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The incidence of bladder cancer (BC) depends on advancing age and other risk factors, significantly impacting on surgical, functional and oncological outcomes. Radical cystectomy (RC) with urinary diversion is the gold standard therapy for muscle invasive bladder cancer; however, it remains a complex surgery and requires careful analysis of risk factors in order to potentially decrease post-surgical complication rates. Age in surgery is a limiting factor that can modify surgical and oncological outcomes, and is correlated with a high rate of post-dimssion hospital readmissions. The reconstruction of the bladder with the intestine represents a crucial point of radical cystectomy and the urinary derivation (UD) is at the center of many debates. A non-continent UD seems to be the best choice in elderly patients (>75 years old), while orthotopic neobladder (ON) is poorly practiced. We reviewed the literature to identify studies reporting outcomes, complications, patient- selection criteria, and quality-of-life data on elderly patients, who underwent ON following radical cystectomy. Reviewing the literature there is no clear evidence on the use of age as an exclusion criterion. Certainly, the elderly patient with multiple comorbidities is not eligible for ON, preferring other UD or rescue therapies. A careful preoperative selection of elderly patients could greatly improve clinical, surgical and oncological outcomes, giving the chance to selected patients to receive an ON., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To compare the prognosis and quality of life between radical cystectomy and bladder conservative treatment for muscle invasive bladder cancer in the real world., Materials and Methods: Patients treated for muscle invasive bladder cancer without metastases were retrospectively evaluated for overall survival, progression-free survival, and rehospitalization., Results: Of the 141 patients, 62 underwent bladder conservative treatment and 79 underwent radical cystectomy. Patients who underwent radical cystectomy had significantly better progression-free survival (HR: 1.83, 95% CI: 1.12-3.00; p < 0.01) and overall survival (HR: 1.82, 95% CI: 0.99-3.34; p = 0.03) than those who underwent conservative treatment. However, there was no significant difference in prognosis between patients who refused to undergo radical cystectomy and those who underwent. In addition, rehospitalization rates for complications and additional treatment were significantly higher in patients who received conservative treatment (69.3% vs. 34.2%; p < 0.01), and the length of hospital stay was also prolonged compared to patients who received radical cystectomy (26 vs. 9 days; p = 0.03)., Conclusions: Overall, conservative treatment had a significantly poorer prognosis than radical cystectomy, but there was no significant difference in prognosis when comparing patients who refused radical cystectomy and received conservative treatment with those who received radical cystectomy. However, hospitalization rates and length of stay were significantly worse for patients who chose conservative treatment, which may lead to a decline in quality of life., (© 2024 The Japanese Urological Association.)

Background: Despite abundant evidence supporting the use of perioperative chemotherapy from clinical trials, no study to date has comprehensively evaluated its use in the treatment of muscle-invasive bladder cancer (MIBC) in the real-world setting. Little is known regarding the impact of pretreatment disease stage and real-world factors such as patient comorbidities preventing timely completion of therapy on its effectiveness. This study aims to assess the usage of perioperative chemotherapy and examines its impact on pathologic downstaging rates and recurrence free survival in patients undergoing radical cystectomy., Methods: A retrospective review was conducted in 805 patients with muscle invasive bladder cancer undergoing radical cystectomy with no perioperative chemotherapy, 761 with presurgical chemotherapy followed by radical cystectomy, and 134 radical cystectomy followed by adjuvant chemotherapy. Relevant clinicopathologic features were reviewed. Recurrence-free survival and Overall Survival probability estimates were calculated using the Kaplan-Meier method and compared using the Log-rank or Gehan-Breslow tests. The prognostic effects of presurgical chemotherapy and adjuvant chemotherapy regimens were evaluated by estimating hazard ratio and 95% confidence interval from an adjusted Cox proportional hazards model. Statistical tests were 2-sided, and significance was defined as P-value < 0.05., Results: In this contemporary, real-world cohort, 5-yr RFS was found to be 65.6% in pT0, 59.1%in pT2, and 10.8% in pN+ patients. Presurgical chemotherapy increased pathologic downstaging rates from 27.5% to 41.1% in patients with ≥cT2 BCa. Stratified by clinical T-stage, only cT2 patients derived recurrence-free survival (Median 45.3 months vs. 29.0 months, P < 0.01) and overall survival (Median 62.3 months vs. 41.9 months, P < 0.001) benefits.  In patients with adverse pathologic features (≥pT3 or pN+), adjuvant chemotherapy improved recurrence-free survival (Median 22.8 months vs. 10.0 months, P < 0.0001) and overall survival (Median OS 32.4 months vs. 16.3 months, P < 0.0001)., Conclusions: We report real-world outcomes from a large cohort of muscle-invasive bladder cancer patients undergoing surgical treatment with/out perioperative chemotherapy. Pathologic response rates to pre-surgical chemotherapy were modest and led to clinical benefit only in cT2 patients. Adjuvant chemotherapy provided survival benefit for pathologically advanced MIBC patients irrespective of pT/N staging., Competing Interests: Declaration of Competing Interest There are no conflicts of interest pertaining to this study. RL: Research support: Predicine, Veracyte, CG Oncology, Valar Labs; Clinical trial protocol committee – CG Oncology; Scientific advisor/consultant – BMS, Merck, Ferring, Fergene, Arquer Diagnostics, Urogen Pharma, Lucence; Honoraria – SAI MedPartners, Solstice Health Communications. JZ: Scientific advisor/consultant — Seagen. PS: COI — Vice Chair, NCCN Bladder and Penile Panel. WS: Consultant/ Advisory Board — Urogen Pharmaceuticals, Pacific Edge Diagnostics., (Copyright © 2023 Elsevier Inc. 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.)

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.)

