Rational peri-operative management of antithrombotic therapy in patients undergoing radical cystectomy: A 30-day morbidity analysis based on the updated European Association of Urology guidelines for standardized complication reporting.

BACKGROUND: Radical cystectomy (RC) in bladder cancer patients with cardiovascular comorbidity poses challenges due to the need for antithrombotic therapy and high perioperative risk. We aimed to assess 30-day complications after RC in patients receiving antithrombotic therapy. PATIENTS AND METHODS: Retrospective study of 416 bladder cancer patients (2009-2017) undergoing open RC with pelvic lymph node dissection, with or without antithrombotic therapy. Antithrombotic therapy and complication reporting followed European guidelines. Procedure-specific 30-day complications were cataloged, graded (Clavien-Dindo), and quantified using the 30-day Comprehensive Complication Index. Multivariable regressions evaluated antithrombotic therapy's independent effect on key morbidity outcomes. RESULTS: Median age was 70 years, 78% were male. Patients on antithrombotic therapy were mostly male, had higher comorbidity burden, worse kidney function, more frequent incontinent diversion, and shorter operative time (all p ≤ 0.027). Bleeding complications occurred in 135 patients (32%; 95%CI = 28-37%), more prevalent with antithrombotic therapy (46% vs. 29%; p = 0.004). Thromboembolic complications occurred in 18 patients (4.3%; 95%CI = 2.6-6.8%), no difference between patients with and without antithrombotic therapy (8.4% vs. 3.3%; p = 0.063). Prevalence of myocardial infarction, new-onset hypertension, acute congestive heart failure, and angina pectoris showed no difference (all p ≥ 0.3). Multivariable analyses indicated no association between antithrombotic therapy and cardiac complications, 30-day major complications, or cumulative morbidity (all p ≥ 0.2). Antithrombotic therapy was associated with bleeding complications (OR = 1.92; 95%CI = 1.07-3.45; p = 0.028), predominantly transfusion-related (75% of 152 bleeding complications). Limitations include retrospective data assessment with biases. CONCLUSIONS: RC in patients on antithrombotic therapy exhibits a higher incidence of adverse events due to underlying comorbidities. Adherence to thromboprophylaxis guidelines enables safe RC in patients with significant comorbidities, without substantial increase in major bleeding or severe thromboembolic events.

Uretero-enteric Strictures After Robot Assisted Radical Cystectomy: Prevalence and Management Over Two Decades.

INTRODUCTION: To evaluate the prevalence, predictors, management, and trends for ureteroenteric strictures (UES) after robot-assisted radical cystectomy (RARC). METHODS: Retrospective review of our RARC database was performed (2005-2022). UES was described in terms of timing, laterality, and management. Kaplan-Meier curves were used to depict time to UES. Local regression was used to assess trend of UES over time and multivariable regression to identify variables associated with UES. RESULTS: UES occurred in 109 patients (15%). UES occurred in 13%, 17%, and 19% at 1, 3, and 5 years after RARC, respectively. Incidence of UES decreased in 2017, coinciding with stentless uretero-enteric anastomosis. UES occurred on the right in 33%, on the left in 46%, and bilaterally in 21%. All patients were initially managed by nephrostomy/stent. Surgical revision was required in 45% of patients, of which 13% developed recurrent UES after revision. On MVA, UES formation was associated with ureteral stents (OR 2.27, 95%CI 1.01-5.10, P = .05) and receipt of neoadjuvant chemotherapy (OR 2.01, 95%CI 1.24-3.25, P = .005). CONCLUSION: UES occurred in 15% of patients after RARC, with 45% of patients requiring surgical reimplantation. Ureteral stents and the receipt of neoadjuvant chemotherapy were associated with UES formation.

Sodium-Glucose Cotransporter 2 Inhibitors and the Short-term Risk of Bladder Cancer: An International Multisite Cohort Study.

