Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO Guideline (2017; Amended 2020, 2024).

PURPOSE: Although representing approximately 25% of patients diagnosed with bladder cancer, muscle-invasive bladder cancer (MIBC) carries a significant risk of death that has not significantly changed in decades. Increasingly, clinicians and patients recognize the importance of multidisciplinary collaborative efforts that take into account survival and quality of life concerns. This guideline provides a risk-stratified, clinical framework for the management of muscle-invasive urothelial bladder cancer. METHODOLOGY/METHODS: In 2024, the MIBC 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 May 2020 to November 2023. This review identified 3739 abstracts, of which 46 met inclusion criteria.When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for 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 regarding neoadjuvant/adjuvant chemotherapy, radical cystectomy, pelvic lymphadenectomy, multi-modal bladder preserving therapy, 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 MIBC based on currently available evidence. Future studies will be essential to further support or refine these statements to improve patient care.

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.

Prophylactic Use of Biologic Mesh in Ileal Conduit (PUBMIC): A Randomized Clinical Trial.

PURPOSE: We assessed the effect of prophylactic biologic mesh on parastomal hernia (PSH) development in patients undergoing cystectomy and ileal conduit (IC). MATERIALS AND METHODS: This phase 3, randomized, controlled trial (NCT02439060) included 146 patients who underwent cystectomy and IC at the University of Southern California between 2015 and 2021. Follow-ups were physical exam and CT every 4 to 6 months up to 2 years. Patients were randomized 1:1 to receive FlexHD prophylactic biological mesh using sublay intraperitoneal technique vs standard IC. The primary end point was time to radiological PSH, and secondary outcomes included clinical PSH with/without surgical intervention and mesh-related complications. RESULTS: The 2 arms were similar in terms of baseline clinical features. All surgeries and mesh placements were performed without any intraoperative complications. Median operative time was 31 minutes longer in patients who received mesh, yet with no statistically significant difference (363 vs 332 minutes, P = .16). With a median follow-up of 24 months, radiological and clinical PSHs were detected in 37 (18 mesh recipients vs 19 controls) and 16 (8 subjects in both arms) patients, with a median time to radiological and clinical PSH of 8.3 and 15.5 months, respectively. No definite mesh-related adverse events were reported. Five patients (3 in the mesh and 2 in the control arm) required surgical PSH repair. Radiological PSH-free survival rates in the mesh and control groups were 74% vs 75% at 1 year and 69% vs 62% at 2 years. CONCLUSIONS: Implementation of biologic mesh at the time of IC construction is safe without significant protective effects within 2 years following surgery.

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.

Radical cystectomy versus trimodality therapy for muscle-invasive bladder cancer: a multi-institutional propensity score matched and weighted analysis.

