Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment.

PURPOSE: The purpose of this American Urological Association (AUA)/Society of Urologic Oncology (SUO) guideline amendment is to provide a useful reference on the effective evidence-based treatment strategies for non-muscle invasive bladder cancer (NMIBC). MATERIALS AND METHODS: In 2023, the NMIBC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the previous 2020 amendment. The updated search gathered literature from July 2019 to May 2023. This review identified 1918 abstracts, of which 75 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) in support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: Updates were made to statements on variant histologies, urine markers after diagnosis of bladder cancer, intravesical therapy, BCG maintenance, enhanced cystoscopy, and future directions. Further revisions were made to the methodology and reference sections as appropriate. CONCLUSIONS: This guideline seeks to improve clinicians' ability to evaluate and treat patients with NMIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

Chronic kidney disease and radical cystectomy for bladder cancer: perioperative and oncologic outcomes in 1,214 patients.

INTRODUCTION AND OBJECTIVE: To assess the impact of chronic kidney disease (CKD) on outcomes after radical cystectomy (RC) in patients with bladder cancer treated within a high-volume tertiary referral center. METHODS: We identified 1,214 patients who underwent RC with intent to cure from 2009 to 2019. The Modification of Diet in Renal Disease (MDRD) GFR (ml/min/1.73 m²) was calculated and patients were categorized by baseline GFR: Group A = GFR > 60, Group B = GFR > 30-59 and Group C = GFR < 30. Pre-, intra- and postoperative characteristics, oncological outcomes, and 90-day perioperative outcomes were compared. Multivariable logistic regression was used to control for confounding variables. RESULTS: We identified 722 (59.5%) patients in Group A, 448 (36.9%) in Group B, and 44 (3.6%) in Group C. Patients with worse CKD were older and had significantly worse overall comorbidity (all P < 0.001). Neoadjuvant chemotherapy was used in 352 patients (29%), including 182 (25.2%) in Group A, 153 in Group B (35.3%), and 12 in Group C (27.3%). On univariate analysis, worse CKD was associated with higher pathologic stage, lymph node metastases and positive soft tissue margins (all P < 0.0001). The rates of blood transfusion, 90-day complications and readmissions were higher in patients with worse CKD (P < 0.0001, P = 0.02, P = 0.04, respectively). Patients with worse CKD had worse overall survival (77% vs. 73% vs. 55%, P < 0.0001). On multivariable analysis, worse CKD was independently associated with adverse pathology (≥pT3 or node positive) (OR = 6.96, 95%CI 3.20-15.12), 90-day readmissions (OR 2.09, 95%CI 1.11-3.94) and perioperative transfusion (OR 2.08, 95%CI 1.05-4.11). Receipt of neoadjuvant chemotherapy was significantly associated with a decreased risk of adverse pathology (OR 0.51, 95%CI 0.36-0.74) and increased risk of transfusion (OR 2.24, 95%CI 1.70-2.96), but not with mortality, complications, readmissions or length or stay. CONCLUSION: CKD is prevalent in patients undergoing radical cystectomy. We found CKD to be independently associated with a higher likelihood of adverse pathology, 90-day readmissions, and transfusion.

Management Trends and Outcomes of Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder: Evolution of the University of Southern California Experience over 3,347 Cases.

PURPOSE: There are conflicting reports on outcome trends following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: Evolution of modern bladder cancer management and its impact on outcomes was analyzed using a longitudinal cohort of 3,347 patients who underwent RC at an academic center between 1971 and 2018. Outcomes included recurrence-free survival (RFS) and overall survival (OS). Associations were assessed using univariable and multivariable models. RESULTS: In all, 70.9% of cases underwent open RC in the last decade, although trend for robot-assisted RC rose since 2009. While lymphadenectomy template remained consistent, nodal submission changed to anatomical packets in 2002 with increase in yield (p <0.001). Neoadjuvant chemotherapy (NAC) use increased with time with concomitant decrease in adjuvant chemotherapy; this was notable in the last decade (p <0.001) and coincided with improved pT0N0M0 rate (p=0.013). Median 5-year RFS and OS probabilities were 65% and 55%, respectively. Advanced stage, NAC, delay to RC, lymphovascular invasion and positive margins were associated with worse RFS (all, multivariable p <0.001). RFS remained stable over time (p=0.73) but OS improved (5-year probability, 1990-1999 51%, 2010-2018 62%; p=0.019). Among patients with extravesical and/or node-positive disease, those who received NAC had worse outcomes than those who directly underwent RC (p ≤0.001). CONCLUSIONS: Despite perioperative and surgical advances, and improved pT0N0M0 rates, there has been no overall change in RFS trend following RC, although OS rates have improved. While patients who are downstaged with NAC derive great benefit, our real-world experience highlights the importance of preemptively identifying NAC nonresponders who may have worse post-RC outcomes.

