Resultados perioperatorios y oncológicos a largo plazo de los pacientes con variantes histológicas de cáncer vesical sometidos a cistectomía radical: un análisis de emparejamiento por índices de propensión con carcinoma urotelial puro / The perioperative and long-term outcomes of patients with variant histology bladder cancer undergoing radical cystectomy: A propensity score-matched analysis with pure urothelial carcinoma

Objetivos Evaluar los resultados perioperatorios y a largo plazo de la cistectomía radical en los pacientes con variantes histológicas frente a los pacientes con patrón histológico de carcinoma urotelial puro. Métodos Los pacientes diagnosticados de carcinoma vesical con variantes histológicas fueron emparejados con aquellos diagnosticados de carcinoma urotelial puro en una proporción de 1:3 mediante un análisis de puntuación de propensión. Los 2 grupos se compararon en términos de resultados perioperatorios y morbimortalidad a largo plazo. Resultados En el presente estudio retrospectivo se incluyeron 148 individuos (37 con variantes histológicas de CU y 111 con carcinoma urotelial puro). Un total de 107 (72,3%) individuos presentaron al menos una complicación perioperatoria según la clasificación de Clavien-Dindo. Esta proporción fue similar entre los pacientes con carcinoma urotelial frente a aquellos con variante histológica (p=0,22). En cuanto a las complicaciones a largo plazo, el número de pacientes con hernia incisional clínicamente significativa que requirió cirugía (14 [12,7%] frente a 3 [8,3%]; p=0,68], estenosis uretero-intestinal/uretero-cutánea o cualquier otra complicación relacionada con la derivación urinaria aplicada (15 [13,6%] frente a 7 [19,4%]; p=0,56], o el número de pacientes que presentaron septicemia (17 [15,5%] frente a 10 [27,8%]; p=0,16] u obstrucción del tracto urinario (12 [10,9%] frente a 4 [11,1%]; p>0,99] durante el seguimiento fue similar para el grupo carcinoma urotelial y el de variante histológica. Según el análisis de supervivencia con curvas de Kaplan-Meier y el modelo de regresión de Cox univariante, el riesgo de muerte por cualquier causa era mayor en los pacientes con variante histológica que en los de patrón histológico puro (log-rank test=0,045; hazard ratio: 1,7; intervalo de confianza del 95%: 1,01-2,87; p=0,047). Conclusiones La morbimortalidad perioperatorias son comparables . (AU)

Objectives To assess the perioperative and long-term outcomes after open radical cystectomy in patients with histological variants versus pure urothelial carcinoma. Methods Patients with a variant histology carcinoma of the urinary bladder were matched through a propensity score analysis with those with pure urothelial carcinoma on a 1:3 ratio. The two groups were compared in terms of perioperative and long-term morbidity and mortality. Results Overall, 148 individuals were included in the present retrospective study (37 with variant histology and 111 with pure urothelial carcinoma). A total of 107 (72.3%) individuals presented at least one perioperative complication based on the Clavien-Dindo classification. This proportion was similar between patients with urothelial versus variant histology carcinoma (P=.22). In the long term, the number of patients with clinically significant incisional hernia requiring surgery [14 (12.7%) vs 3 (8.3%), P=.68], uretero-intestinal/uretero-cutaneous strictures or any other complication related to the applied urinary diversion [15 (13.6%) vs 7 (19.4%), P=.56], as well as the number of patients presenting with septicemia [17 (15.5%) vs 10 (27.8%), P=.16] or with urinary tract obstruction [12 (10.9%) vs 4 (11.1%), P>.99] at follow-up did not differ between urothelial versus variant histology carcinoma. The survival analysis with Kaplan-Meier curves and the univariate Cox regression model suggested that the risk of death from any cause was increased in patients with variant compared to pure urothelial histology (log-rank test=.045, hazard ratio: 1.7, 95% confidence interval: 1.01-2.87, P=.047). Conclusions Perioperative morbidity and mortality are comparable in patients with variant histology versus pure urothelial carcinoma. (AU)

Characteristics Contributing to Survival Differences Between Black and White Patients Following Cystectomy.

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.

Effect of Robot-Assisted Radical Cystectomy With Intracorporeal Urinary Diversion vs Open Radical Cystectomy on 90-Day Morbidity and Mortality Among Patients With Bladder Cancer: A Randomized Clinical Trial.

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.

Perioperative outcomes in a nationwide sample of patients undergoing surgical treatment of ovarian endometriomas.

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.

The impact of patient sex on characteristic-adjusted bladder cancer prognosis.

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.

Phase II Study of Gemcitabine and Split-Dose Cisplatin Plus Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Bladder Cancer.

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/m2 once on day 1, and gemcitabine 1,000 mg/m2 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/m2 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.

Outcomes following open radical cystectomy: an 11-year Christchurch experience.

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.

High IL-22RA1 gene expression is associated with poor outcome in muscle invasive bladder cancer.

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.

Expressions of P-Glycoprotein, Multidrug Resistance Protein 1 and Annexin A2 as Predictive Factors for Intravesical Recurrence of Bladder Cancer after the Initial Transurethral Resection and Immediate Single Intravesical Instillation of Adriamycin.

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.

Impact of perioperative blood transfusions on oncologic outcomes after radical cystectomy: A systematic review and meta-analysis of comparative studies.

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.

Disparities in male versus female oncologic outcomes following bladder preservation: A population-based cohort study.

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.

Efficacy of three BCG strains (Connaught, TICE and RIVM) with or without secondary resection (re-TUR) for intermediate/high-risk non-muscle-invasive bladder cancers: results from a retrospective single-institution cohort analysis.

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 (HRRFS: 0.63; 95% CI 0.46-0.86; HRPFS: 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 (HRTICE: 0.58, 95% CI 0.39-0.86; HRRIVM: 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.

Patterns and timing of perioperative blood transfusion and association with outcomes after radical cystectomy.

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.

The role of neoadjuvant chemotherapy, lymph node dissection, and treatment delay in patients with muscle-invasive bladder cancer undergoing partial cystectomy.

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.

Neoadjuvant Chemotherapy-Guided Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer: Results of a Pilot Phase II Study.

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.

Morbidity and mortality after robot-assisted radical cystectomy with intracorporeal urinary diversion in octogenarians: results from the European Association of Urology Robotic Urology Section Scientific Working Group.

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.

A Nationwide Population-based Study From Taiwan Assessing the Influence of Preventable Hospitalization Rate on Mortality After Oncologic Surgery.

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.

Survival after radical cystectomy: Progressive versus De novo muscle invasive bladder cancer.

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.