and White individuals (HR 0.92, 95% 0.86-0.98). With GBT, Latino and White individuals had similar outcomes (HR = 1.00, 95% 0.91-1.10) and both fared better than Black individuals (HR = 0.88, 95% 0.79-0.99 and HR = 0.88, 95% 0.83-0.94, respectively). Without GBT, Latino individuals fared better than White (HR = 0.85, 95% 0.77-0.93) and Black individuals (HR = 0.74, 95% 0.67-0.82) while White individuals fared better than Black individuals (HR = 0.87, 95% 0.83-0.92). Black individuals with GBT fared worse than Latinos without GBT (HR = 1.02, 95% 0.92-1.14), although not statistically significant., Conclusion: Low GBT levels demonstrated an "under-allocation" of GBT to those who needed it most-Black individuals. Interventions to improve GBT allocation may mitigate race-based survival differences observed in MIBC., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Radical cystectomy is considered the standard treatment for patients with muscle-invasive bladder tumors and has high postoperative complication rates among urological surgeries. High-risk patients, defined as those ≥45 years of age with history of coronary artery disease, stroke, or peripheral artery disease or those ≥65 years of age, can have a higher incidence of cardiac complications. Therefore, we evaluated the incidence, risk factors, and outcomes of myocardial injury after non-cardiac surgery (MINS) in high-risk patients who underwent radical cystectomy.This retrospective observational study analyzed 248 high-risk patients who underwent radical cystectomy. MINS was defined as serum troponin I concentration ≥0.04 mg/L within postoperative 3 days. The risk factors for MINS were evaluated by multivariate logistic regression analysis. Postoperative outcomes were evaluated. The 1-year survival after radical cystectomy was also compared between patients who developed MINS (MINS group) and those who did not (non-MINS group) by Kaplan-Meier analysis.MINS occurred in 35 patients (14.1%). Multivariate logistic regression analysis showed that early diastolic transmitral filling velocity (E)/early diastolic septal mitral annular velocity (E') ratio (odds ratio = 1.102, 95% confidence interval [1.009-1.203], P = .031) and large volume blood transfusion (odds ratio = 2.745, 95% confidence interval [1.131-6.664], P = .026) were significantly associated with MINS in high-risk patients who underwent radical cystectomy. Major adverse cardiac events and 1-year mortality were significantly higher in the MINS group than in the non-MINS group (17.1% vs 6.1%, P = .035; 28.6% vs 12.7%, P = .021, respectively). Kaplan-Meier analysis showed significantly lower 1-year survival in the MINS group than in the non-MINS group (P = .010).MINS occurred in 14.1% of patients. High E/E' ratio and large volume blood transfusion were risk factors for MINS in high-risk patients who underwent radical cystectomy. Postoperative major adverse cardiac events and 1-year mortality were significantly higher in the MINS group than in the non-MINS group. Preoperative evaluation of risk factors for MINS may provide useful information to detect cardiovascular complications after radical cystectomy in high-risk patients.

Urachal carcinoma (UrC) is a rare tumor with remarkable histological and molecular similarities to colorectal cancer (CRC). Adenomatous polyposis coli (APC) is the most frequently affected gene in CRC, but the prevalence and significance of its alterations in UrC is poorly understood. In addition, loss of phosphatase and tensin homologue (PTEN) was shown to be associated with therapy resistance in CRC. Our primary aim was to assess specific genetic alterations including APC and PTEN in a large series of UrC samples in order to identify clinically significant genomic alterations. We analyzed a total of 40 UrC cases. Targeted 5-gene (APC, PTEN, DICER1, PRKAR1A, TSHR, WRN) panel sequencing was performed on the Illumina MiSeq platform (n = 34). In addition, ß-catenin (n = 38) and PTEN (n = 30) expressions were assessed by immunohistochemistry. APC and PTEN genes were affected in 15% (5/34) and 6% (2/34) of cases. Two of five APC alterations (p.Y1075*, p.K1199*) were truncating pathogenic mutations. One of the two PTEN variants was a pathogenic frameshift insertion (p.C211fs). In 29% (11/38) of samples, at least some weak nuclear ß-catenin immunostaining was detected and PTEN loss was observed in 20% (6/30) of samples. The low prevalence of APC mutations in UrC represents a characteristic difference to CRC. Based on APC and ß-catenin results, the Wnt pathway seems to be rarely affected in UrC. Considering the formerly described involvement of PTEN protein loss in anti-EGFR therapy-resistance its immunohistochemical testing may have therapeutic relevance.