OBJECTIVE: To determine whether sodium-glucose cotransporter 2 (SGLT2) inhibitors, compared with glucagon-like peptide 1 receptor agonists (GLP-1RAs) or dipeptidyl peptidase 4 (DPP-4) inhibitors, are associated with an increased risk of early bladder cancer events. RESEARCH DESIGN AND METHODS: We conducted a multisite, population-based, new-user, active comparator cohort study using the U.K. Clinical Practice Research Datalink, Medicare fee-for-service, Optum's de-identifed Clinformatics Data Mart Database (CDM), and MarketScan Health databases from January 2013 through December 2020. We assembled two cohorts of adults with type 2 diabetes initiating 1) SGLT2 inhibitors or GLP-1RAs and 2) SGLT2 inhibitors or DPP-4 inhibitors. Cox proportional hazards models were fit to estimate hazard ratios (HRs) and 95% CIs of incident bladder cancer. The models were weighted using propensity score fine stratification. Site-specific HRs were pooled using random-effects models. RESULTS: SGLT2 inhibitor (n = 453,560) and GLP-1RA (n = 375,997) users had a median follow-up ranging from 1.5 to 2.2 years. Overall, SGLT2 inhibitors were not associated with an increased risk of bladder cancer compared with GLP-1RAs (HR 0.90, 95% CI 0.81-1.00). Similarly, when compared with DPP-4 inhibitors (n = 853,186), SGLT2 inhibitors (n = 347,059) were not associated with an increased risk of bladder cancer (HR 0.99, 95% CI 0.91-1.09) over a median follow-up ranging from 1.6 to 2.6 years. Results were consistent across sensitivity analyses. CONCLUSIONS: Contrary to previous randomized controlled trials, these findings indicate that the use of SGLT2 inhibitors is not associated with an increased risk of bladder cancer compared with GLP-1RAs or DPP-4 inhibitors. This should provide reassurance on the short-term effects of SGLT2 inhibitors on bladder cancer incidence.

Preoperative anemia is associated with increased radical cystectomy complications.

PURPOSE: The impact of anemia in postoperative complications following radical cystectomy (RC) is not completely elucidated and its association with direct hospital costs has not been characterized in depth. Our goal is to determine the association between anemia, 90-day surgical complications and the expenditure attributed to preoperative anemia in patients undergoing RC. MATERIALS AND METHODS: We captured all patients who underwent RC between 2003 and 2017 using the Premier Hospital Database (Premier Inc, Charlotte, NC). Patient, hospital and surgical characteristics were evaluated. Anemia was defined by a corresponding diagnostic code that was present on admission prior to RC. Unadjusted patients' demographic characteristics with and without anemia, hospital and surgeon characteristics were compared, and multivariable regression models were developed to evaluate 90-day complications and total direct hospital costs. RESULTS: The cohort included 83,470 patients that underwent RC between 2003 and 2017 and 11% were found to be anemic. On multivariable analysis, preoperative anemia more than doubled the odds of having a complication (odds ratio 2.19 (1.89-2.53)) and significantly increased the risk of major complications (odds ratio 1.51 (1.31-1.75)) at 90-days after RC. Anemic patients had significantly higher 90-days total direct costs due to higher laboratory, pharmacologic, radiology and operating room costs. CONCLUSIONS: Anemic cystectomy patients face a 50% increase in the risk of major complications within the first 90-days after surgery. This increased risk persisted after adjusting for patient, hospital and surgical factors. Our study suggests hematocrit level prior to RC may be used as a pre-exisitng condition for increased risk of surgical complications.

A comparative population-based analysis of peritoneal carcinomatosis in patients undergoing robotic-assisted and open radical cystectomy.

PURPOSE: To compare the population-based incidence of peritoneal carcinomatosis following open (ORC) vs. robotic-assisted radical cystectomy (RARC). METHODS: Using the Surveillance, Epidemiology and End Results Program (SEER)-Medicare linked data, we identified 1,621 patients who underwent radical cystectomy for bladder cancer during 2009 and 2014; 18.1% (n = 294) and 81.9% (n = 1327) underwent RARC and ORC, respectively. We subsequently evaluated the rates of peritoneal carcinomatosis at 6, 12, and 24 months following surgery. Multivariable proportional hazards regression was performed to determine factors associated with development of peritoneal carcinomatosis. RESULTS: Patients who underwent RARC vs. ORC were more likely to be male (p = 0.04); however, age at diagnosis, race, comorbidities, education, and marital status (all p > 0.05) did not differ by surgical approaches. Our findings showed that there were no significant differences in the rates of peritoneal carcinomatosis between ORC and RARC at 6, 12, and 24 months. In adjusted analyses, factors associated with peritoneal carcinomatosis were advanced N stage (N0 versus N2/3: HR 0.30, 95% CI 0.16-0.55, p < 0.01), preoperative hydronephrosis (HR 1.70, 95% CI 1.09-2.65, p = 0.04), higher T stage (T1 versus T4: HR 0.34, 95% CI 0.15-0.79, p < 0.01; T2 versus T4: HR 0.39, 95% CI 0.20-0.76, p < 0.01), and use of neoadjuvant chemotherapy (HR 1.78, 95% CI 1.11-2.84, p < 0.01). However, RARC was not associated with peritoneal carcinomatosis (HR 1.36, 95% CI 0.78-2.35). CONCLUSION: In this population-based analysis, we found no difference in peritoneal carcinomatosis between robotic or open approaches to radical cystectomy. These data should be reassuring to those utilizing robotic cystectomy.