Chemotherapy in combination with radical cystectomy or radiotherapy has led to improved oncological outcomes in the definitive treatment of muscle-invasive bladder cancer (MIBC). Here we discuss the current role of chemotherapy and immunotherapy in the management of MIBC and discuss future directions of treatment., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Objective: To identify the optimal selection criteria for bladder sparing strategy with transurethral resection of bladder tumor (TURBT) and systemic chemotherapy in patients with muscle-invasive bladder cancer (MIBC)., Methods: We conducted a retrospective cohort study in 71 patients with MIBC (T2-4aN0M0) who desire to bladder preservation received neoadjuvant chemotherapy (NAC) after maximal TURBT, followed by clinical restaging and second-TURBT. Fifty-eight of 71 patients with no residual tumor on the second-TURBT were placed on conservative management for bladder sparing (BS). Noninvasive down-staging (NID) was defined as cT0/Ta/Tis/T1N0 at first-TURBT after NAC and no residual tumor on second-TURBT. Overall survival (OS) and cystectomy-free survival (CFS) were assessed according to the response of NAC in the BS group by using Kaplan-Meier methods. Cox proportional hazards regression model was used to identify independent variables predicting OS., Results: At a median follow-up of 40 months 5-year OS and CFS in patients with NID and non-NID were 89.1% versus 20.8% and 84.8% versus 16.7%, respectively. Multivariate analysis showed that the ≥3 cycles of NAC (hazard ratio [HR] 0.14, 95% confidential index [CI] 0.03-0.7; P = 0.017) and achievement of NID (HR 0.11, 95% CI 0.03-0.46, P = 0.002) favorably associated with OS., Conclusions: Patients who achieved NID might be optimal candidates for the bladder sparing strategy with maximum TURBT plus NAC followed by second-TURBT., Competing Interests: Conflict of interest All authors declare that they have no conflicts of interest, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Trials of adjuvant chemotherapy following radical cystectomy generally require chemotherapy to start within 90 days postoperatively. However, it is unclear, whether the interval between surgery and start of adjuvant therapy (S-AC-interval) impacts the oncological outcome., Methods: Using the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC) data base, we identified patients who underwent radical cystectomy for muscle invasive bladder cancer and subsequent adjuvant chemotherapy. Univariate analysis of patient characteristics, surgical factors and tumor characteristics regarding their impact on S-AC-interval was performed using Kruskal-Wallis testing and Fisher's exact test. Analysis of progression-free (PFS) and overall survival (OS) (follow-up time beginning with the start date of adjuvant chemotherapy) was analyzed in relation to S-AC-interval (continuous and dichotomous with a cut-off at 90 days) using Kaplan-Meier method and COX regression analysis., Results: We identified 238 eligible patients (83.5% male, mean age: 63.4 years, 76.1% T3/T4, 66.4% pN+, 14.7% R+, 70.6% urothelial carcinoma, 71% cisplatin-based adjuvant chemotherapy). The majority of patients (n = 207, 87%) started chemotherapy within 90 days after surgery. Median S-AC-interval was 57 days (interquartile range 32.8). S-AC-interval did not have consistent association with any patient/tumor characteristics or surgery related factors (type of surgery, urinary diversion). Survival analysis using continuous S-AC-interval revealed a trend toward an impact of S-AC-interval on OS (hazard ratio 1.004, 95% confidence ratio 0.9997-1.0084, P = 0.071). With regards to PFS, that impact was shown to be statistically significant (hazard ratio 1.004, 95% confidence ratio 1.0003-1.0075, P = 0.032). In multivariate analysis, however, S-AC-interval was negated by tumor and patient related factors (pathological T-stage, N-stage, ECOG performance status). Accounting for eligibility criteria defined in some clinical trials, we extended our analysis dividing S-AC-interval in ≤90 and >90 days. Although we could confirm the trend toward better outcome in patients with a shorter S-AC interval in dichotomous analysis, neither differences in OS nor in PFS reached statistical significance (P = 0.438 and P = 0.056)., Conclusions: In a large multi-institutional experience, 87% of patients who received adjuvant chemotherapy received it within the guideline recommended window of 90 days. While it was not possible to determine whether this is the optimal cut-off, early start of adjuvant chemotherapy seems to be reasonable. Regarding prognosis, tumor-related pathological factors abrogated the importance of the S-AC-interval in our analysis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Radical cystectomies (RCs) are increasingly centralized, but bladder cancer can be diagnosed in every hospital The aim of this study is to assess the variation between hospitals of diagnosis in a patient's chance to undergo a RC before and after the volume criteria for RCs, to identify factors associated with this variation and to assess its effect on survival., Methods and Materials: Patients diagnosed with muscle-invasive bladder cancer (cT2-4a,N0/X,M0/X) without nodal or distant metastases between 2008 and 2016 were identified through the Netherlands Cancer Registry. Multilevel logistic regression analysis was used to investigate the hospital specific probability of undergoing a cystectomy. Cox proportional hazard regression analysis was used to assess the case-mix adjusted effect of hospital-specific probabilities on survival., Results: Of the 9,215 included patients, 4,513 (49%) underwent a RC. The percentage of RCs varied between 7% and 83% by hospital of diagnosis before the introduction of the first volume criteria (i.e., 2008-2009; minimum of 10 RCs). This variation decreased slightly to 17%-77% after establishment of the second volume criteria (i.e., 2015-2016; minimum of 20 RCs). Age, cT-stage and comorbidity were inversely and socioeconomic status was positively associated with RC. Both being diagnosed in a community hospital and/or being diagnosed in a hospital fulfilling the RC volume criteria were associated with increased use of RC compared to academic hospitals and hospitals not fulfilling the volume criteria. For each 10% increase in the percentage of RC in the hospital of diagnosis, 2-year case-mix adjusted survival increased 4% (hazard ratio 0.96, 95% confidence interval 0.94-0.98)., Conclusion: Probability of RC varied between hospitals of diagnosis and affected 2-year overall survival. Undergoing a RC was associated with age, cT-stage, socioeconomic status, type of hospital, and whether the hospital of diagnosis fulfilled the RC volume criteria. Future research is needed to identify patient, tumor, and hospital characteristics affecting utilization of curative treatment as this may benefit overall survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study aims to assess the impact of facility characteristics on measures of surgical quality (positive surgical margin rates and lymph-node yield) in patients undergoing robot-assisted (RARC) versus open (ORC) radical cystectomy using the National Cancer Database. Patients who received RC between the years of 2010-2013 were stratified according to surgery type (ORC vs. RARC), and corresponding patient and facility-level variables (facility type and volume) were assessed. Logistic regression models for procedure type, positive surgical margins (PSMs), and LN dissection (LND) rates were estimated. Radical cystectomies (ORC = 13,236, RARC = 3687) were performed more often in academic centers (58.3%) compared to community centers (31.6%). As facility volume increased, centers performed more LNDs during ORCs (p = 0.03) and the number of nodes retrieved increased in both ORC and RARC (ORC p < 0.001; RARC p < 0.0001). Increased facility volume also resulted in significantly fewer PSMs within the RARC cohort (p = 0.01). Comparison of ORC and RARC within each facility type cohort identified improved pathological metrics for RARC with fewer PSMs (p = 0.001) as well as increased LNDs (p < 0.0001) and median number of LNs retrieved (p < 0.0001), which suggests that RARC may facilitate comparative outcomes in community centers and academic centers. Overall, higher facility volume and robot-assisted surgery resulted in more favorable pathologic metrics compared to lower facility volume and ORC.