Objective: To prospectively study the impact of smoking on pathological response to neoadjuvant chemotherapy (NAC) in patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB)., Materials & Methods: We collected standard clinicopathological variables, including smoking status (never, former, current) in patients undergoing NAC and RC for UCB at 12 European tertiary care centers between 12/2013-12/2015. Clinicopathological variables were compared according to smoking status. Multivariable logistic regression models were built to assess the association of smoking status and a) complete (no residual disease), b) partial (residual, non-muscle invasive disease), c) no pathological response (residual muscle invasive or lymph node positive disease). Kaplan-Meier and Cox regression analyses were employed to study the impact of response to NAC on survival., Results and Limitations: Our final cohort consisted of 167 NAC patients with a median follow-up of 15 months (interquartile range (IQR) 9-26 months) of whom 48 (29%), 69 (41%), and 50 (30%) where never, former, and current smokers, respectively. Smoking was significantly associated with advanced age (p = 0.013), worse ECOG performance status (p = 0.049), and decreased pathological response to NAC (p = 0.045). On multivariable logistic regression analyses, former and current smoking status was significantly associated with lower odds of complete pathological response (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.16-0.87, p = 0.023, and OR 0.34, 95% CI 0.13-0.85, p = 0.021), while current smoking status was significantly associated with a greater likelihood of no pathological response (OR 2.49, 95% CI 1.02-6.06, p = 0.045). Response to NAC was confirmed as powerful predictor of survival., Conclusions: Smoking status is adversely associated with pathological response to NAC. Smokers should be informed about these adverse effects, counseled regarding smoking cessation, and possibly be considered for immunotherpeutics as they may be more effective in smokers., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Tetramodal bladder-preservation therapy includes maximal transurethral resection (TUR), induction chemoradiotherapy (CRT), and consolidative partial cystectomy with pelvic lymph node dissection. Tetramodal bladder-preservation therapy theoretically provides surgical consolidation of chemotherapy- and radioresistant cells. However, its efficacy in providing optimal cancer control for patients with histologic variants of urothelial carcinoma (VUCs) is currently unknown. We compared the oncologic outcomes between patients with muscle-invasive bladder cancer (MIBC) and pure urothelial carcinoma (PUC) and those with MIBC and VUCs after selective tetramodal bladder-preservation therapy., Patients and Methods: We prospectively enrolled 154 patients. After maximal TUR and induction CRT, patients with a clinical complete response were offered consolidative partial cystectomy to achieve bladder preservation, with radical cystectomy recommended for the others. The VUCs identified in the maximal TUR samples were categorized according to the 2004 World Health Organization classification. The primary endpoint was cancer-specific survival. The secondary endpoints included the clinical and pathologic response rates to induction CRT and MIBC recurrence-free survival., Results: A VUC was identified in 37 patients (24%). The most frequent variants involved glandular differentiation (n = 13), squamous differentiation (n = 11), and micropapillary (n = 8). No difference was found in the clinical complete response rate to CRT between PUC and VUCs (P = .81). On an intention-to-treat basis, the 5-year cancer-specific survival rates for those with PUC (n = 116) and VUC (n = 37) were 82% and 81% (P = .86), respectively., Conclusion: Tetramodal bladder-preservation therapy incorporating partial cystectomy could provide favorable locoregional control and survival for patients with VUC. Thus, patients with MIBC need not be excluded from the bladder-preservation approach because of the presence of a variant histologic type., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The objective of this study was to test the effect of chemotherapy and/or radical cystectomy (RC) and/or radiotherapy (RT) on survival of patients with non-metastatic small-cell carcinoma of the urinary bladder (SCCUB)., Materials and Methods: Within the Surveillance, Epidemiology, and End Results registry (2001-2016), we identified patients with non-metastatic (T1-4, N0, M0) SCCUB. Treatment was defined as: chemotherapy alone, chemotherapy + RC, and chemotherapy + RT. Temporal trends, cumulative incidence plots, and multivariable competing risks regression models were used., Results: Of 595 patients with SCCUB, 230 (38.5%), 159 (27%), and 206 (34.5%) were treated with chemotherapy alone, chemotherapy + RC, and chemotherapy + RT, respectively. The rates of chemotherapy + RC increased (estimated annual percentage changes [EAPC], +5.9%; P = .002). Conversely, chemotherapy alone (EAPC, -1.7%; P = .1) and chemotherapy + RT rates decreased (EAPC: -2.2%; P = .08). Overall, 5-year cancer-specific mortality (CSM) rates were 44%, 29%, and 40% for patients treated with chemotherapy alone, chemotherapy + RC, and chemotherapy + RT, respectively (P = .004). Relative to chemotherapy alone, patients treated with chemotherapy + RC experienced lower CSM (hazard ratio, 0.5; P < .001). Conversely, patients treated with chemotherapy + RT did not exhibit any CSM benefit (hazard ratio, 0.8; P = .2), when compared with chemotherapy alone., Conclusion: In contemporary patients with SCCUB with non-metastatic disease, the rates of chemotherapy + RC are increasing. Conversely, the rates of combined chemotherapy with RT and chemotherapy alone are decreasing. These patterns of treatment are in agreement with better cancer control in patients with SCCUB. In consequence, until more robust data become available, the combination of chemotherapy and RC should represent the recommended treatment strategy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Objectives: To investigate other-cause mortality (OCM) rates over time according to several baseline characteristics in bladder cancer (BCa) patients treated with radical cystectomy (RC)., Methods: Within the Surveillance, Epidemiology, and End Results database (1988-2011), we identified 7702 T 1-2 N 0 M 0 urothelial BCa patients treated with RC. Temporal trends and multivariable Cox regression (MCR) analyses assessed 5-year OCM. Data were stratified according to the year of diagnosis (1988-1995 vs 1996-2000 vs 2001-2004 vs 2005-2008 vs 2009-2011), age group (<60 vs 60-75 vs >75 years), sex, race, marital status, and socioeconomic status., Results: Overall, OCM rates decreased from 13.9% in 1988-1995 to 8.6% in 2009-2011. The greatest decrease was recorded in elderly (>75) patients (32%-16%, slope: -0.55% per year; P = .01), followed by patients aged 60 to 75 (21%-5%, slope: -0.35% per year; P = .01), unmarried patients (16%-10%, slope: -0.26% per year; P < .001), male patients (14%-8.9%, slope: -0.23% per year), and African Americans (16%-11%, slope: -0.27% per year; P < .001). MCR models corroborated these results., Conclusions: Most important decrease in OCM after RC over the last decades was recorded in the elderly, unmarried, and male patients. Nonetheless, these three patient groups still represent ideal targets for efforts aimed at minimizing the morbidity and mortality after RC, as their risk of OCM is higher than in others., (© 2020 Wiley Periodicals, Inc.)