Diagnostic and Cost Implications of the 2020 AUA Microhematuria Guidelines: Modeling Impact in a Large Public Health Care System.

PURPOSE: We sought to model the diagnostic recommendations and associated costs of new hematuria guidelines regarding referral patterns, procedure utilization and urothelial cell carcinoma (UCC) detection. MATERIALS AND METHODS: Patients with microhematuria were identified retrospectively. Initial encounter data were collected from January 2017 to May 2018 from a large public health care system; followup was continued to December 2020. Risk stratification was performed based on the American Urological Association 2020 microhematuria guidelines, and disease outcomes were analyzed within this framework. The guideline-recommended workups and costs were modeled; cost data were sourced from the Centers for Medicare & Medicaid Services Medicare Physician Fee Schedule and Clinical Laboratory Fee Schedule for 2020. Modeled diagnostic volumes and costs were assessed for 2020 and 2012 microhematuria guidelines, respectively. RESULTS: Of the 3,789 patients included for analysis, 1,382 (36.5%), 1,026 (27.1%) and 1,381 (36.4%) were retroactively stratified as low risk, intermediate risk (InR) and high risk (HiR), respectively. A total of 19 cases of UCC (17 bladder, 2 upper tract) were diagnosed, of which 84% were HiR. For high-grade UCC, 92% of cases were HiR. The 2020 guidelines recommended renal ultrasound for 1,117 InR cases, computerized tomography urogram (CTU) for 1,476 HiR cases, and cystoscopy for 2,593 InR and HiR cases combined. Total costs were $1,905,236 (2012) versus $1,260,677 (2020), driven mainly by CTU costs. Per-cancer detected costs were $100,276 (2012) versus $61,760 (2020). CONCLUSIONS: In retrospect, the 2020 guidelines would have effectively risk-stratified microhematuria cases for detection of malignancies. As compared to the 2012 guidelines, application of the 2020 guidelines would result in significant changes to diagnostic and procedural volumes, while substantially reducing total and per-patient costs.

Robot-assisted Versus Open Radical Cystectomy in Bladder Cancer: An Economic Evaluation Alongside a Multicentre Comparative Effectiveness Study.

BACKGROUND: Open radical cystectomy (ORC) is regarded as the standard treatment for muscle-invasive bladder cancer, but robot-assisted radical cystectomy (RARC) is increasingly used in practice. A recent study showed that RARC resulted in slightly fewer minor but slightly more major complications, although the difference was not statistically significant. Some differences were found in secondary outcomes favouring either RARC or ORC. RARC use is expected to increase in coming years, which fuels the debate about whether RARC provides value for money. OBJECTIVE: To assess the cost-effectiveness of RARC compared to ORC in bladder cancer. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation was performed alongside a prospective multicentre comparative effectiveness study. We included 348 bladder cancer patients (ORC, n = 168; RARC, n = 180) from 19 Dutch hospitals. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Over 1 yr, we assessed the incremental cost per quality-adjusted life year (QALY) gained from both healthcare and societal perspectives. We used single imputation nested in the bootstrap percentile method to assess missing data and uncertainty, and inverse probability of treatment weighting to control for potential bias. Deterministic sensitivity analyses were performed to explore the impact of various parameters on the cost difference. RESULTS AND LIMITATIONS: The mean healthcare cost per patient was €17 141 (95% confidence interval [CI] €15 791-€18 720) for ORC and €21 266 (95% CI €19 163-€23 650) for RARC. The mean societal cost per patient was €18 926 (95% CI €17 431-€22 642) for ORC and €24 896 (95% CI €21 925-€31 888) for RARC. On average, RARC patients gained 0.79 QALYs (95% CI 0.74-0.85) compared to 0.81 QALYs (95% CI 0.77-0.85) for ORC patients, resulting in a mean QALY difference of -0.02 (95% CI -0.05 to 0.02). Using a cost-effectiveness threshold of €80 000, RARC was cost-effective in 0.6% and 0.2% of the replications for the healthcare and societal perspectives, respectively. CONCLUSIONS: RARC shows no difference in terms of QALYs, but is more expensive than ORC. Hence, RARC does not seem to provide value for money in comparison to ORC. PATIENT SUMMARY: This study assessed the relation between costs and effects of robot-assisted surgery compared to open surgery for removal of the bladder in 348 Dutch patients with bladder cancer. We found that after 1 year, the two approaches were similarly effective according to a measure called quality-adjusted life years, but robot-assisted surgery was much more expensive. This trial was prospectively registered in the Netherlands Trial Register as NTR5362 (https://www.trialregister.nl/trial/5214).

