Apixaban vs Enoxaparin for Post-Surgical Extended-Duration Venous Thromboembolic Event Prophylaxis: A Prospective Quality Improvement Study.

PURPOSE: Venous thromboembolic events (VTEs) are a major cause of morbidity following abdominopelvic oncologic surgery. Enoxaparin, a subcutaneous injectable low molecular weight heparin, is commonly used for extended-duration VTE prophylaxis (EP), but has been associated with noncompliance. Newer direct oral anticoagulants have not been prospectively studied in the urologic oncology post-discharge setting. We aimed to improve compliance with EP following abdominopelvic oncologic surgery and secondarily test the hypothesis that apixaban is noninferior to enoxaparin for EP. MATERIALS AND METHODS: A single-center prospective quality improvement study measuring patient compliance and safety with EP was conducted between August 10, 2020 and September 21, 2021. Baseline data were continuously collected for 6 months, followed by a uniform departmental change from enoxaparin to apixaban. The duration of data collection was determined a priori using a noninferiority sample size estimation (145 per group). The primary outcome was compliance events (real or potential barriers to EP use). The secondary outcome was 30-day post-discharge safety events (symptomatic VTE or major bleed). RESULTS: A total of 161 patients were discharged with enoxaparin (baseline period) and 154 with apixaban (intervention period). Safety events occurred in 3.1% vs 0% of patients receiving enoxaparin and apixaban, respectively. The absolute risk difference of 3.1% (95% CI: 0.043%-5.8%) met the prespecified noninferiority threshold (p=0.028 for apixaban superiority). Compliance events occurred in 33.5% of enoxaparin patients and 14.3% of apixaban patients (p=0.0001). CONCLUSIONS: There were fewer compliance events using apixaban for EP than enoxaparin after urologic oncology surgery. Regarding safety, apixaban is noninferior to enoxaparin and may in fact have fewer associated major complications.

Patient-Reported Outcomes Are Associated With Enhanced Recovery Status in Patients With Bladder Cancer Undergoing Radical Cystectomy.

BACKGROUND: Bladder cancer is a disease of the elderly that is associated with high morbidity in those treated with radical cystectomy. In this observational study of patients with bladder cancer undergoing radical cystectomy, we analyzed and compared patient-reported outcomes from those treated with Enhanced Recovery After Surgery (ERAS) methods versus those who received traditional perioperative care. METHODS: We enrolled patients who underwent radical cystectomy at a high-volume tertiary care referral center from November 2013 to December 2016, when the ERAS concept was being introduced into postoperative care at our institution. Patients reported symptom outcomes using the MD Anderson Symptom Inventory preoperatively and on postoperative days 1 to 5. Mann-Whitney U tests were used to compare symptom burden between the ERAS and traditional-care groups. General linear mixed-effects models were used for longitudinal data; linear regression models were used for multivariable analysis. RESULTS: Patients (N = 383) reported dry mouth, disturbed sleep, drowsiness, fatigue, pain, and lack of appetite as the most severe symptoms. Compared with the traditional-care group, the ERAS group had significantly less pain (est. = -0.98, P = .005), drowsiness (est. = -0.91, P = .009), dry mouth (est. = -1.21, P = .002), disturbed sleep (est. = -0.97, P = .01), and interference with functioning (est. = -0.70, P = .022) (adjusted for age, sex, surgical technique, and neoadjuvant chemotherapy status). CONCLUSIONS: These results suggest that ERAS practice significantly reduced immediate postoperative symptom burden in bladder cancer patients recovering from radical cystectomy, supporting the use of patient-reported symptom burden as an outcome measure in perioperative care.

Advances in surgical management of muscle invasive bladder cancer.

INTRODUCTION: Bladder cancer remains a disease of the elderly with relatively few advances that have improved survival over the last 20 years. Radical cystectomy (RC) has long remained the principal treatment for muscle-invasive bladder cancer (MIBC). METHODS: A literature search of PubMed was performed. The content was reviewed for continuity with the topic of surgical advances in MIBC. Articles and society guidelines were included in this review. RESULTS: Despite the associated morbidity, even in the elderly, RC is still a reasonable option. Modifications during RC may have a positive or negative impact on survival and quality of life. The extent of pelvic lymph node dissection is one such factor which may positively impact survival outcomes. In addition, preservation of pelvic organs, robotic surgery and the adoption of enhanced recovery after surgery principles continues to improve the postoperative recovery and quality of life in RC patients. CONCLUSION: There are some ongoing studies in many of these areas, but overall the new advances in MIBC may improve patient quality and quantity of life. The advances in surgical treatment of MIBC are important and the focus of the review here.

