Diagnosis, treatment and survival from bladder, upper urinary tract, and urethral cancers: real-world findings from NHS England between 2013 and 2019.

OBJECTIVE: We report NHS England data for patients with bladder cancer (BC), upper tract urothelial cancer (UTUC: renal pelvic and ureteric), and urethral cancers from 2013 to 2019. MATERIALS AND METHODS: Hospital episode statistics, waiting times, and cancer registrations were extracted from NHS Digital. RESULTS: Registrations included 128 823 individuals with BC, 16 018 with UTUC, and 2533 with urethral cancer. In 2019, 150 816 persons were living with a diagnosis of BC, of whom 113 067 (75.0%) were men, 85 117 (56.5%) were aged >75 years, and 95 553 (91.7%) were Caucasian. Incidence rates were stable (32.7-34.3 for BC, 3.9-4.2 for UTUC and 0.6-0.7 for urethral cancer per 100 000 population). Most patients 52 097 (mean [range] 41.3% [40.7-42.0%]) were referred outside the 2-week-wait pathway and 15 340 (mean [range] 12.2% [11.7-12.6%]) presented as emergencies. Surgery, radiotherapy, chemotherapy, or multimodal treatment use varied with disease stage, patient factors and Cancer Alliance. Between 27% and 29% (n = 6616) of muscle-invasive BCs did not receive radical treatment. Survival rates reflected stage, grade, location, and tumour histology. Overall survival rates did not improve over time (relative change: 0.97, 95% confidence interval 0.97-0.97) at 2 years in contrast to other cancers. CONCLUSION: The diagnostic pathway for BC needs improvement. Increases in survival might be delivered through greater use of radical treatment. NHS Digital data offers a population-wide picture of this disease but does not allow individual outcomes to be matched with disease or patient features and key parameters can be missing or incomplete.

What influences adherence to guidance for postoperative instillation of intravesical chemotherapy to patients with bladder cancer?

OBJECTIVE: To understand the barriers and facilitators to single instillation of intravesical chemotherapy (SI-IVC) use after resection of non-muscle-invasive bladder cancer (NMIBC) in Scotland and England using a behavioural theory-informed approach. SUBJECTS AND METHODS: In a cross-sectional descriptive study of practices at seven hospitals, we investigated care pathways, policies, and interviewed 30 urology staff responsible for SI-IVC. We used the Theoretical Domains Framework (TDF) to organise our investigation and conducted deductive thematic analyses, while inductively coding emergent beliefs. RESULTS: Barriers to SI-IVC were present at different organisational levels and professional roles. In four hospitals, there was a policy to not instil SI-IVC in theatre. Six hospitals' staff reported delays in mitomycin C (MMC) ordering and/or local storage. Lack of training, skills and perceived workload affected motivation. Facilitators included access to modern instilling devices (four hospitals) and incorporating reminders in operation proforma (four hospitals). Performance targets (with audit and feedback) within a national governance framework were present in Scotland but not England. Differences in coordinated leadership, sharing best practices, and disliking being perceived as underperforming, were evident in Scotland. CONCLUSIONS: High-certainty evidence shows that SI-IVC, such as MMC, after NMIBC resection reduces recurrences. This evidence underpins international guidance. The number of eligible patients receiving SI-IVC is variable indicating suboptimal practice. Improving SI-IVC adherence requires modifications to theatre instilling policies, delivery and storage of MMC, staff training, and documentation. Centralising care, with bladder cancer expert leadership and best practices sharing with performance targets, likely led to improvements in Scotland. National quality improvement, incorporating audit and feedback, with additional implementation strategies targeted to professional role could improve adherence and patient outcomes elsewhere. This process should be controlled to clarify implementation intervention effectiveness.

Combining two grading systems: the clinical validity and inter-observer variability of the 1973 and 2004 WHO bladder cancer classification systems assessed in a UK cohort with 15 years of prospective follow-up.

