Cost-Effectiveness of Robot-Assisted Radical Cystectomy vs Open Radical Cystectomy for Patients With Bladder Cancer.

Importance: The value to payers of robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) when compared with open radical cystectomy (ORC) for patients with bladder cancer is unclear. Objectives: To compare the cost-effectiveness of iRARC with that of ORC. Design, Setting, and Participants: This economic evaluation used individual patient data from a randomized clinical trial at 9 surgical centers in the United Kingdom. Patients with nonmetastatic bladder cancer were recruited from March 20, 2017, to January 29, 2020. The analysis used a health service perspective and a 90-day time horizon, with supplementary analyses exploring patient benefits up to 1 year. Deterministic and probabilistic sensitivity analyses were undertaken. Data were analyzed from January 13, 2022, to March 10, 2023. Interventions: Patients were randomized to receive either iRARC (n = 169) or ORC (n = 169). Main Outcomes and Measures: Costs of surgery were calculated using surgery timings and equipment costs, with other hospital data based on counts of activity. Quality-adjusted life-years were calculated from European Quality of Life 5-Dimension 5-Level instrument responses. Prespecified subgroup analyses were undertaken based on patient characteristics and type of diversion. Results: A total of 305 patients with available outcome data were included in the analysis, with a mean (SD) age of 68.3 (8.1) years, and of whom 241 (79.0%) were men. Robot-assisted radical cystectomy was associated with statistically significant reductions in admissions to intensive therapy (6.35% [95% CI, 0.42%-12.28%]), and readmissions to hospital (14.56% [95% CI, 5.00%-24.11%]), but increases in theater time (31.35 [95% CI, 13.67-49.02] minutes). The additional cost of iRARC per patient was £1124 (95% CI, -£576 to £2824 [US $1622 (95% CI, -$831 to $4075)]) with an associated gain in quality-adjusted life-years of 0.01124 (95% CI, 0.00391-0.01857). The incremental cost-effectiveness ratio was £100 008 (US $144 312) per quality-adjusted life-year gained. Robot-assisted radical cystectomy had a much higher probability of being cost-effective for subgroups defined by age, tumor stage, and performance status. Conclusions and Relevance: In this economic evaluation of surgery for patients with bladder cancer, iRARC reduced short-term morbidity and some associated costs. While the resulting cost-effectiveness ratio was in excess of thresholds used by many publicly funded health systems, patient subgroups were identified for which iRARC had a high probability of being cost-effective. Trial Registration: ClinicalTrials.gov Identifier: NCT03049410.

Critical Appraisal of Decision Models Used for the Economic Evaluation of Bladder Cancer Screening and Diagnosis: A Systematic Review.

BACKGROUND AND OBJECTIVE: Bladder cancer is common among current and former smokers. High bladder cancer mortality may be decreased through early diagnosis and screening. The aim of this study was to appraise decision models used for the economic evaluation of bladder cancer screening and diagnosis, and to summarise the main outcomes of these models. METHODS: MEDLINE via PubMed, Embase, EconLit and Web of Science databases was systematically searched from January 2006 to May 2022 for modelling studies that assessed the cost effectiveness of bladder cancer screening and diagnostic interventions. Articles were appraised according to Patient, Intervention, Comparator and Outcome (PICO) characteristics, modelling methods, model structures and data sources. The quality of the studies was also appraised using the Philips checklist by two independent reviewers. RESULTS: Searches identified 3082 potentially relevant studies, which resulted in 18 articles that met our inclusion criteria. Four of these articles were on bladder cancer screening, and the remaining 14 were diagnostic or surveillance interventions. Two of the four screening models were individual-level simulations. All screening models (n = 4, with three on a high-risk population and one on a general population) concluded that screening is either cost saving or cost effective with cost-effectiveness ratios lower than $53,000/life-years saved. Disease prevalence was a strong determinant of cost effectiveness. Diagnostic models (n = 14) assessed multiple interventions; white light cystoscopy was the most common intervention and was considered cost effective in all studies (n = 4). Screening models relied largely on published evidence generalised from other countries and did not report the validation of their predictions to external data. Almost all diagnostic models (n = 13 out of 14) had a time horizon of 5 years or less and most of the models (n = 11) did not incorporate health-related utilities. In both screening and diagnostic models, epidemiological inputs were based on expert elicitation, assumptions or international evidence of uncertain generalisability. In modelling disease, seven models did not use a standard classification system to define cancer states, others used risk-based, numerical or a Tumour, Node, Metastasis classification. Despite including certain components of disease onset or progression, no models included a complete and coherent model of the natural history of bladder cancer (i.e. simulating the progression of asymptomatic primary bladder cancer from cancer onset, i.e. in the absence of treatment). CONCLUSIONS: The variation in natural history model structures and the lack of data for model parameterisation suggest that research in bladder cancer early detection and screening is at an early stage of development. Appropriate characterisation and analysis of uncertainty in bladder cancer models should be considered a priority.

