Use of a Risk Stratification Tool to Guide Evaluation of Patients With Asymptomatic Microscopic Hematuria.

OBJECTIVE: To determine if use of the hematuria risk index can reduce testing and cost, while maintaining equivalent lesion detection in patients with asymptomatic microscopic hematuria. MATERIALS AND METHODS: Retrospective cohort study of 1049 patients at single institution. Hematuria risk index score was calculated based on clinical factors including age, sex, smoking history, and degree of hematuria for each patient along with evaluation studies performed and total number of tumors discovered. Cost benefit analysis was performed based on published Medicare averages. RESULTS: Tumor detection rate in overall, low-risk, and moderate-risk groups were 1.2%, 0%, and 2.96% at a total cost of $408,376. When low-risk group is not screened cost decreases to $166,252 with no lesions missed. The cost to discover one lesion/cancer in the overall group was $34,031.3, the cost to find one high-grade clinically significant lesion/cancer was $136,125.3 for the overall group. When the low-risk group was removed, the cost to find a high-grade clinically significant lesion/cancer decreased to $55,417.3 without missing any significant lesions. Ultrasound may be utilized instead of computed tomography with minimal loss of lesion detection in select moderate risk patients. CONCLUSION: None of the low-risk hematuria risk patients were diagnosed with any lesions, as such these patients may not need an evaluation. Furthermore, by utilizing a risk-stratified approach to the assessment of asymptomatic microscopic hematuria health care costs can be significantly decreased with limited negative consequences in terms of lesion detection.

Financial toxicity and its associations with health-related quality of life among urologic cancer patients in an upper middle-income country.

PURPOSE: This study examined the prevalence of financial toxicity (FT) and associated factors among urologic cancer patients. The association between FT and health-related quality of life (HRQoL) was also investigated. METHODS: A total of 429 respondents diagnosed with urologic cancers (prostate cancer, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed using a structured questionnaire. Objective and subjective FT were measured by catastrophic health expenditure (healthcare-cost-to-income ratio greater than 40%) and the Personal Financial Well-being Scale, respectively. HRQoL was measured with the Functional Assessment of Cancer Therapy - General 7 Items scale. RESULTS: Objective and subjective FT were experienced by 16.1 and 47.3% of the respondents, respectively. Respondents who sought treatment at a private hospital and had out-of-pocket health expenditures were more likely to experience objective FT, after adjustment for covariates. Respondents who were female and had a monthly household income less than MYR 5000 were more likely to experience average to high subjective FT. Greater objective FT (OR = 2.75, 95% CI 1.09-6.95) and subjective FT (OR = 4.68, 95% CI 2.63-8.30) were associated with poor HRQoL. CONCLUSIONS: The significant association between both objective and subjective FT and HRQoL highlights the importance of reducing FT among urologic cancer patients. Subjective FT was found to have a greater negative impact on HRQoL.

Cost-effectiveness of Pembrolizumab for Patients with Advanced, Unresectable, or Metastatic Urothelial Cancer Ineligible for Cisplatin-based Therapy.