BACKGROUND: Previous randomised controlled trials comparing bladder preservation with radical cystectomy for muscle-invasive bladder cancer closed due to insufficient accrual. Given that no further trials are foreseen, we aimed to use propensity scores to compare trimodality therapy (maximal transurethral resection of bladder tumour followed by concurrent chemoradiation) with radical cystectomy. METHODS: This retrospective analysis included 722 patients with clinical stage T2-T4N0M0 muscle-invasive urothelial carcinoma of the bladder (440 underwent radical cystectomy, 282 received trimodality therapy) who would have been eligible for both approaches, treated at three university centres in the USA and Canada between Jan 1, 2005, and Dec 31, 2017. All patients had solitary tumours less than 7 cm, no or unilateral hydronephrosis, and no extensive or multifocal carcinoma in situ. The 440 cases of radical cystectomy represent 29% of all radical cystectomies performed during the study period at the contributing institutions. The primary endpoint was metastasis-free survival. Secondary endpoints included overall survival, cancer-specific survival, and disease-free survival. Differences in survival outcomes by treatment were analysed using propensity scores incorporated in propensity score matching (PSM) using logistic regression and 3:1 matching with replacement and inverse probability treatment weighting (IPTW). FINDINGS: In the PSM analysis, the 3:1 matched cohort comprised 1119 patients (837 radical cystectomy, 282 trimodality therapy). After matching, age (71·4 years [IQR 66·0-77·1] for radical cystectomy vs 71·6 years [64·0-78·9] for trimodality therapy), sex (213 [25%] vs 68 [24%] female; 624 [75%] vs 214 [76%] male), cT2 stage (755 [90%] vs 255 [90%]), presence of hydronephrosis (97 [12%] vs 27 [10%]), and receipt of neoadjuvant or adjuvant chemotherapy (492 [59%] vs 159 [56%]) were similar between groups. Median follow-up was 4·38 years (IQR 1·6-6·7) versus 4·88 years (2·8-7·7), respectively. 5-year metastasis-free survival was 74% (95% CI 70-78) for radical cystectomy and 75% (70-80) for trimodality therapy with IPTW and 74% (70-77) and 74% (68-79) with PSM. There was no difference in metastasis-free survival either with IPTW (subdistribution hazard ratio [SHR] 0·89 [95% CI 0·67-1·20]; p=0·40) or PSM (SHR 0·93 [0·71-1·24]; p=0·64). 5-year cancer-specific survival for radical cystectomy versus trimodality therapy was 81% (95% CI 77-85) versus 84% (79-89) with IPTW and 83% (80-86) versus 85% (80-89) with PSM. 5-year disease-free survival was 73% (95% CI 69-77) versus 74% (69-79) with IPTW and 76% (72-80) versus 76% (71-81) with PSM. There were no differences in cancer-specific survival (IPTW: SHR 0·72 [95% CI 0·50-1·04]; p=0·071; PSM: SHR 0·73 [0·52-1·02]; p=0·057) and disease-free survival (IPTW: SHR 0·87 [0·65-1·16]; p=0·35; PSM: SHR 0·88 [0·67-1·16]; p=0·37) between radical cystectomy and trimodality therapy. Overall survival favoured trimodality therapy (IPTW: 66% [95% CI 61-71] vs 73% [68-78]; hazard ratio [HR] 0·70 [95% CI 0·53-0·92]; p=0·010; PSM: 72% [69-75] vs 77% [72-81]; HR 0·75 [0·58-0·97]; p=0·0078). Outcomes for radical cystectomy and trimodality therapy were not statistically different among centres for cancer-specific survival and metastasis-free survival (p=0·22-0·90). Salvage cystectomy was done in 38 (13%) trimodality therapy patients. Pathological stage in the 440 radical cystectomy patients was pT2 in 124 (28%), pT3-4 in 194 (44%), and 114 (26%) node positive. The median number of nodes removed was 39, the soft tissue positive margin rate was 1% (n=5), and the perioperative mortality rate was 2·5% (n=11). INTERPRETATION: This multi-institutional study provides the best evidence to date showing similar oncological outcomes between radical cystectomy and trimodality therapy for select patients with muscle-invasive bladder cancer. These results support that trimodality therapy, in the setting of multidisciplinary shared decision making, should be offered to all suitable candidates with muscle-invasive bladder cancer and not only to patients with significant comorbidities for whom surgery is not an option. FUNDING: Sinai Health Foundation, Princess Margaret Cancer Foundation, Massachusetts General Hospital.

Perioperative mortality for radical cystectomy in the modern Era: experience from a tertiary referral center.

PURPOSE: To evaluate the perioperative mortality and contributing variables among patients who underwent radical cystectomy (RC) for bladder cancer in recent decades, with comparison between modern (after 2010) and premodern (before 2010) eras. MATERIALS AND METHODS: Using our institutional review board-approved database, we reviewed the records of patients who underwent RC for primary urothelial bladder carcinoma with curative intent from January 2003 to December 2019. The primary and secondary outcomes were 90- and 30-day mortality. Univariate and multivariable logistic regression models were applied to assess the impact of perioperative variables on 90-day mortality. RESULTS: A total of 2047 patients with a mean±SD age of 69.6±10.6 years were included. The 30- and 90-day mortality rates were 1.3% and 4.9%, respectively, and consistent during the past two decades. Among 100 deaths within 90 days, 18 occurred during index hospitalization. Infectious, pulmonary, and cardiac complications were the leading mortality causes. Multivariable analysis showed that age (Odds Ratio: OR 1.05), Charlson comorbidity index ≥ 2 (OR 1.82), blood transfusion (OR 1.95), and pathological node disease (OR 2.85) were independently associated with 90-day mortality. Nevertheless, the surgical approach and enhanced recovery protocols had no significant effect on 90-day mortality. CONCLUSION: The 90-day mortality for RC is approaching five percent, with infectious, pulmonary, and cardiac complications as the leading mortality causes. Older age, higher comorbidity, blood transfusion, and pathological lymph node involvement are independently associated with 90-day mortality.

