Management, Surveillance Patterns, and Costs Associated With Low-Grade Papillary Stage Ta Non-Muscle-Invasive Bladder Cancer Among Older Adults, 2004-2013.

Importance: Low-risk non-muscle-invasive bladder cancer (NMIBC) is associated with extremely low rates of progression and cancer-specific mortality; however, patients with low-risk NMIBC may often receive non-guideline-recommended and potentially costly surveillance testing and treatment. Objective: To describe current surveillance and treatment practices, cancer outcomes, and costs of care for low-grade papillary stage Ta (low-grade Ta) NMIBC and identify factors associated with increased cost of care. Design, Setting, and Participants: This population-based cohort study identified 13 054 older adults (aged 66-90 years) diagnosed with low-grade Ta tumors in the Surveillance, Epidemiology and End Results-linked Medicare database from January 1, 2004, through December 31, 2013. Medicare claims data through December 31, 2014, were also reviewed. Data were analyzed from April 1 to October 6, 2021. Exposures: Surveillance testing and treatment among patients with low-grade Ta NMIBC. Main Outcomes and Measures: The primary outcome was patterns in population-level surveillance and treatment practice over time among patients with low-grade Ta NMIBC. Secondary outcomes were recurrence (defined as receipt of subsequent transurethral resection of bladder tumor >3 months after index diagnosis of NMIBC and initial transurethral resection of bladder tumor), progression (defined as receipt of definitive treatment for bladder cancer), and costs of care. Results: Among 13 054 patients who met inclusion criteria, 9596 (73.5%) were male and 3458 (26.5%) were female, with a median age of 76 years (IQR, 71-81 years). A total of 403 patients (3.1%) were Black, 120 (0.9%) were Hispanic, 12 123 (92.9%) were White, and 408 (3.1%) were of other races and/or ethnicities. Rates of surveillance cystoscopy increased over the study period (from 79.3% in 2004 to 81.5% in 2013; P = .007), with patients receiving a median of 3.0 cystoscopies per year (IQR, 2.0-4.0 per year). Rates of upper tract imaging (particularly computed tomography or magnetic resonance imaging) also increased over the study period (from 30.4% in 2004 to 47.0% in 2013; P < .001), with most patients receiving a median of 2.0 imaging tests per year (IQR, 1.0-2.0 per year). The use of urine cytologic testing or other urine biomarker assessment also increased (from 44.8% in 2004 to 54.9% in 2013; P < .001). Rates of adherence to current guidelines were similar over time (eg, a median of 4398 patients [55.2%] received ≤2 cystoscopies per year in 2004-2008 vs a median of 2736 patients [53.8%] in 2009-2013; P = .11), suggesting overuse of all surveillance testing modalities. With regard to treatment, 2250 patients (17.2%) received intravesical bacillus Calmette-Guérin, and 792 patients (6.1%) received intravesical chemotherapy (excluding receipt of a single perioperative dose). Among all patients with low-grade Ta NMIBC, 217 (1.7%) experienced disease recurrence and 52 (0.4%) experienced disease progression. The total annual median costs of low-grade Ta surveillance testing and treatment increased by 60% (from $34 792 in 2004 to $53 986 in 2013), with higher 1-year median expenditures noted among those with disease recurrence ($76 669) vs no disease recurrence ($53 909) at the end of the study period. Conclusions and Relevance: In this cohort study, despite low rates of disease recurrence and progression, rates of surveillance testing increased during the study period. The annual cost of care also increased over time, particularly among patients with recurrent disease. Efforts to improve adherence to current practice guidelines, with the focus on limiting overuse of surveillance testing and treatment, may mitigate associated increasing costs of care.

Long term cost comparisons of radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer.

BACKGROUND: Earlier studies on the cost of muscle-invasive bladder cancer treatments are limited to short-term costs of care. We determined the 2- and 5-year costs associated with trimodal therapy (TMT) vs. radical cystectomy (RC). METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Total Medicare costs at 2 and 5 years following RC vs. TMT were compared using inverse probability of treatment-weighted propensity score models. RESULTS: A total of 2,537 patients aged 66 to 85 years were diagnosed with clinical stage T2-4a muscle-invasive bladder cancer. Total median costs for patients that received no definitive treatment(s) were $73,780 and $88,275 at 2-and 5-years. Costs were significantly higher for TMT than RC at 2-years ($372,839 vs. $191,363, Median Difference $127,815, Hodges-Lehmann Estimate (H-L) 95% Confidence Interval (CI), $112,663-$142,966) and 5-years ($424,570 vs. $253,651, Median Difference $124,466, H-L 95% CI, $105,711-$143,221). TMT had higher outpatient costs than RC (2-years: $318,221 vs. $100,900; 5-years: $367,092 vs. $146,561) with significantly higher costs with radiology, medications, pathology/laboratory, and other professional services. RC had higher inpatient costs than TMT (2-years: $62,240 vs. $33,631, Median Difference $-29,174, H-L 95% CI, $-32,364-$-25,984; 5-years: $75,499 vs. $45,223, Median Difference $-29,843, H-L 95% CI, $-33,905-$-25,781). CONCLUSIONS AND RELEVANCE: The excess spending associated with trimodal therapy vs. radical cystectomy was largely driven by outpatient expenditures. The relatively high long-term trimodal therapy costs are prime targets for cost containment strategies to optimize future value-based care.