BACKGROUND: There is an unmet need for effective therapies for patients with advanced or metastatic urothelial cancer who cannot tolerate cisplatin-based chemotherapy. Cisplatin-ineligible patients experience a high frequency of adverse events from the most commonly used standard of care treatment, carboplatin plus gemcitabine, or alternative treatment with gemcitabine monotherapy. Pembrolizumab is a potent, highly selective humanised monoclonal antibody that releases checkpoint inhibition of the immune response system, and provides a new alternative for these patients. OBJECTIVE: To assess the cost-effectiveness of pembrolizumab for first-line treatment of urothelial carcinoma ineligible for cisplatin-based therapy in patients with strongly PD-L1-positive tumours in Sweden. DESIGN, SETTING, AND PARTICIPANTS: Parametric survival curves were fitted to overall survival, progression-free survival, and time on treatment data from KEYNOTE-052 to extrapolate clinical outcomes. A simulated treatment comparison and a network meta-analysis were conducted to estimate the comparative efficacy of pembrolizumab versus carboplatin plus gemcitabine and gemcitabine monotherapy. EQ-5D data from KEYNOTE-052 were used to estimate utility, while resource use and cost inputs were estimated using Swedish regional pricing lists and clinician opinion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The model reported costs, life years, and quality-adjusted life years (QALYs), and results were tested using deterministic and probabilistic sensitivity analysis. RESULTS AND LIMITATIONS: We estimated that pembrolizumab would improve survival by 2.11 and 2.16 years and increase QALYs by 1.71 and 1.75 compared to carboplatin plus gemcitabine and gemcitabine monotherapy, respectively. Pembrolizumab was associated with a cost increase of €90520 versus carboplatin plus gemcitabine and €95055 versus gemcitabine, with corresponding incremental cost-effectiveness ratios of €53055/QALY and €54415/QALY. CONCLUSIONS: At a willingness-to-pay threshold of €100000/QALY, pembrolizumab is a cost-effective treatment versus carboplatin plus gemcitabine and versus gemcitabine. PATIENT SUMMARY: This is the first analysis to show that pembrolizumab is a cost-effective option for first-line treatment of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma in Sweden.

Pembrolizumab for Locally Advanced or Metastatic Urothelial Cancer Where Cisplatin is Unsuitable: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Merck Sharp & Dohme) of pembrolizumab (Keytruda®) to submit evidence of its clinical and cost effectiveness for the treatment of locally advanced or metastatic urothelial cancer where cisplatin is unsuitable. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company's submission (CS) to NICE. The clinical effectiveness evidence in the CS for pembrolizumab was based on one phase II, single-arm, open-label, non-randomised study (KEYNOTE-052), while the evidence for the comparator (carboplatin plus gemcitabine) was based on four studies, including one randomised controlled trial and three cohort studies. In the absence of head-to-head trials, the company conducted an indirect treatment comparison for both progression-free survival (PFS) and overall survival (OS), by firstly adjusting cross-study differences using a simulated treatment comparison approach and then synthesizing the evidence based on an assumption of constant hazard ratios using a standard meta-analysis model and time-varying hazard ratios using fractional polynomial models. The treatment effect of pembrolizumab was more favourable in the adjusted population compared with the observed effect in the KEYNOTE-052 study. The company submitted a de novo partitioned survival cohort simulation model, which partitions the OS time into PFS and post-progression survival. The probabilistic incremental cost-effectiveness ratio (ICER) for pembrolizumab compared with carboplatin plus gemcitabine was estimated to be £37,081 per quality-adjusted life-year (QALY) gained, based on the results within the company's health economic model. Following a critique of the model, for their preferred base case the ERG corrected some minor model errors, chose a progression approach for estimating utilities, and revised the extrapolation of PFS and OS. The ERG's probabilistic base case ICER was estimated to be £67,068 per QALY gained. The ERG also undertook a range of exploratory sensitivity analyses which suggested that the ICER was highly uncertain. In particular, the choices of extrapolation for the OS of pembrolizumab and the stopping rule for pembrolizumab had the largest impacts on the ICER. The NICE Appraisal Committee recommended pembrolizumab for use within the Cancer Drugs Fund as an option for treating locally advanced or metastatic urothelial carcinoma in adults who have had platinum-containing chemotherapy, provided that pembrolizumab was stopped at 2 years of uninterrupted treatment, or earlier if the disease progresses, and the conditions of the managed access agreement for pembrolizumab are followed.

