Clinical Trial Protocol for "Replace Cysto": Replacing Invasive Cystoscopy with Urine Testing for Non-muscle-invasive Bladder Cancer Surveillance-A Multicenter, Randomized, Phase 2 Healthcare Delivery Trial Comparing Quality of Life During Cancer Surveillance with Xpert Bladder Cancer Monitor or Bladder EpiCheck Urine Testing Versus Frequent Cystoscopy.

"Replace Cysto" is a multisite randomized phase 2 trial including 240 participants with low-grade intermediate-risk non-muscle-invasive bladder cancer, in which participants will be randomized 1:1:1 to one of two urine marker-based approaches alternating a urine marker test (Xpert Bladder Cancer Monitor or Bladder EpiCheck) with cystoscopy or to frequent scheduled cystoscopy. The primary objective is to determine whether urinary quality of life after surveillance is significantly improved in the urine marker arms. The primary outcome will be the patient-reported urinary quality of life domain score of the validated QLQ-NMIBC24 instrument, measured 1-3 d after surveillance. Exploratory outcomes include discomfort after surveillance, the number of invasive procedures that participants undergo per 1000 person years, complications from these procedures per 1000 person years, nonurinary quality of life, acceptability of surveillance, and bladder cancer recurrence and progression. Comparators include surveillance using (1) the Xpert Bladder Cancer Monitor test, (2) the Bladder EpiCheck urinary marker, or (3) frequent cystoscopy alone. After a negative cystoscopy ≤4 mo following bladder tumor resection, all the participants will undergo surveillance at 6, 12, 18, and 24 mo (with time zero defined as the date of the most recent bladder tumor resection). In the urine marker arms, surveillance at 6 and 18 mo will be performed with the marker. Regardless of the arm, participants will undergo cystoscopy at 12 and 24 mo. End of study for each participant will be their 24-mo cystoscopy. Overall trial duration is estimated at 5 yr from when the study opens to enrollment until completion of data analyses. The trial is registered at clinicaltrials.gov (NCT05796375).

Accurate Documentation Contributes to Guideline-concordant Surveillance of Nonmuscle Invasive Bladder Cancer: A Multisite Department of Veterans Affairs Study.

OBJECTIVE: To determine if accurate documentation of bladder cancer risk was associated with a clinician surveillance recommendation that is concordant with AUA guidelines among patients with nonmuscle invasive bladder cancer (NMIBC). METHODS: We prospectively collected data from cystoscopy encounter notes from four Department of Veterans Affairs (VA) sites to ascertain whether they included accurate documentation of bladder cancer risk and a recommendation for a guideline-concordant surveillance interval. Accurate documentation was a clinician-recorded risk classification matching a gold standard assigned by the research team. Clinician recommendations were guideline-concordant if the clinician recorded a surveillance interval that was in line with the AUA guideline. RESULTS: Among 296 encounters, 75 were for low-, 98 for intermediate-, and 123 for high-risk NMIBC. 52% of encounters had accurate documentation of NMIBC risk. Accurate documentation of risk was less common among encounters for low-risk bladder cancer (36% vs 52% for intermediate- and 62% for high-risk, P < .05). Guideline-concordant surveillance recommendations were also less common in patients with low-risk bladder cancer (67% vs 89% for intermediate- and 94% for high-risk, P < .05). Accurate documentation was associated with a 29% and 15% increase in guideline-concordant surveillance recommendations for low- and intermediate-risk disease, respectively (P < .05). CONCLUSION: Accurate risk documentation was associated with more guideline-concordant surveillance recommendations among low- and intermediate-risk patients. Implementation strategies facilitating assessment and documentation of risk may be useful to reduce overuse of surveillance in this group and to prevent unnecessary cost, anxiety, and procedural harms.

Urinary Analysis of FGFR3 and TERT Gene Mutations Enhances Performance of Cxbladder Tests and Improves Patient Risk Stratification.