An Assessment Tool to Provide Targeted Feedback to Robotic Surgical Trainees: Development and Validation of the End-To-End Assessment of Suturing Expertise (EASE).

Purpose: To create a suturing skills assessment tool that comprehensively defines criteria around relevant sub-skills of suturing and to confirm its validity. Materials and Methods: 5 expert surgeons and an educational psychologist participated in a cognitive task analysis (CTA) to deconstruct robotic suturing into an exhaustive list of technical skill domains and sub-skill descriptions. Using the Delphi methodology, each CTA element was systematically reviewed by a multi-institutional panel of 16 surgical educators and implemented in the final product when content validity index (CVI) reached ≥0.80. In the subsequent validation phase, 3 blinded reviewers independently scored 8 training videos and 39 vesicourethral anastomoses (VUA) using EASE; 10 VUA were also scored using Robotic Anastomosis Competency Evaluation (RACE), a previously validated, but simplified suturing assessment tool. Inter-rater reliability was measured with intra-class correlation (ICC) for normally distributed values and prevalence-adjusted bias-adjusted Kappa (PABAK) for skewed distributions. Expert (≥100 prior robotic cases) and trainee (<100 cases) EASE scores from the non-training cases were compared using a generalized linear mixed model. Results: After two rounds of Delphi process, panelists agreed on 7 domains, 18 sub-skills, and 57 detailed sub-skill descriptions with CVI ≥ 0.80. Inter-rater reliability was moderately high (ICC median: 0.69, range: 0.51-0.97; PABAK: 0.77, 0.62-0.97). Multiple EASE sub-skill scores were able to distinguish surgeon experience. The Spearman's rho correlation between overall EASE and RACE scores was 0.635 (p=0.003). Conclusions: Through a rigorous CTA and Delphi process, we have developed EASE, whose suturing sub-skills can distinguish surgeon experience while maintaining rater reliability.

Antiadenovirus Antibodies Predict Response Durability to Nadofaragene Firadenovec Therapy in BCG-unresponsive Non-muscle-invasive Bladder Cancer: Secondary Analysis of a Phase 3 Clinical Trial.

A recent phase 3 trial of intravesical nadofaragene firadenovec reported a promising complete response rate for patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer. This study examined the ability of antiadenovirus antibody levels to predict the durability of therapeutic response to nadofaragene firadenovec. A standardized and validated quantitative assay was used to prospectively assess baseline and post-treatment serum antibody levels among 91 patients from the phase 3 trial, of whom 47 (52%) were high-grade recurrence free at 12 mo (responders). While baseline titers did not predict treatment response, 3-mo titer >800 was associated with a higher likelihood of durable response (p = 0.026). Peak post-treatment titers >800 were noted in 42 (89%) responders versus 26 (59%) nonresponders (p = 0.001; assay sensitivity, 89%; negative predictive value, 78%). Moreover, 22 (47%) responders compared with eight (18%) nonresponders had a combination of peak post-treatment titers >800 and peak antibody fold change >8 (p = 0.004; assay specificity, 82%; positive predictive value, 73%). A majority of responders continued to have post-treatment antibody titers >800 after the first 6 mo of therapy. In conclusion, serum antiadenovirus antibody quantification may serve as a novel predictive marker for nadofaragene firadenovec response durability. Future studies will focus on large-scale validation and clinical utility of the assay. PATIENT SUMMARY: This study reports on a planned secondary analysis of a phase 3 multicenter clinical trial that established the benefit of nadofaragene firadenovec, a novel intravesical gene therapeutic, for the treatment of patients with bacillus Calmette-Guérin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer. Prospective assessment of serum anti-human adenovirus type-5 antibody levels of patients in this trial indicated that a combination of post-treatment titers and fold change from baseline can predict treatment efficacy. While this merits additional validation, our findings suggest that serum antiadenovirus antibody levels can serve as an important predictive marker for the durability of therapeutic response to nadofaragene firadenovec.

Patient Reported Sexual Function Outcomes in Male Patients Following Open Radical Cystoprostatectomy and Urinary Diversion.