Background: Radical cystectomy (RC) is the primary treatment strategy for muscle invasive bladder cancer (MIBC). However, it carries a high risk of urethral recurrence (UR) in male patients. The risk factors and oncological outcomes of UR remain unclear. We aimed to identify the risk factors and oncological outcomes of UR in male patients with MIBC after RC combined with urinary diversion., Methods: After propensity score matching, we evaluated 137 male patients with MIBC who underwent RC combined with urinary diversion at our center between January 1, 2007 and December 31, 2015. Patient demographics, comorbidity, and perioperative data were recorded. Univariate and multivariate Cox proportional hazards regression were used to estimate the hazard ratio and 95% confidence intervals. Cancer-specific survival (CSS) and overall survival (OS) were measured using the Kaplan-Meier curve with log-rank test. P < 0.05 was considered statistically significant., Results: Of the 310 patients, 30 (9.7%) patients underwent UR. In the matched group, the independent risk factors of UR were history of TURB (HR = 3.069, P = 0.018), tumor stage (T3 vs. T2, HR = 3.997, P = 0.014; T4 vs. T2, HR = 2.962, P = 0.015), and tumor multifocality (HR = 2.854, P = 0.011). The CSS and OS of patients with UR were equivalent to the patients without UR (P = 0.295, P = 0.616)., Conclusion: This propensity score-matched case-control study showed that UR is not rare in male patients with MIBC after RC combined with urinary diversion. We identified three independent risk factors of UR: history of TURB, tumor stage, and tumor mutifocality. The oncological outcomes were equivalent between patients with and without UR. These findings could help improve treatment strategies and follow-up schedules.

Background: To determine the peri-operative safety and oncological value of robotic-assisted radical cystectomy (RARC) for older and younger patients in an initial Japanese RARC series., Methods: We retrospectively analyzed the demographics, complications, peri-operative and oncological outcomes of 253 consecutive patients with bladder cancer who underwent RARC at 34 institutions in Japan between April 2009 and March 2017. The patients were assigned to groups according to ages at surgery of < 70 (younger; n = 125) and ≥ 70 (older; n = 128) years., Results: Mean Charlson comorbidity index (p = 0.045) and the incidence of a history of previous abdominal surgery (p = 0.002) were significantly higher, whereas a history of neoadjuvant chemotherapy (p = 0.028) and neobladder (p < 0.001) were significantly lower in the older group. Mean total operative time was significantly shorter (p = 0.019) and mean estimated blood loss (p = 0.013) was significantly lower in the older group. Post-operative Grade ≥ II complications were comparable at 0-30, 31-90 and 91 days after surgery despite urinary tract associations. Rates of positive surgical margins and mean numbers of removed lymph nodes were comparable between the two groups. Although 5-year overall survival rates were significantly lower (p = 0.03) for older patients, 5-year cancer-specific (p = 0.10) and recurrence-free survival rates were comparable (p = 0.20) between the groups., Conclusion: Using RARC potentially allows the application of less invasive procedures and cancer control for septuagenarian patients that are equivalent to those for younger patients.

Objectives: Randomised controlled trials (RCTs) have investigated the use of neoadjuvant chemotherapy (NAC) and its effect on survival patients with non-metastatic muscle-invasive bladder cancer (MIBC). However, these RCTs have limited external validity and generalisability and, therefore, the current study aims to use real world evidence in the form of observational data to identify the effect that NAC may have on survival, compared to the use of radical cystectomy (RC) alone. Materials and methods: The study cohort (consisting of 944 patients) was selected as a target trial from the Bladder Cancer Data Base Sweden (BladderBaSe). This study calculated 5-year survival and risk of bladder cancer (BC)-specific and overall death by Cox proportional hazard models for the study cohort and a propensity score (PS) matched cohort. Results: Those who had received NAC had higher 5-year survival proportions and decreased risk of both overall and BC specific death (HR = 0.71, 95% CI = 0.52-0.97 and HR = 0.67, 95% CI = 0.48-0.94), respectively, as compared to patients who did not receive NAC. The PS matched cohort showed similar estimates, but with larger statistical uncertainty (Overall death: HR = 0.76, 95% CI = 0.53-1.09 and BC-specific death: HR = 0.73, 95% CI = 0.50-1.07). Conclusion: Results from the current observational study found similar point estimates for 5-year survival and of relative risks as previous studies. However, the results based on real world evidence had larger statistical variability, resulting in a non-statistically significant effect of NAC on survival. Future studies with detailed validated data can be used to further investigate the effect of NAC in narrower patient groups.