Elicitation of Health State Utilities Associated with Progression from Bacillus Calmette-Guerin (BCG) Unresponsive Non-muscle Invasive Bladder Cancer (NMIBC).

OBJECTIVES: The treatments for high-grade non-muscle invasive bladder cancer (NMIBC) vary between bladder preserving intravesical approaches and radical cystectomy. The impact of these treatments on health-related quality of life may vary widely. The purpose of this study was to elicit the general public's perspective on quality of life, measured as utility scores associated with treatment for Bacillus Calmette-Guerin (BCG)-unresponsive NMIBC and disease progression, for supporting economic evaluation of newly developed treatments for NMIBC. MATERIALS AND METHODS: Part I involved the development and testing of health states describing NMIBC, which was informed by a rapid review, expert input and a patient advisor. Part II involved elicitation of societal utility values for the different health states. Time trade-off (TTO) interviews were conducted with members of the UK general public. Five health states described different NMIBC scenarios including disease recurrence and progression. Participants ranked each health state, followed by the TTO valuation exercise. Descriptors included NMIBC symptom severity, impact and treatment characteristics. RESULTS: In total, 202 members of the general public participated. The mean age was 46 (standard deviation [SD] 14.6) years. Sample mean (SD) EQ-5D-5L visual analogue scale (VAS) and index scores were 83.2 (12.3) and 0.89 (0.18), respectively. Mean utilities were 0.781 for No High-Grade Recurrence, 0.586 for High-Grade Recurrence, 0.572 for > 1-Year Post-cystectomy and 0.283 for metastatic disease. The First Year Post-cystectomy path health state had a mean utility of 0.288. Pairwise comparisons found statistically significant differences between utilities (p < 0.001), except between High-Grade Recurrence and > 1-Year Post-cystectomy (p = 0.524). There were significant differences in utility scores by age and employment status. CONCLUSION: This study provides utility scores for health states describing living with NMIBC, which is associated with a significant health-related quality-of-life burden. These values address an existing gap in available data and have the potential to be used in models evaluating the cost-effectiveness of both current and newly developed treatments for bladder cancer.

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 development of the Cystectomy-Pathway Assessment Tool (C-PAT): a concise tool to assess the quality of care in the cystectomy pathway.

OBJECTIVES: To develop and test the psychometric properties of a concise, patient-reported questionnaire, designed to assess key aspects of the radical cystectomy (RC) patient pathway that are important to both patients and clinicians. PATIENTS AND METHODS: Draft items were developed by a consultation with a 13-member expert clinical panel, and the in-depth qualitative analysis of 14 semi-structured interviews with patients who had received RC within the previous 18 months. A further nine cognitive interviews with patients refined the items and ensured they were easy to complete. Pilot testing in 122 patients recruited from five hospitals in England tested the properties of validity and reliability of the resulting 17-item questionnaire. RESULTS: Patients and clinicians identified the following aspects as important for the delivery of quality patient care. These included timely referral and initial test results; an explanation of risk/benefits of treatment; access to a cancer nurse specialist; training and support in stoma management; timely surgery, surgical complications, and timely follow-up. Pilot testing showed missing data was low (≤3% for all items), and between 73% and 89% of the responses to items were the most positive about their care (indicating ceiling effects). Five items were identified using factor analysis as being statistically related (Cronbach's α 0.76, intraclass correlation coefficient test-retest reliability of 0.95) and formed the scored part of the tool 'care and support', scored 0-16. There was insufficient evidence at this stage to show the tool was capable of measuring differences between cancer centres. CONCLUSION: We have developed a questionnaire that captures aspects of quality of care within the RC patient pathway. The results support the validity and reliability of the 17-item Cystectomy-Pathway Assessment Tool (C-PAT). We envisage the tool can be the basis for audit of the patient reported assessment of the quality of care for individual cancer centres.

