Variation in the Diagnostic Evaluation among Persons with Hematuria: Influence of Gender, Race and Risk Factors for Bladder Cancer.

PURPOSE: We sought to determine whether race, gender and number of bladder cancer risk factors are significant predictors of hematuria evaluation. MATERIALS AND METHODS: We used self-reported data from SCCS (Southern Community Cohort Study) linked to Medicare claims data. Evaluation of subjects diagnosed with incident hematuria was considered complete if imaging and cystoscopy were performed within 180 days of diagnosis. Exposures of interest were race, gender and risk factors for bladder cancer. RESULTS: Of the 1,412 patients evaluation was complete in 261 (18%). On our adjusted analyses African American patients were less likely than Caucasian patients to undergo any aspect of evaluation, including urology referral (OR 0.72, 95% CI 0.56-0.93), cystoscopy (OR 0.67, 95% CI 0.50-0.89) and imaging (OR 0.75, 95% CI 0.59-0.95). Women were less likely than men to be referred to a urologist (OR 0.59, 95% CI 0.46-0.76). Also, although all patients with 2 or 3 risk factors had 31% higher odds of urology referral (OR 1.31, 95% CI 1.02-1.69), adjusted analyses indicated that this effect was only apparent among men. CONCLUSIONS: Only 18% of patients with an incident hematuria diagnosis underwent complete hematuria evaluation. Gender had a substantial effect on referral to urology when controlling for socioeconomic factors but otherwise it had an unclear role on the quality of evaluation. African American patients had markedly lower rates of thorough evaluation than Caucasian patients. Number of risk factors predicted referral to urology among men but it was otherwise a poor predictor of evaluation. There is opportunity for improvement by increasing the completion of hematuria evaluations, particularly in patients at high risk and those who are vulnerable.

Loss of FOXA1 Drives Sexually Dimorphic Changes in Urothelial Differentiation and Is an Independent Predictor of Poor Prognosis in Bladder Cancer.

We previously found loss of forkhead box A1 (FOXA1) expression to be associated with aggressive urothelial carcinoma of the bladder, as well as increased tumor proliferation and invasion. These initial findings were substantiated by The Cancer Genome Atlas, which identified FOXA1 mutations in a subset of bladder cancers. However, the prognostic significance of FOXA1 inactivation and the effect of FOXA1 loss on urothelial differentiation remain unknown. Application of a univariate analysis (log-rank) and a multivariate Cox proportional hazards regression model revealed that loss of FOXA1 expression is an independent predictor of decreased overall survival. An ubiquitin Cre-driven system ablating Foxa1 expression in urothelium of adult mice resulted in sex-specific histologic alterations, with male mice developing urothelial hyperplasia and female mice developing keratinizing squamous metaplasia. Microarray analysis confirmed these findings and revealed a significant increase in cytokeratin 14 expression in the urothelium of the female Foxa1 knockout mouse and an increase in the expression of a number of genes normally associated with keratinocyte differentiation. IHC confirmed increased cytokeratin 14 expression in female bladders and additionally revealed enrichment of cytokeratin 14-positive basal cells in the hyperplastic urothelial mucosa in male Foxa1 knockout mice. Analysis of human tumor specimens confirmed a significant relationship between loss of FOXA1 and increased cytokeratin 14 expression.

Gender, race, and variation in the evaluation of microscopic hematuria among Medicare beneficiaries.