PURPOSE: Cxbladder tests are urinary biomarker tests for detection of urothelial carcinoma. We developed enhanced Cxbladder tests that incorporate DNA analysis of 6 single nucleotide polymorphisms for the FGFR3 and TERT genes, in addition to the current 5 mRNA biomarkers and clinical risk factors. MATERIALS AND METHODS: Two multicenter, prospective studies were undertaken in: (1) U.S. patients with gross hematuria aged ≥18 years and (2) Singaporean patients with gross hematuria or microhematuria aged >21 years. All patients provided a midstream urine sample and underwent cystoscopy. Samples were retrospectively analyzed using enhanced Cxbladder-Triage (risk stratifies patients), enhanced Cxbladder-Detect (risk stratifies patients and detects positive patients), and the combination enhanced Cxbladder-Triage × Cxbladder-Detect. RESULTS: In the pooled cohort (N=804; gross hematuria: n=484, microhematuria: n=320), enhanced Cxbladder-Detect had a sensitivity of 97% (95% CI 89%-100%), specificity of 90% (95% CI 88%-92%), and negative predictive value of 99.7% (95% CI 99%-100%) for detection of urothelial carcinoma. Overall, 83% of patients were enhanced Cxbladder-Detect-negative (ie, needed no further work-up). Of 133 enhanced Cxbladder-Detect-positive patients, 59 had a confirmed tumor, of which 19 were low-grade noninvasive papillary carcinoma or papillary urothelial neoplasm of low malignant potential. In total, 40 tumors were high-grade Ta, T1-T4, Tis, including concomitant carcinoma in situ. Of the 74 patients with normal cystoscopy, 41 were positive by single nucleotide polymorphism analysis. Enhanced Cxbladder-Triage and enhanced Cxbladder-Detect had significantly better specificity than the first-generation Cxbladder tests (P < .001). CONCLUSIONS: This study in ethnically diverse patients with hematuria showed the analytical validity of the enhanced Cxbladder tests.

Data-driven approach to implementation mapping for the selection of implementation strategies: a case example for risk-aligned bladder cancer surveillance.

BACKGROUND: Implementation Mapping is an organized method to select implementation strategies. However, there are 73 Expert Recommendations for Implementing Change (ERIC) strategies. Thus, it is difficult for implementation scientists to map all potential strategies to the determinants of their chosen implementation science framework. Prior work using Implementation Mapping employed advisory panels to select implementation strategies. This article presents a data-driven approach to implementation mapping, in which we systematically evaluated all 73 ERIC strategies using the Tailored Implementation for Chronic Diseases (TICD) framework. We illustrate our approach using implementation of risk-aligned bladder cancer surveillance as a case example. METHODS: We developed objectives based on previously collected qualitative data organized by TICD determinants, i.e., what needs to be changed to achieve more risk-aligned surveillance. Next, we evaluated all 73 ERIC strategies, excluding those that were not applicable to our clinical setting. The remaining strategies were mapped to the objectives using data visualization techniques to make sense of the large matrices. Finally, we selected strategies with high impact, based on (1) broad scope, defined as a strategy addressing more than the median number of objectives, (2) requiring low or moderate time commitment from clinical teams, and (3) evidence of effectiveness from the literature. RESULTS: We identified 63 unique objectives. Of the 73 ERIC strategies, 45 were excluded because they were not applicable to our clinical setting (e.g., not feasible within the confines of the setting, not appropriate for the context). Thus, 28 ERIC strategies were mapped to the 63 objectives. Strategies addressed 0 to 26 objectives (median 10.5). Of the 28 ERIC strategies, 10 required low and 8 moderate time commitments from clinical teams. We selected 9 strategies based on high impact, each with a clearly documented rationale for selection. CONCLUSIONS: We enhanced Implementation Mapping via a data-driven approach to the selection of implementation strategies. Our approach provides a practical method for other implementation scientists to use when selecting implementation strategies and has the advantage of favoring data-driven strategy selection over expert opinion.

Ileal Conduit Versus Continent Urinary Diversion in Radical Cystectomy: A Retrospective Cohort Study of 30-day Complications, Readmissions, and Mortality.