The Impact of the COVID-19 Pandemic on Genitourinary Cancer Care: Re-envisioning the Future.

CONTEXT: The coronavirus disease 2019 (COVID-19) pandemic necessitated rapid changes in medical practice. Many of these changes may add value to care, creating opportunities going forward. OBJECTIVE: To provide an evidence-informed, expert-derived review of genitourinary cancer care moving forward following the initial COVID-19 pandemic. EVIDENCE ACQUISITION: A collaborative narrative review was conducted using literature published through May 2020 (PubMed), which comprised three main topics: reduced in-person interactions arguing for increasing virtual and image-based care, optimisation of the delivery of care, and the effect of COVID-19 in health care facilities on decision-making by patients and their families. EVIDENCE SYNTHESIS: Patterns of care will evolve following the COVID-19 pandemic. Telemedicine, virtual care, and telemonitoring will increase and could offer broader access to multidisciplinary expertise without increasing costs. Comprehensive and integrative telehealth solutions will be necessary, and should consider patients' mental health and access differences due to socioeconomic status. Investigations and treatments will need to maximise efficiency and minimise health care interactions. Solutions such as one stop clinics, day case surgery, hypofractionated radiotherapy, and oral or less frequent drug dosing will be preferred. The pandemic necessitated a triage of those patients whose treatment should be expedited, delayed, or avoided, and may persist with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in circulation. Patients whose demographic characteristics are at the highest risk of complications from COVID-19 may re-evaluate the benefit of intervention for less aggressive cancers. Clinical research will need to accommodate virtual care and trial participation. Research dissemination and medical education will increasingly utilise virtual platforms, limiting in-person professional engagement; ensure data dissemination; and aim to enhance patient engagement. CONCLUSIONS: The COVID-19 pandemic will have lasting effects on the delivery of health care. These changes offer opportunities to improve access, delivery, and the value of care for patients with genitourinary cancers but raise concerns that physicians and health administrators must consider in order to ensure equitable access to care. PATIENT SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has dramatically changed the care provided to many patients with genitourinary cancers. This has necessitated a transition to telemedicine, changes in threshold or delays in many treatments, and an opportunity to reimagine patient care to maintain safety and improve value moving forward.

Active monitoring, radical prostatectomy and radical radiotherapy in PSA-detected clinically localised prostate cancer: the ProtecT three-arm RCT.

BACKGROUND: Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments. OBJECTIVES: To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years. DESIGN: A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up. SETTING: Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK. PARTICIPANTS: Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring (n = 545), radical prostatectomy (n = 553) or radical radiotherapy (n = 545) and 997 chose a treatment. INTERVENTIONS: The interventions were active monitoring, radical prostatectomy and radical radiotherapy. TRIAL PRIMARY OUTCOME MEASURE: Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants. SECONDARY OUTCOME MEASURES: Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes. RESULTS: There were no statistically significant differences between the groups for 17 prostate cancer-specific (p = 0.48) and 169 all-cause (p = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring (n = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy (n = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy (n = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy). LIMITATIONS: A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed. CONCLUSIONS: At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years. TRIAL REGISTRATION: Current Controlled Trials ISRCTN20141297. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information.

Prostate cancer is the most common cancer in men and is often found through a blood test called a prostate-specific antigen test and through biopsies of the prostate. Over the years, these tests led to the detection of many small cancers that do not cause harm. Some prostate cancers are harmful, but it is difficult to recognise them early. When cancer is still inside the prostate, the conventional treatments are surgery or radiotherapy, which carry side effects including leaking urine and difficulty getting an erection, so another option is repeat investigations at regular intervals (active monitoring), with treatments given if the cancer progresses. These options needed to be compared in a study called a 'randomised trial' in which men agree to be allocated to one of the three treatments. In the Prostate testing for cancer and Treatment (ProtecT) study, 200,000 men aged 50­69 years were invited to have a prostate-specific antigen test. Of the 82,849 men who agreed to be tested, 1643 of whom had prostate cancer that was still contained in the prostate agreed to be allocated to one of the three treatments. After an average of 10 years of follow-up, 99% of men were alive in each of the treatment groups. However, when compared with active monitoring, surgery and radiotherapy reduced the risk of disease spreading outside the prostate by half. Patients reported that urinary leakage and sexual function were worst with surgery, and sexual and bowel functions were affected by radiotherapy. Men on active monitoring had a gradual decline in their urinary and sexual function, particularly as around half of them later had surgery or radiotherapy. Radiotherapy was the treatment that seemed to be the best value for money. The findings from the Prostate testing for cancer and Treatment (ProtecT) study can help men make decisions about being tested and which treatment to have if they are found to have cancer within the prostate. We now need to find out the longer-term effects of these treatments on how long men live and their quality of life.