Background: Treatment choice for muscle invasive bladder cancer continues to be radical cystectomy. However, radical cystectomy carries a relatively high risk of morbidity and mortality compared with other urological procedures., Objective: To compare surgical complications following radical cystectomy in septuagenarians and octogenarians., Design, Setting, and Participants: The National Surgical Quality Improvement Program database (2009-2013) was used to identify patients who were 70 yr and older and underwent radical cystectomy., Outcome Measurements and Statistical Analysis: The data were analyzed for demographics and comorbidities, and compared for complications, including pulmonary, thromboembolic, wound, and cardiac complications. Patients who were 70-79 yr of age were compared with those 80 yr and older. Univariate and multivariate analyses were completed., Results and Limitations: A total of 1710 patients aged ≥70 yr met our inclusion criteria. Of them, 28.8% (n=493) were 80 yr and older, while 71.2% (n=1217) were between 70 and 79 yr old. Operative time (338.4 vs 307.2min, p=0.0001) and the length of stay (11.9 vs 10.4 d, p=0.0016) were higher in the octogenarian group. The intra- and postoperative transfusion rates, reoperative rates, wound dehiscence rates, and pneumonia, sepsis, and myocardial infarction rates were similar between the two groups. The wound infection rate (7.3% vs 4.1%, p=0.01) was higher in the septuagenarians and mortality rate (4.3% vs 2.3%, p=0.04) was higher in the octogenarian group., Conclusions: Radical cystectomy can safely be performed in octogenarians without increased cardiac, pulmonary, and thromboembolic complications when compared with septuagenarians. These patients need to be counseled that the mortality rate is slightly higher compared with that in septuagenarians. Chronological age alone should not be used to decide on offering radical cystectomy., Patient Summary: We looked at complications following radical cystectomy in patients aged 80 yr and older. We found that there was no significant difference for wound, cardiac, or pulmonary complications, but there was an increased risk of mortality in this age group., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: The aim of this study was to validate the value of preoperative patient characteristics in prognosticating survival after radical cystectomy (RC) to guide treatment decisions regarding neoadjuvant systemic treatment., Methods: We evaluated a single cohort of 449 consecutive patients treated with RC for bladder cancer. Patients treated with neoadjuvant therapy were excluded from the study cohort (n = 24). Patients were stratified based on preoperative characteristics into 2 risk groups. The high-risk group included patients harboring clinically non-organ-confined disease (≥ cT3), hydroureteronephrosis, lymphovascular invasion, or variant histology (micropapillary, neuroendocrine, sarcomatoid, or plasmacytoid variants on transurethral resection). The low-risk group included patients with cT2 disease without any of the aforementioned features. Survival expectancies after surgery were evaluated using competing risk and Kaplan-Meier analyses., Results: We identified 153 (44.6%) low-risk and 190 (55.4%) high-risk patients. The majority of high-risk patients had only 1 high-risk feature (n = 111; 58.4%); the most common high-risk feature was preoperative hydroureteronephrosis (n = 107; 56.3%). The majority of low-risk patients were upstaged at time of RC (n = 118; 70.6%), whereas a pathologic downstage occurred only in 27 high-risk patients (14.2%). Cancer-specific mortality-free rates at 5 years after RC were 77.4% versus 64.4% for low-risk versus high-risk patients, respectively., Conclusions: We confirm that preoperative risk features can stratify patients with muscle-invasive bladder cancer into differential risk groups regarding survival. Decision-making regarding neoadjuvant systemic therapy administration is likely to be improved by integrating clinical stage, lymphovascular invasion, variant histology, and hydroureteronephrosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Patients with clinical T4 (cT4) bladder cancer (BCa) infrequently undergo radical cystectomy (RC). We investigated the reliability of preoperative clinical staging, perioperative and survival outcomes in patients treated with RC due to cT4a-b BCa disease at a single tertiary care institution., Methods: The study relied on 917 BCa patients treated with RC and pelvic lymph node dissection (PLND) at a single institution between January 1995 and December 2012. We compared the accuracy of the clinical assessment with final pathology results. Moreover, we evaluated perioperative outcomes, complication rates and survival after surgery., Results: The median follow-up was 62 months. Overall, 74 (8.1%) patients presented cT4 stage at preoperative evaluation. Conversely, a pathological T4 disease was confirmed only in 68.9% patients staged initially as cT4. No differences were recorded in complications, 30 days readmission or 30 days death rates between cT1-T3 vs. cT4a vs. cT4b (p > 0.1). At multivariable Cox regression analyses predicting cancer specific mortality, clinical T4 stage vs. clinical T1-2, clinical T3 stage vs. clinical T1-2 and age were predictors of worst survival after RC (all p < 0.04)., Conclusions: We recorded poor concordance between preoperative imaging and pathology in cT4 patients. No differences in major perioperative outcomes and acceptable survival expectancies were reported in patients treated for cT4 disease., (Copyright © 2016 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: The purpose of this study was to evaluate the prevalence of postoperative weight loss (WL) following radical cystectomy (RC) and its association with mortality. Nutritional status is recognized as a potential modifiable risk factor for postoperative complications following RC for bladder cancer. The American Society for Parenteral and Enteral Nutrition and the Academy of Nutrition and Dietetics recognize WL as a diagnostic measure for malnutrition., Methods: Seventy-one patients underwent RC for bladder cancer between July 2008 and July 2013, in whom peri-operative weights were documented regularly. The primary predictor variable was substantial WL defined as ≥ 10% WL by postoperative month 1. Survival was estimated using Kaplan-Meier analysis; logistic regression was used for multivariate analyses., Results: Mean postoperative WL at 2 weeks was 9.5 lbs (-5.2%), 14.3 lbs (-7.8%) at 1 month, 16.9 lbs (-9.0%) at 2 months, 12.6 lbs (-6.9%) at 3 months, and 8.9 lbs (-4.6%) at 4 months. Forty-two percent of patients met criteria for substantial WL. At 19 months median follow-up, the overall mortality rate was 31% (22 of 71), which rose to 64% (14 of 22) in patients who experienced substantial WL (P < .05). Substantial WL trended towards significance on multivariate analysis (P = .07). There was a significant decrease in 5-year survival in patients with ≥ 10% WL (log rank P < .05)., Conclusions: Patients experience WL following RC, which may be indicative of malnutrition. Substantial WL may predict for poor overall survival. Prospective studies are needed to determine whether nutritional optimization can prevent significant WL and improve outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Muscle invasive bladder cancer is an unforgiving disease, and if untreated, it leads to death within 2 years of the diagnosis in >85 % of the patients. Long-term oncologic efficacy remains the ultimate standard that all procedures have to be measured by. In the past decades, open radical cystectomy (RC), extended pelvic lymph node dissection (PLND), and urinary diversion have been established as the gold standard. In the last few years, however, growing attention has been set on robotic-assisted radical cystectomy (RARC)., Results: Even in the very long term, open RC has good oncological results and if an ileal neobladder is performed excellent functional results. Follow-up of patients after open RC exceeds more than a decade which is unsurpassed by any other technique. Its outcomes have been proven to be durable and cost-effective. Least perioperative complications as well as best oncological and functional results can be achieved if open RC and urinary diversion were performed in a high-volume hospital by high-volume surgeons and an experienced team., Conclusions: Despite upcoming new technologies such as RARC, open RC following extended (PLND) remains the gold standard treatment for high-grade muscle invasive bladder cancer.

Purpose: Ileal conduit (IC) is the most frequent urinary diversion (UD) performed after radical cystectomy (RC). We reviewed the literature to investigate the factors influencing the choice of this diversion and its complications., Methods: A literature search (PubMed) was performed for all English language publications on UDs performed for treatment of bladder cancer from 1950 to 2015. The literature review was focused on studies reporting outcome of IC and its comparison with other types of UDs., Results: IC is the most common UD performed in elderly patients undergoing RC for bladder cancer. Long-term studies looking at the change in renal function after UD report a universal decline in the glomerular filtration rate; however, this decline in renal function is the least for IC. There is a significant morbidity of RC (20-56 %), which can be attributed to patient factors, surgical technique and hospital volume. Modern concepts of bowel preparation, postoperative nutrition, early enteral feeding and involvement of stoma therapists have helped improve the outcomes. The quality of life is preserved, and in many including elderly, it may be improved with IC UD., Conclusions: IC is the most commonly performed UD following radical cystectomy. It is associated with acceptable morbidity and has the lowest reoperation rates as compared to continent diversion. It is also the procedure of choice for most patients' elderly patients as well as patients with limited dexterity, poor motivation, anatomical restrictions and poor renal function. Studies measuring HRQOL report excellent patient acceptability, especially in the elderly population.