Assessment of a clinical pathway for investigation of haematuria that reduces the need for cystoscopy.

AIM: To evaluate prospectively a clinical pathway for investigation of haematuria that involves an initial screening using a urinary biomarker of bladder cancer (Cxbladder Triage™ (CxbT)) in combination with either a renal ultrasound or a computed tomography imaging. Only test-positive patients are referred for specialist assessment and flexible cystoscopy. METHODS: The clinical outcomes of 884 patients with haematuria who presented to their general practitioner were reviewed. Outcome measurements included the findings of laboratory tests, imaging, cystoscopies, specialist assessment and histology. RESULTS: Forty-eight transitional cell carcinomas (TCC) and three small cell carcinomas were diagnosed in the study cohort. The clinical pathway missed a solitary, small, low-risk TCC. When combined, imaging and CxbT had a sensitivity of 98.1% and a negative predictive value of 99.9% to detect a bladder cancer. Follow-up for a median of 21 months showed no further new cases of bladder cancer had occurred in the patient cohort. Review of all new bladder cancers diagnosed in the 15 months following the study showed that none had been missed by haematuria assessment using the clinical pathway. CONCLUSIONS: The combination of CxbT and imaging reliably identifies patients with haematuria who can be managed safely in primary care without the need for a secondary care referral and a flexible cystoscopy.

The cost of obesity in radical cystectomy.

INTRODUCTION: The prevalence of obesity is on the rise in the Unites States, and obesity has been associated with increased complications and costs in a variety of complex surgeries. However, the contribution of obesity to the overall costs of radical cystectomy has not been studied in detail using contemporary data. Our objective is to assess the variation in healthcare costs due to obesity on the index hospitalization for radical cystectomy in the United States between 2003 and 2015. MATERIALS AND METHODS: This was a retrospective cohort study, using the Premier Healthcare Database, of 1,242 patients who underwent radical cystectomy and were either overweight (25  ≤  body mass index [BMI] < 30), obese (30  ≤  BMI < 40), or morbidly obese (BMI ≥ 40). The primary outcome costs of the index hospitalization for each BMI category. Multivariable median regression was used to identify drivers of increased costs. RESULTS: The cost of the index hospitalization for cystectomy was $24,596 (95% confidence interval [CI], $22,599-$26,592) for overweight patients. The costs for obese and morbidly obese patients were $2,158 (95% CI, -$80 to $4,395, P = 0.059) and $5,308 (95% CI, $2,652-$7,964, P < 0.001) higher compared to overweight patients, respectively. After adjustment for operative time or length of stay in the multivariable models, there were no longer any differences in cost. Operative time was prolonged as BMI increased (median operative time for overweight, obese, and morbidly obese: 346, 391, and 420 minutes, respectively P = 0.0001). Median length of stay was 1 day shorter for overweight vs. morbidly obese patients (P = 0.0030), with each additional day costing $1,738 (95% CI, $1,654 to $1,821, P < 0.0001) on multivariable analysis. CONCLUSIONS: The cost of radical cystectomy is greater for obese and morbidly obese patients compared to overweight patients. The increased financial cost is driven by increased operative times and longer length of stay.

Unmet needs in sexual health in bladder cancer patients: a systematic review of the evidence.