OBJECTIVE: To quantify the short-term burden associated with continent diversion relative to ileal conduit creation. METHODS: Bladder cancer patients who underwent radical cystectomy in 2019 and 2020 were identified in the American College of Surgeons National Surgical Improvement Program database using current procedural terminology codes and pathology reports. Patients were grouped by urinary diversion performed: ileal conduit versus continent diversion (neobladder or cutaneous reservoir). Multiple logistic regression was used to examine the association between type of urinary diversion and 30-day outcomes, including postoperative complications, all-cause readmissions, and mortality, adjusting for baseline differences. RESULTS: Of 4,755 patients who underwent radical cystectomy, 677 underwent continent diversion (14.2%). These patients were significantly younger (median 62 vs 71 years, P <.01) and less likely to have diabetes (13.6% vs 20.1%, P <.01), COPD (3.7% vs 7.1%, P<0.01), and prior pelvic radiation (5.5% vs 13.1%, P <.01). A greater proportion of continent diversion patients experienced a postoperative complication (56.0% vs 48.9%, P <.01) and all-cause readmission (30.3% vs 20.4%, P <.0). After adjustment, continent diversion patients had 1.4 (95% CI: 1.1-1.7) and 1.7 (95% CI: 1.4-2.1) times the odds of experiencing a postoperative complication or all-cause readmission, respectively. There was no statistically significant difference in mortality (OR 1.2, 95% CI: 0.5-2.9). CONCLUSION: Compared to ileal conduit creation, continent urinary diversion is associated with increased odds of postoperative complications and readmission to the hospital within 30 days of surgery. Bladder cancer patients undergoing cystectomy and seeking continent diversion should be counseled on the increased short-term morbidity associated with this specific type of diversion.

Using electronic health records to streamline provider recruitment for implementation science studies.

BACKGROUND: Healthcare providers are often targeted as research participants, especially for implementation science studies evaluating provider- or system-level issues. Frequently, provider eligibility is based on both provider and patient factors. Manual chart review and self-report are common provider screening strategies but require substantial time, effort, and resources. The automated use of electronic health record (EHR) data may streamline provider identification for implementation science research. Here, we describe an approach to provider screening for a Veterans Health Administration (VHA)-funded study focused on implementing risk-aligned surveillance for bladder cancer patients. METHODS: Our goal was to identify providers at 6 pre-specified facilities who performed ≥10 surveillance cystoscopy procedures among bladder cancer patients in the 12 months prior to recruitment start on January 16, 2020, and who were currently practicing at 1 of 6 pre-specified facilities. Using VHA EHR data (using CPT, ICD10 procedure, and ICD10 diagnosis codes), we identified cystoscopy procedures performed after an initial bladder cancer diagnosis (i.e., surveillance procedures). Procedures were linked to VHA staff data to determine the provider of record, the number of cystoscopies they performed, and their current location of practice. To validate this approach, we performed a chart review of 105 procedures performed by a random sample of identified providers. The proportion of correctly identified procedures was calculated (Positive Predictive Value (PPV)), along with binomial 95% confidence intervals (CI). FINDINGS: We identified 1,917,856 cystoscopies performed on 703,324 patients from October 1, 1999-January 16, 2020, across the nationwide VHA. Of those procedures, 40% were done on patients who had a prior record of bladder cancer and were completed by 15,065 distinct providers. Of those, 61 performed ≥ 10 procedures and were currently practicing at 1 of the 6 facilities of interest in the 1 year prior to study recruitment. The random chart review of 7 providers found 101 of 105 procedures (PPV: 96%; 95% CI: 91% to 99%) were surveillance procedures and were performed by the selected provider on the recorded date. IMPLICATIONS: These results show that EHR data can be used for accurate identification of healthcare providers as research participants when inclusion criteria consist of both patient- (temporal relationship between diagnosis and procedure) and provider-level (frequency of procedure and location of current practice) factors. As administrative codes and provider identifiers are collected in most, if not all, EHRs for billing purposes this approach can be translated from provider recruitment in VHA to other healthcare systems. Implementation studies should consider this method of screening providers.

Context-Based Identification of Muscle Invasion Status in Patients With Bladder Cancer Using Natural Language Processing.