OBJECTIVE: To report sexual health outcomes in male patients undergoing open radical cystoprostatectomy using a validated questionnaire. MATERIALS AND METHODS: Beginning in 2017, male patients were asked to complete a validated questionnaire during scheduled post-cystectomy clinic visits that assessed sexual function using the 5 item International Index of Erectile Function (IIEF-5) and supplemental questions which evaluated libido, orgasm, partner interest, and adequacy of pre-operative counselling. Baseline data and functional outcomes were compared and multivariable analysis performed. RESULTS: A total of 134 patients who met inclusion criteria completed the questionnaire. Pre-operative IIEF-5 was available in 78 patients with a median score of 16 (IQR:5-23). In those patients, median age at cystectomy was 68.9 years (IQR:60.2-72.4) and median duration of follow-up was 17.3 months (IQR:6.3-28.7). Median IIEF-5 score at time of survey completion was 1 (IQR:1-11). Increasing age, shorter follow-up duration, insufficient counselling, and absence of partner interest were predictive of lower scores. Younger age, pre-operative erectile function, and neurovascular preservation were predictive of a higher IIEF-5 score on univariate and multivariate analysis. Median libido score was 2 "low" (IQR:1-3) and ability to orgasm was reported by 34 (43.6%) patients. Neurovascular preservation (OR:3.03 95% CI:1.10-8.26, P = .03) and sufficient preoperative counselling (OR:3.078 95% CI:1.17-8.098, P = .02) were associated with preserved ability to orgasm. Libido was influenced by partner interest (OR 11.7, 95% CI:3.793-6.14, P <.0001). CONCLUSION: Sexual dysfunction after radical cystoprostatectomy is prevalent with many contributing factors. As such, establishing appropriate expectations and goals during preoperative counseling, performing neurovascular preservation when appropriate, and readily identifying and treating dysfunction in follow-up may improve sexual recovery.

Perioperative outcomes of goal-directed versus conventional fluid therapy in radical cystectomy with enhanced recovery protocol.

PURPOSE: The aim of this study is to evaluate the intra/perioperative fluid management and early postoperative outcomes of patients who underwent radical cystectomy with Enhanced Recovery After Surgery protocol, using goal-directed fluid therapy compared to conventional fluid therapy. METHODS: This cohort study included patients who underwent open RC for urothelial bladder carcinoma with intent to cure and Enhanced Recovery After Surgery protocol between May 2012 and August 2019. Patients who had palliative or salvage cystectomy and/or adjunct procedures, as well as those with missing detailed perioperative data were excluded. Data were compared between patients who received goal-directed fluid therapy using stroke volume variation by FloTrac™/Vigileo system (n = 119) and conventional fluid therapy based on the anesthesiologist discretion (n = 192). Primary outcome variable was 90-day complications and secondary outcome measures included in-hospital GFR trend, length of stay, and 90-day readmission. RESULTS: The goal-directed fluid therapy group received less total and net intra/perioperative fluid, yet early postoperative glomerular filtration rate trends were similar between both groups (p = 0.7). Estimated blood loss, blood transfusion, index hospital stay, 90-day complication and readmission rates were also comparable between the two groups. Multivariable logistic regression showed no significant association between perioperative fluid management method and 90-day complication rate (OR 1.4, 95% CI 0.8-2.4, p = 0.2). CONCLUSION: Stroke volume variation guided goal-directed fluid therapy is safe in radical cystectomy without compromising the renal function. It is associated with less intra- and perioperative fluid infusion; however, no association with hospital stay, 90-day complication or readmission rates were noted.

Enhanced recovery after cystectomy in patients with preoperative narcotic use.

INTRODUCTION: The aim of this study was to evaluate the outcomes of radical cystectomy with an enhanced recovery after surgery (ERAS) protocol in patients with a history of chronic preoperative narcotic use compared to narcotic-naive patients. METHODS: We identified 553 patients who underwent open radical cystectomy with ERAS. Preoperative narcotic use was identified in 34 patients who were then matched to 68 narcotic-naive patients. Postoperative outcomes, opioid use, and visual analog scale (VAS) pain scores were analyzed and compared. All routes of opioid use were recorded and converted to a morphine equivalent dose (MED). RESULTS: Patients with preoperative narcotic use reported higher median VAS pain scores per day (postoperative day [POD1]: 5.2 vs. 3.9, p=0.003; POD2: 5.1 vs. 3.6, p<0.001; POD3: 4.6 vs. 3.8, p=0.004) and used significantly more opioids (median MED) per day (POD1: 13.2 vs. 10.0, p=0.02; POD2: 11.3 vs. 6.4, p=0.003; POD3: 10.2 vs. 5.0, p=0.005) following surgery. Preoperative narcotic users were noted to have a significantly higher incidence of 90-day re-admissions (41.2% vs. 20.6%, p=0.03). There was no difference in median hospital stay (4 vs. 4 days, p=0.6), 30-or 90-day complications (64.7% vs. 60.3%, p=0.8 and 82.4% vs. 75.0%, p=0.4, respectively) or gastrointestinal complications (29.4% vs. 26.5%, p=0.8), including postoperative ileus (11.8% vs. 20.6%, p=0.2). CONCLUSIONS: Patients with preoperative narcotic exposure report higher pain scores and require more opioid use following radical cystectomy with ERAS and are more likely to be re-admitted within 90 days. However, there was no observed difference in hospital stay or complications.