BACKGROUND: Bladder cancer (BC) treatment can have a detrimental effect on the sexual organs of patients and yet assessment of sexual health needs has been greatly overlooked for these patients compared to those who have undergone other cancer therapies. METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines in July 2019. Studies were identified by conducting searches for Medline (using the PubMed interface), the Cochrane Central Register of Controlled Trials (CENTRAL) and Ovid Gateway (Embase and Ovid) using a list of defined search terms. RESULTS: 15 out of 37 studies included men only, 10 studies women only and 11 both sexes. Most participants were aged 50 to 65 years. Most studies (n = 34) focused on muscle invasive BC and only three on non-muscle invasive BC. Measurements of sexual dysfunction, including erection, ejaculation, firmness and desire, were the most commonly used measurements to report sexual health in men. In women, lubrification/dryness, desire, orgasm and dyspareunia were the most commonly reported. Twenty-one studies evaluated sexual dysfunction based on validated questionnaires, two with a non-validated questionnaire and through interviewing participants. CONCLUSION: While recognition of the importance of the inclusion of psychometric measurements to assess sexual health is growing, there is a lack of consistent measures to assess sexual health in BC. With the focus on QoL arising in cancer survivorship, further studies are needed to develop, standardize and implement use of sexual health questionnaires with appropriate psychometrics and social measures to evaluate QoL in BC patients. TRIAL REGISTRATION: "PROSPERO does not currently accept registrations for scoping reviews, literature reviews or mapping reviews. PROSPERO is therefore unable to accept your application or provide a registration number. This decision should not stop you from submitting your project for publication to a journal."

Nutrition risk and assessment process in patients with bladder cancer undergoing radical cystectomy.

Malnutrition and depleted muscle stores adversely affect bladder cancer patients and contribute to poorer outcomes. These nutrition-related problems are often not addressed, in part because they are not being identified with screening and assessment tools. In this essay, we discuss validated nutrition screening and assessment tools such as the Patient-Generated Subjective Global Assessment; however, each healthcare team must decide on the one which will work best for their clinic. Patients with bladder cancer may be at risk for specific nutrient deficiencies which should be monitored and corrected to improve outcomes and overall health.

Differences in short-term outcomes between open versus robot-assisted radical cystectomy in frail malnourished patients.

INTRODUCTION: We tested whether frail patients may benefit from robot-assisted (RARC) relative to open radical cystectomy (ORC). MATERIALS AND METHODS: Frail patients treated with RC were identified within the National Inpatient Sample database (2008-2015). The effect of RARC vs. ORC was tested in five separate multivariable models predicting: complications, failure to rescue (FTR), in-hospital mortality, length of stay (LOS) and total hospital charges (THCs). As internal validity measure, analyses were repeated among non-frail patients. All models were weighted and adjusted for clustering, as well as all available patient and hospital characteristics. RESULTS: Of 11,578 RC patients, 3477 (30.0%) were frail. RARC was performed in 488 (14.0%) frail patients and 1386 (17.1%) non-frail patients. Among frail, RARC was only independently associated with shorter LOS (median 8 vs. 9 days, relative ratio [RR] 0.79, p < 0.001). Conversely, among non-frail, RARC was independently associated with lower complications (57.3 vs. 59.1%, odds ratio [OR] 0.82, p = 0.004) and shorter LOS (median 6 vs. 7 days, RR 0.88, p < 0.001), but also predicted higher THCs (+2850.3 US dollars, p = 0.001). CONCLUSIONS: In frail patients, the use of RARC did not result in better short-term outcomes except for one-day advantage in LOS. Conversely, in non-frail patients, the use of RARC resulted in lower complication rates and shorter LOS at the cost of higher THCs. In consequence, the benefit of RARC appears relatively marginal in frail patients and our data do not suggest a clear and clinically-meaningful benefit of RARC over ORC in frail radical cystectomy population.

Frailty and preoperative risk assessment before radical cystectomy.