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.

Long-term renal function in patients with chronic kidney disease following radical cystectomy and orthotopic neobladder.

OBJECTIVE: To evaluate long-term renal function in patients with chronic kidney disease (CKD) Stage IIIa who underwent radical cystectomy and orthotopic neobladder (RC/ONB) compared to matched controls. PATIENTS AND METHODS: Using our Institutional Review Board-approved institutional database, patients with a glomerular filtration rate (GFR) of 45-59.9 mL/min/1.73 m2 who underwent RC/ONB were identified. A control group of patients with a GFR of ≥60 mL/min/1.73 m2 was selected. Groups were matched based on age, baseline hypertension/diabetes mellitus, perioperative chemotherapy, and preoperative hydronephrosis. A decrease in GFR of >10 mL/min/1.73 m2 during the follow-up was considered significant. A multivariate Cox regression analysis was performed to identify predictors of GFR decline in each group. RESULTS: Of 1237 patients who underwent RC/ONB, 508 patients were included (254 per group). The mean preoperative GFR was 53.3 mL/min/1.73 m2 in the study group and 78.8 mL/min/1.73 m2 in controls. The median follow-up was 3.7 years. During follow-up, GFR stayed at or above baseline in 51% of the study patients compared to 46% of the controls (P = 0.5). The mean time to a significant GFR decline in the study patients was significantly longer compared to the controls (5.6 vs 2 years, respectively; P < 0.001). In multivariate analysis, neoadjuvant chemotherapy was found to be the strongest predictor of a significant GFR decline as well as GFR decline below baseline (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.4-3.29, P = 0.004; and HR 2.15, 95% CI 1.4-3.29, P < 0.001, respectively). CONCLUSION: Patients with CKD Stage IIIa who undergo ONB appear to have comparable long-term renal function to those with a GFR of ≥60 mL/min/1.73 m2 . An ONB reconstruction is a safe option for patients with CKD Stage IIIa desiring a continent diversion.

Risk factors and natural history of parastomal hernia after radical cystectomy and ileal conduit.

OBJECTIVE: To investigate the incidence, risk factors and natural history of parastomal hernia (PSH). MATERIALS AND METHODS: We reviewed the records of patients who underwent radical cystectomy (RC) and ileal conduit (IC) procedure between 2007 and 2020. Patients who had available follow-up computed tomography (CT) imaging were included in this study. All CT scans were re-reviewed for detection of PSH according to Moreno-Matias classification. Patients who developed hernia were followed up and classified into stable or progressive (defined as radiological upgrading and/or need for surgical intervention) groups. Multivariable Cox regression was performed to identify independent predictors of hernia development and progression. RESULTS: A total of 361 patients were included in this study. The incidence of radiological PSH was 30%, graded as I (56.5%), II (12%) and III (31.5%). The median (interquartile range [IQR]) time to radiological hernia was 8 (5-15) months. During the median (IQR) follow-up of 27 (13-47) months in 108 patients with a hernia, 26% patients progressed. The median (IQR) time to progression was 12 (6-21) months. On multivariable analysis, female gender (hazard ratio [HR] 1.86), diabetes (HR 1.81), chronic obstructive pulmonary disease (COPD; HR 1.78) and higher body mass index (BMI; HR 1.07 for each unit) were independent predictors for radiological PSH development. No significant factor was found to be associated with hernia progression. CONCLUSION: Radiological PSH after RC and IC occurred in 30% of patients, a quarter of whom progressed in a median time of 12 months. Female gender, diabetes, COPD and high BMI were independent predictors for radiological hernia development.