Background: Urachal carcinoma is a rare nonurothelial malignant tumor with high rates of local recurrence and systemic metastasis. Although radical resection is widely considered the standard treatment, there is still a debate regarding the benefits of lymphadenectomy. To explore these factors, we investigated the recurrence pattern of urachal cancer and the impact of lymphadenectomy on long-term survival., Methods: The data of 62 patients pathologically diagnosed with urachal carcinoma at Sun Yat-sen University Cancer Center from 2002 to 2019 were retrospectively reviewed. Lymphadenectomy was defined as lymph nodes retrieved from the obturator, internal iliac, and external iliac lymph node stations. The Kaplan-Meier method and Cox regression model were used to identify prognostic factors. OS and DFS were the primary endpoints., Results: Of the 47 males and 15 females included, 54 patients underwent partial cystectomy, and 27 patients underwent lymphadenectomy. The number of patients with Sheldon stage IIIA, IIIB, IIIC, IVA, and IVB were 43 (69.4%), 4 (6.5%) 3 (4.8%), 6 (9.7%), and 6 (9.7%), respectively. The median DFS was 32.7 months, and the mean OS was 114.6 months. Sheldon stage (P < .001) and tumor size (P = .001) were identified as independent prognostic factors for DFS, whereas Sheldon stage (P = .003), peritoneal metastasis (P = .006), distant metastasis (P = .024), and recurrence in pelvic lymph nodes (P = .015) were independent prognostic factors for OS., Conclusions: Urachal carcinoma has a high recurrence rate, but only peritoneal metastasis, distant metastasis, and recurrence in pelvic lymph nodes were found to be associated with OS. Lymphadenectomy was recommended because of its role in accurately staging the disease, and further research is needed to focus on lymphadenectomy and standardized the procedure., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Brief Description: The results demonstrate that the European Organisation for Research and Treatment of Cancer (EORTC) scale provides the best recurrence and progression prediction in comparison with European Association of Urology (EAU) and Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk scores among a mixed population of patients with non-muscle-invasive bladder who were treated with, or without, Bacillus Calmette-Guerin (BCG) and without any immediate postoperative chemotherapy. The study highlights the role of tumor diameter and extent in transition prediction. This retrospective cohort analysis of 322 patients with newly diagnosed non-muscle-invasive bladder cancer (NMIBC) assesses the concordance and accuracy of predicting recurrence and progression by EAU-recommended tools (EAU risk groups, EORTC, and CUETO). One-year and five-year c-indices ranged from 0.55 to 0.66 for recurrence and from 0.72 to 0.82 for progression. AUCROC of predictions ranged from 0.46 for 1-year recurrence risk based on CUETO groups, to 0.82 for 1-year progression risk based on EAU risk groups. Diameter (HR: 1.91; 95% CI: 1.39-2.61) and tumor extent (HR: 1.21; 95% CI: 1.01-1.46 for recurrence; HR: 3.1; 95% CI: 1.40-6.87 for progression) were shown to be significant predictors in multistate analysis. Lower accuracy of prediction was observed for patients treated with BCG maintenance immunotherapy. The EORTC model (overall c-index c = 0.64; 95% CI: 0.61-0.68) was superior to the EAU (P = .035; .62; 95% CI: 0.59-0.66) and CUETO (P < .001; c = 0.53; 95% CI: 0.50-0.56) models in predicting recurrence. The EORTC model (c = 0.82; 95% CI: 0.77-0.86) also performed better than CUETO (P = .008; c = 0.73; 95% CI: 0.66-0.81) but there was no sufficient evidence that it performed better than EAU (P = .572; c = 0.81; 95% CI: 0.77-0.84) for predicting progression. EORTC and CUETO gave similar predictions for progression in BCG-treated EAU high-risk patients (P = .48). We share anonymized individual patient data. In conclusion, despite moderate accuracy, EORTC provided the best recurrence and progression prediction for a mixed population of patients treated with, or without BCG, and without immediate postoperative chemotherapy., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: We compared retrograde extraperitoneal open radical cystoprostatectomy (REORC) and robot-assisted radical cystoprostatectomy with intracorporeal diversion (iRARC) and have reported the early perioperative outcomes., Patients and Methods: REORC and iRARC were each performed at a different tertiary high-volume center in 2 countries. Men aged ≥ 18 years with precystectomy clinical stage T1-T3 disease were included. Patients with previous major pelvic and/or intra-abdominal surgery, those who had undergone previous pelvic and/or abdominal irradiation, women, and patients with clinical stage T4 disease were excluded. All cases were managed according to a standardized enhanced recovery after surgery protocol, and all the patients had undergone ileal conduit urinary diversion. Bowel recovery was one of the main endpoints; thus, the intervals to passing flatus, tolerating oral feeding, and bowel opening were determined. The operative time, estimated blood loss, intraoperative complications, length of hospital stay, postcystectomy tumor type, stage, margin status, lymph node yield, and 30- and 90-day complications were analyzed., Results: We performed a retrospective analysis of prospectively collected data from October 2016 to December 2018 of 99 patients, 50 of whom had undergone REORC and 49 iRARC. The demographic data and preoperative parameters were comparable between the 2 groups. REORC resulted in a significantly shorter mean operative time (P < .001), significantly greater mean estimated blood loss (P < .001), and greater percentage of patients requiring blood transfusion (98% vs. 12.24%). No significant differences in the length of stay were observed (P = .412). The rate of prolonged postoperative ileus was 16% and 18.4% in the REORC and iRARC groups, respectively (P = .3). Differences in the interval to passing flatus, tolerating solid oral intake, and bowel opening were not statistically significant between the 2 groups (P = .423, P = .770, and P = .700, respectively). No statistically significant difference was observed in the postcystectomy pathologic outcomes and overall and major complications rates at 30 and 90 days., Conclusion: REORC resulted in quicker bowel recovery and a shorter length of stay compared with conventional open procedures, with advantages comparable to those realized with iRARC. Thus, REORC can be adopted as the preferred open approach at institutions without surgical robots available., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: In bladder cancer patients treated with radical cystectomy (RC), controversy exists regarding the impact of the annual hospital volume (HV) and/or surgeon volume (SV) on oncological outcomes and quality of care., Objective: A systematic review was performed to evaluate the impact of HV and SV on clinical outcomes. Primary outcomes included in-hospital, 30-d, and 90-d mortality. Secondary outcomes included complications, long-term survival, positive surgical margin rate, lymphadenectomy performance, length of hospital stay, neobladder performance, and blood loss/transfusion rate., Evidence Acquisition: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched. Comparative studies published after the year of 2000 including patients who underwent RC for bladder cancer were eligible for inclusion. Partial cystectomy was an exclusion criterion. Risk of bias (RoB) assessment was performed according to the ROBINS-1 tool., Evidence Synthesis: After screening of 1190 abstracts, 39 studies recruiting 549 542 patients were included. All studies were retrospective observation cohort studies (level of evidence 3). Twenty-two studies reported on HV only, six studies on SV only, and 12 on both. Higher HV, specifically an HV of >10, was associated with improved primary and secondary outcomes in most studies. In addition, there is some evidence that an HV of >20 improves outcomes. For SV, limited and conflicting data are reported. Most studies had moderate to high RoB. The results were synthesized narratively., Conclusions: Acknowledging the lower level of evidence, HV is likely associated with in-hospital, 30- and 90-d mortality, as well as the secondary outcomes assessed. Based on this study, the European Association of Urology Muscle-invasive and Metastatic Bladder Cancer Guideline Panel recommends hospitals to perform at least 10, and preferably >20, RCs annually or refer the patient to a center that reaches this number. For SV, limited and conflicting data are available. The available evidence suggests HV rather than SV to be the main driver of perioperative outcomes., Patient Summary: Current literature suggests that the number of bladder removal operations per hospital per year is associated with postoperative survival as well as the quality of care provided., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Relatively few studies investigated the importance of frailty in radical cystectomy (RC) patients. We tested the ability of frailty, using the Johns Hopkins Adjusted Clinical Groups indicator, to predict early perioperative outcomes after RC., Methods: RC patients were identified within the National Inpatient Sample database (2000-2015). The effect of frailty, age and Charlson Comorbidity Index were tested in five separate multivariable models predicting: (1) complications, (2) failure to rescue (FTR), (3) in-hospital mortality, (4) length of stay (LOS) and (5) total hospital charges (THCs). All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics., Results: Of 23,967 RC patients, 5833 (24.3%) were frail, 7721 (32.2%) were aged ≥75 years and 2832 (11.8%) had CCI ≥2. Frailty, age ≥75 years and CCI ≥2 were non-overlapping in 86.3% of the cohort. Any two or three of these features were recorded in 12.4 and 1.3%, respectively. Frailty was an independent predictor of all five examined endpoints and the magnitude of its association was stronger or at least equal than that of age ≥75 years and CCI ≥2., Conclusion: Frailty, advanced age and comorbidities represent non-overlapping patients' characteristics. Of those, frailty represents the most consistent and strongest predictor of early adverse outcomes after RC. Ideally, all three indicators should be considered in retrospective, as well as prospective analyses. Pre-surgical recognition of frail patients should be ideally incorporate in clinical practice in order to address these patients to multimodal pre-habilitation programs that may potentially improve the perioperative prognosis., Competing Interests: Declaration of competing interest All the authors declare no potential conflicts of interest to disclose., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To describe the natural history of untreated muscle-invasive bladder cancer (MIBC) and compare the oncological outcomes of treated and untreated patients., Patients and Methods: We utilised a database encompassing all patients with newly diagnosed bladder cancer in Stockholm, Sweden between 1995 and 1996. The median follow-up for survivors was 14.4 years. Overall, 538 patients were diagnosed with bladder cancer of whom 126 had clinically localised MIBC. Patients were divided into two groups: those who received radical cystectomy or radiation therapy, and those who did not receive any form of treatment. Multivariable Cox or competing-risks regressions were adopted to predict metastasis, overall survival (OS), and cancer-specific mortality (CSM), when appropriate. Analyses were adjusted for age at diagnosis, sex, tumour stage, clinical N stage, and treatment., Results: In all, 64 (51%) patients did not receive any definitive local treatment. In the untreated group, the median (interquartile range) age at diagnosis was 79 (63-83) vs 69 (63-74) years in the treated group (P < 0.001). Overall, 