PURPOSE: Paucity of reliable long-term data on the prognostic implications of the 2004 WHO bladder cancer classification system necessitates utilisation of both this and the 1973 grading systems. This study evaluated, in noninvasive (pTa) bladder tumours, the prognostic value of the 2004 system independently and in combination with the 1973 system while establishing concordance between tertiary centre uropathologists. METHODS: We used a cohort of non-muscle invasive bladder cancer (NMIBC) patients diagnosed between 1991 and 93 where tumour features were gathered prospectively with detailed cystoscopic follow-up data recorded over 15 years. Initial grading was by one senior expert uropathologist (UP1) using the 1973 WHO classification alone. Subsequently, two other expert uropathologists (UP2 and UP3), blinded to the previous grading, re-evaluated the pathology slides and graded the tumours using both the 1973 and 2004 systems. Association between grade and recurrence/progression was analysed and the Cohen Kappa test assessed concordance between pathologists. RESULTS: Of 370 new NMIBC, 229 were staged noninvasive (pTa). Recurrence rates were 46.2% and 50.0% for LGPUC (low-grade papillary urothelial carcinoma) and HGPUC (high-grade papillary urothelial carcinoma), respectively, while progression was seen in 3.9% and 10.0% of LGPUC and HGPUC, respectively. Concordance between uropathologists UP2 and UP3 for the 2004 and 1973 systems was good (Kappa = 0.69) and fair (Kappa = 0.25), respectively. CONCLUSIONS: With good inter-observer concordance, the 2004 WHO classification system of noninvasive bladder tumours appears to accurately predict recurrence and progression risks. The combination of both grading systems to low-grade tumours allows further refinement of the natural history.

ICUD-SIU International Consultation on Bladder Cancer 2017: management of non-muscle invasive bladder cancer.

PURPOSE: To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). METHODS: A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. RESULTS: Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. CONCLUSION: NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

'Real-life experience': recurrence rate at 3 years with Hexvix® photodynamic diagnosis-assisted TURBT compared with good quality white light TURBT in new NMIBC-a prospective controlled study.

PURPOSE: To compare the recurrence rate at 3 years (RR-3y) for non-muscle invasive bladder cancer (NMIBC) between good quality (GQ) PDD-TURBT and GQWL-TURBT where PDD is used in routine practice for all new tumours. METHODS: All new, consecutive, NMIBC that received "good quality" criteria first TURBT across a university hospital service were prospectively recruited to this study over a 4-year period. Data were prospectively collected on all WL-TURBTs performed in 2007/8 and compared with PDD-TURBT from 2009/10. Only resection meeting strict "good quality criteria" were included from each cohort to control for resection quality, then cases were further matched 1:1 based on demographic and pathological criteria. The primary outcome was overall and risk group-specific recurrence rate at 3 years. RESULTS: Of 808 patients recruited, 345 had GQ-TURBT for NMIBC and were included. RR-3y was significantly less for GQ-PDD overall [RR-3y: GQ-PDD: 57/146 (39.0%), GQ-WL: 72/135 (53.3%) OR = 0.56 (0.35-0.90) p = 0.02] and on a 1:1 matched pair basis [RR GQ-PDD: 29/118 (24.6) vs. 59/118 (50.0) OR 0.33 (0.19-0.57) p < 0.001)]. Benefit was most marked in high-risk patients: RR-3y in high-risk patients treated with GQ-PDD was 25/48 (52.1%) vs. 28/35 (80%) for GQ-WL [OR 0.27 (0.10-0.74) p = 0.01]. CONCLUSION: When adopted for all new bladder tumour resections in routine practice, PDD appears to be associated with significantly reduced recurrence rates at 3 years in our "real life" experience, particularly in high-risk patients.

Is there seasonal variation in symptom severity, uroflowmetry and frequency-volume chart parameters in men with lower urinary tract symptoms?

PURPOSE: There is a widely held perception that lower urinary tract symptoms may be exacerbated by cold weather. In this study, we examine the effect of seasonal variation in ambient temperatures on frequency-volume chart derivatives, symptom severity scores and uroflowmetry parameters in men with lower urinary tract symptom. METHODS: Between January 2000 and April 2004, men presenting with lower urinary tract symptom were prospectively recruited and assessed in Edinburgh, UK (55°52'N) with maritime temperate climates (Köppen classification Cfb). Local monthly temperatures were extracted from national meteorological records. Patients completed the International Prostate Symptom Score and 3-day frequency volume chart before undergoing free uroflowmetry with post-micturition volume measurement. Exclusion criteria were previous bladder outflow surgery and anti-cholinergic medication. RESULTS: Data on 296 patients were suitable for analysis. Mean age was 62.3 years (range, 26-90). Over the period of study, the coldest month was January (mean = 4.7℃) and the warmest month was August (mean = 15.8℃). There was no significant variation in either International Prostate Symptom Score symptom scores by season (p > 0.05) or any frequency-volume chart parameters, with the exception on an increase in median actual nightly voids over the summer months (p = 0.021). There was no significant correlation between maximal flow rate and post-micturition residual volumes and mean monthly temperatures (p > 0.05). CONCLUSIONS: Seasonal variation in nocturia, but not other frequency-volume parameters, symptom severity or uroflowmetry parameters, is significant in men with lower urinary tract symptom. Future work should consider the impact of seasonal variation in lower urinary tract symptoms in both sexes across a wider range of climates.

Clinical Implementation of Urinary Biomarkers for Surveillance of Non-muscle-invasive Bladder Cancer (NMIBC): Considerations from the European Association of Urology NMIBC Guideline Panel.