Geographic distribution of racial differences in mortality in muscle-invasive bladder cancer patients: an opportunity for improvement.

OBJECTIVES: To determine the geographic distribution of muscle-invasive bladder cancer mortality according to race in the United States (US). African Americans (AAs) have up to two times the risk of bladder cancer mortality compared to Caucasians. Bladder cancer mortality increases exponentially once it invades the muscle. Geographic heterogeneity in bladder cancer mortality according to race remains to be determined. DESIGN: Analysis of Surveillance, Epidemiology, and End Results (SEER)-Medicare data for 6,044 patients aged 66-85 diagnosed with clinical stage T2-T4 N0M0 bladder cancer from 1 January 2002 to 31 December 2011. Fine and Gray-competing risks regression models were used to assess the association of race with bladder cancer-specific mortality (BCSM) according to tumor registry. RESULTS: Out of 6,044 patients, 5,408 (89.5%) were Caucasian, 352 (5.82%) were non-Hispanic AA, 85 (1.4%) were Hispanic, and 199 (3.29%) were other. Of the 18 registries, AAs with bladder cancer were largely concentrated in Louisiana (19%), New Jersey (17.9%), and Georgia (17.6%). New Jersey was the only registry where AAs had increased risk of BCSM than Caucasians and only for stage T2 disease: (AHR, 1.74; 95% CI 1.22-2.47, p = 0.002). According to treatment, AAs in New Jersey had worse BCSM than Caucasians when they underwent radical cystectomy (AHR, 2.05; 95% CI 1.26-3.35, p = 0.0039) and radiotherapy or chemotherapy alone (AHR, 1.55; 95% CI 1.03-2.35, p = 0.0367). CONCLUSIONS: We observed geographic variation in bladder cancer mortality which impacted only one registry with one of the largest population of AAs. These findings support further investigation into the social determinants of race (i.e., socioeconomic status and distance to healthcare facility) and culturally centered healthcare decision making which may drive these results.

Macro and microeconomics of blue light cystoscopy with CYSVIEW® in non-muscle invasive bladder cancer.

OBJECTIVE: To determine the estimated budget impact to practices that incorporate blue light cystoscopy (BLC) with hexaminolevulinate HCl (HAL) for the surveillance of non-muscle-invasive bladder cancer (NMIBC) in the clinic setting. With the introduction of advanced technologies in the clinic setting such as HAL, further cost comparative research is needed to justify HAL as a high value option. MATERIAL AND METHODS: A budget impact model was developed from the facility perspective assessing projected costs at 2 years for a simulated facility with 50 newly diagnosed bladder cancer patients. Treatment and surveillance cystoscopy intervals were based on clinical guidelines. Clinical inputs, including tumor stage and grade at diagnosis, rates of recurrence and relative risk reduction when using BLC with HAL, were derived from published studies. Cost inputs were based on Medicare reimbursement rates and facility costs. RESULTS: Use of BLC identified 9 additional recurrences over two years compared to white light cystoscopy alone. Use of flexible BLC for surveillance marginally increased costs to the practice, with a net difference of $0.76 per cystoscopy over 2 years. CONCLUSIONS: From the office/clinic perspective, the model suggests that the use of flexible BLC for the surveillance of NMIBC may not impact cost per cystoscopy and identifies 9 recurrences over 2 years that would be missed using white light cystoscopy alone. These findings could have important implications in the management of NIMBC and help guide clinical practice guidelines that promote cost-effective care and improved patient outcomes.

Critical analysis of quality of life and cost-effectiveness of enhanced recovery after surgery (ERAS) for patient's undergoing urologic oncology surgery: a systematic review.