109 patients died during follow-up. At 6 months after diagnosis, 38% of the untreated patients had developed metastatic disease and 41% had CSM. The 5-year OS rate for untreated and treated patients was 5% (95% confidence interval [CI] 1, 12%) vs 48% (95% CI 36, 60%), respectively. Patients not receiving any treatment had a 5-year cumulative incidence of CSM of 86% (95% CI 75, 94%) vs 48% (95% CI 36, 60%) for treated patients. Untreated patients had a higher risk of progression to metastatic disease (hazard ratio [HR] 2.40, 95% CI 1.28, 4.51; P = 0.006), death from any cause (HR 2.63, 95% CI 1.65, 4.19; P < 0.001) and CSM (subdistribution HR 2.02, 95% CI 1.24, 3.30; P = 0.004)., Conclusions: Untreated patients with MIBC are at very high risk of near-term CSM. These findings may help balance the risks vs benefits of integrating curative intent therapy particularly in older patients with MIBC., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Patients undergoing radical pelvic surgery such as proctectomy or radical cystectomy are at risk of experiencing a variety of complications. Frailty renders patients vulnerable to adverse events. We hypothesize that frailty measured preoperatively using a validated scoring system correlates with increased likelihood of experiencing Clavien-Dindo grade IV complications and 30-day mortality and may be used as a predictive model for patients preoperatively. The NSQIP database was queried for patients who underwent proctectomy or radical cystectomy from 2008 to 2012. Preoperative frailty was calculated using the 11-point modified frailty index (MFI). Patients were scored based on the presence of indicators and categorized into two groups (<3 or ≥3). Major postoperative morbidities and mortality were identified and analyzed in each group. 10,048 proctectomy and cystectomy patients were identified. The MFI was found to be predictive of both 30-day mortality ( P < 0.0001) and Clavien-Dindo grade IV complications ( P < 0.0001). Receiver operating characteristic analysis demonstrated improved discriminative power of the MFI with the addition of American Society of Anesthesiologists class for both prediction of complications and 30-day mortality. An MFI score of ≥3 is predictive of postoperative morbidity and mortality. Providers should be encouraged to calculate frailty preoperatively to predict adverse outcomes.

Background: Despite treatment with radical cystectomy, patients with muscle invasive bladder cancer (MIBC) have a poor survival. It has been reported that survival is worse in NMIBC patients who progressed to MIBC in comparison to patients with de novo MIBC. The objective of this study was to compare survival of progressive versus de novo MIBC. Secondary objective was to explain this difference in survival by clinicopathological factors., Methods: 431 patients with MIBC who underwent radical cystectomy between 1998 and 2016 in the Radboudumc, Nijmegen, were retrospectively analyzed. 313 patients were identified with de novo MIBC and 118 with progressive MIBC., Results: 5- and 10-year overall survival (OS) of patients with progressive MIBC was 37% and 20%, respectively. Patients with de novo MIBC had significantly better survival, with a 5- and 10-year OS of 49% and 39%, respectively. Patients with progressive MIBC were more frequently diagnosed with concomitant carcinoma in situ and positive surgical margins in bladder, ureters or urethra. In multivariable analysis that adjusted for these factors, progressive MIBC was associated with a hazard ratio of 1.40 (0.99 - 1.98). Kaplan-Meier survival curves show a detrimental effect of progressive MIBC in patients with pT2 versus pT3-4 tumors and in patients with negative versus positive surgical margins. In multivariable analysis, this effect modification disappeared., Conclusions: Progressive MIBC is associated with poorer survival than de novo MIBC. Because most patients with progressive MIBC had a history of high risk NMIBC, considering radical cystectomy is most important in the highest risk NMIBC., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The effect of anesthetic techniques on cancer recurrence has been the subject of intensive research in the past years, as it affects a large proportion of the population. The use of opioids and halogenated agents in cancer patients during the perioperative period may be related to higher rates of cancer recurrence and reduced disease-free survival., Methods: This was a prospective study. The sample was composed of 100 patients who underwent a radical cystectomy for infiltrating bladder cancer in a reference center. We compared disease-free survival associated with combined anesthesia versus opiate-based analgesia. The relationship between the administered hypnotic and disease-free survival was also investigated., Results: The median disease-free survival of the patients who received combined anesthesia was 585 (240-1,005) days versus 210 (90-645) days in the other group. A significant difference was observed between the two groups (p = 0.01). Combined analysis of all groups revealed significant differences in disease-free survival between patients who received combined anesthesia with propofol (510 [315-1,545] disease-free days) and those who received sevoflurane and opioids (150 [90-450] disease-free days) (p = 0.02)., Conclusions: Anesthesia may play a crucial role in tumor relapse, as it is administered at the moment of the greatest risk of dissemination: surgical handling of the tumor. Opioids and volatile agents have been related to an increased risk for cancer recurrence. We compared the use of propofol + local anesthesia versus sevoflurane + opioids and also found that disease-free survival was longer among patients who received propofol + local anesthesia. Disease-free survival increases with the use of propofol in combination with epidural anesthesia in patients who undergo surgery for infiltrating bladder cancer., (© 2020 S. Karger AG, Basel.)