BACKGROUND: Female gender and black race are associated with delayed diagnosis and inferior survival in patients with bladder cancer. OBJECTIVE: We aimed to determine the association between gender, race, and evaluation of microscopic hematuria (an early sign of bladder cancer). DESIGN AND PARTICIPANTS: This was a cohort study using a 5 % random sample of fee-for-service Medicare beneficiaries diagnosed with incident hematuria (International Classification of Diseases, Ninth Revision [ICD-9] code 599.7x) between January 2009 and June 2010 in a primary care setting. Beneficiaries with pre-existing explanatory diagnoses or genitourinary procedures were excluded. MAIN MEASURES: The main endpoint was completeness of the hematuria evaluation in the 180 days after diagnosis. Evaluations were categorized as complete, incomplete, or absent based on receipt of relevant diagnostic procedures and imaging studies. KEY RESULTS: In all, 9,211 beneficiaries met the study criteria. Hematuria evaluations were complete in 14 %, incomplete in 21 %, and absent in 65 % of subjects. Compared to males, females were less likely to have a procedure (26 vs. 12 %), imaging (41 vs. 30 %), and a complete evaluation (22 vs. 10 %) (p < 0.001 for each comparison). Receipt of a complete evaluation did not differ by race. Controlling for baseline characteristics, a complete evaluation was less likely in white women (OR, 0.40 [95 % CI, 0.35-0.46]) and black women (OR, 0.46 [95 % CI, 0.29-0.70]) compared to white men; no difference was found between black and white men. CONCLUSIONS: Women are less likely than men to undergo a complete and timely hematuria evaluation, a finding likely relevant to women's more advanced stage at bladder cancer diagnosis. System-level process improvement between providers of urologic and primary care in the evaluation of hematuria may benefit women harboring malignancy.

Impact of complications and hospital-free days on health related quality of life 1 year after radical cystectomy.

PURPOSE: We determined the extent to which complications as well as number of hospital-free days within 30 and 90 days of surgery predicted health related quality of life 1 year after radical cystectomy. MATERIALS AND METHODS: We used data from a prospective health related quality of life study using a validated instrument, the Vanderbilt Cystectomy Index-15. Complications were graded by the Clavien system, and hospital length of stay and length of stay during readmissions were used to calculate 30 and 90-day hospital-free days, respectively. We compared the number of hospital-free days among patients with varying levels of complications. Multivariate analysis was performed to determine predictors of Vanderbilt Cystectomy Index-15 score 1 year after surgery adjusting for demographic (age, gender, comorbidities) and clinical variables (stage and diversion type). RESULTS: A total of 100 patients with complete baseline and 1-year followup health related quality of life data were included in the analysis. Median (IQR) 30 and 90-day hospital-free days were 24 (22-25) and 84 (82-85), respectively. Patients who experienced any complications had significantly fewer 30-day hospital-free days (22 vs 24 days, p <0.01) and 90-day hospital-free days (81 vs 84 days, p <0.01), and patients with higher grade complications had fewer hospital-free days than those with lower grade or no complications (p <0.01). On multivariate analysis female gender and baseline Vanderbilt Cystectomy Index-15 score independently predicted higher 1-year health related quality of life scores. CONCLUSIONS: Patients who experience complications after radical cystectomy have fewer 30 and 90-day hospital-free days. However, neither predicts health related quality of life at 1 year. Instead, long-term health related quality of life appears to be driven largely by baseline health related quality of life and gender.

Biochemical recurrence-free survival after robotic-assisted laparoscopic vs open radical prostatectomy for intermediate- and high-risk prostate cancer.

OBJECTIVE: To compare biochemical recurrence (BCR)-free survival and predictors of BCR in intermediate-risk (IR) and high-risk (HR) patients undergoing robotic-assisted laparoscopic prostatectomy (RALP) vs open radical prostatectomy (ORP). MATERIALS AND METHODS: We conducted a retrospective study on 1336 men with D'Amico IR or HR prostate cancer who underwent RALP or ORP between 2003 and 2009. Exclusion criteria were use of neoadjuvant therapy, <6 months of follow-up, and insufficient clinicopathologic data. We compared demographic, clinical, and pathologic variables between groups. Kaplan-Meier analysis was performed to compare the 5-year BCR-free survival between groups. Multivariate models were developed to determine whether surgical approach influences BCR. RESULTS: A total of 979 IR and HR patients (237 ORP and 742 RALP patients) met inclusion criteria. Median follow-up was shorter for RALP (43 vs 63 months; P<.001). ORP patients had a higher median prostate-specific antigen level (7.9 vs 6.7 ng/mL; P<.002), significantly more Gleason sum 8-10 tumors, and more adverse pathologic features overall. There was no difference in positive surgical margins between groups. Pathologic features including extraprostatic extension, seminal vesicle involvement, lymph node involvement, pathologic Gleason sum, and positive surgical margin were significant independent predictors of BCR in multivariate analysis. Surgical approach (RALP vs ORP) did not predict BCR when controlling for other known predictors of BCR. CONCLUSION: Among IR and HR prostate cancer patients, the oncologic outcomes are similar between RALP and ORP. Not surprisingly, adverse pathologic features are harbingers of BCR.