PURPOSE: Mortality from bladder cancer (BC) increases exponentially once it invades the muscle, with inherent challenges delineating at the population level. We sought to develop and validate a natural language processing (NLP) model for automatically identifying patients with muscle-invasive bladder cancer (MIBC). METHODS: All patients with a Current Procedural Terminology code for transurethral resection of bladder tumor (TURBT; n = 76,060) were selected from the Department of Veterans Affairs (VA) database. A sample of 600 patients (with 2,337 full-text notes) who had TURBT and confirmed pathology results were selected for NLP model development and validation. The NLP performance was assessed by calculating the sensitivity, specificity, positive predictive value, negative predictive value, F1 score, and overall accuracy at the individual note and patient levels. RESULTS: In the validation cohort, the NLP model had average overall accuracies of 94% and 96% at the note and patient levels. Specifically, the F1 score and overall accuracy for predicting muscle invasion at the patient level were 0.87% and 96%, respectively. The model classified nonmuscle-invasive bladder cancer (NMIBC) with overall accuracies of 90% and 93% at the note and patient levels. When applying the model to 71,200 patients VA-wide, the model classified 13,642 (19%) as having MIBC and 47,595 (66%) as NMIBC and was able to identify invasion status for 96% of patients with TURBT at the population level. Inherent limitations include a relatively small training set, given the size of the VA population. CONCLUSION: This NLP model, with high accuracy, may be a practical tool for efficiently identifying BC invasion status and aid in population-based BC research.

Determinants of Risk-Aligned Bladder Cancer Surveillance-Mixed-Methods Evaluation Using the Tailored Implementation for Chronic Diseases Framework.

PURPOSE: For many patients with cancer, the frequency of surveillance after primary treatment depends on the risk for cancer recurrence or progression. Lack of risk-aligned surveillance means too many unnecessary surveillance procedures for low-risk patients and not enough for high-risk patients. Using bladder cancer as an example, we examined whether practice determinants differ between Department of Veterans Affairs sites where risk-aligned surveillance was more (risk-aligned sites) or less common (need improvement sites). METHODS: We used our prior quantitative data to identify two risk-aligned sites and four need improvement sites. We performed semistructured interviews with 40 Veterans Affairs staff guided by the Tailored Implementation for Chronic Diseases framework that were deductively coded. We integrated quantitative data (risk-aligned site v need improvement site) and qualitative data from interviews, cross-tabulating salient determinants by site type. RESULTS: There were 14 participants from risk-aligned sites and 26 participants from need improvement sites. Irrespective of site type, we found a lack of knowledge on guideline recommendations. Additional salient determinants at need improvement sites were a lack of resources ("the next available without overbooking is probably seven to eight weeks out") and an absence of routines to incorporate risk-aligned surveillance ("I have my own guidelines that I've been using for 35 years"). CONCLUSION: Knowledge, resources, and lack of routines were salient barriers to risk-aligned bladder cancer surveillance. Implementation strategies addressing knowledge and resources can likely contribute to more risk-aligned surveillance. In addition, reminders for providers to incorporate risk into their surveillance plans may improve their routines.

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.

Partial Versus Complete Bacillus Calmette-Guérin Intravesical Therapy and Bladder Cancer Outcomes in High-risk Non-muscle-invasive Bladder Cancer: Is NIMBUS the Full Story?