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.

Predictors of need for catheterisation and urinary retention after radical cystectomy and orthotopic neobladder in male patients.

OBJECTIVES: To investigate the prevalence of catheterisation and urinary retention in male patients with bladder cancer after radical cystectomy (RC) and orthotopic neobladder (ONB) and to identify potential predictors. PATIENTS AND METHODS: Using an Institutional Review Board approved, prospectively maintained bladder cancer database, we collected information using a diversion-related questionnaire from 299 consecutive male patients with bladder cancer upon postoperative clinic visit. Urinary retention was defined as ≥3 catheterisations/day or a self-reported inability to void without a catheter. Uni- and multivariable Cox regression analysis was performed to identify predictors of catheterisation and urinary retention. RESULTS: Self-catheterisation was reported in 51 patients (17%), of whom, 22 (7.4% of the total patients) were in retention. Freedom from any catheterisation at 3, 5, and 10 years after RC was 85%, 77%, and 62%, respectively. Freedom from retention at 3, 5, and 10 years after RC was 93%, 88%, and 79%, respectively. Multivariable Cox regression showed that higher body mass index (BMI; ≥27 kg/m2 ) significantly increased the need for catheterisation (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.26-4.32) as well as retention (HR 5.20, 95% CI 1.74-15.51). Greater medical comorbidity (Charlson Comorbidity Index score ≥2) correlated with the need for any catheterisation (HR 1.84, 95% CI 1.02-3.3), but not retention. Pathological stage and type of diversion were not significant predictors of the need to catheterise or urinary retention. CONCLUSION: In males undergoing RC with ONB, retention requiring catheterisation to void is uncommon. Patients with a BMI of ≥27 kg/m2 are at significantly increased risk of retention and need for self-catheterisation.

Stoma complications and quality of life in patients with Indiana pouch versus appendico/neo-appendico-umbilicostomy urinary diversions.

OBJECTIVES: To evaluate three subtypes of continent-cutaneous urinary diversion (CCUD); Indiana pouch (IP), right colon pouch with appendico-umbilicostomy (AU), and right colon pouch with neo-appendico-umbilicostomy (NAU), by investigating diversion-specific complications and quality-of-life outcomes. MATERIALS AND METHODS: A retrospective review of an IRB-approved database was conducted for perioperative and outcome data. The EORTC QLQ-C30 questionnaire was used to assess quality of life; all responses were obtained > 6 months after diversion. RESULTS: Fifty-eight patients who underwent a CCUD at our institution from 2010 to 2016 (33 IP by two surgeons, 15 AU and ten NAU by third surgeon) were identified for this study. Higher age and Charlson Comorbidity Index (CCI) ≥ 3 were seen in the AU cohort when compared to the IP cohort (P = 0.02 and 0.02, respectively). NAU group were also older when compared to the IP group (P = 0.02). After a median follow-up of 21 months (range: 0.8-81.0), more high-grade diversion-related complications were reported for AU and NAU patients comparing to the IP group (P < 0.01 and P = 0.02, respectively). More stoma complications were also reported for the NAU cohort than the IP cohort (70% vs 30%, P = 0.03). In all groups, > 60% of stoma complications occurred at the skin or fascia level. In the 90-day postoperative period, a higher continence rate was reported for the IP cohort, and this difference was significant when compared to the NAU cohort (P = 0.04). Length of stay after surgery and revision rates were not significantly different. For all groups, the majority of patients reported little-to-no disturbance of daily functions and rated overall quality of life as good-to-excellent. CONCLUSION: Urinary diversion using the Indiana pouch and right colon pouch with appendico/neo-appendico-umbilicostomy are all associated with high rates of continence and patient satisfaction. When compared to IP, AU and NAU patients had higher rates of high-grade diversion-related complications and NAU patients had a higher stoma complications with lower 90-day continence rate.

Internal audit of an enhanced recovery after surgery protocol for radical cystectomy.