Purpose: to assess the respective outcomes of patients with localized muscle-invasive bladder cancer (MIBC) treated by either radical cystectomy (RC) or trimodal treatment (TMT) depending on pathological response to previous neoadjuvant chemotherapy (NAC) assessed on cystectomy specimen or post-NAC transurethral resection (TURB) specimen, respectively. Patient and methods: We retrospectively included all consecutive patients treated in one academic center with cisplatin-based NAC followed by RC or TMT for cT2-3N0M0 MIBC between 2014 and 2021. Primary endpoint was metastasis-free survival (MFS) in both treatment groups and according to pathological response to NAC. Local recurrence-free survival and conservative management failure (metastasis-free bladder-intact survival) for patients treated with TMT were assessed. Results: 104 patients were included, 26 treated with TMT and 78 with RC. The rate of complete pathological response was 47.4% in patients treated with RC (ypT0) and 66.7% in patients treated with TMT (ycT0). Median follow-up was 34.9 months. Four-year MFS was 72% in both treatment groups. Four-year MFS was 85% in both ypT0 RC patients and ycT0 TMT patients. ycT0 stage was associated with low rates of intravesical recurrence and conservative management failure. Conclusion: Patients with post-NAC ycT0 stage treated with TMT have favorable oncological outcomes similar to those of ypT0 patients treated with RC. Assessment of complete histological response with TURB after NAC may help in selecting the best candidates for bladder preservation with TMT. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer is ranked the ninth most common cancer in the world. Locally, the incidence of bladder cancer has increased tenfold over the past 26 years. Radical cystectomy (RC) is considered a gold standard management option for muscle-invasive bladder cancer (MIBC), but trimodal therapy (TMT) has shown comparable oncological outcomes in selected patients. Materials and Methods: This is a retrospective study in which we reviewed medical records of patients diagnosed with MIBC without nodal disease or distant metastasis (cT2N0M0) who underwent either RC or TMT. Demographic data, comorbidities, histopathological and clinical staging, neoadjuvant/adjuvant therapy, and follow-up were analyzed. Results: We included a total of 31 patients in the study, with 10 patients in the TMT group and 21 patients in the RC group. There was no significant difference in recurrence between the TMT and RC groups (P = 0.58). The TMT group had a higher percentage of local recurrence (40% vs. RC 5.2%, P = 0.018) but no significant difference in metastasis (0% vs. 10%, P = 0.420). The difference in overall survival between the TMT and RC groups was not significant (P = 0.25). Conclusion: TMT may be considered an alternative option for patients unwilling to undergo RC due to related complications and prioritize a better quality of life. However, the decision should be made after considering the cost of extensive follow-ups and patient compliance with surveillance. [ABSTRACT FROM AUTHOR]

Nomogram prediction of overall survival that includes LODDS in carcinoma bladder. Retrospective cohort study of 282 cases from a tertiary care centre. The nomogram has superior predictive ability and higher clinical use than AJCC system. It will help clinicians for better patient counselling, planning follow-up strategies and designing clinical trials for newer adjuvant therapy (eg immunotherapy) in patients of MIBC. Background: To develop and validate a nomogram based on LODDS (Log ODDS of positive lymph-nodes) for prediction of overall survival (OS) in post radical cystectomy (RC) patients of muscle invasive bladder cancer (MIBC). Materials and Methods: Data was retrospectively collected from 282 cases of MIBC that underwent RC from 2011 to 2017 at our institute. Significant independent predictors were identified using Cox regression model and incorporated into a nomogram to predict 1, 2, and 4-year OS. Results: Multivariate analysis showed that Neo-Adjuvant Chemo-Therapy (NACT) (P < .001), LODDS (P < .001), T-stage (Pi = .001), CCI (Charlson Comorbidity Index) (P = .034) and grade (P = .003) were independent predictors of OS. The C-index of nomogram (0.740) was higher than that of the American Joint Committee on Cancer (AJCC) staging system (0.614). The bias-corrected calibration plots showed that the predicted risks were in excellent accordance with the actual risks. The results of NRI, IDI, and DCA exhibited superior predictive capability and higher clinical use of the nomogram. Conclusion: A simple, easy to use nomogram to predict OS in cases of MIBC has been constructed. To best of our knowledge, LODDS has been incorporated for the first time. It has superior predictive ability and higher clinical use than AJCC system. It would help the clinicians for better patient counselling, planning follow-up strategies and designing a clinical trial for newer adjuvant therapy (eg immunotherapy) in post radical cystectomy patients of MIBC. [ABSTRACT FROM AUTHOR]

Objective: To cross-sectionally assess erectile and ejaculatory functions after tetramodal bladder-sparing therapy consisting of transurethral resection, chemoradiotherapy, and consolidative partial cystectomy in patients with muscle invasive bladder cancer. Materials and Methods: Among 72 enrolled male patients who underwent tetramodal bladder-sparing therapy from 2006 to 2019, 42 who visited the outpatient clinic from February to October 2020 received questionnaires. Erectile function, ejaculatory function, and quality of life were assessed using the International Index of Erectile Function short form, the Male Sexual Health Questionnaire Ejaculatory Dysfunction short form, and the Functional Assessment of Cancer Therapy. Results: Among the 42 patients, 9 were excluded because of incomplete responses and 33 were eligible for analyses. The median (range) age at survey and the time from treatment completion to responding to the questionnaires was 70 (50-87) years and 4.2 (0.4-14.0) years, respectively. The median International Index of Erectile Function short form-5 score was 11 (5-25), and 3 (9.1%) and 9 (27.3%) patients had no and mild erectile dysfunction, respectively. The Male Sexual Health Questionnaire Ejaculatory Dysfunction short form results showed that 23 (69.7%) patients responded that they could ejaculate. Patients with higher Male Sexual Health Questionnaire Ejaculatory Dysfunction short form scores had better erectile function and quality of life than those with lower Male Sexual Health Questionnaire Ejaculatory Dysfunction short form scores. Conclusion: Preservation of erectile and ejaculatory functions was demonstrated in muscle invasive bladder cancer patients treated with tetramodal bladder-sparing therapy. In addition to lower urinary tract function, preservation of male sexual function, especially ejaculatory function, in bladder-sparing therapy can be an advantage over radical cystectomy. [ABSTRACT FROM AUTHOR]

The current study aimed to report on the perioperative and long-term oncological outcomes of patients with muscle invasive bladder cancer who underwent radical cystectomy. Between January 2012 and December 2018, 207 patients were diagnosed with muscle invasive bladder cancer at our center, among whom 61 underwent radical cystectomy with a mean follow-up duration of 45.7 months. Postoperative complications were graded based on the Clavien–Dindo classification within 90 days after radical cystectomy. Disease-free survival and overall survival rates were determined according to tumor stage. Risk factors for perioperative complications, recurrence, and survival were assessed. The patients (n = 61) had a mean hospital stay of 20.9 days, with urinary diversion (23%), infection (18%), and blood transfusion (11.4%) being the most common complications following radical cystectomy. All complications were classified below Clavien–Dindo classification grade 3, most of which were controlled by conservative treatment. Re-operation within 90 days was required in 7 patients (11.5%) for enterolysis or cystorrhaphy, with no reported mortality after radical cystectomy. Carefully selected patients who underwent radical cystectomy, especially those with a Charlson Comorbidity Index of 0, 1, and 2 and clinical stage of T2 and T3, demonstrated better oncological outcomes compared to those who underwent trimodal therapy. The current study showed that adequately selected patients who underwent radical cystectomy had better oncological outcome compared to those who underwent trimodal therapy. The risk factors for perioperative complications included diabetes mellitus, male sex, smoking habit, alcohol consumption, and betel nut consumption. [ABSTRACT FROM AUTHOR]