PURPOSE: Enhanced recovery after surgery (ERAS) protocols have been implemented across a variety of disciplines to improve outcomes. Herein we describe the impact of ERAS on quality of life (QOL) and cost for patients undergoing urologic oncology surgery. METHODS: A systematic literature search using the MEDLINE, Scopus, Clinictrials.gov, and Cochrane Review databases for studies published between 1946 and 2020 was conducted. Articles were reviewed and assigned a risk of bias by two authors and were included if they addressed ERAS and either QOL or cost-effectiveness for patients undergoing urologic oncology surgery. RESULTS: The literature search yielded a total of 682 studies after removing duplicates, of which 10 (1.5%) were included in the review. Nine articles addressed radical cystectomy, while one addressed ERAS and QOL for laparoscopic nephrectomy. Six publications assessed the impact of ERAS on QOL domains. Questionnaires used for assessment of QOL varied across studies, and timing of administration was heterogeneous. Overall, ERAS improved patient QOL during early phases of recovery within the realms of bowel function, physical/social/cognitive functioning, sleep and pain control. Costs were assessed in 4 retrospective studies including 3 conducted in the United States and one from China all addressing radical cystectomy. Studies demonstrated either decreased costs associated with ERAS as a result of decreased length of stay or no change in cost based on ERAS implementation. CONCLUSION: While limited studies are published on the subject, ERAS implementation for radical cystectomy and laparoscopic nephrectomy improved patient-reported QOL during early phases of recovery. For radical cystectomy, there was a decreased or neutral overall financial cost associated with ERAS. Further studies assessing QOL and cost-effectiveness over the entire global period of care in a variety of urologic oncology surgeries are warranted.

The Impact of Progression on Healthcare Resource Utilization and Costs Among Patients with High-Grade Non-Muscle Invasive Bladder Cancer After Bacillus Calmette-Guérin Therapy: A Retrospective SEER-Medicare Analysis.

INTRODUCTION: We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guérin (BCG) therapy. METHODS: Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics. RESULTS: Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p < 0.05). Total mean annualized costs per patient after BCG among those who progressed [$65,668 (SD $53,943)] were more than double compared with patients who did not [$29,780 ($36,425)]. CONCLUSIONS: Existing treatments for HG-NMIBC after BCG therapy are associated with substantial HRU and medical costs, particularly after progression. Novel treatments and earlier detection are needed to reduce progression rates and associated costs in this difficult-to-treat population.

Use of psychotropic drugs among older patients with bladder cancer in the United States.

OBJECTIVE: Older patients diagnosed with cancer are at increased risk of physical and emotional distress; however, prescription utilization patterns largely remain to be elucidated. Our objective was to comprehensively assess prescription patterns and predictors in older patients with bladder cancer. METHODS: A total of 10,516 older patients diagnosed with clinical stage T1-T4a, N0, M0 bladder urothelial carcinoma from 1 January 2008 to 31 December 2012 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare were analyzed. We used multivariable analysis to determine predictors associated with psychotropic prescription rates (one or more). Medication possession ratio (MPR) was used as an index to measure adherence in intervals of 3 months, 6 months, 1 year, and 2 years. Evaluation of psychotropic prescribing patterns and adherence across different drugs and demographic factors was done. RESULTS: Of the 10,516 older patients, 5621 (53%) were prescribed psychotropic drugs following cancer diagnosis. Overall, 3972 (38%) patients had previous psychotropic prescriptions prior to cancer diagnosis, and these patients were much more likely to receive a post-cancer diagnosis prescription. Prescription rates for psychotropic medications were higher among patients with higher stage BC (p < 0.001). Gamma aminobutyric acid modulators/stimulators and serotonin reuptake inhibitors/stimulators were the highest prescribed psychotropic drugs in 21% of all patients. Adherence for all drugs was 32% at 3 months and continued to decrease over time. CONCLUSION: Over half of the patients received psychotropic prescriptions within 2 years of their cancer diagnosis. Given the chronicity of psychiatric disorders with observed significantly low adherence to medications that warrants an emphasis on prolonged patient monitoring and further investigation.

Contribution of bladder cancer pathology assessment in planning clinical trials.

Bladder cancer is a heterogeneous disease that demonstrates a wide spectrum of histologic features. The modern classification of bladder cancer is largely based on pathologic analysis, which assesses tumor grade, stage, type, size, and other features that are essential for understanding the biological behavior of bladder cancer. Bladder cancers with similar histologic features are likely to show comparable responses to a new therapeutic agent in clinical trial. Furthermore, pathologic analysis also evaluates the quality of tissue samples in clinical trial to ensure the integrity of various molecular tests. In spite of the emerging role of genomic and molecular studies, pathology remains the cornerstone in the diagnosis, prognosis, and treatment of bladder cancer. Herein, the pathologic considerations for bladder cancer clinical trial planning are reviewed.

Comparing Costs of Radical Versus Partial Cystectomy for Patients Diagnosed With Localized Muscle-Invasive Bladder Cancer: Understanding the Value of Surgical Care.