PURPOSE: To perform an internal audit 5 years after implementation of our enhanced recovery after surgery (ERAS) protocol for patients undergoing radical cystectomy and to investigate the importance of physician driven compliance on outcomes. METHODS: Using a prospectively maintained database, 472 consecutive patients were identified who underwent radical cystectomy with ERAS from July 2013 to July 2017. Compliance was measured by a Composite Compliance Score (CCS) generated as a percentage of 16 interventions. Patients with higher than median compliance were compared to patients with lower compliance. The primary outcome was length of stay. Secondary outcomes included complication and readmission rates. Multivariable regressions were used to control for differences between groups. RESULTS: In 2013, median CCS was 81% and subsequently ranged from 81 to 88%. Five-year median CCS was 88%. Patients with higher compliance (CCS ≥ 88%, n = 262), as compared to those with lower compliance (CCS < 88%, n = 210), were younger (median 70.3 vs 72.7 years, p = 0.047), healthier (ASA3-4 81% vs 89.9%, p = 0.007), received more orthotopic diversions (59.2% vs 37.6%, p < 0.0001), more often had open surgery (78.5% vs 51.9%, p < 0.0001) and had shorter median operative times (5.5 vs 6.3 h, p = 0.005). Median length of stay was 4 days. Higher compliance was associated with shorter hospital stays (ß = - 0.85, 95% CI - 1.62 to - 0.07) and decreased 30-day readmissions (OR 0.58, 95% CI 0.35-0.96). CONCLUSIONS: Greater ERAS compliance was achieved in younger and healthier patients. Patients with greater compliance had a decreased length of stay by almost 1 day and reduced odds of 30-day readmissions.

An evaluation of the real world use and clinical utility of the Cxbladder Monitor assay in the follow-up of patients previously treated for bladder cancer.

BACKGROUND: Surveilling recurrent urothelial carcinoma (UC) requires frequent cystoscopy, which is invasive, expensive and time-consuming. An accurate urinary biomarker has the potential to reduce the number of cystoscopies required during post-treatment surveillance. OBJECTIVE: To audit the clinical utility of a new surveillance protocol incorporating the Cxbladder Monitor (CxbM) test in real-world practice. METHODS: Three hospitals implemented a new surveillance protocol. Patients were risk stratified, and then provided urine samples for CxbM testing. Low-risk CxbM-positive patients and all high-risk patients had cystoscopy at 2-3 months. Low-risk CxbM-negative patients had cystoscopy at ~ 12 months. RESULTS: 443 CxbM tests were conducted on samples from 309 patients: 257 (83.2%) low-risk and 52 (16.8%) high-risk. No pathology-confirmed recurrences were seen in low-risk CxbM-negative patients (n = 108) during the first post-CxbM cystoscopy undertaken a mean ± SD 10.3 ± 3.9 months after testing. Three recurrences were detected during cystoscopy at 2.7 ± 3.4 months in 53 low-risk CxbM-positive patients. In 49 high-risk patients, 39 (79.6%) were CxbM-negative with no pathology-confirmed recurrences. Ten high-risk patients (20.4%) were CxbM-positive with four confirmed recurrences; 2 high-grade and 2 low-grade. The median time to first cystoscopy was 12.13 (95% CI: 11.97-12.4) months in patients with a CxbM-negative result versus 1.63 (95% CI: 1.13-2.3) months in patients with a CxbM-positive result (p < 0.00001). No positive cases were missed, no patients progressed to invasive or metastatic disease, and no patient died of cancer over 35 months of follow-up. CONCLUSIONS: CxbM accurately identified a high proportion of patients (77.8%) who were safely managed with only one cystoscopy per year. Including CxbM in the protocol for patient surveillance provided clinical utility by reducing the average number of annual cystoscopies by approximately 39%, thereby sparing patients the potential discomfort and anxiety, without compromising detection rates. No advantage was observed for risk stratification prior to CxbM.

Factors influencing intraoperative conversion from planned orthotopic to non-orthotopic urinary diversion during radical cystectomy.