Telemedicine and Smart Working: Recommendations of the European Association of Urology.

CONTEXT: Telemedicine provides remote clinical support using technological tools. It may facilitate health care delivery while reducing unnecessary visits to the clinic. The coronavirus disease 2019 (COVID-19) outbreak has caused an abrupt change in our daily urological practice, converting many of us to be reliant on telehealth. OBJECTIVE: To provide practical recommendations for effective use of technological tools in telemedicine. EVIDENCE ACQUISITION: A Medline-based and gray literature search was conducted through April 2020. We selected the most relevant articles related to "telemedicine" and "smart working" that could provide important information. EVIDENCE SYNTHESIS: Telemedicine refers to the use of electronic information and telecommunications tools to provide remote clinical health care support. Smart working is a model of work that uses new or existing technologies to improve performance. Telemedicine is becoming a useful invaluable tool during and even beyond the COVID-19 pandemic. It is time for us to formalize the place of telemedicine in routine urological practice, and it is our responsibility to adapt and learn about all the tools and possible strategies for their optimal implementation during the pandemic to ensure that the quality of care received by patients and the outcomes of patients and their families are of the highest standard. CONCLUSIONS: Telemedicine facilitates specialized urological clinical support at a distance, solves problems of limitations in mobility, reduces unnecessary visits to clinics, and is useful for reducing the risk of viral transmission in the current COVID-19 outbreak. Furthermore, both personal and societal considerations may favor continued use of telemedicine, even beyond the COVID-19 pandemic. PATIENT SUMMARY: Telemedicine in urology offers specialized remote clinical support to patients, similar to face-to-face visits. It is very useful for reducing unnecessary visits to the clinic, as well as reducing the risk of contagion in the current coronavirus disease 2019 (COVID-19) pandemic.

The ProtecT randomised trial cost-effectiveness analysis comparing active monitoring, surgery, or radiotherapy for prostate cancer.

BACKGROUND: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer. METHODS: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years' median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk. RESULTS: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups. CONCLUSIONS: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man's lifetime. TRIAL REGISTRATION: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Prospective Assessment of Vesical Imaging Reporting and Data System (VI-RADS) and Its Clinical Impact on the Management of High-risk Non-muscle-invasive Bladder Cancer Patients Candidate for Repeated Transurethral Resection.

BACKGROUND: Vesical Imaging Reporting and Data System (VI-RADS) score is adopted to provide preoperative bladder cancer (BCa) staging. Repeated transurethral resection of bladder tumor (Re-TURBT) is recommended in most of high-risk non-muscle-invasive bladder cancers (HR-NMIBCs) due to possibility of persistent/understaged disease after initial TURBT. No diagnostic tools able to improve patient's stratification for such recommendation exist. OBJECTIVE: To (1) prospectively validate VI-RADS for discriminating between NMIBC and muscle-invasive bladder cancer (MIBC) at TURBT, and (2) evaluate the accuracy of VI-RADS for identifying HR-NMIBC patients who could avoid Re-TURBT and detecting those at higher risk for understaging after TURBT. DESIGN, SETTING, AND PARTICIPANTS: Patients with BCa suspicion were offered multiparametric magnetic resonance imaging (mpMRI) before TURBT. According to VI-RADS, a cutoff of ≥3 to define MIBC was assumed. TURBT reports were compared with preoperative VI-RADS scores to assess accuracy of mpMRI for discriminating between NMIBC and MIBC. HR-NMIBC Re-TURBT reports were compared with preoperatively recorded VI-RADS scores to assess mpMRI accuracy in predicting Re-TURBT outcomes. INTERVENTION: Multiparametric MRI of the bladder before TURBT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated for mpMRI performance in patients undergoing TURBT and for HR-NMIBC patients candidate for Re-TURBT. Performance of mpMRI was assessed by receiver operating characteristic curve analysis. Ƙ statistics was used to estimate inter- and intrareader variability. RESULTS AND LIMITATIONS: A total of 231 patients were enrolled. Multiparametric MRI showed sensitivity, specificity, PPV, and NPV for discriminating NMIBC from MIBC at initial TURBT of 91.9% (95% confidence interval [CI]: 82.2-97.3), 91.1% (95% CI: 85.8-94.9), 77.5% (95% CI: 65.8-86.7), and 97.1% (95% CI: 93.3-99.1), respectively. The area under the curve (AUC) was 0.94 (95% CI: 0.91-0.97). Among HR-NMIBC patients (n=114), mpMRI before TURBT showed sensitivity, specificity, PPV, and NPV of 85% (95% CI: 62.1-96.8), 93.6% (95% CI: 86.6-97.6), 74.5% (95% CI: 52.4-90.1), and 96.6% (95% CI: 90.5-99.3) respectively, to identify patients with MIBC at Re-TURBT. The AUC was 0.93 (95% CI: 0.87-0.97). CONCLUSIONS: VI-RADS is accurate for discriminating between NMIBC and MIBC. Within HR-NMIBC cases, VI-RADS could, in future, improve the selection of patients who are candidate for Re-TURBT. PATIENT SUMMARY: We investigated the accuracy of Vesical Imaging Reporting and Data System (VI-RADS) score to asses bladder cancer staging before transurethral resection of bladder tumors, and we explored the performance of VI-RADS score as a future preoperative predictive tool for the selection of high-risk non-muscle-invasive bladder cancer patients who are candidate for undergoing early repeated transurethral resection of the primary tumor site.