OBJECTIVE: To compare costs associated with radical versus partial cystectomy. Prior studies noted substantial costs associated with radical cystectomy, however, they lack surgical comparison to partial cystectomy. METHODS: A total of 2305 patients aged 66-85 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer from January 1, 2002 to December 31, 2011 were included. Total Medicare costs within 1 year of diagnosis following radical versus partial cystectomy were compared using inverse probability of treatment-weighted propensity score models. Cox regression and competing risks analysis were used to determine overall and cancer-specific survival, respectively. RESULTS: Median total costs were not significantly different for radical than partial cystectomy in 90 days ($73,907 vs $65,721; median difference $16,796, 95% CI $10,038-$23,558), 180 days ($113,288 vs $82,840; median difference $36,369, 95% CI $25,744-$47,392), and 365 days ($143,831 vs $107,359; median difference $34,628, 95% CI $17,819-$53,558), respectively. Hospitalization, surgery, pathology/laboratory, pharmacy, and skilled nursing facility costs contributed largely to costs associated with either treatment. Patients who underwent partial cystectomy had similar overall survival but had worse cancer-specific survival (Hazard Ratio 1.45, 95% Confidence Interval, 1.34-1.58, P < .001) than patients who underwent radical cystectomy. CONCLUSION: While treatments for bladder cancer are associated with substantial costs, we showed radical cystectomy had comparable total costs when compared to partial cystectomy among patients with muscle-invasive bladder cancer. However, partial cystectomy resulted in worse cancer-specific survival further supporting radical cystectomy as a high-value surgical procedure for muscle-invasive bladder cancer.

Utilizing time-driven activity-based costing to determine open radical cystectomy and ileal conduit surgical episode cost drivers.

OBJECTIVES: Patients undergoing radical cystectomy represent a particularly resource-intensive patient population. Time-driven activity based costing (TDABC) assigns time to events and then costs are based on the people involved in providing care for specific events. To determine the major cost drivers of radical cystectomy care we used a TDABC analysis for the cystectomy care pathway. SUBJECTS AND METHODS: We retrospectively reviewed a random sample of 100 patients out of 717 eligible patients undergoing open radical cystectomy and ileal conduit for bladder cancer at our institution between 2012 and 2015. We defined the cycle of care as beginning at the preoperative clinic visit and ending with the 90-day postoperative clinic visit. TDABC was carried out with construction of detailed process maps. Capacity cost rates were calculated and the care cycle was divided into 3 phases: surgical, inpatient, and readmissions. Costs were normalized to the lowest cost driver within the cohort. RESULTS: The mean length of stay was 6.9 days. Total inpatient care was the main driver of cost for radical cystectomy making up 32% of the total costs. Inpatient costs were mainly driven by inpatient staff care (76%). Readmissions were responsible for 29% of costs. Surgery was 31% of the costs, with the majority derived from operating room staff costs (65%). CONCLUSION: The major driver of cost in a radical cystectomy pathway is the inpatient stay, closely followed by operating room costs. Surgical costs, inpatient care and readmissions all remain significant sources of expense for cystectomy and efforts to reduce cystectomy costs should be focused in these areas.

Global Trends of Bladder Cancer Incidence and Mortality, and Their Associations with Tobacco Use and Gross Domestic Product Per Capita.

BACKGROUND: Bladder cancer is a major urological disease, with approximately 550 000 new cases diagnosed in 2018. OBJECTIVE: We examined gender-specific incidence and mortality patterns, and trends of bladder cancer from a global perspective. We further investigated their associations with tobacco use and gross domestic product (GDP) per capita. DESIGN, SETTING, AND PARTICIPANTS: We retrieved data on the incidence and mortality of bladder cancer from the GLOBOCAN database, Cancer Incidence in Five Continents, and the WHO mortality database. Data on the rate of tobacco use were retrieved from the WHO Global Health Observatory. Data on GDP per capita was retrieved from the United Nations Human Development Report. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We performed two sets of analyses. The first set of analysis is based on bladder cancer incidence and mortality data in 2018. The gender-specific age-standardised rates (ASRs) of incidence and mortality, and their correlations with the rate of tobacco use and GDP per capita were investigated. A multivariable linear regression analysis was also performed. In the second set of analysis, we examined the 10-yr temporal trends of bladder cancer incidence and mortality by average annual percent change using joinpoint regression analysis. A further exploratory analysis on GDP per capita in countries with decreasing trends of tobacco use was also performed. RESULTS AND LIMITATIONS: Wide variations in bladder cancer incidence and mortality were observed globally. There were positive correlations between the rate of tobacco use and the ASRs of bladder cancer incidence (r=0.20) and mortality (r=0.38) in men, and between the rate of tobacco use and the ASRs of bladder cancer incidence (r=0.67) and mortality (r=0.22) in women. There were positive correlations between GDP per capita, and the ASRs of bladder cancer incidence in men (r=0.48) and women (r=0.44). There was a weak positive correlation between GDP per capita and bladder cancer mortality in men (r=0.19), but no correlation with bladder cancer mortality in women (r=0.06). Upon multivariable linear regression analysis, tobacco use was significantly associated with bladder cancer incidence and mortality in men, and bladder cancer incidence in women. Regarding the 10-yr temporal trends of bladder cancer, Europe has an increasing incidence but decreasing mortality, and Asia has a decreasing incidence but increasing male mortality. Among countries with decreasing trends of tobacco use, the mean GDP per capita was higher in countries with decreasing trends of bladder cancer mortality than in those with increasing trends of bladder cancer mortality. A major limitation of the study is that cancer incidence might be underdetected and under-reported in less developed nations. CONCLUSIONS: There were observable trends of bladder cancer incidence and mortality globally. Tobacco use was significantly associated with both bladder cancer incidence and mortality. A certain level of economic capacity might be needed to further reduce bladder cancer mortality in countries with a decreasing trend of tobacco use. PATIENT SUMMARY: There are different trends of bladder cancer incidence and mortality globally. Smoking is significantly associated with the incidence and mortality of bladder cancer. A higher financial capacity may be needed to further improve the disease outcomes.