PURPOSE OF REVIEW: The current review covers recent research examining the utility of preoperative frailty assessments to predict worse postoperative outcomes after radical cystectomy. It also discusses how to implement frailty assessments into routine clinical practice. RECENT FINDINGS: Frailty is associated with worse postoperative outcomes after radical cystectomy, including increased complications and nonhome discharge. Although the majority of these studies have been retrospective using a frailty index, prospective studies using a preoperative frailty assessment have also shown frailty to be associated with worse outcomes. Preoperative frailty assessments based on patients' physiologic fitness, such as the Fried Frailty Criteria or psoas muscle volume, have been the best predictors of worse outcomes on prospective cohorts. However, no study to date has directly compared a prospective frailty assessment and frailty index to determine the most effective tool for routine clinical care. National guidelines are lacking on how to assess frailty preoperatively before radical cystectomy. SUMMARY: Frailty has been consistently shown to correlate with worse postoperative outcomes after radical cystectomy. Although the most effective and efficient method for preoperative assessment has yet to be determined, assessments based on physiologic fitness are likely to be most useful. Improved guidelines will likely increase implementation of frailty assessments into routine management.

Bladder Cancer Survivorship.

PURPOSE OF REVIEW: Bladder cancer (BC) is the second most common genitourinary malignancy, with a growing population of survivors globally. Over the past two decades, there has been a growing awareness of not only the oncologic, but also the quality of life ramifications of a BC diagnosis, treatment, and surveillance. In the current review, the literature surrounding the many domains that encompass bladder cancer survivorship is summarized and analyzed. RECENT FINDINGS: There have been ongoing efforts to decrease perioperative morbidity, particularly in patients undergoing radical cystectomy, with mixed results. There is a growing emphasis on the short and long-term health-related quality of life (HR-QoL) impacts of bladder cancer spanning the domains of physical and mental QoL related to urinary function, sexual function, and financial and psychological burden, with validated measures specific to BC patients. There continue to be disparities in oncologic outcomes by race and gender. The impact of BC is prolonged and there is an unmet need for long term support and survivorship resources to address this. There is a growing global population of bladder cancer patients, and their needs are complex and vary by stage, treatment, and certain demographic features. Outcome-centered perioperative strategies show potential to diminish treatment morbidity, and validated BC specific HR-QoL tools have helped to define the impact and burden of BC, but there continue to be large areas of unmet need that warrant greater study and intervention.

Health-related quality of life after BCG or MMC induction for non-muscle invasive bladder cancer.

INTRODUCTION: To evaluate health-related quality of life (HRQoL) in patients with non-muscle invasive bladder cancer (NMIBC) during the induction phase of intravesical instillations with BCG or MMC. MATERIALS AND METHODS: HRQoL was measured by two questionnaires from EORTC (QLQ-C30 and QLQ-BLS24), stratifying results by gender, age and therapy at the start of the therapy (T0), at last instillation (T1) and at 3 months after T1 (T2). The persistence of QoL-related side effects after 3 months from the end of the induction cycle was evaluated. RESULTS: We enrolled 108 naïve patients and 103 patients self-completed the questionnaires. Treatment was well tolerated in both groups. Side effects were reported by 46.6% of patients at T1 and 47.5% of patients at T2. QoL dropped at T1, returning to the baseline at T2. Drop of QoL was greater in the physical, role, emotional and social functioning domains and in some clinical domains as pain, fatigue and insomnia. Our stratified analysis showed that patients > 70 years have a worsening of QoL, a higher incidence of patient-reported side effects or symptoms in the BCG arm as compared to MMC arm. CONCLUSIONS: Our study shows that intravesical instillations of BCG or MMC during the induction phase might have a relevant effect on HRQoL.

Geographic Variation in Cystoscopy Rates for Suspected Bladder Cancer between Female and Male Medicare Beneficiaries.