BACKGROUND: It is important to understand the implications of reduced bacillus Calmette-Guérin (BCG) treatment intensity, given global shortages and early termination of the NIMBUS trial. OBJECTIVE: To assess the association of partial versus complete BCG induction with outcomes. DESIGN SETTING AND PARTICIPANTS: This is a retrospective cohort study of veterans diagnosed with high-risk non-muscle-invasive bladder cancer (NMIBC; high grade [HG] Ta, T1, or carcinoma in situ) between 2005 and 2011 with follow-up through 2014. INTERVENTION: Patients were categorized into partial versus complete BCG induction (one to five vs five or more instillations). Partial BCG induction subgroups were defined for comparison with the NIMBUS trial. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Propensity score-adjusted regression models were used to assess the association of partial BCG induction with risk of recurrence and bladder cancer death. RESULTS AND LIMITATIONS: Among 540 patients, 114 (21.1%) underwent partial BCG induction. Partial versus complete BCG induction was not significantly associated with the risk of recurrence in HG Ta (cumulative incidence [CIn] 46.6% vs 53.9% at 5 yr, p = 0.38) or T1 (CIn 47.1% vs 56.7 at 5 yr, p = 0.19) disease. Similarly, we found no increased risk of bladder cancer death (HG Ta: CIn 4.7%7vs 5.4% at 5 yr, p = 0.87; T1: CIn 10.0% vs 11.4% at 5 yr, p = 0.77). NIMBUS-like induction was associated with an increased risk of recurrence in patients with HG Ta disease, although not statistically significant. Unmeasured confounding is a limitation. CONCLUSIONS: Cancer outcomes were similar among high-risk NMIBC patients who underwent partial versus complete BCG induction, suggesting that future research is needed to determine how to optimize BCG delivery for the greatest number of patients, especially during global shortages. PATIENT SUMMARY: Outcomes were similar between patients receiving partial and complete courses of bacillus Calmette-Guérin (BCG) therapy. Future research is needed to determine how to best deliver BCG to the greatest number of patients, particularly during medication shortages.

Improvement Science and Implementation Science in Cancer Care: Identifying Areas of Synergy and Opportunities for Further Integration.

Efforts to improve cancer care primarily come from two fields: improvement science and implementation science. The two fields have developed independently, yet they have potential for synergy. Leveraging that synergy to enhance alignment could both reduce duplication and, more importantly, enhance the potential of both fields to improve care. To better understand potential for alignment, we examined 20 highly cited cancer-related improvement science and implementation science studies published in the past 5 years, characterizing and comparing their objectives, methods, and approaches to practice change. We categorized studies as improvement science or implementation science based on authors' descriptions when possible; otherwise, we categorized studies as improvement science if they evaluated efforts to improve the quality, value, or safety of care, or implementation science if they evaluated efforts to promote the implementation of evidence-based interventions into practice. All implementation studies (10/10) and most improvement science studies (6/10) sought to improve uptake of evidence-based interventions. Improvement science and implementation science studies employed similar approaches to change practice. For example, training was employed in 8/10 implementation science studies and 4/10 improvement science studies. However, improvement science and implementation science studies used different terminology to describe similar concepts and emphasized different methodological aspects in reporting. Only 4/20 studies (2 from each category) described using a formal theory or conceptual framework to guide program development. Most studies were multi-site (10/10 implementation science and 6/10 improvement science) and a minority (2 from each category) used a randomized design. Based on our review, cancer-related improvement science and implementation science studies use different terminology and emphasize different methodological aspects in reporting but share similarities in purpose, scope, and methods, and are at similar levels of scientific development. The fields are well-positioned for alignment. We propose that next steps include harmonizing language and cross-fertilizing methods of program development and evaluation.

Posttraumatic stress disorder and suicide among veterans with prostate cancer.

OBJECTIVE: To evaluate the effect of a preexisting posttraumatic stress disorder (PTSD) diagnosis on suicide and non-suicide mortalities among men with newly diagnosed prostate cancer, and examine potential mediating factors for the relationship between PTSD and suicide. METHODS: We used patient-level data from Veterans Health Administration electronic medical records to identify men (age ≥40 years) diagnosed with prostate cancer between 2004 and 2014. We used Fine and Gray regression model to estimate the risk for competing mortality outcomes (suicide, non-suicide, and alive). We used structural equation models to evaluate the mediating factors. RESULTS: Our cohort comprised 214,649 men with prostate cancer, of whom 12,208 (5.7%) had a preexisting PTSD diagnosis. Patients with PTSD compared to those without utilized more healthcare services and had lower risk cancer at diagnosis. Additionally, they experienced more suicide deaths (N = 26, 0.21% vs. N = 269, 0.13%) and fewer non-suicide deaths (N = 1399, 11.5% vs. N = 45,625, 22.5%). On multivariable analysis, PTSD was an independent suicide risk factor (HR = 2.35; 95% CI: 1.16, 4.78). Depression, substance use disorder, and any definitive prostate cancer treatment were partial mediators. However, PTSD was associated with lower non-suicide mortality risk (HR = 0.86; 95% CI: 0.77, 0.96). CONCLUSION: Patients with PTSD experienced greater suicide risk even after adjusting for important mediators. They may have experienced lower non-suicide mortality risk due to favorable physical health resulting from greater healthcare service use and early diagnosis of lower risk cancer. Our findings highlight the importance of considering psychiatric illnesses when treating patients with prostate cancer and the need for interventions to ameliorate suicide risk.