OBJECTIVES: To determine and investigate the intraoperative factors that contribute to a change in plan from continent orthotopic neobladder to ileal conduit or continent cutaneous diversion at the time of radical cystectomy. SUBJECTS AND METHODS: A retrospective review of our prospectively maintained bladder cancer database was performed. Of the 711 patients who underwent radical cystectomy from 2012 to 2016, 387 (54.4%) had given consent to have a NB. Of these 387 patients, 348 (89.9%) ultimately received a neobladder while 34 (8.8%) received an ileal conduit and 5 (1.3%) continent cutaneous diversion. The factors involved in the intraoperative change of plan were examined in this study. RESULTS: Patients who ultimately received a neobladder were significantly more likely to have clinical node-negative disease (p = 0.045), negative soft tissue margins (p = 0.001), lower body mass index (p = 0.045) and higher volume surgeons (p < 0.001). Oncologic reasons for intraoperative conversions were more common than technical reasons (58.3% vs 35.9%), in both robotic and open surgical techniques. The choice of surgical approach (open vs robotic) did not influence the rate of intraoperative conversion. CONCLUSION: The factors influencing intraoperative decision not to perform neobladder are predominantly oncologic rather than technical. A clear understanding of the factors involved in influencing the intraoperative change in the urinary diversion plan may improve shared decision making in patients undergoing radical cystectomy in the future.

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.

The association between intraoperative fluid intake and postoperative complications in patients undergoing radical cystectomy with an enhanced recovery protocol.

PURPOSE: To evaluate the association between intraoperative fluid intake and postoperative complications in patients who underwent radical cystectomy (RC) for bladder cancer with an enhanced recovery protocol. METHODS: 287 patients underwent open RC with enhanced recovery protocol (ERAS) from 2012 to 2016. 107 were excluded; non-urothelial (30), palliative (37), had adjunct procedures or not-consented (40). We prospectively evaluated intraoperative fluid intake (crystalloid, colloid and blood) and correlated with length of stay, 30- and 90-day complications. RESULTS: 180 patients enrolled into the study with median age of 70 years (78% male). 71% underwent orthotopic diversion. Median intraoperative crystalloid and colloid intake were 4000 and 500 cc, respectively. Nineteen percent of patients received blood transfusion. Median length of stay was 4 days. The overall 30- and 90-day complication rates were 59 and 75%, respectively. Multivariate logistic regressions controlling for a subset of clinically relevant variables showed no significant association between intraoperative fluid intake and complications at 30 or 90 days (p = 0.88 and 0.62, respectively). A multivariable linear regression similarly showed no association between total intraoperative fluid intake and length of stay (p = 0.099). CONCLUSION: Higher intraoperative fluid intake was not found to independently increase the complication rate following radical cystectomy. Larger studies and prospective trials are needed to determine if fluid optimization may play a role in decreasing morbidity after this major surgery.

90-Day complication rate in patients undergoing radical cystectomy with enhanced recovery protocol: a prospective cohort study.

PURPOSE: To report 90-day complication rates following radical cystectomy (RC) with enhanced recovery after surgery (ERAS) protocol. METHODS: All consecutive patients who underwent open RC with ERAS protocol from 2012 to 2014 were included. The protocol includes no bowel preparation or NGT, early feeding, predominantly non-narcotic pain management and µ-opioid antagonists. Non-consenting and lost to follow-up patients were excluded. All patients were closely followed up, and 90-day complication (Clavien-Dindo grading), readmission and emergency room (ER) visits were prospectively recorded. RESULTS: One hundred and sixty-nine cases with a median age of 71 years were included in the study. 90-Day major and minor complication rates were 24.3 and 53.9 %, respectively. The most common complications were infectious and gastrointestinal. The 90-day ER visit rate was 37.9 %, whereas the readmission rate was 29.6 %. The most common cause of hospital readmission and ER visits was infections. CONCLUSION: Radical cystectomy and urinary diversion with enhanced recovery protocol is a morbid surgery. The most common complication, cause of ER visit and readmission is yet infections. Further studies on methods to decrease these rates are underway.