Variation in the intensity of hematuria evaluation: a target for primary care quality improvement.

BACKGROUND: Hematuria is a common clinical finding and represents the most frequent presenting sign of bladder cancer. The American Urological Association recommends cystoscopy and abdomino-pelvic imaging for patients aged more than 35 years. Nonetheless, less than half of patients presenting with hematuria undergo proper evaluation. We sought to identify clinical and nonclinical factors associated with evaluation of persons with newly diagnosed hematuria. METHODS: We performed a retrospective cohort study, using claims data and laboratory values. The primary exposure was practice site, as a surrogate for nonclinical, potentially modifiable sources of variation. Primary outcomes were cystoscopy or abdomino-pelvic imaging within 180 days after hematuria diagnosis. We modeled the association between clinical and nonclinical factors and appropriate hematuria evaluation. RESULTS: We identified 2455 primary care patients aged 40 years or more and diagnosed with hematuria between 2004 and 2012 in the absence of other explanatory diagnosis; 13.7% of patients underwent cystoscopy within 180 days. Multivariate logistic regression revealed significant variation between those who did and did not undergo evaluation in age, gender, and anticoagulant use (P < .001, P = .036, P = .028, respectively). Addition of practice site improved the predictive discrimination of each model (P < .001). Evaluation was associated with a higher rates of genitourinary neoplasia diagnosis. CONCLUSIONS: Patients with hematuria rarely underwent complete evaluation. Although established risk factors for malignancy were associated with increasing use of diagnostic testing, factors unassociated with risk, such as practice site, also accounted for significant variation. Inconsistency across practice sites is undesirable and may be amenable to quality improvement interventions.

Benchmarking the use of a rapid response team by surgical services at a tertiary care hospital.

BACKGROUND: Rapid response teams (RRT) are used to prevent adverse events in patients with acute clinical deterioration, and to save costs of unnecessary transfer in patients with lower-acuity problems. However, determining the optimal use of RRT services is challenging. One method of benchmarking performance is to determine whether a department's event rate is commensurate with its volume and acuity. STUDY DESIGN: Using admissions between 2009 and 2011 to 18 distinct surgical services at a tertiary care center, we developed logistic regression models to predict RRT activation, accounting for days at-risk for RRT and patient acuity, using claims modifiers for risk of mortality (ROM) and severity of illness (SOI). The model was used to compute observed-to-expected (O/E) RRT use by service. RESULTS: Of 45,651 admissions, 728 (1.6%, or 3.2 per 1,000 inpatient days) resulted in 1 or more RRT activations. Use varied widely across services (0.4% to 6.2% of admissions; 1.39 to 8.73 per 1,000 inpatient days, unadjusted). In the multivariable model, the greatest contributors to the likelihood of RRT were days at risk, SOI, and ROM. The O/E RRT use ranged from 0.32 to 2.82 across services, with 8 services having an observed value that was significantly higher or lower than predicted by the model. CONCLUSIONS: We developed a tool for identifying outlying use of an important institutional medical resource. The O/E computation provides a starting point for further investigation into the reasons for variability among services, and a benchmark for quality and process improvement efforts in patient safety.

Racial variation in the quality of surgical care for bladder cancer.

BACKGROUND: Differences in quality of care may contribute to racial variation in outcomes of bladder cancer (BCa). Quality indicators in patients undergoing surgery for BCa include the use of high-volume surgeons and high-volume hospitals, and, when clinically indicated, receipt of pelvic lymphadenectomy, receipt of continent urinary diversion, and undergoing radical cystectomy instead of partial cystectomy. The authors compared these quality indicators as well as adverse perioperative outcomes in black patients and white patients with BCa. METHODS: The Healthcare Cost and Utilization Project State Inpatient Databases for New York, Florida, and Maryland (1996-2009) were used, because they consistently included race, surgeon, and hospital identifiers. Quality indicators were compared across racial groups using regression models adjusting for age, sex, Elixhauser comorbidity sum, insurance, state, and year of surgery, accounting for clustering within hospital. RESULTS: Black patients were treated more often by lower volume surgeons and hospitals, they had significantly lower receipt of pelvic lymphadenectomy and continent diversion, and they experienced higher rates of adverse outcomes compared with white patients. These associations remained significant for black patients who received treatment from surgeons and at hospitals in the top volume decile. CONCLUSIONS: Black patients with BCa had lower use of experienced providers and institutions for BCa surgery. In addition, the quality of care for black patients was lower than that for whites even if they received treatment in a high-volume setting. This gap in quality of care requires further investigation.