Although high-level evidence is currently lacking, noninferiority randomised controlled trials in predefined risk groups in non-muscle-invasive bladder cancer are under way to scientifically prove the safety of urinary biomarker-guided follow-up. To facilitate recommendations for clinical use, it is essential to comply with the EU certification for in vitro diagnostics and to demonstrate cost effectiveness.

The Value of Negative Urinary Dipstick Tests for Haematuria in Patients Undergoing Surveillance for Low-grade Ta Urothelial Cancer: A Two-stage Prospective Clinical Study in 524 Patients.

Background and objective: The risk of first recurrence beyond 5 yr for patients with low-grade (LG) Ta non-muscle-invasive bladder cancer (NMIBC) is low enough to consider discontinuing cystoscopic surveillance at that point. However, a positive urinary dipstick test for haematuria (UDH) during and beyond the period of cystoscopic surveillance can disrupt plans to cease surveillance because the association between UDH positivity and recurrence in LG Ta NMIBC is unknown. In a two-stage study, we evaluated this association and explored the role of UDH negativity in predicting the absence of recurrence. Methods: Because of previously demonstrated changes in recurrence patterns over time, two prospective cohorts were assessed: an "exploratory" cohort (January 2007-March 2008) and a "validation" cohort (November 2017-August 2018). UDH was performed before flexible cystoscopy. Patient, operative, and surveillance data have been recorded prospectively using standard pro forma sheets since 1978 in our institution. Only patients with primary LG Ta pTa NMIBC were included for analysis. Key findings and limitations: We assessed 231 patients in the exploratory group and 293 in the validation group. The proportion of smokers (67% vs 70%; p = 0.5) and mean follow-up (72.2 vs 79.9 mo; p = 0.2) were similar between the groups. The recurrence rate was higher in the exploratory group (19% vs 11%; p = 0.009), as was the UDH positivity rate (37% vs 11%; p < 0.001). The specificity and negative predictive value were 64% and 83% in the exploratory group, and 90% and 90%, respectively, in the validation group. These values increased further for the subgroup with solitary primary tumours the subgroup without recurrence for 3 yr. Conclusions and clinical implications: UDH negativity has a high probability of being associated with the absence of recurrence in small LG Ta NMIBC and could be an inexpensive adjunct during surveillance. Ongoing validation, which started in 2019, is being performed in a now-nationalised Scottish protocol in which UDH replaces cystoscopy in years 2 and 4 for patients in the low-risk group. Patient summary: We investigated the accuracy of a dipstick test for blood in the urine for patients undergoing surveillance for low-grade noninvasive bladder cancer. We found that a negative dipstick test result was highly associated with the absence of tumour recurrence, particularly for patients with the lowest risk. These findings have been introduced into a national protocol designed to reduce the frequency of telescopic inspection of the bladder during surveillance to reduce the burden for patients.

Emergency and non-emergency routes to cancer diagnoses in 2020 and 2021: A Population-based study of 154,863 patients.

INTRODUCTION: The COVID-19 pandemic disrupted normal pathways to cancer diagnosis, particularly for screening and non-acute symptomatic patients. While reductions in overall cancer diagnoses have been reported elsewhere, any differential effects on emergency presentations, which are associated with poorer outcomes, have not been described. MATERIAL AND METHODS: Cross-sectional descriptive study from 2015 to 2021, based on International Cancer Benchmarking Partnership methods, where emergency route to diagnosis is defined as presenting as an emergency admission in the 30 days prior to cancer incidence date. Acute hospital records and cancer registrations were individually linked. Includes all individuals with a new diagnosis of specific cancers on the national cancer registry. RESULTS: All cancers included showed reductions in non-emergency diagnoses in 2020, with varying recovery in 2021. The largest reductions in non-emergency diagnoses of about a third were for colorectal and cervical cancers in 2020. Non-emergency diagnoses of prostate cancer remained lower but upper GI higher in 2021. Emergency routes to diagnosis were significantly higher in 2020 for breast, cervical, colorectal and upper GI cancers and were higher in 2021 for breast and cervical cancers. The absolute magnitude of reductions in non-emergency diagnoses was greater than any increases in emergency diagnoses. CONCLUSIONS: In 2020, there were large reductions in numbers of cancers diagnosed through non-emergency pathways in Scotland, while those diagnosed via emergency routes fell only for prostate cancer. Some effects persisted or emerged through 2021. It is likely that opportunities to diagnose cancers in a favourable, elective manner have been lost. Further work is needed to describe outcomes among these patients.

European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ)-A Summary of the 2024 Guidelines Update.

