Faculty Bibliography

Non-muscle invasive bladder cancer (NMIBC) represents approximately 70% of all incident cases of bladder cancer. The financial burden of NMIBC continues to increase, underscoring the importance of efficient, evidence-based management of this disease. Consensus guidelines differ on risk definition and in management recommendations. This article reviews the incidence and financial impact of NMIBC and details the recommendations for diagnosis, treatment, and surveillance made by the American Urological Association, International Consultation on Bladder Cancer-European Association of Urology, and National Comprehensive Cancer Network. Established and developing adjunctive laboratory and imaging tests directed at diagnosis and management of NMIBC are also discussed.

PURPOSE/OBJECTIVE:In 2010 the AJCC (American Joint Committee on Cancer) excluded urothelial carcinoma with subepithelial prostatic stromal invasion from the pT4a bladder cancer staging class, which is otherwise defined by direct prostatic invasion transmurally from the bladder. We determined if the new guidelines were reflective of differences in survival between subepithelial prostatic stromal invasion and transmural pT4a disease. MATERIALS AND METHODS/METHODS:A retrospective, multi-institutional cohort of cystectomy cases with subepithelial prostatic stromal invasion from the University of Chicago and Cleveland Clinic were compared to a cohort with transmural pT4a disease. All pathological specimens were rereviewed at the respective institutions. Patients were excluded from the final cohort if variant bladder cancer histology, pT3 bladder disease or extraprostatic extension of urothelial carcinoma were identified. The primary end points were cancer specific and overall survival. RESULTS:Our study sample consisted of 48 patients with subepithelial prostatic stromal invasion and 49 patients with transmural pT4a disease. Median followup was 12.8 months (IQR 4.9 to 31.4). Patients with subepithelial prostatic stromal invasion had lower rates of lymph node involvement than those with transmural pT4a disease (14.6% vs 61.2%, p <0.001) and lower rates of positive surgical margins (18.7% vs 61.2%, p <0.001). Rates of perioperative chemotherapy were similar in both groups. When comparing subepithelial prostatic stromal invasion and transmural pT4a groups, overall survival was 64.0 vs 9.8 months and median cancer specific survival was not achieved vs 16.5 months, respectively (p <0.001). CONCLUSIONS:Subepithelial prostatic stromal invasion from urothelial carcinoma has more favorable outcomes compared to transmural pT4a disease. Our results support the exclusion of subepithelial prostatic stromal invasion from the pT4a bladder urothelial carcinoma staging class.

OBJECTIVE:To identify the risk factors for, and complications associated with, the development of delirium after radical cystectomy. MATERIALS AND METHODS/METHODS:From July 2008 to December 2009, 59 patients, aged ≥65 years and undergoing radical cystectomy, were prospectively enrolled. The baseline cognitive status was assessed using the Mini-Mental Status Examination. Postoperative delirium was assessed using the Confusion Assessment Method. RESULTS:A total of 49 patients completed the surgery and all assessments. The incidence of postoperative delirium was 29%, with duration of 1-5 days. On univariate analysis, older age and preoperative Mini-Mental Status Examination score were associated with postoperative delirium. On multivariate analysis, only age was associated with postoperative delirium (odds ratio 1.52, 95% confidence interval 1.04-2.22, P=.03). The 2 groups did not differ in pathologic stage, length of surgery, intraoperative and postoperative narcotic usage, body mass index, age-adjusted Charlson comorbidity index, activities of daily living scores, smoking history, preoperative hematocrit, estimated blood loss, urinary tract infection, interval to a regular diet, or length of hospital stay. The patients who developed postoperative delirium were more likely to undergo readmission (odds ratio 10.7, 95% confidence interval 2.2-51.8, P=.01) and reoperation (odds ratio 9.2, 95% confidence interval 1.5-55.3, P=.03) but did not differ in the 90-day and 1-year mortality rates or incidence of postoperative complications. CONCLUSION/CONCLUSIONS:In patients aged≥65 years, a lower preoperative Mini-Mental Status Examination score and older age were significantly associated with the development of postcystectomy delirium, as measured using the Confusion Assessment Method. The patients who developed delirium were more likely to undergo readmission and reoperation. Larger studies with multiple surgeons are needed to validate these findings.

Purpose. Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy is indicated for high-grade nonmuscle-invasive bladder cancer (NMIBC). The efficacy of BCG in patients with a history of previous pelvic radiotherapy (RT) may be diminished. We evaluated the outcomes of radical cystectomy for BCG-treated recurrent bladder cancer in patients with a history of RT for prostate cancer (PC). Methods. A retrospective chart review was performed to identify patients with primary NMIBC. We compared the outcomes of three groups of patients who underwent radical cystectomy for BCG-refractory NMIBC: those with a history of RT for PC, those who previously underwent radical prostatectomy (RP), and a cohort without PC or RT exposure. Results. From 1996 to 2008, 53 patients underwent radical cystectomy for recurrent NMIBC despite BCG. Those with previous pelvic RT were more likely to have a higher pathologic stage and decreased recurrence-free survival compared to the groups without prior RT exposure. Conclusion. Response rates for intravesical BCG therapy may be impaired in those with prior prostate radiotherapy. Patients with a history of RT who undergo radical cystectomy after failed BCG are more likely to be pathologically upstaged and have decreased recurrence-free survival. Earlier consideration of radical cystectomy may be warranted for those with NMIBC who previously received RT for PC.