Incidence and predictors of understaging in patients with clinical T1 urothelial carcinoma undergoing radical cystectomy.

OBJECTIVE: To evaluate predictors of understaging in patients with presumed non-muscle-invasive bladder cancer (NMIBC) identified on transurethral resection of bladder tumour (TURBT) who underwent radical cystectomy (RC) with attention to the role of a restaging TURBT. PATIENTS AND METHODS: We retrospectively evaluated 279 consecutive patients with clinically staged T1 (cT1) disease after TURBT who underwent RC at our institution from April 2000 to July 2011. In all, 60 of these cT1 patients had undergone a restaging TURBT before RC. The primary outcome measure was pathological staging of ≥T2 disease at the time of RC. RESULTS: In all, 134 (48.0%) patients were understaged. Of the 60 patients who remained cT1 after a restaging TURBT, 28 (46.7%) were understaged. Solitary tumour (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.25-0.76, P = 0.004) and fewer prior TURBTs (OR 0.84, 95% CI 0.71-1.00, P = 0.05) were independent risk factors for understaging. CONCLUSIONS: Despite the overall improvement in staging accuracy linked to restaging TURBTs, the risk of clinical understaging remains high in restaged patients found to have persistent T1 urothelial carcinoma who undergo RC. Solitary tumour and fewer prior TURBTs are independent risk factors for being understaged. Incorporating these predictors into preoperative risk stratification may allow for augmented identification of those patients with clinical NMIBC who stand to benefit most from RC.

Roadmap for the development of the University of North Carolina at Chapel Hill Genitourinary OncoLogy Database--UNC GOLD.

BACKGROUND: The management of genitourinary malignancies requires a multidisciplinary care team composed of urologists, medical oncologists, and radiation oncologists. A genitourinary (GU) oncology clinical database is an invaluable resource for patient care and research. Although electronic medical records provide a single web-based record used for clinical care, billing, and scheduling, information is typically stored in a discipline-specific manner and data extraction is often not applicable to a research setting. A GU oncology database may be used for the development of multidisciplinary treatment plans, analysis of disease-specific practice patterns, and identification of patients for research studies. Despite the potential utility, there are many important considerations that must be addressed when developing and implementing a discipline-specific database. METHODS AND MATERIALS: The creation of the GU oncology database including prostate, bladder, and kidney cancers with the identification of necessary variables was facilitated by meetings of stakeholders in medical oncology, urology, and radiation oncology at the University of North Carolina (UNC) at Chapel Hill with a template data dictionary provided by the Department of Urologic Surgery at Vanderbilt University Medical Center. Utilizing Research Electronic Data Capture (REDCap, version 4.14.5), the UNC Genitourinary OncoLogy Database (UNC GOLD) was designed and implemented. RESULTS: The process of designing and implementing a discipline-specific clinical database requires many important considerations. The primary consideration is determining the relationship between the database and the Institutional Review Board (IRB) given the potential applications for both clinical and research uses. Several other necessary steps include ensuring information technology security and federal regulation compliance; determination of a core complete dataset; creation of standard operating procedures; standardizing entry of free text fields; use of data exports, queries, and de-identification strategies; inclusion of individual investigators' data; and strategies for prioritizing specific projects and data entry. CONCLUSIONS: A discipline-specific database requires a buy-in from all stakeholders, meticulous development, and data entry resources to generate a unique platform for housing information that may be used for clinical care and research with IRB approval. The steps and issues identified in the development of UNC GOLD provide a process map for others interested in developing a GU oncology database.