Pembrolizumab for Previously Treated Advanced or Metastatic Urothelial Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Pembrolizumab is an intravenously administered monoclonal antibody licensed for locally advanced or metastatic urothelial carcinoma after platinum-containing chemotherapy. This summary presents the perspective of Warwick Evidence, the Evidence Review Group (ERG) appointed by the National Institute of Health and Care Excellence (NICE) for the single technology appraisal of pembrolizumab for this indication. Pembrolizumab is manufactured by Merck, Sharp and Dohme (MSD). The major source of clinical effectiveness was the KEYNOTE-045 trial, where 542 patients received either pembrolizumab or clinician's choice of docetaxel, paclitaxel or vinflunine as a second-line treatment. No indirect treatment comparison was performed. The clinical effectiveness was assessed using hazard ratios for overall survival (OS) and progression-free survival (PFS) of the intention-to-treat (ITT) population, together with the subpopulations positive for programmed cell death 1 ligand 1 (PD-L1) expression (combined positive score [CPS] ≥ 1%) and strongly positive for PD-L1 expression (CPS ≥ 10%). In the ITT population, OS improved with pembrolizumab (HR 0.73, 95% CI 0.59-0.91) while PFS outcomes showed no difference (HR 0.98, 95% CI 0.81-1.19). Pembrolizumab demonstrated a better safety profile than its combined comparators, with fewer patients experiencing adverse events (60.9 vs 90.2%). Similar results were observed in populations expressing PD-L1. MSD estimated the cost effectiveness of pembrolizumab using a de novo partitioned survival model. The model had three health states: pre-progression, post-progression and death, where OS and PFS estimates excluded patients who received vinflunine. The largest uncertainty was over the selection of the parametric models used to extrapolate OS and PFS and the time point for when to begin their extrapolation. The company preferences for extrapolation were not well supported and the ERG disagreed with their selection for OS. Utility values were also contentious, with the company preferring to use pooled time-to-death-based utilities pooled across treatment arms, whilst the ERG preferred pooled progression-based utilities. The company preferred to use data from patients receiving vinflunine when calculating the utility values, which the ERG disagreed with as this is not recommended treatment within the UK. The company assumed a lifetime treatment effect for their model; however, the lack of evidence made it difficult to confidently provide a realistic estimate of treatment effect duration. Various durations were explored (3, 5 and 10 years). The first appraisal committee meeting concluded that pembrolizumab was not cost effective, largely due to uncertainty in the OS and PFS extrapolations. The company's second submission included an additional 4 months follow-up to survival data. The company in this new submission maintained their original assumptions in their base-case analysis, changing only the choice of parametric curve for PFS. This change resulted in the OS and PFS curves intersecting at 6 years in the pembrolizumab arm, at which point PFS identically followed OS. This resulted in no patients in the post-progression health state beyond this time point, and therefore, the majority of pembrolizumab's benefit came from pre-progression survival. Given the unclear PFS benefit, the ERG found this implausible and maintained their original base-case model assumptions. Considerable uncertainty remained over the specification of the extrapolations and the duration of treatment effect. Based on a new-value proposition submitted by the company, the appraisal committee concluded that pembrolizumab had plausible potential to be cost effective. Pembrolizumab was referred for funding through the Cancer Drugs Fund, so that further data could be collected with the aim of diminishing the outstanding uncertainties pertaining to its clinical effectiveness.

Beyond classic risk adjustment: Socioeconomic status and hospital performance in urologic oncology surgery.

BACKGROUND: Safety-net hospitals (SNHs) care for more patients of low socioeconomic status (SES) than non-SNHs and are disproportionately punished under SES-naive Medicare readmission risk-adjustment models. This study was designed to develop a risk-adjustment framework that incorporates SES and to assess the impact on readmission rates. METHODS: California Office of Statewide Health Planning and Development data from 2007 to 2011 were used to identify patients undergoing radical cystectomy (RC) for bladder cancer (n = 3771) or partial nephrectomy (PN; n = 5556) or radical nephrectomy (RN; n = 13,136) for kidney cancer. Unadjusted hospital rankings and predicted rankings under models simulating the Medicare Hospital Readmissions Reduction Program were compared with predicted rankings under models incorporating SES and hospital factors. SES, derived from a multifactorial neighborhood score, was calculated from US Census data. RESULTS: The 30-day readmission rate was 26.1% for RC, 8.3% for RN, and 9.5% for PN. The addition of SES, geographic, and hospital factors changed hospital rankings significantly in comparison with the base model (P < .01) except for SES for RC (P = .07) and SES and rural factors for PN (P = .12). For RN and PN, the addition of SES predicted lower percentile ranks for SNHs and thus improved observed-to-expected rankings (P < .01). For RC, there were no changes in hospital rankings. CONCLUSIONS: SES is important for risk adjustments for complex surgical procedures such as RC. Patient SES affects overall hospital rankings across cohorts, and critically, it differentially and punitively affects rankings for SNHs for some procedures. Cancer 2018. © 2018 American Cancer Society.