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer. METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849. FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths. INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state. FUNDING: FKD Therapies Oy.

Feasibility and Outcomes of Orthotopic Ileal Neobladder Reconstruction Following Pelvic Irradiation.

OBJECTIVES: To evaluate the complications and oncologic outcomes of orthotopic ileal neobladder reconstruction (ONB) following pelvic radiotherapy (RT) compared to patients with no prior pelvic RT. METHODS: Our institutional database was queried for all patients with pT0-4bN0-3M0 urothelial carcinoma of the bladder who underwent radical cystectomy with curative intent and ONB between 1990 and 2018. We then queried this cohort for patients who had prior pelvic RT (>3900 cGy) and compared baseline characteristics, perioperative complications, and recurrence free survival between patients with and without prior pelvic RT. RESULTS: One thousand eight hundred and forty-six patients matched our inclusion criteria; 34 had prior pelvic RT with a median dose of 6280 cGy. Prior RT targeted the bladder, prostate, and cervix in 27, 6, and 1 patient, respectively. Median time from RT to cystectomy was 15.5 months. Patients with prior RT had a longer time from diagnosis to cystectomy, more frequently had ≥5 TURBT and neoadjuvant chemo, and less frequently had multifocal disease. Perioperative complications including operative time, estimated blood loss, days hospitalized, as well as 30- and 90-day complication rates, were not statistically different. There was no statistical difference in recurrence free survival between the 2 groups (P = .48). CONCLUSION: ONB in highly selected patients with prior pelvic RT is feasible with statistically similar perioperative complication rates compared to ONB without prior RT.

Heterotopic Bone Formation in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma is associated with calcium deposition in a significant percentage of patients. However, frank ossification within a tumor is extremely rare. We report a case of a 41-year-old male with a slow-growing left renal mass who underwent minimally invasive nephron-sparing surgery. Final pathology revealed clear cell renal cell carcinoma with focal areas of heterotopic bone formation. While prognostic implications of this variant are unclear, patients with renal cell carcinoma with osseous metaplasia can present with slow growth kinetics and early-stage disease.

Pelvic hemangiopericytoma: A case report and review of the literature.

Extrauterine pelvic hemangiopericytomas are rare tumors with malignant potential. Herein, we report a case of a 55-year-old male who presented with hydronephrosis and obstructive urinary symptoms. Cystoscopy, imaging and biopsy were unable to provide a definitive preoperative diagnosis. He underwent pelvic mass resection, and final pathology revealed malignant hemangiopericytoma. The patient is being closely monitored with serial imaging, and remains disease-free at 23 months of post-operative follow-up without adjuvant therapy. Our experience and evidence from the existing literature suggests that given the rarity of these tumors, adherence to standard oncologic principles is necessary to ensure adequate resection and appropriate follow-up.

Perioperative Outcome of Suprarenal Resection of Vena Cava Without Reconstruction in Urologic Malignancies: A Case Series and Review of the Literature.