Purpose: To investigate prevalence and variables associated with early oncologic mortality (EOM; within ≥30 to ≤90 days) of open radical cystectomy (RC) for bladder cancer. The unexpected rapidity of tumour recurrence and the huge metastatic burden of these patients drew us to analyse this cohort., Methods: We reviewed our RC database. All 1,487 patients were treated with curative intent between January 1986 and December 2008. Imaging for staging was done by CT (chest) and CT or MRI (abdomen). Clinical and histopathological variables were recorded until death to determine whether disease- or treatment-related factors were associated with mortality., Results: There were 93 deaths within 90 days of surgery. Twenty-four patients died from early progression to high volume disseminated metastatic disease. Group 1: unresectable tumours, which were never free of disease. Group 2: resectable tumours, considered tumour-free after RC. Group 1 is characterized by local tumour spread and a low distant failure rate. Group 2 has a low local and a high distant failure rate., Conclusions: Disease related (advanced tumour stage, positive soft tissue surgical margins (+STSM), non urothelial histology, unresectable tumours, atypical occult metastasis), rather than technical factors, had the leading role in EOM. Understaging was universal., (© 2019 S. Karger AG, Basel.)

Background: Pelvic lymphadenectomy (PLND) is an integral part of curative surgery for high-risk non-muscle invasive and muscle-invasive bladder cancer. The therapeutic value of extended PLND is controversial., Methods: We conducted a comprehensive online search in PubMed, EMBASE, and the Cochrane Library databases for relevant literature directly comparing extended PLND (e-PLND) with non-extended PLND (ne-PLND) from database inception to June 2019. We performed the meta-analysis to evaluate the impact of PLND templates on recurrence-free survival (RFS), disease-specific survival (DSS), overall survival (OS), rates of postoperative major complications, and mortality within 90 days of surgery., Results: A total of 10 studies involving 3979 patients undergoing either e-PLND or ne-PLND were included. The results showed that e-PLND was significantly associated with better RFS (HR 0.74, 95% CI 0.62-0.90, p = 0.002) and DSS (HR 0.66, 95% CI 0.55-0.79, p < 0.001). However, no correlation was found between e-PLND template and a better OS (HR 0.93, 95% CI 0.55-1.58, p = 0.79). Postoperative major complications were similar between e-PLND group and ne-PLND group, as was mortality within 90 days of surgery., Conclusion: e-PLND template is correlated with favorable RFS and DSS outcomes for patients with bladder cancer. e-PLND did not have more postoperative major complications than did ne-PLND.

Background: To test the effect of radical cystectomy (RC) with chemotherapy vs only chemotherapy on overall mortality (OM) in metastatic urothelial carcinoma of the urinary bladder (mUCUB)., Methods: Within the Surveillance, Epidemiology, and End Results registry (2004-2016), we identified patients with mUCUB. Stratification was made according to treatment: RC with chemotherapy vs only chemotherapy. Kaplan-Meier plots and multivariable Cox regression models were used before and after 1:1 propensity score (PS) matching and inverse probability of treatment weighting (IPTW)., Results: Of 2414 patients with mUCUB, 500 (21.0%) vs 1914 (79.0%) were treated with RC with chemotherapy vs only chemotherapy, respectively. In multivariable Cox regression models, RC with chemotherapy was associated with lower OM in the overall cohort (hazard ratio [HR], 0.5; P < .001), after 1:1 PS matching (HR, 0.5; P < .001), after IPTW (HR, 0.5; P < .001) and after accounting for number and location of metastases (HR, 0.5; P < .001). However, higher overall survival after RC with chemotherapy was only observed in patients with one metastatic site (21 vs 16 months; P = .001)., Conclusion: In contemporary patients with mUCUB, RC with chemotherapy is associated with lower OM rates, relative to chemotherapy alone, but only in patients with a single metastatic site. These individuals accounted for the vast majority of patients in whom an RC was performed, despite the presence of metastatic disease., (© 2019 Wiley Periodicals, Inc.)

Background: Increasing evidence suggests that cancer progression is strongly influenced by the host immune response, which is represented by immune cell infiltrates. The T-lymphocyte-based Immunoscore is reported to be a reliable prognostic factor in colon cancer, but its significance in urothelial carcinoma of the bladder (UCB) is at an early stage of exploration. This study aimed to determine whether the tumor immune infiltrate, as evaluated by the Immunoscore, could act as a useful prognostic marker for UCB patients who have undergone radical cystectomy (RC)., Methods: In this study, immunohistochemistry was used to examine the Immunoscore of 221 UCB patients who underwent RC. The Immunoscore of the patients was determined by the densities of CD3+ and CD8+ T cells at the tumor center and the invasive margin., Results: A highly significant association between a low Immunoscore and a shortened patient survival (P < 0.001, log-rank test) was demonstrated. In different subsets of UCB patients, a low Immunoscore also was a prognostic indicator of pT ≤ 2, pN(-)-status tumors, negative vascular invasion, or both (P < 0.05). Importantly, the Immunoscore together with the patient's pT status provided significant independent prognostic parameters in the multivariate analysis (P < 0.05). Furthermore, a significant correlation (P = 0.003) of a low Immunoscore with an increased UCB labeling index of Ki-67 (a cell proliferation marker) was observed in this UCB cohort., Conclusions: The findings suggest that the Immunoscore, as examined by immunohistochemistry, might serve as a novel prognostic marker for UCB patients who have undergone RC.