PURPOSE/OBJECTIVE:The benefit of routine mechanical bowel preparation for patients undergoing radical cystectomy is not well established. We compared postoperative complications in patients who did or did not undergo mechanical bowel preparation before radical cystectomy. MATERIALS AND METHODS/METHODS:In 2008 a single surgeon (GDS) performed open radical cystectomy with an ileal conduit or orthotopic neobladder in 105 consecutive patients with preoperative mechanical bowel preparation consisting of 4 l GoLYTELY®. In 2009 radical cystectomy with an ileal conduit or orthotopic neobladder was performed in 75 consecutive patients without mechanical bowel preparation. A comprehensive database provided clinical, pathological and outcome data. RESULTS:All patients had complete perioperative data available. The 2 groups were similar in age, Charlson comorbidity score, diversion type, receipt of neoadjuvant radiation or chemotherapy, blood loss, hospital stay, time to diet and pathological stage. Postoperative urinary tract infection, wound dehiscence and perioperative death rates were similar in the 2 groups. Clostridium difficile infection developed within 30 days of surgery in 11 of 105 vs 2 of 75 patients with vs without mechanical bowel preparation (p = 0.08). When adjusted for the annual hospital-wide C. difficile rate, the difference remained insignificant (p = 0.21). Clavien grade 3 or greater abdominal and gastrointestinal complications, including fascial dehiscence, abdominal abscess, small bowel obstruction, bowel leak and entero-diversion fistula, developed in 7 of 105 patients with (6.7%) vs 11 of 75 without (14.7%) mechanical bowel preparation (p = 0.08). CONCLUSIONS:The use of mechanical bowel preparation for patients undergoing radical cystectomy with an ileal conduit or orthotopic neobladder does not seem to impact the rates of perioperative infectious, wound and bowel complications. Larger series with multiple surgeons are necessary to confirm these findings.

OBJECTIVE:Radical cystectomy (RC) for bladder cancer can be associated with significant morbidity and alterations in health-related quality of life (HRQOL). The Functional Assessment of Cancer Therapy--Vanderbilt Cystectomy Index (FACT-VCI) is a condition-specific HRQOL survey for patients undergoing RC and urinary diversion (UD) for bladder cancer. This study evaluates the reliability, validity, and responsiveness of the Vanderbilt cystectomy index (VCI). METHODS:The FACT-VCI was administered to patients with bladder cancer undergoing RC and UD (n = 190) at 2 major cancer centers. Statistical methods included principal components analysis, Cronbach's coefficient alpha, and nonparametric correlation coefficients. The Functional Assessment of Cancer Therapy--General (FACT-G) was used to test criterion-related validity and a linear mixed model tested the effects of time and diversion type on longitudinal VCI scores. RESULTS:A single summary score of 15 gender-neutral items (VCI-15) represented the optimum solution for postoperative data, which was internally consistent (α = 0.85), had strong retest reliability (ρ = 0.891), and was associated with all FACT-G scales and total score (ρ ≥ 0.38, P <.001). Preoperatively, the VCI-15 was internally consistent (α = 0.77) and was associated with the FACT-G physical and functional scales and total score (ρ ≥ 0.41, P <.001). Although VCI-15 scores at postoperative year 1 did not differ from preoperative values overall (P = .145), they did differ by diversion type (P = .027), with no substantive change after orthotopic neobladder (40 ± 9 vs 39 ± 10) but with a clinically significant improvement after an ileal conduit (39 ± 11 vs 44 ± 11). CONCLUSION/CONCLUSIONS:The VCI-15 is a reliable and valid condition-specific HRQOL survey for patients with bladder cancer undergoing RC and UD. Future studies of RC patients should measure HRQOL using validated, condition-specific forms, such as the FACT-VCI.

Approximately 50% of bladder cancer incidence in the United States has been attributed to known carcinogens, mainly from cigarette smoking. Following the identification of this important causative factor, many investigators have attempted to identify other major causes of bladder cancer in the environment. Genetic and epigenetic alterations related to carcinogenesis in the bladder have been linked to environmental and occupational factors unrelated to cigarette smoking and may account for a significant portion of bladder cancer cases in non-smokers. The interaction between genetics and exposures may modulate bladder cancer risk and influence the differing incidence, progression, and mortality of this disease in different genders and races. Comparative molecular studies are underway to measure the relative effects of environment and inheritance to account for observed differences in the epidemiology of bladder cancer. The use of geospatial tools and population-based data will offer further insight into the environmentally-linked causes of bladder cancer.