Patient Perspectives on the Implementation of Risk-Aligned Bladder Cancer Surveillance: Systematic Evaluation Using the Tailored Implementation for Chronic Diseases Framework.

PURPOSE: Many patients living with bladder cancer do not undergo surveillance that is aligned with their risk for recurrence or progression, which exposes them to unnecessary risk and burden of procedures. To implement risk-aligned surveillance as recommended by multiple guidelines, we need to understand patient-, provider-, and system-level factors contributing to the delivery of risk-aligned surveillance. In this study, we sought to systematically assess patient-level factors. PARTICIPANTS AND METHODS: Guided by the Tailored Implementation for Chronic Diseases framework, we conducted semistructured interviews with 22 patients with bladder cancer undergoing surveillance cystoscopy procedures at three facilities within the Department of Veterans Affairs. Patients were sampled using quantitative data on bladder cancer risk category (low v high) and on surveillance category (aligned v not aligned with cancer risk). Interview transcripts were analyzed using a priori codes from the Tailored Implementation for Chronic Diseases framework. Quantitative and qualitative data were integrated by cross-tabulating determinants across risk and surveillance categories. RESULTS: Participants included seven low-risk and 15 high-risk patients; 10 underwent risk-aligned surveillance and 12 did not. In mixed-methods analyses, perception of risk appropriately differed by risk but not by surveillance category. Participants understood the recommended surveillance schedule according to their risk category. Participants emphatically expressed that adhering to providers' recommendations is prudent; intentions to adhere did not vary across risk and surveillance categories. CONCLUSION: Participants intended to adhere to providers' recommendations and strongly endorsed the importance of adherence. These findings suggest implementation strategies to improve risk-aligned surveillance may be most effective when targeting provider- and system-level factors rather than patient-level factors.

The impact of low- versus high-intensity surveillance cystoscopy on surgical care and cancer outcomes in patients with high-risk non-muscle-invasive bladder cancer (NMIBC).

PURPOSE: To assess the association of low- vs. guideline-recommended high-intensity cystoscopic surveillance with outcomes among patients with high-risk non-muscle invasive bladder cancer (NMIBC). MATERIALS & METHODS: A retrospective cohort study of Veterans Affairs patients diagnosed with high-risk NMIBC between 2005 and 2011 with follow-up through 2014. Patients were categorized by number of surveillance cystoscopies over two years following diagnosis: low- (1-5) vs. high-intensity (6 or more) surveillance. Propensity score adjusted regression models were used to assess the association of low-intensity cystoscopic surveillance with frequency of transurethral resections, and risk of progression to invasive disease and bladder cancer death. RESULTS: Among 1,542 patients, 520 (33.7%) underwent low-intensity cystoscopic surveillance. Patients undergoing low-intensity surveillance had fewer transurethral resections (37 vs. 99 per 100 person-years; p<0.001). Risk of death from bladder cancer did not differ significantly by low (cumulative incidence [CIn] 8.4% [95% CI 6.5-10.9) at 5 years) vs. high-intensity surveillance (CIn 9.1% [95% CI 7.4-11.2) at 5 years, p = 0.61). Low vs. high-intensity surveillance was not associated with increased risk of bladder cancer death among patients with Ta (CIn 5.7% vs. 8.2% at 5 years p = 0.24) or T1 disease at diagnosis (CIn 10.2% vs. 9.1% at 5 years, p = 0.58). Among patients with Ta disease, low-intensity surveillance was associated with decreased risk of progression to invasive disease (T1 or T2) or bladder cancer death (CIn 19.3% vs. 31.3% at 5 years, p = 0.002). CONCLUSIONS: Patients with high-risk NMIBC undergoing low- vs. high-intensity cystoscopic surveillance underwent fewer transurethral resections, but did not experience an increased risk of progression or bladder cancer death. These findings provide a strong rationale for a clinical trial to determine whether low-intensity surveillance is comparable to high-intensity surveillance for cancer control in high-risk NMIBC.