BACKGROUND AND OBJECTIVE: This publication represents a summary of the updated 2024 European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ. The information presented herein is limited to urothelial carcinoma, unless specified otherwise. The aim is to provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation. METHODS: For the 2024 guidelines on NMIBC, new and relevant evidence was identified, collated, and appraised via a structured assessment of the literature. Databases searched included Medline, EMBASE, and the Cochrane Libraries. Recommendations within the guidelines were developed by the panel to prioritise clinically important care decisions. The strength of each recommendation was determined according to a balance between desirable and undesirable consequences of alternative management strategies, the quality of the evidence (including the certainty of estimates), and the nature and variability of patient values and preferences. KEY FINDINGS AND LIMITATIONS: Key recommendations emphasise the importance of thorough diagnosis, treatment, and follow-up for patients with NMIBC. The guidelines stress the importance of defining patients' risk stratification and treating them appropriately. CONCLUSIONS AND CLINICAL IMPLICATIONS: This overview of the 2024 EAU guidelines offers valuable insights into risk factors, diagnosis, classification, prognostic factors, treatment, and follow-up of NMIBC. These guidelines are designed for effective integration into clinical practice.

Achieving Benchmarks for National Quality Indicators Reduces Recurrence and Progression in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Noncompliance with evidence-based interventions and guidelines contributes to significant and variable recurrence and progression in patients with non-muscle-invasive bladder cancer (NMIBC). The implementation of a quality performance indicator (QPI) programme in Scotland's National Health Service (NHS) aimed to improve cancer outcomes and reduce nationwide variance. OBJECTIVE: To evaluate the effect of hospitals achieving benchmarks for two specific QPIs on time to recurrence and progression in NMIBC. DESIGN, SETTING, AND PARTICIPANTS: QPIs for bladder cancer (BC) were enforced nationally in April 2014. NHS health boards collected prospective data on all new BC patients. Prospectively recorded surveillance data were pooled from 12 collaborating centres. INTERVENTION: QPIs of interest were (1) hospitals achieving detrusor muscle (DM) sampling target at initial transurethral resection of bladder tumour (TURBT) and (2) use of single instillation of mitomycin C after TURBT (SI-MMC). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary and secondary endpoints were time to recurrence and progression, respectively. Kaplan-Meier and Cox multivariable regression analyses were performed. KEY FINDINGS AND LIMITATIONS: Between April 1, 2014 and March 31, 2017, we diagnosed 3899 patients with new BC, of which 2688 were NMIBC . With a median follow up of 60.3 mo, hospitals achieving the DM sampling target had a 5.4% lower recurrence rate at 5 yr than hospitals not achieving this target (442/1136 [38.9%] vs 677/1528 [44.3%], 95% confidence interval [CI] = 1.6-9.2, p = 0.005). SI-MMC was associated with a 20.4% lower recurrence rate (634/1791 [35.4%] vs 469/840 [55.8%], 95% CI = 16.4-24.5, p < 0.001). On Cox multivariable regression, meeting the DM target and SI-MMC were associated with significant improvement in recurrence (hazard ratio [HR] 0.81, 95% CI = 0.73-0.91, p = 0.0002 and HR 0.66, 95% CI = 0.59-0.74, p < 0.004, respectively) as well as progression-free survival (HR 0.62, 95% CI = 0.45-0.84, p = 0.002 and HR 0.65, 95% CI = 0.49-0.87, p = 0.004, respectively). We did not have a national multicentre pre-QPI control. CONCLUSIONS: Within a national QPI programme, meeting targets for sampling DM and SI-MMC in the real world were independently associated with delays to recurrence and progression in NMIBC patients. PATIENT SUMMARY: Following the first 3 yr of implementing a novel quality performance indicator programme in Scotland, we evaluated compliance and outcomes in non-muscle-invasive bladder cancer. In 2688 patients followed up for 5 yr, we found that achieving targets for sampling detrusor muscle and the single instillation of mitomycin C during and after transurethral resection of bladder tumour, respectively, were associated with delays in cancer recurrence and progression.

The Importance of Being Grade 3: A Plea for a Three-tier Hybrid Classification System for Grade in Primary Non-muscle-invasive Bladder Cancer.