OBJECTIVE: To assess geographic variation in cystoscopy rates among women vs men with suspected bladder cancer, lending insight into gender-specific differences in cystoscopic evaluation. METHODS: We conducted a cross-sectional study of all fee-for-service Medicare beneficiaries within 306 Hospital Referral Regions (HRRs) who received care in 2014. For each HRR, we calculated the age- and race-adjusted cystoscopy rate for women and men as our primary outcome. The rate was the number of beneficiaries who underwent cystoscopy for bladder cancer symptoms (using procedure and ICD-9 diagnosis codes) divided by all beneficiaries in the HRR. We used the coefficient of variation to compare relative variability of cystoscopy rates. RESULTS: Overall, 173,551 women (n = 14.8 million) and 286,090 men (n = 11.5 million) underwent cystoscopy in 2014. While women received less cystoscopies compared to men (mean 11.0 vs 23.5 per 1000, P < .001), there was greater variation in cystoscopy rates among women (coefficient of variation 27.5 vs 23.5, P = .010). When restricting to ICD-9 codes for hematuria only, women continued to demonstrate greater variation in cystoscopy rates (coefficient of variation 27.8 vs 24.2, P = .022). Findings were robust across larger HRR sizes-thereby removing some random variation seen in smaller HRRs-as well as across years 2010, 2011, 2012, and 2013. CONCLUSION: Cystoscopy rates are lower in women than men, likely due to their lower bladder cancer incidence. However, there is greater variation in cystoscopy rates among women with symptoms of bladder cancer. This may reflect increased provider uncertainty whether to refer and work-up women with suspected bladder cancer.

Impact of psychiatric illness on decreased survival in elderly patients with bladder cancer in the United States.

BACKGROUND: Treatments for muscle-invasive bladder cancer are multimodal, complex, and often carry significant risks of physical and psychological morbidity. The objectives of this study were to define the incidence and types of psychiatric illnesses diagnosed after treatment and to determine their impact on survival outcomes. METHODS: In total, 3709 patients who were diagnosed with clinical stage T2 through T4a bladder cancer from January 1, 2002, to December 31, 2011, from the Surveillance, Epidemiology, and End Results-Medicare were analyzed. Multivariable analysis and Cox proportional-hazards models were used to determine the predictors associated with psychiatric diagnosis and impact on survival outcomes. RESULTS: Of 3709 patients, 1870 (50.4%) were diagnosed with posttreatment psychiatric disorders. Patients who underwent radical cystectomy were identified as being at significantly greater risk of having a posttreatment psychiatric illness compared with those who received radiotherapy and/or chemotherapy (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In adjusted analyses, diagnosis of a psychiatric disorder resulted in significantly worse overall survival (HR, 2.80; 95% CI, 2.47-3.17; P < .001) and cancer-specific survival (HR, 2.39; 95% CI, 2.05-2.78; P < .001). CONCLUSIONS: One-half of patients with muscle-invasive bladder cancer who underwent treatment were diagnosed with a psychiatric disorder, which resulted in worse survival outcomes compared with patients who did not have a posttreatment psychiatric diagnosis. This information can be used to inform interventions to educate patients with muscle-invasive bladder cancer regarding the impact of different treatments on mental health. Cancer 2018. © 2018 American Cancer Society.

Comparative safety of pioglitazone versus clinically meaningful treatment alternatives concerning the risk of bladder cancer in older US adults with type 2 diabetes.

AIMS: To compare bladder cancer incidence between patients initiating pioglitazone treatment and patients initiating treatment with dipeptidyl-peptidase-4 inhibitors [DPP-4s] or sulfonylureas. METHODS: We identified Medicare beneficiaries aged >65 years who initiated treatment with pioglitazone (N = 38 700), DPP-4s (N = 82 552) or sulfonylureas (N = 126 104) between 2007 and 2014 after at least 6 months without prescriptions for these drug classes. Patients were followed from second prescription until bladder cancer outcome (2 claims within 60 days) using a 6-month induction/latency period, censoring for treatment change, death or end of 2014. We used propensity score-weighted Cox proportional-hazards models to obtain adjusted hazard ratios (aHR) and their 95% confidence intervals. RESULTS: Overall mean age of participants was 75 years and 41% were men. Over a median of 1.2 treatment years, 727 beneficiaries developed bladder cancer. Pioglitazone initiators had an increased incidence of bladder cancer (308 vs 204 [DPP-4s] or 231 [sulfonylureas] per 100 000 person-years; aHR, 1.57 [1.23-2.00] vs DPP-4s and 1.32 [1.02-1.70] vs sulfonylureas). The increased risk emerged within the first 2 years of treatment (aHR, 1.63 [1.22-2.17] vs DPP-4s and 1.32 [0.98-1.78] vs sulfonylureas). If treatment was discontinued within the first 2 years, the risk after 2 years post initiation was attenuated (aHR, 0.89 [0.61-1.28]) compared with patients treated for more than 2 years (aHR, 1.45 [0.93-2.26]) both vs DPP-4s. Findings were consistent across secondary and sensitivity analyses. CONCLUSIONS: Pioglitazone was associated with an elevated risk of bladder cancer compared with DPP-4s and sulfonylureas. The elevated risk emerged within the first 2 years of treatment and was attenuated after discontinuing. Pioglitazone's relative effectiveness should be weighed against a small absolute increase in risk of bladder cancer.