OBJECTIVE: To describe the feasibility and perioperative outcome of suprarenal resection of inferior vena cava (IVC) in urologic neoplasms without reconstruction. METHODS: We retrospectively reviewed the patients who underwent suprarenal resection of IVC without reconstruction for urologic neoplasms in our institution between September 2010 and October 2019. Patients' demographic, clinical, radiologic, and 90-day perioperative complications were recorded. RESULTS: Twenty-eight (79% male) patients with a median age of 59 (25-75) years were included in the study. Twenty-five (89%) of patients had renal cell carcinoma, 1 had renal leiomyosarcoma, and 2 had metastatic testicular teratoma. Twenty-two patients had Mayo level 3 thrombus, 3 had level 2, and 3 had level 4. The mean radiologic thrombus length was 12.6 cm. Eleven patients had radiologic bland thrombosis in the infrarenal IVC. Twenty-seven patients underwent open, and 1 robotic surgery. The median operating time was 411 (range 240-808) minutes, median blood loss was 3750 cc, and all but 1 patient received perioperative transfusion (median 11 units of packed red blood cells). Median hospital stay was 5 (3-50) days. Ninety-day complication rate was 35% (Clavien-Dindo grade I/II and III/IV were 21% and 14%, respectively). Four patients (14%) developed transient nondisabling leg edema. The 90-day mortality rate was 7%. CONCLUSION: Suprarenal inferior vena cava resection without reconstruction is feasible, yet high-risk operation that should be performed in experienced centers in selected patients with urologic malignancies.

Urinary tract infections following radical cystectomy with enhanced recovery protocol: A prospective study.

OBJECTIVES: Urinary tract infection (UTI) following radical cystectomy (RC) is a common complication associated with significant morbidity and risk of readmission. Recent literature has assessed the effect of perioperative antibiotic regimens on the rate of postoperative infections but not yet yielded with significant changes in UTI rates. Our study focused on the effect of postoperative suppressive regimens on the rate of UTI following radical cystectomy with Enhanced Recovery After Surgery (ERAS) protocol. METHODS: We retrospectively reviewed 427 patients who underwent RC with ERAS protocol between May 2012 and January 2017 at our institution. The ERAS protocol infection prevention measures included 24-hr perioperative antibiotic followed by suppressive antibiotic until removal of catheter/stents. A patient was found to have a UTI if they had a positive urine culture and documented symptoms, positive urine culture with treatment per practitioner discretion, or negative or unavailable urine culture but the clinical presumption of UTI that got treatment. Urosepsis was defined if any of UTI episodes were associated with positive blood culture. Patients' characteristics, UTI events, and urine culture sensitivities were reviewed for analysis. RESULTS: The incidence of UTI and urosepsis was 36.1% and 7.13% within 90-days following RC, respectively. The median time to the first UTI was 13 days (IQR 8-35). Candida (25.57%) and Escherichia coli (22.16%) were the most commonly identified pathogens. UTI and urosepsis were significantly lower in patients who received suppressive fluoroquinolones compared to other antibiotic regimens (32.72% vs. 45.24%, P = 0.04 for UTI and 5.25% vs. 11.90%, P = 0.04 for urosepsis). In multivariable analysis, orthotopic neobladder and perioperative transfusion were significantly associated with increased UTI rate (OR = 2.3 and 1.71, p < 0.05, respectively). CONCLUSIONS: UTI is common following RC and urinary diversion with ERAS protocol. The most common isolated pathogens are candida and Escherichia coli. Orthotopic neobladder and perioperative transfusion are independent risk factors for postoperative UTI. The use of suppressive fluoroquinolones is associated with a significant decrease in UTI rate.

National Practice Patterns and Overall Survival After Adjuvant Radiotherapy Following Radical Cystectomy for Urothelial Bladder Cancer in the USA, 2004-2013.

BACKGROUND: Adjuvant radiation therapy (ART) after radical cystectomy (RC) for urothelial bladder cancer (UBC) may play a role in the management of muscle-invasive BC, particularly in patients with locally advanced disease and adverse pathologic features (pT3/4 or positive surgical margins [PSMs]). Evidence regarding the effect of ART on overall survival (OS) is lacking. OBJECTIVE: To evaluate national practice patterns for the use of ART and assess its impact on OS for patients with adverse pathologic features (APF) after RC. DESIGN, SETTING, AND PARTICIPANTS: Using the National Cancer Data Base, we analyzed all UBC cases with APF after RC from 2004 to 2013. Patients were divided into ART and no-ART groups. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with oncological outcomes were analyzed using multivariable Cox regression and log-rank analyses. RESULTS AND LIMITATIONS: Use of ART decreased during the study period from 3.1% in 2004 to 1.7% in 2013 (p=0.03). ART was administered in 1.4%, 4.0% and 5.2% of patients with pT3 UBC, pT4 UBC, and PSMs (any pT stage), respectively. The rate of ART was significantly higher among younger ages, female sex, low-volume hospitals, nonacademic community care centers, higher stages, PSMs, perioperative chemotherapy, and lymph node-positive disease. Predictors of ART receipt were PSMs (odds ratio [OR] 3.4; p<0.0001), pT4 (OR 2.6; p=0.02), community based centers (OR 2.1; p<0.0001), and female sex (OR 1.8; p<0.0001). Risk factors for worse OS included age, higher tumor stage and comorbidities, PSMs, positive nodes, and suboptimal lymph node dissection (<10 nodes removed; all p<0.001). ART was not independently associated with better OS in the full cohort (p=0.54). However, subgroup analyses suggested an OS benefit for patients with PSMs (hazard ratio 0.73; p=0.047). Limitations include the retrospective design and limited details regarding cancer-specific survival. CONCLUSIONS: Use of ART for APF following RC is not common in the USA and the rate of ART has been decreasing over time. ART may have an OS benefit after RC for patients with PSMs. PATIENT SUMMARY: In this report we looked at the outcomes for patients with locally advanced bladder cancer receiving adjuvant radiation therapy following cystectomy in a large US population. We found that adding radiation therapy after removing the bladder cancer may have some survival benefits for patients with positive surgical margins.