Grade is an important determinant of progression in non-muscle-invasive bladder cancer. Although the World Health Organization (WHO) 2004/2016 grading system is recommended, other systems such as WHO1973 and WHO1999 are still widely used. Recently, a hybrid (three-tier) system was proposed, separating WHO2004/2016 high grade (HG) into HG/grade 2 (G2) and HG/G3 while maintaining low grade. We assessed the prognostic performance of HG/G3 and HG/G2. Three independent cohorts with 9712 primary (first diagnosis) Ta-T1 bladder tumors were analyzed. Time to progression was analyzed with cumulative incidence functions and Cox regression models. Harrell's C-index was used to assess discrimination. Time to progression was significantly shorter for HG/G3 than for HG/G2 in multivariable analyses (cohort 1: hazard ratio [HR] = 1.92; cohort 2: HR = 2.51, and cohort 3: HR = 1.69). Corresponding progression risks at 5 yr were 18%, 20%, and 18% for HG/G3 versus 7.3%, 7.5%, and 9.3% for HG/G2, respectively. Cox models using hybrid grade performed better than models with WHO2004/2016 (all cohorts; p < 0.001). For the three cohorts, C-indices for WHO2004/2016 were 0.69, 0.62, and 0.75, while, for hybrid grade, C-indices were 0.74, 0.68, and 0.78, respectively. Subdividing the HG category into HG/G2 and HG/G3 stratifies time to progression and supports the recommendation to adopt the hybrid grading system for Ta/T1 bladder cancers.

Consistencies in Follow-up After Radical Cystectomy for Bladder Cancer: A Framework Based on Expert Practices Collaboratively Developed by the European Association of Urology Bladder Cancer Guideline Panels.

BACKGROUND AND OBJECTIVE: There is no standardized regimen for follow-up after radical cystectomy (RC) for bladder cancer (BC). To address this gap, we conducted a multicenter study involving urologist members from the European Association of Urology (EAU) bladder cancer guideline panels. Our objective was to identify consistent post-RC follow-up strategies and develop a practice-based framework based on expert opinion. METHODS: We surveyed 27 urologist members of the EAU guideline panels for non-muscle-invasive bladder cancer and muscle-invasive and metastatic bladder cancer using a pre-tested questionnaire with dichotomous responses. The survey inquired about follow-up strategies after RC and the use of risk-adapted strategies. Consistency was defined as >75% affirmative responses for follow-up practices commencing 3 mo after RC. Descriptive statistics were used for analysis. KEY FINDINGS AND LIMITATIONS: We received responses from 96% of the panel members, who provided data from 21 European hospitals. Risk-adapted follow-up is used in 53% of hospitals, with uniform criteria for high-risk (at least ≥pT3 or pN+) and low-risk ([y]pT0/a/1N0) cases. In the absence of agreement for risk-based follow up, a non-risk-adapted framework for follow-up was developed. Higher conformity was observed within the initial 3 yr, followed by a decline in subsequent follow-up. Follow-up was most frequent during the first year, including patient assessments, physical examinations, and laboratory tests. Computed tomography of the chest and abdomen/pelvis was the most common imaging modality, initially at least biannually, and then annually from years 2 to 5. There was a lack of consistency for continuing follow-up beyond 10 yr after RC. CONCLUSIONS AND CLINICAL IMPLICATIONS: This practice-based post-RC follow-up framework developed by EAU bladder cancer experts may serve as a valuable guide for urologists in the absence of prospective randomized studies. PATIENT SUMMARY: We asked urologists from the EAU bladder cancer guideline panels about their patient follow-up after surgical removal of the bladder for bladder cancer. We found that although urologists have varying approaches, there are also common follow-up practices across the panel. We created a practical follow-up framework that could be useful for urologists in their day-to-day practice.

Bladder-sparing Therapy for Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer: International Bladder Cancer Group Recommendations for Optimal Sequencing and Patient Selection.

BACKGROUND AND OBJECTIVE: There has been a recent surge in the development of agents for bacillus Calmette-Guérin-unresponsive (BCG-U) non-muscle-invasive bladder cancer (NMIBC). Critical assessment of these agents and practical recommendations for optimal selection of patients and therapies are urgently needed, especially in the absence of randomized trials on bladder-sparing treatment (BST) options. METHODS: A global committee of bladder cancer experts was assembled to develop recommendations on BST for BCG-U NMIBC. Working groups reviewed the literature and developed draft recommendations, which were then voted on by International Bladder Cancer Group (IBCG) members using a modified Delphi process. During a live meeting in August 2023, voting results and supporting evidence were presented, and recommendations were refined on the basis of meeting discussions. Final recommendations achieved >75% agreement during the meeting, and some were further refined via web conferences and e-mail discussions. KEY FINDINGS AND LIMITATIONS: There is currently no single optimal agent for patients with BCG-U disease who seek to avoid radical cystectomy (RC). BST selection should be personalized, taking into account individual patient characteristics and preferences, tumor attributes, and efficacy/toxicity data for the agents available. For patients with BCG-U carcinoma in situ (CIS), gemcitabine/docetaxel (GEM/DOCE), nadofaragene firadenovec (NFF), and nogapendekin alfa inbakicept-pmln (NAI) + BCG are recommended; because of its systemic toxicity, pembrolizumab should only be offered after other options are exhausted. For patients with BCG-U papillary-only tumors, GEM/DOCE, NFF, NAI + BCG, single-agent chemotherapy, hyperthermic mitomycin C, and pembrolizumab are recommended. Given the modest efficacy of available options, clinical trial participation is encouraged. For unapproved agents with reported data, IBCG recommendations await the final results of pivotal trials. CONCLUSIONS AND CLINICAL IMPLICATIONS: The IBCG consensus recommendations provide practical guidance on BST for BCG-U NMIBC.