Asymptomatic recurrence detection and cost-effectiveness in urothelial carcinoma.

For the management of muscle-invasive bladder cancer or upper tract urothelial carcinoma, the set guidelines recommend regular surveillance after radical cystectomy or radical nephroureterectomy. However, the prognostic benefit of regular oncological surveillance remains controversial in the absence of prospective studies although several retrospective studies with relatively large sample sizes have demonstrated the association between asymptomatic recurrence and better oncological outcomes. Seven out of eight studies reported that patients diagnosed with symptomatic recurrence showed significantly poorer prognosis in comparison to those diagnosed with asymptomatic recurrence. However, potential lead-time and length-time biases prevent the determination of any benefit of regular surveillance. In addition, an optimal surveillance protocol has yet to be established because conventional pathology-based protocols cannot identify the heterogenetic tumor biology of urothelial carcinoma, such as rapid- or slow-growing form of the disease. Several studies suggest that conventional pathology-based surveillance resulted in reduced cost-effectiveness. Recurrence risk-score stratified surveillance protocol including clinical and pathological factors may improve cost-effectiveness. The establishment of optimal risk stratification and surveillance strategies are required to improve the efficacy of regular oncological surveillance. Well-planned prospective studies are necessary to address the prognostic benefit of regular oncological surveillance and shared decision making.

Cost and cost-effectiveness studies in urologic oncology using large administrative databases.

OBJECTIVE: Urologic cancers are not only among the most common types of cancers, but also among the most expensive cancers to treat in the United States. This study aimed to review the use of CEAs and other cost analyses in urologic oncology using large databases to better understand the value of management strategies of these cancers. METHODS: A literature review on CEAs and other cost analyses in urologic oncology using large databases. RESULTS: The options for and costs of diagnosing, treating, and following patients with urologic cancers can be expected to rise in the coming years. There are numerous opportunities in each urologic cancer to use CEAs to both lower costs and provide high-quality services. Improved cancer care must balance the integration of novelty with ensuring reasonable costs to patients and the health care system. CONCLUSION: With the increasing focus cost containment, appreciating the value of competing strategies in caring for our patients is pivotal. Leveraging methods such as CEAs and harnessing large databases may help evaluate the merit of established or emerging strategies.

Episode-based Payment Variation for Urologic Cancer Surgery.

OBJECTIVE: To investigate payment variation for 3 common urologic cancer surgeries and evaluate the potential for applying bundled payment programs to these procedures. METHODS: Using 2008-2011 Surveillance, Epidemiology, and End Results-Medicare linked data, we identified all beneficiaries aged greater than 65 years who underwent cystectomy, prostatectomy, or nephrectomy for cancer. Total episode payments were determined by aggregating hospital, professional, and post-acute care claims from the index surgical hospitalization through 90 days post discharge. Total episode payments were then compared to examine hospital level-variation within each procedure type and the specific payment components (ie, index hospitalization, professional, readmission, and post-acute care) driving spending variation. RESULTS: Ninety-day episodes of care were identified for 1849 cystectomies, 8770 prostatectomies, and 4304 nephrectomies. We observed wide variation in mean episode payments for all 3 conditions (cystectomy mean $35,102: range $24,112-$57,238, prostatectomy mean $10,803: range $8,816-$17,877, nephrectomy mean $17,475: range $11,681-$26,711). Majority of payment variation was attributable to index hospitalization and post-acute care for cystectomy and nephrectomy and professional payments for prostatectomy. The most expensive hospitals by procedure each demonstrated a unique opportunity for spending reduction due to individual differences in component payment patterns between hospitals. CONCLUSION: Ninety-day episode payments for urologic cancer surgery vary widely across hospitals in the United States. The key drivers of this payment variation differ for individual procedures and hospitals. Accordingly, hospitals will need individualized data and clinical re-design strategies to succeed with implementation of episode-based payment models for urologic cancer care.