Impact of Alzheimer's disease and related dementia diagnosis following treatment for bladder cancer.

OBJECTIVES: Our objective was to assess the incidence of Alzheimer's Disease and related dementia diagnosis following treatment for muscle-invasive bladder cancer and impact on survival outcomes. MATERIALS AND METHODS: A total of 4814 patients diagnosed with clinical stage T2-T4a, N0, M0 bladder cancer between January 1, 2002 to December 31, 2011 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database were identified. Alzheimer's disease and related dementia diagnosis was identified using International Statistical Classification of Disease-Ninth Edition outpatient and inpatient codes. Incidence of dementia following treatment were calculated and reported as dementia cases per 10,000 person-years. Cox proportional hazards models were used to assess the impact of dementia on survival outcomes. RESULTS: Of the 4814 patients, 2403 (49.9%) underwent radical cystectomy (RC) and 2411 (50.1%) underwent radiotherapy (RTX) and/or chemotherapy (CTX). Overall, 837 (17.4%) patients developed Alzheimer's disease and related dementia following bladder cancer treatment. There was no significant difference in the incidence of Alzheimer's disease and related dementia following either treatment. Patients diagnosed with Alzheimer's disease and related dementia had worse overall (Hazard Ratio (HR), 2.64; 95% Confidence Interval (CI), 2.41-2.89) and cancer-specific (HR, 2.45; 95% CI, 2.18-2.76) survival than those without a dementia diagnosis following treatment. CONCLUSION: While we observed no difference in new-onset Alzheimer's disease and related dementia diagnosis following RC or RTX and/or CTX, patients with a Alzheimer's and related dementia diagnosis was associated with worse overall and cancer-specific survival. These findings have important implications for screening and the development of targeted interventions for improving outcomes in older adults following complex cancer treatments, as observed in this bladder cancer population.

Evidence-based Assessment of Current and Emerging Bladder-sparing Therapies for Non-muscle-invasive Bladder Cancer After Bacillus Calmette-Guerin Therapy: A Systematic Review and Meta-analysis.

CONTEXT: Currently, there is no standard of care for patients with non-muscle-invasive bladder cancer (NMIBC) who recur despite bacillus Calmette-Guerin (BCG) therapy. Although radical cystectomy is recommended, many patients decline to undergo or are ineligible to receive it. Multiple agents are being investigated for use in this patient population. OBJECTIVE: To systematically synthesize and describe the efficacy and safety of current and emerging treatments for NMIBC patients after treatment with BCG. EVIDENCE ACQUISITION: A systematic literature search of MEDLINE, Embase, and the Cochrane Controlled Register of Trials (period limited to January 2007-June 2019) was performed. Abstracts and presentations from major conference proceedings were also reviewed. Randomized controlled trials were assessed using the Cochrane risk of bias tool. Data for single-arm trials were pooled using a random-effect meta-analysis with the proportions approach. Trials were grouped based on the minimum number of prior BCG courses required before enrollment and further stratified based on the proportion of patients with carcinoma in situ (CIS). EVIDENCE SYNTHESIS: Thirty publications were identified with data from 23 trials for meta-analysis, of which 17 were single arm. Efficacy and safety outcomes varied widely across studies. Heterogeneity across trials was reduced in subgroup analyses. The pooled 12-mo response rates were 24% (95% confidence interval [CI]: 16-32%) for trials with two or more prior BCG courses and 36% (95% CI: 25-47%) for those with one or more prior BCG courses. In a subgroup analysis, inclusion of ≥50% of patients with CIS was associated with a lower response. CONCLUSIONS: The variability in efficacy and safety outcomes highlights the need for consistent endpoint reporting and patient population definitions. With promising emerging treatments currently in development, efficacious and safe therapeutic options are urgently needed for this difficult-to-treat patient population. PATIENT SUMMARY: We examined the efficacy and safety outcomes of treatments for non-muscle-invasive bladder cancer after bacillus Calmette-Guerin therapy. Outcomes varied across studies and patient populations, but emerging treatments currently in development show promising efficacy.

Cost-Effectiveness of Robot-assisted Radical Cystectomy Using a Propensity-matched Cohort.