Non-muscle-invasive Bladder Cancer: Side-by-Side Guideline Comparison.

Clinical guidelines from the European Association of Urology, American Urological Association, Society of Urologic Oncology, and National Comprehensive Cancer Network are some of the most frequently accessed publications. These guidelines are published at varying frequency and use different methods to formulate their recommendations. Many guidelines still rely on expert opinion in areas where there is a lack of data. To be well executed guidelines they need to involve comprehensive panels who are content experts and multispecialty. This article reviews the strengths and weaknesses of current guidelines for non-muscle-invasive bladder cancer and possible opportunities for future improvements. PATIENT SUMMARY: Quality recommendations in guidelines are critical to provide the most effective care for patients with non-muscle-invasive bladder cancer.

Discomfort and relieving factors among patients with bladder cancer undergoing office-based cystoscopy.

OBJECTIVE: To evaluate the degree of discomfort among patients with bladder cancer undergoing office-based cystoscopy and identify factors and interventions that influence discomfort and anxiety. METHODS: We conducted a survey of the Bladder Cancer Advocacy Network Patient Survey Network (BCAN PSN) to investigate the degree of discomfort associated with office-based cystoscopy and prevalence of interventions used to reduce discomfort. All patients had undergone at least one previous cystoscopy. Bivariable and multivariable logistic regression were used to identify factors associated with moderate-to-severe cystoscopy discomfort. RESULTS: Among 488 BCAN PSN respondents (50% response rate), 392 responded with demographic data and discomfort score. Cystoscopy was associated with moderate-to-severe discomfort in 52% of patients. Respondents who reported moderate-to-severe discomfort were more likely to describe their most recent cystoscopy discomfort as worse than prior (P<0.001) and to be interested in planning discomfort mitigation for cystoscopy (P<0.001). On multivariable analysis, gender was the only factor independently associated with discomfort, with women reporting less discomfort than men (OR 0.59, 95%CI 0.37-0.95,P=0.03). Patients reported a wide variety of cystoscopy-specific interventions with differing perceived effectiveness, the most common being intraurethral lidocaine. CONCLUSIONS: Over half of patients undergoing office-based cystoscopy for bladder cancer report moderate-to-severe discomfort, constituting a substantial problem among patients undergoing the procedure. Future large pragmatic comparative effectiveness trials are needed to better understand which interventions work most effectively to reduce discomfort associated with cystoscopy.

Oncologic Equipoise Between Robotic and Open Radical Cystectomy.

Purpose: Our objective was to establish the incidence of positive surgical margins, recurrence patterns, and recurrence-free (RFS) and overall survival (OS) in a large cohort of patients undergoing robotic (robot-assisted radical cystectomy [RARC]) and open radical cystectomy (ORC). Materials and Methods: We performed a large retrospective cohort study at a high-volume academic tertiary referral center. Patients were those who underwent RC for bladder cancer from 2005 to 2017. Patients were allocated to ORC or RARC by patient and surgeon choice. Propensity matching and a multivariable analysis were performed to determine factors predictive of RFS and OS after RC. All analyses were done with SAS 9.4. Results: The study included 1885 patients, 13.5% of whom underwent RARC. There was no difference in positive soft tissue surgical margins (2.4% in ORC and 1.2% in RARC). There were no differences in recurrence patterns, nor in the severity of pathology distribution between the two cohorts. Peritoneal carcinomatosis was seen in 1.1% of ORC and 0.8% in RARC. Shorter RFS was associated with younger age (hazard ratio [HR] 1.04, 95% confidence interval [CI] 1.03-1.05, p < 0.001), neoadjuvant chemotherapy (HR 1.41, 95% CI 1.14-1.75, p = 0.002), higher pathologic stage (stage ≥T2 HR 2.45, 95% CI 1.91-3.16, p < 0.001), lymph node positivity at cystectomy (HR 1.92, 95% CI 1.50-2.47, p < 0.001), and positive surgical margins (HR 1.49, 95% CI 1.09-2.05, p = 0.01). RFS and OS did not differ by surgical approach (HR 1.04, 95% CI 0.83-1.30), p = 0.75 and (HR 0.89, 95% CI 0.67-1.19), p = 0.43, respectively. Conclusion: The data from this study support continued use of RARC as a safe oncologic procedure, with similar outcomes to ORC.