A three-gene methylation marker panel for the nodal metastatic risk assessment of muscle-invasive bladder cancer.

PURPOSE: In this study, we aimed to identify a DNA methylation pattern suitable for prognosis assessment of muscle-invasive bladder cancer and to investigate metastasis-associated processes regulated by DNA methylation. METHODS: Genome-wide methylation analysis was performed on 23 muscle-invasive bladder tumors by microarray analysis. Validation was performed by the qAMP technique in two different patient cohorts (n = 32 and n = 100). mRNA expression was analyzed in 12 samples. Protein expression was determined using tissue microarrays of 291 patients. Bladder cancer cell lines T24 and 253JB-V were used for functional analyses. RESULTS: Microarray analyses revealed KISS1R, SEPT9 and CSAD as putative biomarkers with hypermethylation in node-positive tumors. The combination of the three genes predicted the metastatic risk with sensitivity of 73% and specificity of 71% in cohort 1, and sensitivity of 82% and specificity of 54% in cohort 2. mRNA expression differences were detected for KISS1R (p = 0.04). Protein expression of KISS1R was significantly reduced (p < 0.001). Knockdown of SEPT9v3 resulted in increased cell migration by 28% (p = 0.04) and increased invasion by 22% (p = 0.004). KISS1R overexpression resulted in decreased cell migration (25%, p = 0.1). CONCLUSIONS: We identified a methylation marker panel suitable to differentiate between patients with positive and negative lymph nodes at time of cystectomy. This enables a risk assessment for patients who potentially benefit from extended lymph node resection as well as from neoadjuvant chemotherapy and could improve the survival rates. Furthermore, we examined the impact of putative markers on tumor behavior. Hence, KISS1R and SEPT9 could represent a starting point for the development of novel therapy approaches.

Partial ablation versus radical prostatectomy in intermediate-risk prostate cancer: the PART feasibility RCT.

BACKGROUND: Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT). OBJECTIVES: To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture. DESIGN: We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation. SETTING: Five NHS hospitals in England. PARTICIPANTS: Men with unilateral, intermediate-risk, clinically localised PCa. INTERVENTIONS: Radical prostatectomy compared with HIFU. PRIMARY OUTCOME MEASURE: The randomisation of 80 men. SECONDARY OUTCOME MEASURES: Findings of the QRI and assessment of data capture methods. RESULTS: Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and 'tips' documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) - with University College Hospital failing to enrol any participants - than centres offering HIFU in the trial context only. CONCLUSIONS: Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted. FUTURE WORK: Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99760303. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 52. See the NIHR Journals Library website for further project information.

Staging the Host: Personalizing Risk Assessment for Radical Cystectomy Patients.