Urologist practice structure and quality of prostate cancer care.

OBJECTIVE: To examine three aspects of urologist practice structure that may affect quality of prostate cancer care: practice size, ownership of an intensity modulated radiation therapy (IMRT) device, participation within a multi-specialty group (MSG). Health care reforms focused on improving quality are particularly relevant for prostate cancer given its prevalence and concerns for overdiagnosis and overtreatment. METHODS: Using data from the Surveillance, Epidemiology and End-Results (SEER)-Medicare linked registry, we examined quality of prostate cancer treatment according to each treating urologist's practice size, type (single-specialty vs. MSG) and ownership of IMRT. Mixed models were used to adjust for patient differences. RESULTS: We identified 22,412 men with newly diagnosed prostate cancer treated by 2,199 urologists during the study. We observed minimal differences for most quality metrics according to practice size, type, and ownership of IMRT. Adherence to all eligible quality metrics was better among MSGs compared to single specialty groups (20.0% adherence versus 18.2%, p=0.01) whereas there was no significant difference by ownership of IMRT (17.1% adherence in owners versus 18.9% non-owners, p=0.09). CONCLUSION: Differences in quality across practice size, type and ownership of IMRT were modest, with substantial room for improvement regardless of practice structure.

Sex and the Diagnostic Pathway to Bladder Cancer among Veterans: No Evidence of Disparity.

BACKGROUND: Longer time intervals from presentation with hematuria to bladder cancer diagnosis have been reported among women compared with men. Despite women being the fastest growing cohort within the Department of Veterans Affairs, little is known about women veterans with bladder cancer. Our objectives were to quantify the time from hematuria to bladder cancer diagnosis in Department of Veterans Affairs and assess differences between sexes. METHODS: This was a retrospective cohort study of patients diagnosed with bladder cancer from 2001 to 2016. Included were patients with hematuria for fewer than 365 days before a bladder cancer diagnosis and who had a record of diagnostic cystoscopy after hematuria but before diagnosis. We evaluated the number of days from hematuria to diagnostic cystoscopy (clinical appraisal), cystoscopy to bladder cancer diagnosis (surgical appraisal), and hematuria to bladder cancer diagnosis (total diagnostic appraisal). We used quantile regression models to separately evaluate the effect of sex on the three appraisal intervals. RESULTS: Data from 213 women and 24,295 men were analyzed. The median clinical appraisal time was 78 days for women and 72 for men (p = .49). The median surgical appraisal time was 32 days for women and 33 for men (p = .74). The median total diagnostic appraisal time was 135 days for women and 130 for men (p = .71). Multivariable analyses showed no differences between men and women for any of the three appraisal intervals. CONCLUSIONS: The majority of time from hematuria to bladder cancer diagnosis is spent in clinical appraisal, but little difference was observed between men and women in Department of Veterans Affairs.

Reduction of Pain during Flexible Cystoscopy: A Systematic Review and Meta-Analysis.

PURPOSE: The BCAN (Bladder Cancer Advocacy Network) Patient Survey Network identified pain during intravesical procedures as a research priority for patients. Although intraurethral lidocaine is the standard of care in this setting, evidence of its use is equivocal. We systematically reviewed studies of interventions to reduce discomfort during cystoscopy and intravesical therapy of bladder cancer. We performed a meta-analysis of interventions using available randomized, controlled trials. MATERIALS AND METHODS: Search terms derived from the key questions were incorporated into the literature search constructed by a research librarian and the English medical literature from 1990 to 2017 was accessed. The initial search yielded 626 potential studies and the final review incorporated 62. We combined 12 trials into a meta-analysis with a random effects model of the efficacy of intraurethral lidocaine vs plain lubricant to reduce pain during flexible cystoscopy as measured on a 10-point visual analogue scale. RESULTS: Data from 12 randomized controlled trials in a total of 1,549 patients were included in the final intraurethral lidocaine meta-analysis. The standardized mean difference between visual analogue scale pain scores in patients who underwent flexible cystoscopy with intraurethral lidocaine and plain lubricant was -0.22 (95% CI -0.39--0.05). Evidence was insufficient to evaluate other interventions to mitigate the discomfort of invasive bladder procedures. CONCLUSIONS: Intraurethral lidocaine provides statistically significant pain reduction in men who undergo flexible cystoscopy, particularly with a longer dwell time. The evidence was insufficient for other tested interventions. A prospective study is needed to further clarify interventions to decrease patient discomfort during cystoscopy and other intravesical procedures in a diverse population.