Utilizing time-driven activity-based costing to determine open radical cystectomy and ileal conduit surgical episode cost drivers.

OBJECTIVES: Patients undergoing radical cystectomy represent a particularly resource-intensive patient population. Time-driven activity based costing (TDABC) assigns time to events and then costs are based on the people involved in providing care for specific events. To determine the major cost drivers of radical cystectomy care we used a TDABC analysis for the cystectomy care pathway. SUBJECTS AND METHODS: We retrospectively reviewed a random sample of 100 patients out of 717 eligible patients undergoing open radical cystectomy and ileal conduit for bladder cancer at our institution between 2012 and 2015. We defined the cycle of care as beginning at the preoperative clinic visit and ending with the 90-day postoperative clinic visit. TDABC was carried out with construction of detailed process maps. Capacity cost rates were calculated and the care cycle was divided into 3 phases: surgical, inpatient, and readmissions. Costs were normalized to the lowest cost driver within the cohort. RESULTS: The mean length of stay was 6.9 days. Total inpatient care was the main driver of cost for radical cystectomy making up 32% of the total costs. Inpatient costs were mainly driven by inpatient staff care (76%). Readmissions were responsible for 29% of costs. Surgery was 31% of the costs, with the majority derived from operating room staff costs (65%). CONCLUSION: The major driver of cost in a radical cystectomy pathway is the inpatient stay, closely followed by operating room costs. Surgical costs, inpatient care and readmissions all remain significant sources of expense for cystectomy and efforts to reduce cystectomy costs should be focused in these areas.

Cost-Effectiveness of Robot-assisted Radical Cystectomy Using a Propensity-matched Cohort.

BACKGROUND: Health-related quality of life is important for patients undergoing radical cystectomy (RC). OBJECTIVE: To determine the cost-effectiveness of robotic-assisted RC (RARC) compared to open cystectomy (OC) for bladder cancer and factors that contribute to cost-effectiveness. DESIGN, SETTING, AND PARTICIPANTS: A decision analytic model was used to compare health-related quality of life and medical costs for RARCs with intracorporeal urinary diversion and OCs performed between 2007 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Propensity matching was performed among 1322 cases to yield a final cohort of 100 RARC and 96 ORC cases. Probabilities were obtained from the clinical study data, while quality-adjusted life years (QALYs) and health utility values were derived from the literature. A complication, readmission, or transfusion was included in the 90-d time horizon model. RESULTS AND LIMITATIONS: There were no differences between the groups in patient demographics, pathologic staging, or length of stay. Multivariable analysis revealed that the RARC group had fewer transfusions and complications compared to the OC group. The incremental cost-effectiveness ratio was $2969. RARC cost $2969 less per QALY when compared to OC. While RARC was $17000 more expensive, it also associated with an increase of 0.32 QALYs. One-way sensitivity analysis identified RARC as the preferred strategy if a complication can be prevented 74% of the time. RARC is preferred as long as it is 70% effective in preventing a transfusion. Two-way sensitivity analysis showed that as long as RARC can prevent complications and transfusions, it is the preferred cost-effective treatment when compared to OC. The study is limited by the omission of a societal perspective and the lack of health utility values for RC. CONCLUSIONS: RARC is cost-effective compared to OC when the rates of complications and transfusions are significantly lower. PATIENT SUMMARY: Bladder removal via a robotic approach is more expensive, but it improves health-related quality of life. Robotic surgery is cost-effective compared to an open approach for bladder removal if there are low rates of complications and blood transfusion.

Organizing a clinical trial for the new investigator.

BACKGROUND AND PURPOSE: Clinical trials organization can be daunting especially when orienting to a new system. The steps to a successful clinical trial are not concrete and vary based on the system. METHODS: In this section the discussion centers on how to shape the question for the clinical trial which is rational and feasible to answer within the planned study design. FINDINGS: Senior mentorship, collaboration and early involvement of stakeholders can help shape a successful clinical trial. Keeping in mind ethics and the processes within a system will make planning easier. Questions about key elements of the trial should be answered early to prevent delays of study initiation. CONCLUSION: Clinical trial development and implementation can be very rewarding, but successful outcomes require careful planning and considerations.

Absence of Tumor on Repeat Transurethral Resection of Bladder Tumor Does Not Predict Final Pathologic T0 Stage in Bladder Cancer Treated with Radical Cystectomy.