CONTEXT: Perioperative and long-term functional and oncologic outcomes following radical cystectomy (RC) for localized bladder cancer remain unchanged despite advances in technique and perioperative management, as well as neoadjuvant and adjuvant therapy. Accurate assessment of a patient's perioperative risk is critical to inform preoperative counseling and determine a patient's fitness for RC. OBJECTIVE: To review and synthesize conventional and novel objective patient-specific risk assessment tools that may be incorporated into clinical practice for perioperative risk prognostication with respect to both postoperative complications and long-term oncologic outcomes, patient counseling, and decision-making when RC is being considered. EVIDENCE ACQUISITION: A collaborative review was performed to synthesize currently available evidence on comorbidity, age, body composition, nutrition, frailty, and geriatric assessments for patients undergoing RC. EVIDENCE SYNTHESIS: Current guidelines recommend that pre-RC risk assessment should take into account age, performance status, and comorbidity. However, conventional comorbidity indices perform inconsistently in accurate assessment of the risk of perioperative complications, prolonged rehabilitation, and long-term oncologic outcomes. Novel metrics including standardized assessments of dependency, comorbidity severity, sarcopenia, malnutrition, physical and cognitive frailty, and comprehensive geriatric assessments may offer more precise estimates of physiologic age and relative vulnerability to adverse outcomes following RC. CONCLUSIONS: Perioperative risk assessment before RC should incorporate objective measures of physiologic age, physical function, nutrition, lean muscularity, and frailty. The use of standardized multidimensional instruments should be encouraged for patients undergoing consideration for RC to identify potentially modifiable risk factors that can be targeted with prehabilitation interventions. Future work is needed to validate the performance of these metrics with respect to predicting perioperative complications and oncologic outcomes and to define and assess the effectiveness of specific prehabilitation interventions to optimize patients before surgery. PATIENT SUMMARY: We review several metrics that doctors can use to measure the risks associated with bladder removal, a major surgical procedure. Moving beyond evaluating a patient's age, the burden of other health problems, and surgeon intuition, these tools may be used to counsel patients regarding their surgical risk, to predict oncologic outcomes, and to help identify potential interventions to improve surgical readiness.

Life after prostate cancer diagnosis: protocol for a UK-wide patient-reported outcomes study.

BACKGROUND: Prostate cancer and its treatment may impact physically, psychologically and socially; affecting the health-related quality of life of men and their partners/spouses. The Life After Prostate Cancer Diagnosis (LAPCD) study is a UK-wide patient-reported outcomes study which will generate information to improve the health and well-being of men with prostate cancer. METHODS AND ANALYSIS: Postal surveys will be sent to prostate cancer survivors (18-42 months postdiagnosis) in all 4 UK countries (n=∼70 000). Eligible men will be identified and/or verified through cancer registration systems. Men will be surveyed twice, 12 months apart, to explore changes in outcomes over time. Second, separate cohorts will be surveyed once and the design will include evaluation of the acceptability of online survey tools. A comprehensive patient-reported outcome measure has been developed using generic and specific instruments with proven psychometric properties and relevance in national and international studies. The outcome data will be linked with administrative health data (eg, treatment information from hospital data). To ensure detailed understanding of issues of importance, qualitative interviews will be undertaken with a sample of men who complete the survey across the UK (n=∼150) along with a small number of partners/spouses (n=∼30). ETHICS AND DISSEMINATION: The study has received the following approvals: Newcastle and North Tyneside 1 Research Ethics Committee (15/NE/0036), Health Research Authority Confidentiality Advisory Group (15/CAG/0110), NHS Scotland Public Benefit and Privacy Panel (0516-0364), Office of Research Ethics Northern Ireland (16/NI/0073) and NHS R&D approval from Wales, Scotland and Northern Ireland. Using traditional and innovative methods, the results will be made available to men and their partners/spouses, the funders, the NHS, social care, voluntary sector organisations and other researchers.

Defining a standard set of patient-centered outcomes for men with localized prostate cancer.