Overuse of Cystoscopic Surveillance Among Patients With Low-risk Non-Muscle-invasive Bladder Cancer - A National Study of Patient, Provider, and Facility Factors.

OBJECTIVE: To understand cystoscopic surveillance practices among patients with low-risk non-muscle-invasive bladder cancer (NMIBC) within the Department of Veterans Affairs (VA). METHODS: Using a validated natural language processing algorithm, we included patients newly diagnosed with low-risk (ie low-grade Ta) NMIBC from 2005 to 2011 in the VA. Patients were followed until cancer recurrence, death, last contact, or 2 years after diagnosis. Based on guidelines, surveillance overuse was defined as >1 cystoscopy if followed <1 year, >2 cystoscopies if followed 1 to <2 years, or >3 cystoscopies if followed for 2 years. We identified patient, provider, and facility factors associated with overuse using multilevel logistic regression. RESULTS: Overuse occurred in 75% of patients (852/1135) - with an excess of 1846 more cystoscopies performed than recommended. Adjusting for 14 factors, overuse was associated with patient race (odds ratio [OR] 0.49, 95% confidence interval [CI]: 0.28, 0.85 unlisted race vs White), having 2 comorbidities (OR 1.60, 95% CI: 1.00, 2.55 vs no comorbidities), and earlier year of diagnosis (OR 2.50, 95% CI: 1.29, 4.83 for 2005 vs 2011, and OR 2.03, 95% CI: 1.11, 3.69 for 2006 vs 2011). On sensitivity analyses assuming all patients were diagnosed with multifocal or large low-grade tumors (ie, intermediate-risk), overuse would have still occurred in 45% of patients. CONCLUSION: Overuse of cystoscopy among patients with low-risk NMIBC was common, raising concerns about bladder cancer surveillance cost and quality. However, few factors were associated with overuse. Further qualitative research is needed to identify other determinants of overuse not readily captured in administrative data.

The impact of frequent cystoscopy on surgical care and cancer outcomes among patients with low-risk, non-muscle-invasive bladder cancer.

BACKGROUND: Surveillance recommendations for patients with low-risk, non-muscle-invasive bladder cancer (NMIBC) are based on limited evidence. The objective of this study was to add to the evidence by assessing outcomes after frequent versus recommended cystoscopic surveillance. METHODS: This was a retrospective cohort study of patients diagnosed with low-risk (low-grade Ta (AJCC)) NMIBC from 2005 to 2011 with follow-up through 2014 from the Department of Veterans Affairs. Patients were classified as having undergone frequent versus recommended cystoscopic surveillance (>3 vs 1-3 cystoscopies in the first 2 years after diagnosis). By using propensity score-adjusted models, the authors estimated the impact of frequent cystoscopy on the number of transurethral resections, the number of resections without cancer in the specimen, and the risk of progression to muscle-invasive cancer or bladder cancer death. RESULTS: Among 1042 patients, 798 (77%) had more frequent cystoscopy than recommended. In adjusted analyses, the frequent cystoscopy group had twice as many transurethral resections (55 vs 26 per 100 person-years; P < .001) and more than 3 times as many resections without cancer in the specimen (5.7 vs 1.6 per 100 person-years; P < .001). Frequent cystoscopy was not associated with time to progression or bladder cancer death (3% at 5 years in both groups; P = .990). CONCLUSIONS: Frequent cystoscopy among patients with low-risk NMIBC was associated with twice as many transurethral resections and did not decrease the risk for bladder cancer progression or death, supporting current guidelines.