Intermediate and high-risk non-muscle-invasive bladder cancer: an overview of epidemiology, burden, and unmet needs.

Bladder cancer ranks among the most common cancers globally. At diagnosis, 75% of patients have non-muscle-invasive bladder cancer (NMIBC). Patients with low-risk NMIBC have a good prognosis, but recurrence and progression rates remain high in intermediate- and high-risk NMIBC, despite the decades-long availability of effective treatments for NMIBC such as intravesical Bacillus Calmette-Guérin (BCG). The present review provides an overview of NMIBC, including its burden and treatment options, and then reviews aspects that counteract the successful treatment of NMIBC, referred to as unmet treatment needs. The scale and reasons for each unmet need are described based on a comprehensive review of the literature, including insufficient adherence to treatment guidelines by physicians because of insufficient knowledge, training, or access to certain therapy options. Low rates of lifestyle changes and treatment completion by patients, due to BCG shortages or toxicities and adverse events as well as their impact on social activities, represent additional areas of potential improvement. Highly heterogeneous evidence for the effectiveness and safety of some treatments limits the comparability of results across studies. As a result, efforts are underway to standardize treatment schedules for BCG, but intravesical chemotherapy schedules remain unstandardized. In addition, risk-scoring models often perform unsatisfactorily due to significant differences between derivation and real-world cohorts. Reporting in clinical trials suffers from a lack of consistent outcomes reporting in bladder cancer clinical trials, paired with an under-representation of racial and ethnic minorities in many trials.

Photodynamic Diagnosis-guided Transurethral Resection of Bladder Tumour in Participants with a First Suspected Diagnosis of Intermediate- or High-risk Non-muscle-invasive Bladder Cancer: Cost-effectiveness Analysis Alongside a Randomised Controlled Trial.

Background: Recurrence of non-muscle-invasive bladder cancer (NMIBC) is common after transurethral resection of bladder tumour (TURBT). Photodynamic diagnosis (PDD) may reduce recurrence. PDD uses a photosensitiser in the bladder that causes the tumour to fluoresce to guide resection. PDD provides better diagnostic accuracy and allows more complete tumour resection. Objective: To estimate the economic efficiency of PDD-guided TURBT (PDD-TURBT) in comparison to white light-guided TURNT (WL-TURBT) in individuals with a suspected first diagnosis of NMIBC at intermediate or high risk of recurrence on the basis of routine visual assessment before being scheduled for TURBT. Design setting and participants: This is a health economic evaluation alongside a pragmatic, open-label, parallel-group randomised trial from a societal perspective. A total of 493 participants (aged ≥16 yr) were randomly allocated to PDD-TURBT (n = 244) or WL-TURBT (n = 249) in 22 UK National Health Service hospitals. Outcome measurements and statistical analysis: Cost effectiveness ratios were based on the use of health care resources associated with PDD-TURBT and WL-TURBT and quality-adjusted life years (QALYs) gained within the trial. Uncertainties in key parameters were assessed using sensitivity analyses. Results and limitations: On the basis of the use of resources driven by the trial protocol, the incremental cost effectiveness of PDD-TURBT in comparison to WL-TURBT was not cost saving. At 3 yr, the total cost was £12 881 for PDD-TURBT and £12 005 for WL-TURBT. QALYs at three years were 2.087 for PDD-TURBT and 2.094 for WL-TURBT. The probability that PDD-TURBT is cost effective was never >30% above the range of societal cost-effectiveness thresholds. Conclusions: There was no evidence of a difference in either costs or QALYs over 3-yr follow-up between PDD-TURBT and WL-TURBT in individuals with suspected intermediate- or high-risk NMIBC. PDD-TURBT is not supported for the management of primary intermediate- or high-risk NMIBC. Patient summary: We assessed overall costs for two approaches for removal of bladder tumours in noninvasive cancer and measured quality-adjusted life years gained for each. We found that use of a photosensitiser in the bladder was not more cost effective than use of white light only during tumour removal.

Adjuvant Intravesical Chemohyperthermia Versus Passive Chemotherapy in Patients with Intermediate-risk Non-muscle-invasive Bladder Cancer (HIVEC-II): A Phase 2, Open-label, Randomised Controlled Trial.