BACKGROUND: Value-based health care has been proposed as a unifying force to drive improved outcomes and cost containment. OBJECTIVE: To develop a standard set of multidimensional patient-centered health outcomes for tracking, comparing, and improving localized prostate cancer (PCa) treatment value. DESIGN, SETTING, AND PARTICIPANTS: We convened an international working group of patients, registry experts, urologists, and radiation oncologists to review existing data and practices. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The group defined a recommended standard set representing who should be tracked, what should be measured and at what time points, and what data are necessary to make meaningful comparisons. Using a modified Delphi method over a series of teleconferences, the group reached consensus for the Standard Set. RESULTS AND LIMITATIONS: We recommend that the Standard Set apply to men with newly diagnosed localized PCa treated with active surveillance, surgery, radiation, or other methods. The Standard Set includes acute toxicities occurring within 6 mo of treatment as well as patient-reported outcomes tracked regularly out to 10 yr. Patient-reported domains of urinary incontinence and irritation, bowel symptoms, sexual symptoms, and hormonal symptoms are included, and the recommended measurement tool is the Expanded Prostate Cancer Index Composite Short Form. Disease control outcomes include overall, cause-specific, metastasis-free, and biochemical relapse-free survival. Baseline clinical, pathologic, and comorbidity information is included to improve the interpretability of comparisons. CONCLUSIONS: We have defined a simple, easily implemented set of outcomes that we believe should be measured in all men with localized PCa as a crucial first step in improving the value of care. PATIENT SUMMARY: Measuring, reporting, and comparing identical outcomes across treatments and treatment centers will provide patients and providers with information to make informed treatment decisions. We defined a set of outcomes that we recommend being tracked for every man being treated for localized prostate cancer.

Hexyl aminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: a critical review of the current literature.

CONTEXT: Controversy exists regarding the therapeutic benefit and cost effectiveness of photodynamic diagnosis (PDD) with 5-aminolevulinic acid (5-ALA) or hexyl aminolevulinate (HAL) in addition to white-light cystoscopy (WLC) in the management of non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To systematically evaluate evidence regarding the therapeutic benefits and economic considerations of PDD in NMIBC detection and treatment. EVIDENCE ACQUISITION: We performed a critical review of PubMed/Medline, Embase, and the Cochrane Library in October 2012 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) and Standards for the Reporting of Diagnostic Accuracy Studies (STARD) criteria. Forty-four publications were selected for inclusion in this analysis. EVIDENCE SYNTHESIS: Included reports used 5-ALA (in 26 studies), HAL (15 studies), or both (three studies) as photosensitising agents. PDD increased the detection of both papillary tumours (by 7-29%) and flat carcinoma in situ (CIS; by 25-30%) and reduced the rate of residual tumours after transurethral resection of bladder tumour (TURBT; by an average of 20%) compared to WLC alone. Superior recurrence-free survival (RFS) rates and prolonged RFS intervals were reported for PDD, compared to WLC in most studies. PDD did not appear to reduce disease progression. Our findings are limited by tumour heterogeneity and a lack of NMIBC risk stratification in many reports or adjustment for intravesical therapy use in most studies. Although cost effectiveness has been demonstrated for 5-ALA, it has not been studied for HAL. CONCLUSIONS: Moderately strong evidence exists that PDD improves tumour detection and reduces residual disease after TURBT compared with WLC. This has been shown to improve RFS but not progression to more advanced disease. Further work to evaluate cost effectiveness of PDD is required.

EORTC risk tables - their usefulness in the assessment of recurrence and progression risk in non-muscle-invasive bladder cancer in Polish patients.

INTRODUCTION: The assessment of risk of recurrence and progression of bladder cancer (BC) is still rather difficult. We decided to check the rates of the changes mentioned above in the group of the Polish patients after a year-long observation and next to compare them with the results calculated in the European Organisation of Research and Treatment of Cancer (EORTC) risk tables. METHODS: The tested group consisted of 91 patients who underwent transurethral resection of bladder tumour (TURBT). When being diagnosed, 60 cases were in the pTa clinical stage, whereas 30 cases were in T1. The coexisting carcinoma in situ (CIS) was observed in four cases. On the basis of the scores obtained from the EORTC tables, the patients were divided into the groups of low, intermediate or high risk of disease recurrence and progression. RESULTS: Recurrence was noticed in 23 patients (25%), while progression was observed in 11 patients (12.1%). The rate of the observed recurrences proved to be lower than it had been predicted in all the groups, except for one of the intermediate-risk group (score 1- 4). Moreover, the rate of the progressions predicted according to the EORTC risk tables was higher in all the risk groups. CONCLUSIONS: It can be noticed that the rate of real recurrences is lower than expected, whereas the rate of the observed progressions is overestimated. Partly, it could be the result of using a relatively small group of patients for observation and applying a different method of treatment.