Objective: We aim to describe and highlight the current use of immune checkpoint inhibitors (ICIs) in the muscle invasive bladder cancer (MIBC) treatment landscape, particularly focusing on the perioperative setting. We provide a comprehensive review of key trials of the use of ICI in the perioperative setting, discussing trial outcomes and limitations and reviewing the role of biomarkers. Introduction: ICIs have recently been integrated into the treatment algorithm for metastatic urothelial carcinoma. More than 30 published studies have investigated the role of these agents in the radical treatment of MIBC. Some studies have demonstrated conflicting results, affecting widespread adoption in clinical practice. Methods: We performed a narrative overview of the literature from databases including PubMed, MEDLINE, Embase, European society of Medical Oncology/American Society of Clinical Oncology Annual Proceedings, and clinicaltrials.gov databases up until December 2021. Discussion: We described the results of key trials in the neoadjuvant and adjuvant setting, some of the reasons for conflicting study results, and the implications for clinical practice. Relevant biomarkers in the field are discussed, alongside a brief overview of the immune microenvironment in bladder cancer. Conclusions: Perioperative ICIs have shown promising efficacy with low toxicity in the neoadjuvant setting. The two large trials in the adjuvant setting have been contradictory. The efficacy of perioperative ICIs combined with favorable tolerability and better toxicity profile compared with chemotherapy, with the potential for biomarker-driven patient selection, may lead to a change in future practice. There is, however, a lack of long-term survival and toxicity data for those treated with ICIs, and this needs to be developed further to demonstrate an added survival benefit by using ICIs. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy followed by radical cystectomy is the standard of care for muscle invasive non-metastatic bladder cancer patients. While cisplatin based neoadjuvant chemotherapy has been recommended, systemic therapy in a neoadjuvant setting for cisplatin ineligible patients still needs to be addressed. Various strategies like split dosing cisplatin chemotherapy, carboplatin based chemotherapy and taxanes based chemotherapy have been tried as neoadjuvant therapy for cisplatin ineligible patients. Immunotherapy is a promising tool in this regard with a need for the development of predictive and prognostic biomarkers which can bring out the true potential of these immunotherapeutic agents. [ABSTRACT FROM AUTHOR]

PurposeWe evaluated the survival of patients with muscle invasive bladder cancer undergoing radical cystectomy without neoadjuvant chemotherapy to confirm the utility of existing clinical tools to identify low risk patients who could be treated with radical cystectomy alone and a high risk group most likely to benefit from neoadjuvant chemotherapy.Materials and methodsWe identified patients with muscle invasive bladder cancer who underwent radical cystectomy without neoadjuvant chemotherapy at our institution between 2000 and 2010. Patients were considered high risk based on the clinical presence of hydroureteronephrosis, cT3b-T4a disease, and/or histological evidence of lymphovascular invasion, micropapillary or neuroendocrine features on transurethral resection. We evaluated survival (disease specific, progression-free and overall) and rate of pathological up staging. An independent cohort of patients from another institution was used to confirm our findings.ResultsWe identified 98 high risk and 199 low risk patients eligible for analysis. High risk patients exhibited decreased 5-year overall survival (47.0% vs 64.8%) and decreased disease specific (64.3% vs 83.5%) and progression-free (62.0% vs 84.1%) survival probabilities compared to low risk patients (p

This study sought to assess the role of neoadjuvant chemotherapy in the management of urothelial carcinoma of the bladder with squamous variant histology. Patients were stratified by both receipt of neoadjuvant chemotherapy and by the percentage of squamous variant histology in the transurethral resection specimen. Overall, we found favorable results in patients with < 50% involvement by squamous variant histology who received neoadjuvant chemotherapy. Background: The purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT. Materials and Methods: The records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (< 50% SV vs. ≥ 50% SV). Results: The median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P = .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P < .001). The non-organeconfined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P = .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P = .003). In the subgroup analysis, the lower rate of non-organeconfined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival. Conclusions: The effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has < 50% involvement by the variant histology. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to investigate the oncologic outcomes of patients who were diagnosed with primary (muscle invasive cancer at the time of diagnosis) and secondary (cancer that showed progression from non-muscle invasive bladder cancer) muscle invasive bladder carcinoma (MIBC) before radical cystectomy (RC). Materials and Methods: Patients who underwent RC at our clinic for MIBC between July 2008 and June 2017 were included in the study. They were divided into two groups based on their diagnosis as primary and secondary MIBC. Their clinical, pathological, and oncologic data (upstaging, adjuvant chemotherapy, overall mortality, overall survival, cancer-specific mortality, and cancer-specific survival) were evaluated retrospectively. Results: A total of 80 patients underwent RC due to bladder cancer with a mean age of 64.4±7.8 years (range: 42-83 years) and a mean follow-up time of 32.9±32.1 months (range: 1-113 months). The overall and cancer-specific survivals of the patients were 64.7±6.6 and 74±6.8 months, respectively. Sixty-five and 15 patients were evaluated in the primary and secondary MIBC groups, respectively. Lymph node metastasis was higher in primary MIBC group (p=0.031). Although, there were no statistical differences between the groups, in secondary MIBC group, the overall survival (67.3±7.2 months vs 42.5±8.4 months; p=0.835) and cancerspecific survival (77.6±7.4 months vs 46.6±8.6 months; p=0.546) were lower, while the overall mortality (44.6% vs 53.3%; p=0.372) and cancer-specific mortality (32.3% vs 46.7%; p=0.293) were higher compared to primary MIBC group. Conclusion: The pre- and postoperative pathological T stages were similar between the groups, whereas postoperative lymph node positivity was lower for secondary MIBC patients. The mortality was higher and overall and cancer-specific survivals were lower in secondary MIBC patients; however, these findings were not statistically significant. [ABSTRACT FROM AUTHOR]

Purpose of Review: To identify components representing optimal delivery of follow-up care after radical cystectomy because of bladder cancer and report the current level of evidence. Methods: We conducted a systematic literature search of the following databases: Cochrane, MEDLINE, Embase, CINAHL, Web of Science, Physiotherapy Evidence Database and ClinicalTrials.gov. The search results were managed in Covidence Reference Manager and abstracts were screened by title. Articles relevant to the subject of interest were included and the results are reported narratively. Results: Several studies have evaluated the positive impact of enhanced recovery after surgery (ERAS) on length of stay, albeit not on the further impact on 90-day postoperative complication rate, functional recovery, or mortality. Minimally invasive surgery may result in a slighter shorter length of stay compared to open surgery. Physical training combined with nutritional intervention can improve functional recovery up to one year after surgery. Nutritional supplements can preserve muscle and bone mass, and potentially improve recovery. Patient education in stoma care and prevention of infection can significantly improve self-efficacy and avoid symptoms of infection postoperatively. Moreover, specific devices like applications (apps) can support these efforts. Continued smoking increases the risk of developing postoperative complications while no evidence was found on the impact of continued alcohol drinking. Currently, there is no evidence on psychological well-being, sexual health, or shared decision making interventions with an impact on rehabilitation after radical cystectomy. Conclusion: Data are scarce but indicate that peri- and postoperative multi-professional interventions can reduce prevalence of sarcopenia, and improve functional recovery, physical capacity, nutritional status, and self-efficacy in stoma care (level 1 evidence). Continued smoking increases the risk of complications, but the effects of a smoking and alcohol intervention remain unclear (level 3 evidence). The results of this review provide guidance for future directions in research and further attempts to develop and test an evidence-based program for follow-up care after radical cystectomy. [ABSTRACT FROM AUTHOR]