Factors affecting the timeliness and adequacy of haematuria assessment in bladder cancer: a systematic review.

OBJECTIVES: To review the literature to identify factors affecting haematuria assessment in bladder cancer. METHODS: We performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Publications indexed in EMBASE and Medline (PubMed) in March 2016 were searched, using the keywords 'hematuria', 'urinary bladder neoplasm(s)' and 'bladder tumor'. Studies evaluating the timeliness and adequacy of haematuria assessment in the context of bladder cancer were included. Exclusion criteria included age <18 years, animal studies and non-English articles. RESULTS: Following our search strategy, a total of 17 articles were included in our study. All 17 studies commented on gender, with female gender associated with delayed and inadequate haematuria evaluation. Women waited longer than men for urological review (three studies) and bladder cancer diagnosis (three studies). Women were also less likely to be referred to urology (two studies), receive imaging (three studies) or have cystoscopy (two studies). In all, 10 studies commented on age, with the impression that advancing age is associated with a more thorough assessment. Smokers and those with microscopic haematuria appear to undergo a less thorough evaluation. CONCLUSION: Female gender is associated with sub-optimal haematuria evaluation, while older patients are evaluated more thoroughly. Smokers paradoxically undergo less comprehensive assessment. Further research on the impact of other factors is required.

Evaluation of gender-based disparities in time from initial haematuria presentation to upper tract urothelial carcinoma diagnosis: analysis of a nationwide insurance claims database.

OBJECTIVE: To investigate the length of time from initial haematuria presentation to upper tract urothelial carcinoma (UTUC) diagnosis and the effect of gender on this duration. PATIENTS AND METHODS: Patients with haematuria claims in the year prior to UTUC diagnosis were identified from the MarketScan database (2010-2014). Delayed diagnosis was defined as >90 days from haematuria presentation to UTUC diagnosis. Multivariable Poisson regression models were used to determine factors associated with delayed UTUC diagnosis. RESULTS: Among 1 326 patients with UTUC, 469 (35.4%) experienced delayed diagnosis. Men (n = 866) had a longer median interval from haematuria to diagnosis than women (60 vs 49 days; P = 0.04). In the multivariable model, male gender (relative risk [RR] 1.13, 95% confidence interval [CI] 0.95-1.34) was not associated with delayed diagnosis, while urinary tract infection (UTI; RR 1.52, 95% CI 1.32-1.76), nephrolithiasis (RR 1.23, 95% CI 1.06-1.44), new (RR 1.37, 95% CI 1.12-1.66) and recurrent prostate-related diagnoses (RR 1.61, 95% CI 1.23-2.10) were. For men presenting to non-urologists, UTI (RR 1.44, 95% CI 1.22-1.71), nephrolithiasis (RR 1.25 95% CI 1.05-1.49), new (RR 1.41, 95% CI 1.12-1.78) and recurrent prostate-related diagnoses (RR 1.94, 95% CI 1.45-2.58) were associated with delayed diagnosis; however, for men presenting to urologists, nephrolithiasis (RR 1.08 95% CI 0.78-1.49), new (RR 1.15, 95% CI 0.79-1.68) and recurrent prostate-related diagnoses (RR 1.17, 95% CI 0.69-1.97) were not associated with delayed diagnosis, while UTI diagnosis (RR 1.74, 95% CI 1.31-2.31) was still associated with delayed diagnosis. CONCLUSION: A UTUC diagnosis was made >90 days after haematuria presentation in approximately one-third of patients. Men experienced a longer median interval from haematuria to UTUC diagnosis compared with women, but male gender was not an independent predictor of delayed diagnosis. Benign diagnoses during haematuria evaluation were strongly associated with delayed diagnosis, especially among patients initially seen by non-urologists. Future interventions should focus on development of non-invasive techniques to improve clinical risk stratification of patients presenting with haematuria and to educate practitioners, especially non-urologists, with regard to the importance of a thoughtful haematuria evaluation and the common mimickers of UTUC, to help reduce delays in diagnosis.