Surgical approach as a determinant factor of clinical outcome following radical cystectomy: Does Enhanced Recovery After Surgery (ERAS) level the playing field?

PURPOSE: To determine whether surgical approach is a determinant of clinical outcomes following radical cystectomy (RC) and urinary diversion when using an Enhanced Recovery After Surgery (ERAS) protocol. MATERIALS AND METHODS: We studied all patients undergoing both open radical cystectomy (ORC) and robotic-assisted radical cystectomy (RARC) and urinary diversion with ERAS for bladder urothelial carcinoma from May 2012 to December 2016. Surgical and clinical outcomes within 90 days after surgery were compared between ORC and RARC, including readmission and major complication rates (Clavien-Dindo grade ≥III). Multivariable logistic regression modeling was used to determine factors that predict readmission and major complications. RESULTS: A total of 345 and 143 patients underwent ORC and RARC, respectively. The ORC group had a greater proportion of continent urinary diversion (71.9 vs. 40.6%, P< 0.001), shorter operative time (5.4 vs. 7.3 hours, P< 0.001), higher estimated blood loss (500 vs. 200 ml, P< 0.001), and higher intraoperative and postoperative transfusion rates (20.9 vs. 9.1%, P= 0.002 and 20 vs. 11.9%, P= 0.04, respectively). Median length of stay was 4 days for ORC (interquartile range 4-6 days) and 6 days for RARC (interquartile range 4-7 days; P< 0.001). There was no significant difference between ORC and RARC groups in major complication rates (20 vs. 23.8%, P= 0.51) or readmission rates (32.2 vs. 36.4%, P= 0.4) within 90 days after surgery. Multivariable logistic regression analysis showed that surgical approach was not an independent factor predictive of readmission (P= 0.33) or major complications (P= 0.76). CONCLUSIONS: Surgical approach is not a determinant of readmission or major complications following RC in the context of an ERAS protocol.

Extended hospital stay after radical cystectomy with enhanced recovery protocol.

INTRODUCTION: To evaluate the reasons leading to an extended hospital stay (EHS) in patients undergoing radical cystectomy (RC) with postoperative enhanced recovery after surgery (ERAS) protocol. MATERIALS AND METHODS: A total of 509 patients underwent RC and urinary diversion with ERAS between May 2012 and March 2017. The protocol includes no bowel preparation, early feeding, predominantly non-narcotic pain control and µ opioid antagonists. Non-consenting/lost to follow up patients, and those with non-urothelial carcinoma were excluded. We defined EHS as ≥ 5 postoperative days and compared the cohort to those with a LOS of ≤ 4 days. Demographics including modifiable and non-modifiable factors as well as in-house complications as possible contributing factors to EHS was reviewed. RESULTS: There were 279/509 (54.8%) patients had an EHS. Median age was 73 years, 82.4% were male, and 36.6% had a Charlson comorbidity index (CCI) of > 2. Univariate analysis demonstrated that age > 65 years, CCI > 2, increased operative time, anemia requiring transfusion and non-orthotopic diversion were associated with EHS. On multivariate analysis, advanced age, operative time, postop transfusion, CCI > 2 as well as surgeon specific preferences was associated with EHS. Within EHS patients, 86% stayed due to an in-house complication; ileus (34.3%), anemia requiring transfusion (9.8%), UTIs (9.4%) and atrial fibrillation (8.5%). CONCLUSIONS: Advanced age, operative time, postop transfusion, CCI > 2 and surgeon-specific preferences are associated with an EHS following RC with ERAS. The common causes of EHS are in-house complications, mainly ileus.