BACKGROUND: Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC. DESIGN, SETTING, AND PARTICIPANTS: HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415). Randomisation was stratified by treating hospital. INTERVENTIONS: Patients were randomly assigned (1:1) to adjuvant CHT with mitomycin C at 43°C or to room-temperature mitomycin C (control). Both treatment arms received six weekly instillations of 40 mg of mitomycin C lasting for 60 min. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 24-mo disease-free survival as determined via cystoscopy and urinary cytology. Analysis was by intention to treat. RESULTS: A total of 259 patients (131 CHT vs 128 control) were randomised. At 24 mo, 42 patients (32%) in the CHT group and 49 (38%) in the control group had experienced recurrence. Disease-free survival at 24 mo was 61% (95% confidence interval [CI] 51-69%) in the CHT arm and 60% (95% CI 50-68%) in the control arm (hazard ratio [HR] 0.92, 95% CI 0.62-1.37; log-rank p = 0.8). Progression-free survival was higher in the control arm (HR 3.44, 95% CI 1.09-10.82; log-rank p = 0.02) on intention-to-treat analysis but was not significantly higher on per-protocol analysis (HR 2.87, 95% CI 0.83-9.98; log-rank p = 0.06). Overall survival was similar (HR 2.55, 95% CI 0.77-8.40; log-rank p = 0.09). Patients undergoing CHT were less likely to complete their treatment (n =75, 59% vs n = 111, 89%). Adverse events were reported by 164 patients (87 CHT vs 77 control). Major (grade III) adverse events were rare (13 CHT vs 7 control). CONCLUSIONS: CHT cannot be recommended over chemotherapy alone for intermediate-risk NMIBC. Adverse events following CHT were of low grade and short-lived, although patients were less likely to complete their treatment. PATIENT SUMMARY: The HIVEC-II trial investigated the role of heated chemotherapy instillations in the bladder for treatment of intermediate-risk non-muscle-invasive bladder cancer. We found no cancer control benefit from heated chemotherapy instillations over room-temperature chemotherapy. Adverse events following heated chemotherapy were low grade and short-lived, although these patients were less likely to complete their treatment.

European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2023 Update.

CONTEXT: The European Association of Urology (EAU) guidelines panel on upper urinary tract urothelial carcinoma (UTUC) has updated the guidelines to aid clinicians in evidence-based management of UTUC. OBJECTIVE: To provide an overview of the EAU guidelines on UTUC as an aid to clinicians. EVIDENCE ACQUISITION: The recommendations provided in these guidelines are based on a review of the literature via a systematic search of the PubMed, Ovid, EMBASE, and Cochrane databases. Data were searched using the following keywords: urinary tract cancer, urothelial carcinomas, renal pelvis, ureter, bladder cancer, chemotherapy, ureteroscopy, nephroureterectomy, neoplasm, (neo)adjuvant treatment, instillation, recurrence, risk factors, metastatic, immunotherapy, and survival. The results were assessed by a panel of experts. EVIDENCE SYNTHESIS: Even though data are accruing, for many areas there is still insufficient high-level evidence to provide strong recommendations. Patient stratification on the basis of histology and clinical examination (including imaging) and assessment of patients at risk of Lynch syndrome will aid management. Kidney-sparing management should be offered as a primary treatment option to patients with low-risk UTUC and two functional kidneys. In particular, for patients with high-risk or metastatic UTUC, new treatment options have become available. In high-risk UTUC, platinum-based chemotherapy after radical nephroureterectomy, and adjuvant nivolumab for unfit or patients who decline chemotherapy, are options. For metastatic disease, gemcitabine/carboplatin chemotherapy is recommended as first-line treatment for cisplatin-ineligible patients. Patients with PD-1/PD-L1-positive tumours should be offered a checkpoint inhibitor (pembrolizumab or atezolizumab). CONCLUSIONS: These guidelines contain information on the management of individual patients according to the current best evidence. Urologists should take into account the specific clinical characteristics of each patient when determining the optimal treatment regimen according to the risk stratification of these tumours. PATIENT SUMMARY: Cancer of the upper urinary tract is rare, but because 60% of these tumours are invasive at diagnosis, timely and appropriate diagnosis is most important. A number of known risk factors exist.

Audit, Feedback, and Education to Improve Quality and Outcomes in Transurethral Resection and Single-Instillation Intravesical Chemotherapy for Nonmuscle Invasive Bladder Cancer Treatment: Protocol for a Multicenter International Observational Study With an Embedded Cluster Randomized Trial.

