Faculty Bibliography

PURPOSE/OBJECTIVE:In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. METHODS AND MATERIALS/METHODS:Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined using follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. RESULTS:A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. CONCLUSIONS:Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.

OBJECTIVES/OBJECTIVE:To determine the time to bladder cancer diagnosis from initial infection-like symptoms and its impact on cancer outcomes. METHODS:Using Surveillance, Epidemiology and End Results-Medicare, we designed a retrospective cohort study identifying beneficiaries aged ≥ 66 years diagnosed with bladder cancer from 2007 to 2009. Patients were required to have a hematuria or urinary tract infection claim within 1 year of bladder cancer diagnosis (n = 21 216), and have 2 years of prior Medicare data (n = 18 956) without any precedent hematuria, bladder cancer or urinary tract infection claims (n = 12 195). The number of days to bladder cancer diagnosis was measured, as well as the impact of sex and presenting symptom on time to diagnosis, pathology, and oncological outcomes. RESULTS:The mean time to bladder cancer diagnosis was 72.2 days in women versus 58.9 days in men (P < 0.001). A logistic regression model identified the greatest predictors of ≥ pT2 pathology were both women (odds ratio 2.08, 95% confidence interval 1.70-2.55) and men (odds ratio 1.71, 95% confidence interval 1.49-1.97) presenting with urinary tract infection. Cox proportional hazards analysis identified an increased risk of mortality from bladder cancer and all causes in women presenting with urinary tract infection (hazard ratio 1.37, 95% confidence interval 1.10-1.71, and hazard ratio 1.47, 95% confidence interval 1.28-1.69) compared with women with hematuria. CONCLUSIONS:Women have a longer interval from urinary tract infection to diagnosis of bladder cancer. Urinary tract infection presentation can adversely affect time to diagnosis, pathology and survival. Time to diagnosis seems not to be an independent predictor of bladder cancer outcomes.

Introduction: There have been no randomized controlled trials (RCTs) evaluating the clinical or economic benefit of mitomycin C intravesical therapy vs. radical cystectomy in patients with high-risk non-muscle invasive bladder cancer (NMIBC). We used the Archimedes computational model to simulate RCT comparing radical cystectomy versus intravesical mitomycin C (MMC) therapy to evaluate the clinical and economic outcomes for BCG-refractory NMIBC as well demonstrate the utility of computer based models to simulate a clinical trial. Methods: The Archimedes model was developed to generate a virtual population using the Surveillance Epidemiology and End Results database, other clinical trials, and expert opinions. Patients selected were diagnosed with NMIBC (<cT2 disease) who recurred or progressed despite BCG therapy and were randomized to 1) immediate radical cystectomy vs. 2) MMC induction intravesical therapy. Clinical (progression, overall survival, and disease specific survival) and economic outcomes were reported. Results: A total of 1300 virtual patients were evaluation. Progression to MIBC in the MMC treatment arm was 30% over the lifetime. Disease specific death at 5 years was 1.6% and 8.7% for the immediate cystectomy and MMC treatment arms respectively; while, overall death was 17.8% and 23.8% at 5 years. Over a 5-year period the average cost of immediate cystectomy was $64,675 vs $68,517 in the MMC arm. Conclusion: Immediate radical cystectomy after BCG failure for NMIBC has improved survival and is more cost-effective when compared to those undergoing MMC. Simulation of clinical trials using computational models similar to the Archimedes model can overcome shortcomings of real-world clinical trials and may prove useful in the face of current medical cost-conscious era.

OBJECTIVE:To examine the outcomes of endoscopic procedures for bladder neck contracture (BNC) in the orthotopic neobladder (ONB) after radical cystectomy focusing on success rates for patients who require multiple treatments. MATERIALS AND METHODS/METHODS:Patients who underwent treatment for cystoscopically confirmed BNC in an ONB from 2007 to 2014 were studied. Treatment information included procedure type, use of adjuvant clean intermittent catheterization (CIC), and follow-up procedures. Procedures followed by additional interventions were categorized as failures. Success was defined as no additional surgical procedure with at least 1 year of follow-up. Procedures were classified by a number of prior endoscopic treatments. RESULTS:Seventy-one patients underwent 155 individual endoscopic procedures (146 urethrotomy, 3 dilation, and 6 transurethral resection of bladder neck). All patients were male without prior radiation. Median follow-up after initial endoscopic treatment was 26.8 months (interquartile range: 16.6-51.7), and time to recurrence was 3.5 months (1.6-6.3). Success was experienced for 50 of 136 individual procedures (37%) after excluding 19 procedures for inadequate follow-up. Success rates remained 25%-43% even after multiple prior interventions. Adjuvant CIC was associated with a higher success rate (14/24 or 58%) compared to procedures without CIC (36/112 or 32%, P = .02). Successful outcomes were seen in 50 of 71 patients (73%) with 2 patients requiring ONB removal. CONCLUSION/CONCLUSIONS:Individual endoscopic treatments of BNC in the ONB were met with 37% success. The rate did not decrease with subsequent procedures. Adjuvant CIC improved the outcomes. Overall, a successful outcome was achieved for most patients, but the majority required more than one procedure.

Left ventricular assist device (LVAD) is an option for the surgical management of severe heart failure, and radical cystectomy remains the standard of care for muscle-invasive bladder cancer. Given a complicated population in terms of comorbidities and management for patients with an LVAD, there is little experience with major urologic procedures, which require balancing the benefits of surgery with considerable perioperative risks. We report our experience performing the first radical cystectomy with ileal conduit in a patient with an LVAD and muscle-invasive bladder cancer.