BACKGROUND: Health-related quality of life is important for patients undergoing radical cystectomy (RC). OBJECTIVE: To determine the cost-effectiveness of robotic-assisted RC (RARC) compared to open cystectomy (OC) for bladder cancer and factors that contribute to cost-effectiveness. DESIGN, SETTING, AND PARTICIPANTS: A decision analytic model was used to compare health-related quality of life and medical costs for RARCs with intracorporeal urinary diversion and OCs performed between 2007 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Propensity matching was performed among 1322 cases to yield a final cohort of 100 RARC and 96 ORC cases. Probabilities were obtained from the clinical study data, while quality-adjusted life years (QALYs) and health utility values were derived from the literature. A complication, readmission, or transfusion was included in the 90-d time horizon model. RESULTS AND LIMITATIONS: There were no differences between the groups in patient demographics, pathologic staging, or length of stay. Multivariable analysis revealed that the RARC group had fewer transfusions and complications compared to the OC group. The incremental cost-effectiveness ratio was $2969. RARC cost $2969 less per QALY when compared to OC. While RARC was $17000 more expensive, it also associated with an increase of 0.32 QALYs. One-way sensitivity analysis identified RARC as the preferred strategy if a complication can be prevented 74% of the time. RARC is preferred as long as it is 70% effective in preventing a transfusion. Two-way sensitivity analysis showed that as long as RARC can prevent complications and transfusions, it is the preferred cost-effective treatment when compared to OC. The study is limited by the omission of a societal perspective and the lack of health utility values for RC. CONCLUSIONS: RARC is cost-effective compared to OC when the rates of complications and transfusions are significantly lower. PATIENT SUMMARY: Bladder removal via a robotic approach is more expensive, but it improves health-related quality of life. Robotic surgery is cost-effective compared to an open approach for bladder removal if there are low rates of complications and blood transfusion.

Eligibility and Radiologic Assessment in Adjuvant Clinical Trials in Bladder Cancer.

Objective: To harmonize eligibility criteria and radiographic disease assessments in clinical trials of adjuvant therapy for muscle-invasive bladder cancer (MIBC). Methods: National experts in bladder cancer clinical trial research, including medical and urologic oncologists, radiologists, biostatisticians, and patient advocates, convened at a public workshop on November 28, 2017, to discuss eligibility, radiographic entry criteria, and assessment of disease recurrence in adjuvant clinical trials in patients with MIBC. Results: The key workshop conclusions for adjuvant MIBC clinical trials included the following points: (1) patients with urothelial carcinoma with divergent histologic differentiation should be allowed to enroll; (2) neoadjuvant chemotherapy is defined as at least 3 cycles of neoadjuvant cisplatin-based combination chemotherapy; (3) patients with muscle-invasive, upper-tract urothelial carcinoma should be included in adjuvant trials of MIBC; (4) patients with severe renal insufficiency can enroll into trials using agents that are not renally excreted; (5) patients with microscopic surgical margins can be included; (6) patients should undergo a standard bilateral lymph node dissection prior to enrollment; (7) computed tomographic (CT) imaging should be performed within 4 weeks prior to enrollment. For patients with renal insufficiency who cannot undergo CT imaging with contrast, noncontrast chest CT and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be done; (8) biopsy of indeterminate lesions to evaluate for malignant disease should be done when feasible; (9) a uniform approach to evaluate indeterminate radiographic lesions when biopsy is not feasible should be included in any trial design; (10) a uniform approach to determining the date of recurrence is important in interpreting adjuvant trial results; and (11) new high-grade, upper-tract primary tumors and new MIBC tumors should be considered recurrence events. Conclusions and Relevance: A uniform approach to eligibility criteria, definitions of no evidence of disease, and definitions of disease recurrence may lead to more consistent interpretations of adjuvant trial results in MIBC.

Discerning Patterns and Quality of Neoadjuvant Chemotherapy Use Among Patients with Muscle-invasive Bladder Cancer.

BACKGROUND: Neoadjuvant chemotherapy is underutilized in bladder cancer patients who undergo radical cystectomy. However, the quality of regimens used in this setting remains largely unknown. OBJECTIVE: To determine utilization treatment patterns and survival outcomes according to regimens administered. DESIGN, SETTING, AND PATIENTS: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked database to identify patients diagnosed with clinical stage TII-IV bladder cancer from January 1, 2001 to December 31, 2011. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Temporal trends were assessed using the Cochran-Armitage test. Multivariable logistic regression models were used to identify predictors for neoadjuvant chemotherapy use. Cox proportional hazards models were used to compare overall survival according to regimens administered. RESULTS AND LIMITATIONS: Of 2738 patients treated with radical cystectomy, 344 (12.6%) received neoadjuvant chemotherapy. The agents most commonly used were gemcitabine (72.3%), cisplatin (55.2%), and carboplatin (31.1%). The regimens most commonly used were gemcitabine-cisplatin (45.3%), gemcitabine-carboplatin (24.1%), and methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC; 6.7%). Use of neoadjuvant chemotherapy more than tripled during the study period, from 5.7% in 2001 to 17.3% in 2011 (p<0.001). The quality of the regimen administered impacted survival outcomes, as M-VAC use was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer (hazard ratio 0.24, 95% confidence interval 0.07-0.86; p=0.030]. Limitations include the limited ability of retrospective analysis to control for selection bias. CONCLUSIONS: Neoadjuvant chemotherapy was underused, and the quality of neoadjuvant chemotherapy regimens administered for bladder cancer was inconsistent with guideline recommendations. These findings are important when interpreting population-based data on the use of chemotherapy and extrapolating survival outcomes. PATIENT SUMMARY: In a large population-based study, 12.6% of patients undergoing radical cystectomy for bladder cancer received neoadjuvant chemotherapy, half of whom received guideline-recommended regimens. The quality of the regimen impacted survival outcomes, as use of cisplatin-based chemotherapy was significantly associated with better overall survival among patients diagnosed with stage II bladder cancer. However, <1% of radical cystectomy patients received this regimen.