Purpose: Radical cystectomy (RC) is the primary treatment strategy for patients with muscular invasive bladder cancer (MIBC). However, the prognosis is poor and tumor recurrence is not rare, in particular, urethral recurrence (UR) in male patients who underwent RC combined with urinary diversion. Here, we have developed and validated a model for predicting UR in these patients. Patients and Methods: The development cohort comprised 310 patients who underwent RC combined with urinary diversion at our center between 1 January 2007 and 31 December 2015. Clinicopathologic data of patients were comprehensively recorded. Multivariate Cox proportional hazard regression was used for building a predictive model with regression coefficients and backward stepwise selection applied by utilizing the likelihood ratio test with Akaike's information criterion as the stopping rule. An independent cohort consisting of 131 consecutive patients treated from 1 January 2016 to 31 December 2017 was used for validation. The performance of this predictive model was assessed with respect to discrimination, calibration, and clinical usefulness. Results: The predictors of this model included body mass index, history of transurethral resection of bladder tumor, tumor grade, tumor stage, and concomitant carcinoma in situ. In the validation cohort, the model showed good discrimination with a concordance index of 0.777 (95% CI, 0.618 to 0.937) and calibration. Decision curve analysis also demonstrated the clinical utility of the model. Conclusion: The predictive model facilitated postoperative individualized prediction of UR in male patients with MIBC after RC combined with urinary diversion and it may therefore serve to improve follow-up strategies. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate anxiety, depression and quality of life (QoL) by patients' self-report scales and the predictive factors for their aggravation in muscle invasive bladder cancer (MIBC) patients receiving adjuvant chemotherapy. One hundred and ninety-four MIBC patients who received adjuvant chemotherapy and underwent radical cystectomy were consecutively enrolled. HADS was used to evaluate anxiety and depression, and EORTC QLQ-C30 Scale was used to assess QoL. Post adjuvant chemotherapy, HADS-Anxiety score (P = 0.042), anxiety percentage (P = 0.036), HADS-Depression score (P < 0.001), depression percentage (P = 0.002) and the EORTC QLQ-C30 Functional score (P = 0.002) were elevated compared with baseline. Age (P < 0.001), BMI (P = 0.021) and hypertension (P = 0.001) correlated with aggravation of HADS-Anxiety score, while gender (P < 0.001) correlated with aggravation of HADS-Depression score independently during adjuvant chemotherapy. And smoking, alcohol use, hypertension, diabetes, ECOG performance, pT stage as well as pN stage independently predicted the worsening of EORTC QLQ-C30 Scale subscale scores during adjuvant chemotherapy (all P < 0.05). In conclusion, patients' self-report anxiety and depression were increased while QoL was not deteriorated in MIBC patients during adjuvant chemotherapy, and age, gender, BMI, hypertension, smoking, alcohol use, diabetes, ECOG performance, pT stage as well as pN stage were potential predicting factors for their aggravation. [ABSTRACT FROM AUTHOR]

Bladder cancer is the ninth most common cancer in the world. Twenty to twenty-five percent of all newly diagnosed bladder cancers are muscle invasive in nature, and further, 20-25% of patients who are diagnosed with high-risk non-muscle invasive disease will eventually progress to muscle invasive disease in due course of time irrespective of adjuvant intravesical therapies. Availability of newer imaging modalities improves appropriate identification of patients with muscle invasive disease. Radical cystectomy remains the mainstay of treatment for management of muscle invasive disease. Availability of neoadjuvant chemotherapy has improved overall survival. Risk stratification systems are now in consideration to identify patients who benefit maximally from neoadjuvant chemotherapy. Urinary diversion is a major cause of morbidity in these patients, and several strategies are being employed to reduce morbidity. In this article, we review available literature on various aspects of management of muscle invasive disease. [ABSTRACT FROM AUTHOR]

Growing evidence supports the importance of timely care for muscle‐invasive bladder cancer, with multiple studies demonstrating that delays longer than 3 months are associated with worse outcomes. Causes for treatment delays are multifactorial and may be compounded by increasing regionalization; contemporary efforts to minimize delays must address cross‐team communication, care transitions, patient empowerment, socioeconomic differences, and access disparities. [ABSTRACT FROM AUTHOR]

Despite the rise of neo-adjuvant chemotherapy in the management of muscle invasive bladder cancer (MIBC), locoregional recurrence (LRR) is an early event impacting the oncological outcome of patients treated with radical cystectomy and pelvic lymph-node dissection. Data from surgical series have defined the frequency and preferential sites of this LRR. Risk stratification based on pathological findings was established. Historically, perioperative radiotherapy has been evaluated but the radiation technique used failed to validate the toxicity involved in this strategy. Modern techniques, such as intensity-modulated and image-guided radiotherapy, could lead to reconsider the indication of adjuvant radiotherapy with limited dose to adjacent healthy organs. New prospective trials evaluating the benefit of this approach should be undertaken. [ABSTRACT FROM AUTHOR]

Urothelial carcinoma of bladder being the commonest malignancy of the urinary tract progresses through successive accumulation of genetic alterations and bears high metastatic potential. Despite significant advances in its prognosis and treatment, including surgical techniques, various adjuvant therapies, radical cystectomy and robot-assisted radical cystectomy, tumor recurs with a poor 5 year survival rate thereby necessitating the need to institute an additional form of novel target based therapies to improve the overall outcome. Improved understanding of the molecular pathways critical for both early and late stage disease not only leads to better prognostication but may also enhance therapeutic index. This review article highlights the recent progress in the development of novel anti-cancer targeted therapies that may modulate clinical response of cytotoxic drugs with minimal adverse side effects and provide insight for the potential reversion of the resistance in patients failing therapy. [ABSTRACT FROM AUTHOR]

Radical cystectomy completed with an extended pelvic lymph node dissection represents the most adequate curative treatment for muscle-invasive bladder cancer . After surgery, the tumor should be considered as completely removed only if the pathologist finds negative surgical margins. However, although the presence of positive surgical margins (PSM) intuitively appears as a factor conditioning a poor prognosis, the studies published at data could not definitively confirm this relationship. This fact may be mainly attributed to the lack of statistical independence between the presence of PSM and other pathologic factors such as tumor stage and lymph node status, that are themselves well known predictors of poor prognosis. The incidence of PSM has been estimated to be 3-9%. Although the persistence of tumor at both urethral and ureteral margins has been correlated with an increased risk of local recurrence, only perivesical soft tissue PSM have been associated with a significantly reduced risk of cancer-specific survival. Female gender, locally advanced cancer, presence of vascular invasion and rare/mixed histology have been recognized as consistent risk factors for soft tissue PSM. Although, to date, the predictive role of both number and location of PSM remains totally to be investigated, there is general agreement that patients found with soft tissue PSM at the time of radical cystectomy should be proposed for adjuvant strategies, including radiation and chemotherapy. In this direction, many recent studies suggest to include the status of surgical margins in the pathologic report of any radical cystectomy. [ABSTRACT FROM AUTHOR]