Trends in utilisation, perioperative outcomes, and costs of nephroureterectomies in the management of upper tract urothelial carcinoma: a 10-year population-based analysis.

OBJECTIVE: To perform a population-based study to evaluate contemporary utilisation trends, morbidity, and costs associated with nephroureterectomies (NUs), as contemporary data for NUs are largely derived from single academic institution series describing the experience of high-volume surgeons and it is unclear if the same favourable results occur at a national level. PATIENTS AND METHODS: Using the Premier Hospital Database, we captured patients undergoing a NU with diagnoses of renal pelvis or ureteric neoplasms from 2004 to 2013. We fitted regression models, adjusting for clustering by hospitals and survey weighting to evaluate 90-day postoperative complications, operating-room time (OT), prolonged length of stay (pLOS), and direct hospital costs among open (ONU), laparoscopic (LNU) and robotic (RNU) approaches. RESULTS: After applying sampling and propensity weights, we derived a final study cohort of 17 254 ONUs, 13 317 LNUs and 3774 RNUs for upper tract urothelial carcinoma (UTUC) in the USA between 2004 and 2013. During that period, minimally invasive NU (miNU) increased from 36% to 54%, while the total number of NUs decreased by nearly 20%. No differences were noted in perioperative outcomes between the three surgical approaches, including when the analysis was restricted to the highest-volume hospitals and highest-volume surgeons. The OT was longer for LNU and RNU (P < 0.001), while the pLOS rates were decreased (P < 0.001). Adjusted 90-day median direct hospital costs were higher for LNU and RNU (P < 0.001), which disappeared when adjusting for the highest-volume groups, except for RNUs performed by high-volume surgeons. CONCLUSIONS: During this contemporary 10-year study, miNU has been replacing ONU for UTUC with a recent surge in RNU, along with a concurrent reduction in total NUs performed. Despite not being associated with a clinically significant improvement in perioperative outcomes, the costs for miNUs were consistently higher. However, higher hospital volumes suggest a potential cost containment strategy when performing miNUs.

Robotic surgery in urological oncology: patient care or market share?

Surgical robotic use has grown exponentially in spite of limited or uncertain benefits and large costs. In certain situations, adoption of robotic technology provides value to patients and society. In other cases, however, the robot provides little or no increase in surgical quality, with increased expense, and, therefore, does not add value to health care. The surgical robot is expensive to purchase, maintain and operate, and can contribute to increased consumerism in relation to surgical procedures, and increased reliance on the technology, thus driving future increases in health-care expenditure. Given the current need for budget constraints, the cost-effectiveness of specific procedures must be evaluated. The surgical robot should be used when cost-effective, but traditional open and laparoscopic techniques also need to be continually fostered.

Anticipating the effect of the Patient Protection and Affordable Care Act for patients with urologic cancer.

The Affordable Care Act seeks to overhaul the US health care system by providing insurance for more Americans, improving the quality of health care delivery, and reducing health care expenditures. Although the law's intent is clear, its implementation and effect on patient care remains largely undefined. Herein, we discuss major components of the Affordable Care Act, including the proposed insurance expansion, payment and delivery system reforms (e.g., bundled payments and Accountable Care Organizations), and other reforms relevant to the field of urologic oncology. We also discuss how these proposed reforms may affect patients with urologic cancers.

The PACT study protocol: a time series study investigating the impact, acceptability and cost of an integrated model for psychosocial screening, care and treatment of patients with urological and head and neck cancers.