Comparison of Costs of Radical Cystectomy vs Trimodal Therapy for Patients With Localized Muscle-Invasive Bladder Cancer.

Importance: Earlier studies on the cost of muscle-invasive bladder cancer treatments lack granularity and are limited to 180 days. Objective: To compare the 1-year costs associated with trimodal therapy vs radical cystectomy, accounting for survival and intensity effects on total costs. Design, Setting, and Participants: This population-based cohort study used the US Surveillance, Epidemiology, and End Results-Medicare database and included 2963 patients aged 66 to 85 years who had received a diagnosis of clinical stage T2 to T4a muscle-invasive bladder cancer from January 1, 2002, through December 31, 2011. The data analysis was performed from March 5, 2018, through December 4, 2018. Main Outcomes and Measures: Total Medicare costs within 1 year of diagnosis following radical cystectomy vs trimodal therapy were compared using inverse probability of treatment-weighted propensity score models that included a 2-part estimator to account for intrinsic selection bias. Results: Of 2963 participants, 1030 (34.8%) were women, 2591 (87.4%) were white, 129 (4.4%) were African American, and 98 (3.3%) were Hispanic. Median costs were significantly higher for trimodal therapy than radical cystectomy in 90 days ($83 754 vs $68 692; median difference, $11 805; 95% CI, $7745-$15 864), 180 days ($187 162 vs $109 078; median difference, $62 370; 95% CI, $55 581-$69 160), and 365 days ($289 142 vs $148 757; median difference, $109 027; 95% CI, $98 692-$119 363), respectively. Outpatient care, radiology, medication expenses, and pathology/laboratory costs contributed largely to the higher costs associated with trimodal therapy. On inverse probability of treatment-weighted adjusted analyses, patients undergoing trimodal therapy had $136 935 (95% CI, $122 131-$152 115) higher mean costs compared with radical cystectomy 1 year after diagnosis. Conclusions and Relevance: Compared with radical cystectomy, trimodal therapy was associated with higher costs among patients with muscle-invasive bladder cancer. The differences in costs were largely attributed to medication and radiology expenses associated with trimodal therapy. Extrapolating cost figures resulted in a nationwide excess spending of $468 million for trimodal therapy compared with radical cystectomy for patients who received a diagnosis of bladder cancer in 2017.

Patient-reported outcomes of blue-light flexible cystoscopy with hexaminolevulinate in the surveillance of bladder cancer: results from a prospective multicentre study.

OBJECTIVE: To evaluate blue-light flexible cystoscopy (BLFC) with hexaminolevulinate in the office surveillance of patients with non-muscle-invasive bladder cancer with a high risk of recurrence by assessing its impact on pain, anxiety, subjective value of the test and patient willingness to pay. MATERIALS AND METHODS: A prospective, multicentre, phase III study was conducted during which the Patient-Reported Outcomes Measurement Information System (PROMIS) Anxiety, Pain and 'Was It Worth It' questionnaires were administered at baseline, after surveillance with BLFC and after resection for those referred to the operating room. Comparisons of scores were performed between groups. RESULTS: A total of 304 patients were enrolled, of whom 103 were referred for surgical examination. Of these, 63 were found to have histologically confirmed malignancy. Pain levels were low throughout the study. Anxiety levels decreased after BLFC (∆ = -2.6), with a greater decrease among those with negative pathology results (P = 0.051). No differences in anxiety were noted based on gender, BLFC results, or test performance (true-positive/false-positive). Most patients found BLFC 'worthwhile' (94%), would 'do it again' (94%) and 'would recommend it to others' (91%), with no differences based on BLFC results or test performance. Most patients undergoing BLFC (76%) were willing to pay out of pocket. CONCLUSIONS: Anxiety decreased after BLFC in patients with negative pathology, including patients with false-positive results. Most of the patients undergoing BLFC were willing to pay out of pocket, found the procedure worthwhile and would recommend it to others, irrespective of whether they had a positive BLFC result or whether this was false-positive after surgery.