Introduction: Studies evaluating outcomes in bladder cancer sub stratified into T2a and T2b pathologic staging have demonstrated inconsistent results. Survival outcomes in a cohort of pure urothelial carcinoma patient undergoing radical cystectomy were evaluated to determine the prognostic value of T2 sub staging.Methods: Using our prospectively maintained institutional cystectomy database, we identified patients with pure urothelial carcinoma of the bladder, either pT2aN0 or pT2bN0. We excluded any patients with variant histology, patients that underwent neoadjuvant chemotherapy, and patients that had margin positive disease. Demographic and clinicopathologic data were collected, and Cox proportional hazard regression assessed overall survival (OS), cancer specific survival (CSS), and recurrence free survival (RFS).Results: From 2001 to 2019, we identified 1,929 patients that underwent radical cystectomy, 61 patients had pT2a and 65 had pT2b pure urothelial carcinoma that met inclusion criteria. Only age (P = 0.02) and the initial transurethral resection of bladder tumor pathology (P < 0.01) were notably different when comparing the clinical characteristics of patients with pT2a and pT2b. No differences were noted in OS, CSS, or RFS between the 2 groups on Kaplan-Meier analysis. On univariate Cox regression analysis, age, TURBT stage, cystectomy pathology stage, carcinoma in situ, and lymphovascular invasion status, and Bacillus Calmette-Guérin therapy status was not found to be significant factors for OS, CSS, or RFS between patients with pT2aN0 or pT2bN0 tumors.Conclusion: Prior studies have sub stratified pT2a and pT2b, studying survival outcomes with equivocal results. Many of these studies included variant histology or use of chemotherapy in the analysis. Here, we identified a pure urothelial cohort to compare survival outcomes between pT2a and pT2b and found no difference in OS, CSS, and RFS. [ABSTRACT FROM AUTHOR]

Abstract: At the 11th annual meeting of the Society of Urologic Oncology, an expert panel was convened to discuss the practical use of perioperative chemotherapy for muscle-invasive bladder cancer. The discussion was structured as a case-based debate among the panelists. The topics included: neoadjuvant chemotherapy with a focus on T2 disease, pros and cons, survival data, tolerability of cisplatin-based therapy, can we avoid radical cystectomy in complete responders, limitations and alternatives to cisplatin-based therapy, management of ‘suboptimal’ chemotherapy, residual disease after neoadjuvant chemotherapy, adjuvant chemotherapy, and key aspects of radical cystectomy and lymph-node dissection in multimodal therapy. The presentations were derived from published literature. The panelists agreed that patients with muscle-invasive bladder cancer should be managed with a multidisciplinary team, including urologist and medical oncologist. Cisplatin-based neoadjuvant chemotherapy has demonstrated improved survival and should be incorporated into the management of all eligible patients with muscle-invasive bladder cancer. However, in some centers, neoadjuvant chemotherapy is reserved for patients with >T2 disease or high-risk features. There are no data for the administration of non-cisplatin-based neoadjuvant chemotherapy, such as carboplatin-combinations. Cisplatin-ineligible patients should proceed directly to surgical extirpation with adjuvant cisplatin-based chemotherapy considered based on pathologic findings. However, the data for adjuvant chemotherapy is less compelling. As our refinement of the selection process continues, we may be able to better identify subsets of patients who may be spared chemotherapy, but much work remains to be done in this arena. The current standard for muscle-invasive bladder cancer patients is cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy and pelvic lymph-node dissection. [Copyright &y& Elsevier]

To assess treatments and survival of patients with muscle invasive bladder cancer (MIBC) in the Comprehensive Cancer Center Northern Netherlands (CCCN) region. Retrospective cohort analysis. Data of 548 patients with MIBC diagnosed between 1997 and 2002 were collected from the CCCN cancer registry. All had a follow-up of at least 5 years. Logistic regression analysis on treatments as well as survival analysis was performed. The treatments were radical cystectomy in 205/548 (37.5%) patients. TUR plus radiotherapy in 246 (44.9%) and palliation in 97 (17.7%). Multivariate analysis identified TNM stage ( P < 0.0001) and age ( P < 0.0001) as independent variables for cystectomy. Hospital type and year of diagnosis were not significant different between patients treated by cystectomy versus other type of treatment. TNM stage ( P < 0.0001), age ( P = 0.0043), and comorbidity ( P = 0.0028) were independent variables for disease-specific survival (DSS) after cystectomy. In the CCCN region, only 1/3 of patients with MIBC were treated with radical cystectomy. TNM stage and age were identified as main variables for the choice for cystectomy. TNM stage, age, and comorbidity were independent variables for disease-specific survival after cystectomy. [ABSTRACT FROM AUTHOR]

Abstract: Context: New data regarding diagnosis and treatment of muscle-invasive and metastatic bladder cancer (MiM-BC) has emerged and led to an update of the European Association of Urology (EAU) guidelines for MiM-BC. Objective: To review the new EAU guidelines for MiM-BC. Evidence acquisition: A comprehensive workup of the literature obtained from Medline, the Cochrane central register of systematic reviews, and reference lists in publications and review articles was developed and screened by a group of urologists, oncologists, and radiologist appointed by the EAU Guideline Committee. Previous recommendations based on the older literature on this subject were taken into account. Levels of evidence and grade of guideline recommendations were added, modified from the Oxford Centre for Evidence-based Medicine Levels of Evidence. Evidence synthesis: The diagnosis of muscle-invasive bladder cancer (BCa) is made by transurethral resection (TUR) and following histopathologic evaluation. Patients with confirmed muscle-invasive BCa should be staged by computed tomography (CT) scans of the chest, abdomen, and pelvis, if available. Adjuvant chemotherapy is currently only advised within clinical trials. Radical cystectomy (RC) is the treatment of choice for both sexes, and lymph node dissection should be an integral part of cystectomy. An orthotopic bladder substitute should be offered to both male and female patients lacking any contraindications, such as no tumour at the level of urethral dissection. Multimodality bladder-preserving treatment in localised disease is currently regarded only as an alternative in selected, well-informed, and compliant patients for whom cystectomy is not considered for clinical or personal reasons. An appropriate schedule for disease monitoring should be based on (1) natural timing of recurrence, (2) probability of disease recurrence, (3) functional deterioration at particular sites, and (4) consideration of treatment of a recurrence. In metastatic disease, the first-line treatment for patients fit enough to sustain cisplatin is cisplatin-containing combination chemotherapy. Presently, there is no standard second-line chemotherapy. Conclusions: These EAU guidelines are a short, comprehensive overview of the updated guidelines of (MiM-BC) as recently published in the EAU guidelines and also available in the National Guideline Clearinghouse. [Copyright &y& Elsevier]