INTRODUCTION/BACKGROUND:Transurethral resection of bladder tumor (TURBT) is the gold standard initial diagnostic intervention for bladder cancer and provides diagnostic, therapeutic and prognostic benefit in non-muscle-invasive bladder cancer (NMIBC). However, TURBT alone is inadequate for optimal management of NMIBC, as patients will experience recurrence or progression depending on tumor characteristics. Adjuvant intravesical therapy with either immunotherapy or chemotherapy has been shown to reduce recurrence and/or progression in appropriately selected patients through immunostimulation or direct cell ablation. AREAS COVERED/METHODS:This review will discuss risk stratification of patients with NMIBC and role of intravesical therapies in reducing recurrence and progression of disease in these patients. A Medline search was performed to identify the best available evidence available from various systematic reviews, meta-analyses, and clinical trials on various immunotherapy and chemotherapy agents. In addition, the main aspects of drug pharmacology (mechanism of action, dosing and administration) and side effects will be reviewed. EXPERT OPINION/CONCLUSIONS:The selection of the appropriate intravesical agent for NMIBC is complex and is dependent on risk stratification and intravesical agent toxicity. Intravesical induction and maintenance immunotherapy with Bacillus Calmette-Guerin (BCG) is the preferred and most effective agent for patients with high-risk NMIBC (carcinoma in situ and high-grade disease) and reduces both recurrence and progression.

OBJECTIVES/OBJECTIVE:To assess the effect of the length of the ureter resected and other clinical variables on ureterointestinal anastomotic (UIA) stricture rate following radical cystectomy and ileal segment urinary diversion. METHODS AND MATERIALS/METHODS:We identified 519 consecutive patients who underwent cystectomy and ileal conduit or ileal orthotopic neobladder diversion from January 2007 to August 2012. The length of the ureter resected was defined as the length of the ureter in the cystectomy specimen plus the length of the distal ureter submitted for pathologic analysis. The primary end point was the risk of UIA stricture formation, assessed by Cox proportional hazards analysis. RESULTS:A total of 463 patients met the inclusion criteria with complete data. Median follow-up was 459 days (interquartile range [IQR]: 211-927). Median time to stricture formation was 235 (IQR: 134-352) and 232 days (IQR: 132-351) on the right and the left ureter, respectively. Overall stricture rate per ureter was 5.9% on the right vs. 10.0% on the left (P = 0.03). There was no difference in demographic, operative, or perioperative variables between patients with and without UIA strictures. On multivariate analysis adjusted for age, sex, anastomosis technique (running vs. interrupted), and length of ureter resected, only a Clavien complication≥III (hazard ratio = 2.11, 1.01-4.40) and urine leak (hazard ratio = 3.37, 1.08-10.46) significantly predicted for left- and right-sided stricture formation, respectively. The length of the ureter resected did not predict UIA stricture formation on either side. CONCLUSIONS:The etiology of benign UIA strictures following ileal urinary diversion is likely multifactorial. Our data suggest that a complicated postoperative course and urine leak are risk factors for UIA stricture formation. The length of the distal ureter resected did not significantly affect stricture rate.

The role of tissue engineering in the cystectomy population rests on the principle of sparing healthy intestinal tissue while replacing diseased bladder. Over the last 25 years advances in cell biology and material science have improved the quality and durability of bladder replacement in animals. The neo-urinary conduit ([NUC]-Tengion) employs autologous fat smooth muscle cells which are seeded onto synthetic, biodegradable scaffolds. This seeded construct is then implanted in the patient and purportedly regenerates native urinary tissue to serve as a passive channel connecting the ureters to the skin surface. Preclinical animal studies as well as the first phase I human trial implanting the NUC are reviewed. While the ultimate goal of creating a durable, effective, tissue-engineered conduit is still in its infancy, important technical and experimental strides have been made.

PURPOSE/OBJECTIVE:We evaluated the effect of alvimopan treatment vs placebo on health care utilization and costs related to gastrointestinal recovery in patients treated with radical cystectomy in a randomized, phase 4 clinical trial. MATERIALS AND METHODS/METHODS:Resource utilization data were prospectively collected and evaluated by cost consequence analysis. Hospital costs were estimated from 2012 Medicare reimbursement rates and medication wholesale acquisition costs. Differences in base case mean costs between the study cohorts for total postoperative ileus related costs (hospital days, study drug, nasogastric tubes, postoperative ileus related concomitant medication and postoperative ileus related readmissions) and total combined costs (postoperative ileus related, laboratory, electrocardiograms, nonpostoperative ileus related concomitant medication and nonpostoperative ileus related readmission) were evaluated by probabilistic sensitivity analysis using a bootstrap approach. RESULTS:Mean hospital stay was 2.63 days shorter for alvimopan than placebo (mean±SD 8.44±3.05 vs 11.07±8.23 days, p=0.005). Use of medications or interventions likely intended to diagnose or manage postoperative ileus was lower for alvimopan than for placebo, eg total parenteral nutrition 10% vs 25% (p=0.001). Postoperative ileus related health care costs were $2,340 lower for alvimopan and mean total combined costs were decreased by $2,640 per patient for alvimopan vs placebo. Analysis using a 10,000-iteration bootstrap approach showed that the mean difference in postoperative ileus related costs (p=0.04) but not total combined costs (p=0.068) was significantly lower for alvimopan than for placebo. CONCLUSIONS:In patients treated with radical cystectomy alvimopan decreased hospitalization cost by reducing the health care services associated with postoperative ileus and decreasing the hospital stay.