INTRODUCTION: While there is good evidence of the effectiveness of a variety of interventions and services to prevent and/or relieve distress experienced by people affected by cancer, much of this psychosocial morbidity is undetected and untreated, with consequent exacerbated suffering, decreased satisfaction with care, impaired adherence to treatment regimens and poorer morbidity and mortality outcomes. The objective of this study is to develop, implement and assess the impact, acceptability and cost of an integrated, patient-centred Psychosocial Assessment, Care and Treatment (PACT) model of care for patients with urological and head and neck cancers. METHODS AND ANALYSIS: A time series research design will be used to test the PACT model of care, newly introduced in an Australian tertiary hospital. The primary outcome is system-level impact, assessed through audit of patients' medical records and Medicare claims for follow-up care. The secondary outcomes are impact of the model on patients' experience and healthcare professionals' (HCPs) knowledge and confidence, assessed via patient and HCP surveys at baseline and at follow-up. Acceptability of the intervention will be assessed through HCP interviews at follow-up, and cost will be assessed from Medicare and Pharmaceutical Benefits Scheme claims information and information logged pertaining to intervention activities (eg, time spent by the newly appointed psycho-oncology staff in direct patient contact, providing training sessions, engaging in case review) and their associated costs (eg, salaries, training materials and videoconferencing). ETHICS AND DISSEMINATION: Ethics approval was obtained from the Human Research Ethics Committees of Hunter New England Local Health District and the University of NSW. RESULTS: The results will be widely disseminated to the funding body and through peer-reviewed publications, HCP and consumer publications, oncology conferences and meetings. TRIAL REGISTRATION: The study is registered with the Australian New Zealand Clinical Trials Registry with registration number ACTRN12613000916741.

The Patient Protection and Affordable Care Act: the impact on urologic cancer care.

In March 2010, the Patient Protection and Affordable Care Act as well as its amendments were signed into law. This sweeping legislation was aimed at controlling spiraling healthcare costs and redressing significant disparities in healthcare access and quality. Cancer diagnoses and their treatments constitute a large component of rising healthcare expenditures and, not surprisingly, the legislation will have a significant influence on cancer care in the USA. Because genitourinary malignancies represent an impressive 25% of all cancer diagnoses per year, this legislation could have a profound impact on urologic oncology. To this end, we will present key components of this landmark legislation, including the proposed expansion to Medicaid coverage, the projected role of Accountable Care Organizations, the expected creation of quality reporting systems, the formation of an independent Patient-Centered Outcomes Research Institute, and enhanced regulation on physician-owned practices. We will specifically address the anticipated effect of these changes on urologic cancer care. Briefly, the legal ramifications and current barriers to the statutes will be examined.

The practice of urologic oncology: some economic realties.

The future practice of urologic oncology in the United States will be influenced by a variety of factors. The national economic crisis has already impacted reimbursement and coverage for clinical care and has had a direct effect on the level of research funding. Unhealthy lifestyles by a significant segment of the American population contributes to a increased risk of most urologic cancers. Compounding these challenges is the aging of the urological workforce and projected significant manpower shortages. These multiple factors must be confronted directly or the future quality of urologic cancer care will be jeopardized.

Robotic surgery in urologic oncology: gathering the evidence.

In less than a decade, the widespread application of robotic technology to the field of urologic oncology has permanently altered the way urologists approach malignancy. The short-term benefits of minimally invasive surgery using robotic assistance (i.e., decreased blood loss, improved convalescence and ergonomic appeal), as well as a broad marketing campaign, have helped the technology gain traction in the field of urology. Although the long-term benefits of its use in urologic surgery are less clear and the costs of robotic surgery are consistently greater than those of other approaches, the numbers of prostate, kidney and bladder cancer cases continue to rise. Identifying transferable surgical processes of care that matter most for each of the robotic cases in urologic oncology (e.g., prostatectomy, cystectomy and partial nephrectomy) is a next step toward broadly improving the quality of urologic cancer care. To this end, urologic professional societies and their surgeons should aim to identify underwriters for and participate in large clinical registries and surgical quality collaboratives.

The potential of proton beam radiation therapy in prostate cancer, other urological cancers and gynaecological cancers.

A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In prostate cancer it is estimated that annually about 300 patients and in gynaecological cancer about 50 patients, are candidates for proton beam therapy. Owing to major uncertainties, it has not been possible to give an estimate of the number of potential patients with urinary bladder cancer.