BACKGROUND: For patients with bladder cancer (BC) receiving neoadjuvant chemotherapy (NAC), complete pathologic absence of tumor (pT0) at radical cystectomy (RC) is associated with better survival. It is unclear if pT0 status can be attributed to the absence of residual disease (cT0) on transurethral resection of bladder tumor (TURBT) or to the effects of NAC. OBJECTIVE: To determine how often cT0 is associated with pT0 and identify preoperative and postoperative factors associated with survival. DESIGN, SETTING, AND PARTICIPANTS: Between 1995 and 2011, 157 out of 1897 RC patients were identified as stage cT0 after at least two TURBT procedures at a single center. INTERVENTION: RC with or without NAC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Initial TURBT pathology and clinical staging were reviewed. The primary endpoint was pathologic stage at RC. Cox proportional hazards ratios identified factors associated with residual disease at RC, overall survival (OS), recurrence-free survival (RFS), and disease-specific survival (DSS). RESULTS AND LIMITATIONS: Of the cT0 patients, 49.7% (n=78) underwent NAC. pT0 was found in 35.7% (n=56). Residual tumor was found at RC in 63.7% (n=101), of whom 24.8% (n=39) had advanced disease (≥pT3 or node-positive disease). Positive lymph nodes at RC were found in 12.7% (n=20) of the patients. There was no significant difference in achieving pT0 status between patients with and without NAC. The presence of advanced BC was most predictive of OS. NAC was associated with longer OS and RFS. During median follow-up of 6.3 yr, the 5-yr RFS was 81% for those with non-advanced disease and 46% for advanced BC (p<0.001). The 5-yr OS rate was 77% for non-advanced BC and 46% for invasive BC (p<0.001). Limitations include the retrospective design. CONCLUSIONS: Complete TURBT does not predict pT0 at RC. A notable fraction of patients with cT0 bladders have locally advanced and/or lymph node-positive disease. These findings may be of value when counseling patients on bladder preservation strategies for muscle-invasive BC. PATIENT SUMMARY: Among patients thought to have had the entire tumor in their bladder removed via cystoscopy, a majority have persistent tumors when their bladders were removed. In a sizable proportion, these persistent tumors were even more invasive than initially thought.

Antibiogram Directed Prophylaxis for Transrectal Prostate Biopsy: An Application of Recommendations in the Setting of High Fluoroquinolone Escherichia coli Resistance.

INTRODUCTION: We investigated local resistance patterns to guide antibiotic use for the prevention of infections associated with transrectal prostate biopsy with ultrasound guidance. METHODS: Per the AUA (American Urological Association) recommendations (2014 and 2016) for transrectal prostate biopsy with ultrasound guidance prophylaxis, local antibiogram resistance was reviewed. Rates of Escherichia coli fluoroquinolone resistance were between 20% and 28%. Thus, the antibiotics chosen were a single dose of oral ciprofloxacin and intramuscular ceftriaxone at least 30 minutes before transrectal prostate biopsy with ultrasound guidance. Data were reviewed retrospectively between July 2012 and December 2015. There was no standard prophylaxis before protocol implementation in August 2014. Univariable analyses were performed with appropriate testing followed by multivariable logistic regression. RESULTS: Of 2,351 biopsies 799 were performed in patients in the protocol group. Before protocol implementation 26 different antibiotic regimens were used. The protocol group had significantly more cases of chronic kidney disease, a history of cancer, larger prostate volume and greater number of cores during transrectal prostate biopsy with ultrasound guidance. The overall hospital admission rate after transrectal prostate biopsy with ultrasound guidance was 1.35% for the nonprotocol group and 0.4% for the protocol group (p = 0.026). The incidence of organisms with antimicrobial resistance in blood and urine decreased from 20.7% (23 cases) in the nonprotocol group and 7.1% (4) in the protocol group (p=0.030). All positive blood cultures occurred in the nonprotocol group and all were ciprofloxacin resistant E. coli. On multivariable logistic regression those patients requiring hospitalization were 12.9 (95% CI 2.81-58.96) times more likely to have resistant organisms cultured (p=0.001). CONCLUSIONS: The transrectal prostate biopsy with ultrasound guidance antibiotic prophylaxis protocol decreased unwanted variation among practitioners, which is ultimately associated withimproved quality. Antibiogram directed prophylaxis where there is high fluoroquinolone resistance maintains low infection and hospital admission rates after transrectal prostate biopsy with ultrasound guidance.