BACKGROUND: Nonmuscle invasive bladder cancer (NMIBC) accounts for 75% of bladder cancers. It is common and costly. Cost and detriment to patient outcomes and quality of life are driven by high recurrence rates and the need for regular invasive surveillance and repeat treatments. There is evidence that the quality of the initial surgical procedure (transurethral resection of bladder tumor [TURBT]) and administration of postoperative bladder chemotherapy significantly reduce cancer recurrence rates and improve outcomes (cancer progression and mortality). There is surgeon-reported evidence that TURBT practice varies significantly across surgeons and sites. There is limited evidence from clinical trials of intravesical chemotherapy that NMIBC recurrence rate varies significantly between sites and that this cannot be accounted for by differences in patient, tumor, or adjuvant treatment factors, suggesting that how the surgery is performed may be a reason for the variation. OBJECTIVE: This study primarily aims to determine if feedback on and education about surgical quality indicators can improve performance and secondarily if this can reduce cancer recurrence rates. Planned secondary analyses aim to determine what surgeon, operative, perioperative, institutional, and patient factors are associated with better achievement of TURBT quality indicators and NMIBC recurrence rates. METHODS: This is an observational, international, multicenter study with an embedded cluster randomized trial of audit, feedback, and education. Sites will be included if they perform TURBT for NMIBC. The study has four phases: (1) site registration and usual practice survey; (2) retrospective audit; (3) randomization to audit, feedback, and education intervention or to no intervention; and (4) prospective audit. Local and national ethical and institutional approvals or exemptions will be obtained at each participating site. RESULTS: The study has 4 coprimary outcomes, which are 4 evidence-based TURBT quality indicators: a surgical performance factor (detrusor muscle resection); an adjuvant treatment factor (intravesical chemotherapy administration); and 2 documentation factors (resection completeness and tumor features). A key secondary outcome is the early cancer recurrence rate. The intervention is a web-based surgical performance feedback dashboard with educational and practical resources for TURBT quality improvement. It will include anonymous site and surgeon-level peer comparison, a performance summary, and targets. The coprimary outcomes will be analyzed at the site level while recurrence rate will be analyzed at the patient level. The study was funded in October 2020 and began data collection in April 2021. As of January 2023, there were 220 hospitals participating and over 15,000 patient records. Projected data collection end date is June 30, 2023. CONCLUSIONS: This study aims to use a distributed collaborative model to deliver a site-level web-based performance feedback intervention to improve the quality of endoscopic bladder cancer surgery. The study is funded and projects to complete data collection in June 2023. TRIAL REGISTRATION: ClinicalTrials.org NCT05154084; https://clinicaltrials.gov/ct2/show/NCT05154084. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42254.

Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: validation across time and place and recommendation for benchmarking.

UNLABELLED: Study Type - Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Apart from bladder tumour multiplicity, size, stage, grade and presence of cis, early recurrence following white light TURBT for new bladder tumours is also determined by surgeon experience, completeness of resection and presence or absence of detrusor muscle in the specimen. This study aims to validate surgeon experience and detrusor muscle as independent predictors of early recurrence following apparently complete white light TURBT in new bladder tumours. OBJECTIVE: To validate in patients undergoing first transurethral resection of bladder tumour (TURBT) for non-muscle-invasive bladder cancer (NMIBC), the presence/absence of detrusor muscle (DM) in the specimen and surgeon experience as independent predictors of the quality of TURBT. PATIENTS AND METHODS: Patients with new NMIBC, who had undergone complete first resections were recruited from a prospectively maintained cohort from the 1980s at the Western General Hospital, Edinburgh, UK and a contemporary cohort from the Aberdeen Royal Infirmary, UK. Tumour size, multiplicity, surgeon category, presence or absence of DM in the specimen, grade, stage, findings at first check cystoscopy and early re-TURBT were evaluated. Surgeons were stratified into a senior group (consultant and trainees in year five or six) and a junior group (trainees below year five). Early recurrence, or recurrence rate at the first follow up cystoscopy (RRFFC), was used to measure quality and was defined as finding pathologically confirmed tumour at early re-TURBT or the first check cystoscopy. RESULTS: From a total of 566 patients evaluated from both cohorts, 473 NMIBC specimens were suitable for analysis. Logistic regression multivariate analysis revealed that the absence of DM was associated with a higher RRFFC (odds ratio [OR]= 3.6, 95% CI = 1.7-7.5, P < 0.001). Senior surgeons were more likely to resect DM (OR = 4.9, 95% CI = 2.3-10.7, P < 0.001) Senior surgeons were independently associated with a lower RRFFC (OR = 5.3, 95% CI = 2.1-12.9, P < 0.001). CONCLUSIONS: Detrusor muscle status at the first, apparently complete, TURBT and surgeon's experience independently predict the quality of TURBT. • Documented complete resection by experienced surgeons with DM presence (good quality white-light TURBT) should be considered a benchmark for white-light TURBT in NMIBC.