Hospital length of stay following radical cystectomy for muscle-invasive bladder cancer: Development and validation of a population-based prediction model.

OBJECTIVE: Length of hospital stay for patients following radical cystectomy is an important determinant for improved quality of care. We sought to develop and validate a predictive model for length of hospital stay following radical cystectomy. METHODS: Patients aged 66 to 90 years diagnosed with clinical stage T2-4a muscle-invasive bladder cancer who underwent radical cystectomy were included from January 1, 2002 through December 31, 2011 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Linear regression analyses were used to develop and validate a predictive model for length of hospital stay. RESULTS: A total of 2,448 patients met inclusion criteria. After random assignment, 1,224 patients were included in the discovery cohort and 1,224 patients included in the validation cohort. The cohorts were well balanced with no significant difference in any of the preoperative variables. A best model was developed using marital status, Surveillance, Epidemiology, and End Results (SEER) region, clinical stage, Charlson comorbidity index, logarithm of hospital cystectomy volume, and use of neoadjuvant chemotherapy in a backward selection to predict the length of stay. There was robust internal validation (sum square error (SSE): 258.1 vs. predicted sum of squares (PRESS): 264.0 at SLS = 0.10), consistent with the external validation (average square error (ASE): discovery (0.248) vs. validation (0.258)) cohort. The strength of the model in predicting length of stay for the entire cohort was (R2 = 0.048). CONCLUSION: In this large population-based study, we developed and validated a model to predict length of hospital stay following radical cystectomy. Identification of at-risk patients for prolonged hospital stay may aid in targeted interventions to reduce length of stay, improve quality of care, and decrease healthcare costs.

Comparing Survival Outcomes and Costs Associated With Radical Cystectomy and Trimodal Therapy for Older Adults With Muscle-Invasive Bladder Cancer.

Importance: Radical cystectomy is the guidelines-recommended treatment of muscle-invasive bladder cancer, but a resurgence of trimodal therapy has occurred. Limited comparative data are available on outcomes and costs attributable to these 2 treatments. Objective: To compare the survival outcomes and costs between trimodal therapy and radical cystectomy in older adults with muscle-invasive bladder cancer. Design, Setting, and Participants: This population-based cohort study used data from the Surveillance, Epidemiology, and End Results-Medicare linked database. A total of 3200 older adults (aged ≥66 years) with clinical stage T2 to T4a bladder cancer diagnosed from January 1, 2002, to December 31, 2011, and with claims data available through December 31, 2013, were included in the analysis. Patients who received radical cystectomy underwent either only surgery or surgery in combination with radiotherapy or chemotherapy. Patients who received trimodal therapy underwent transurethral resection of the bladder followed by radiotherapy and chemotherapy. Propensity score matching by sociodemographic and clinical characteristics was used. Data analysis was performed from August 1, 2017, to March 11, 2018. Main Outcomes and Measures: Overall survival and cancer-specific survival were evaluated using the Cox proportional hazards regression model and the Fine and Gray competing risk model. All Medicare health care costs for inpatient, outpatient, and physician services within 30, 90, and 180 days of treatment were compared. The total amount spent nationwide was estimated, using 180-day medical costs between treatments, by the total number of new cases of muscle-invasive bladder cancer in the United States in 2011. Results: Of the 3200 patients who met the inclusion criteria, 2048 (64.0%) were men and 1152 (36.0%) were women, with a mean (SD) age of 75.8 (6.0) years. After propensity score matching, 687 patients (21.5%) underwent trimodal therapy and 687 patients (21.5%) underwent radical cystectomy. Patients who underwent trimodal therapy had significantly decreased overall survival (hazard ratio [HR], 1.49; 95% CI, 1.31-1.69) and cancer-specific survival (HR, 1.55; 95% CI, 1.32-1.83). No differences in costs at 30 days were observed between trimodal therapy ($15 233 in 2002 vs $18 743 in 2011) and radical cystectomy ($17 990 in 2002 vs $21 738 in 2011). However, median total costs were significantly higher with trimodal therapy than with radical cystectomy at 90 days ($80 174 vs $69 181; median difference, $8964; Hodges-Lehmann 95% CI, $3848-$14 079) and at 180 days ($179 891 vs $107 017; median difference, $63 771; Hodges-Lehmann 95% CI, $55 512-$72 029). Extrapolating these figures to the total US population revealed $335 million in excess spending for trimodal therapy compared with the less costly radical cystectomy ($492 million) for patients who received a muscle-invasive bladder cancer diagnosis in 2011. Conclusions and Relevance: Trimodal therapy was associated with significantly decreased overall survival and cancer-specific survival as well as $335 million in excess spending in 2011. These findings have important health policy implications regarding the appropriate use of high value-based care among older adults with invasive bladder cancer who are candidates for either radical cystectomy or trimodal therapy.