Background: Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease, and gene expression profiling has identified several molecular subtypes with distinct biological and clinicopathological characteristics. While MIBC subtyping has primarily been based on messenger RNA (mRNA), long non-coding RNAs (lncRNAs) may provide additional resolution., Methods: LncRNA expression was quantified from microarray data of a MIBC cohort treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) (n = 223). Unsupervised consensus clustering of highly variant lncRNAs identified a four-cluster solution, which was characterized using a panel of MIBC biomarkers, regulon activity profiles, gene signatures, and survival analysis. The four-cluster solution was confirmed in The Cancer Genome Atlas (TCGA) cohort (n = 405). A single-sample genomic classifier (GC) was trained using ridge-penalized logistic regression and validated in two independent cohorts (n = 255 and n = 94)., Results: NAC and TCGA cohorts both contained an lncRNA cluster (LC3) with favorable prognosis that was enriched with tumors of the luminal-papillary (LP) subtype. In both cohorts, patients with LP tumors in LC3 (LPL-C3) were younger and had organ-confined, node-negative disease. The LPL-C3 tumors had enhanced FGFR3, SHH, and wild-type p53 pathway activity. In the TCGA cohort, LPL-C3 tumors were enriched for FGFR3 mutations and depleted for TP53 and RB1 mutations. A GC trained to identify these LPL-C3 patients showed robust performance in two validation cohorts., Conclusions: Using lncRNA expression profiles, we identified a biologically distinct subgroup of luminal-papillary MIBC with a favorable prognosis. These data suggest that lncRNAs provide additional information for higher-resolution subtyping, potentially improving precision patient management.

Radical cystectomy, which is a standard treatment of muscle invasive and high-grade non-invasive bladder tumour, is accompanied with high rates of postoperative complications including major adverse cardiac events (MACE). Diastolic dysfunction is associated with postoperative complications. We evaluated perioperative risk factors including diastolic dysfunction related with MACE within 6 months after radical cystectomy. The 546 patients who underwent elective radical cystectomy were included. Diastolic dysfunction was defined as early transmitral flow velocity (E)/early diastolic mitral annulus velocity (e') > 15. Logistic regression analysis, Kaplan-Meier survival analysis and log-rank test were performed. MACE within 6 months after radical cystectomy developed in 43 (7.9%) patients. MACE was related with female (odds ratio 2.546, 95% confidence interval 1.166-5.557, P = 0.019) and diastolic dysfunction (odds ratio 3.077, 95% confidence interval 1.147-8.252, P = 0.026). The 6-month mortality were significantly higher in the MACE group, and hospital stay and intensive care unit stay were significantly longer in the MACE group compared to the non-MACE group. Accordingly, preoperative diastolic dysfunction (E/e' > 15) was related with postoperative MACE and MACE was related with 6-month survival after radical cystectomy. These results suggest that preoperative diastolic dysfunction can provide useful information on postoperative complications.

Background: Hydronephrosis is a common finding in patients with bladder cancer. The aim of the study was to appraise the prognostic value of preoperative hydronephrosis in bladder cancer patients undergoing radical cystectomy., Methods: We conducted a literature search using PubMed and Embase databases in Aug 2018. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effects models. The primary endpoint was overall survival (OS). Secondary endpoints were cancer-specific survival (CSS) and recurrence-free survival (RFS)., Results: Overall, 13 studies published between 2008 and 2018 including 4,820 patients were selected for the meta-analysis. The age of bladder cancer patients ranged from 27 to 90.4 years, and the overall proportion of males was 72.5%. Preoperative hydronephrosis was reported in 27.4% of patients. The pooled HR was statistically significant for OS (HR, 1.36; 95% CI [1.20-1.55]) and CSS (HR, 1.64; 95% CI [1.33-2.02]), with no heterogeneity among the enrolled studies. Patients with bilateral hydronephrosis showed a poorer CSS compared to those with no hydronephrosis (HR 5.43, 95% CI [3.14-9.40]). However, there was no difference in CSS between no hydronephrosis and unilateral hydronephrosis groups (HR 1.35, 95% CI [0.84-2.14]). Despite a tendency towards poorer RFS (HR, 1.27; 95% CI [0.96-1.96]), the results demonstrated no significant association between presence of preoperative hydronephrosis and RFS after radical cystectomy., Conclusion: This meta-analysis indicates that preoperative hydronephrosis is significantly associated with poorer OS and CSS after radical cystectomy for patients with bladder cancer. Preoperative hydronephrosis has a stronger effect on CSS in patients with bilateral hydronephrosis. The presence of preoperative hydronephrosis not only predicts prognosis, but may also help to identify patients who benefit the most from neoadjuvant chemotherapy., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate the association between hospital volume and overall survival (OS), cancer-specific survival (CSS), and quality of care of patients with bladder cancer who undergo radical cystectomy (RC), defined as the use of extended lymphadenectomy (eLND), continent reconstruction, neoadjuvant chemotherapy (NAC), and treatment delay of <3 months., Patients and Methods: We used the Bladder Cancer Data Base Sweden (BladderBaSe) to study survival and indicators of perioperative quality of care in all 3172 patients who underwent RC for primary invasive bladder cancer stage T1-T3 in Sweden between 1997 and 2014. The period-specific mean annual hospital volume (PSMAV) during the 3 years preceding surgery was applied as an exposure and analysed using univariate and multivariate mixed models, adjusting for tumour and nodal stage, age, gender, comorbidity, educational level, and NAC. PSMAV was either categorised in tertiles, dichotomised (at ≥25 RCs annually), or used as a continuous variable for every increase of 10 RCs annually., Results: PSMAV in the highest tertile (≥25 RCs annually) was associated with improved OS (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.75-1.0), whereas the corresponding HR for CSS was 0.87 (95% CI 0.73-1.04). With PSMAV as a continuous variable, OS was improved for every increase of 10 RCs annually (HR 0.95, 95% CI 0.90-0.99). Moreover, higher PSMAV was associated with increased use of eLND, continent reconstruction and NAC, but also more frequently with a treatment delay of >3 months after diagnosis., Conclusions: The current study supports centralisation of RC for bladder cancer, but also underpins the need for monitoring treatment delays associated with referral., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)

Background: Regionalization to higher volume centers has been proposed as a mechanism to improve short-term outcomes following complex surgery., Objective: The objective of this study was to assess trends in regionalization and mortality for patients undergoing radical cystectomy (RC)., Research Design: An observational study of patients receiving RC in the United States from 2004 to 2013., Subjects: Data for patients receiving RC were extracted from the National Cancer Database., Measures: The primary exposure was hospital volume; low-volume hospitals (LVH) included those with <5 RC/year and high-volume hospitals (HVH) were those with ≥30 RC/year. Trends in the volume were assessed, as were 30- and 90-day mortality. Cochrane-Armitage tests were performed for volume, and propensity score-weighted proportional hazard regression was used to assess mortality., Results: A total of 47,028 RC were performed in 1162 hospitals from 2004 to 2013. The proportion of RC at LVH declined from 29% to 17% (P<0.01), whereas that of HVH increased from 16% to 33% (P<0.01). Unadjusted 30- (P=0.02) and 90-day (P<0.001) mortality decreased, and the absolute decrease was greatest at LVH (4.8% vs. 2.6%, P=0.03), whereas rates for HVH remained stable (1.9% vs. 1.4%, P=0.34). Following risk-adjustment, relative to treatment at HVH, treatment at LVH was associated with increased 30-day (hazard ratio: 1.66, 95% CI: 1.53-1.80) and 90-day mortality (hazard ratio: 1.37, 95% confidence interval: 1.30-1.44)., Conclusions: Regionalization of RC to HVH was observed from 2004 to 2013. Treatment at LVH was associated with 66% and 33% relative increases in hazard of death at 30 and 90 days, respectively. These findings support the selective referral of complex cases to higher volume centers.

Objectives: To determine if the presence of non-urothelial variant histology (NUVH) is associated with a poorer prognosis following radical cystectomy (RC) compared to pure urothelial carcinoma (PUC)., Patients and Methods: A prospectively maintained database of all patients undergoing RC at a high-volume regional tertiary bladder cancer service between January 2010 and January 2017 was retrospectively analysed looking for patients with NUVH. Multivariate Cox proportional hazards regression analysis was used to determine disease recurrence, overall survival and bladder cancer-specific survival, as well as lymph node positivity. Association of tumour stage was determined using chi-squared analysis., Results: In total, 430 patients underwent RC of which 73 (17%) had NUVH and 357 (83%) had PUC. The median (range) follow-up was 45.0 (8.5-100.2) months. The presence of NUVH was associated with both increased overall (hazard ratio [HR] 1.86, 95% confidence interval [CI] 1.21-2.85) and bladder cancer-specific mortality (HR 1.81, 95% CI 1.91-3.01), as well as disease recurrence (HR 1.71, 95% CI 1.06-2.75) in multivariate analysis. Squamous cell variant was also associated with increased overall mortality (HR 1.91, 95% CI 1.16-3.13), cancer-specific mortality (HR 2.03, 95% CI 1.21-3.42) and disease recurrence (HR 2.08, 95% CI 1.23-3.52), although this was not seen in other variant subtypes. Lymph node positivity was not associated with NUVH in multivariate analysis (HR 1.28, 95% CI 0.59-2.75), but NUVH was associated with advanced tumour stage on chi-squared analysis (P < 0.001)., Conclusion: Our results showed a risk of shorter survival in NUVH compared to PUC. This suggests NUVH as an independent predictor of worse outcomes. As a result, patients with NUVH should be counselled preoperatively that overall and disease-specific outcomes are worse postoperatively and about the possible need for adjuvant treatment., (© 2019 The Authors BJU International © 2019 BJU International Published by John Wiley & Sons Ltd.)