The Financial Burden of Guideline-recommended Cancer Medications for Metastatic Urothelial Carcinoma.

Bladder cancer is a significant global health concern owing to its prevalence, negative impact on quality of life, and high treatment costs. Treatment for metastatic urothelial carcinoma (mUC) traditionally relies on platinum-based chemotherapy regimens. However, clinical trial results have led to the approval of immune checkpoint inhibitors (ICIs) as viable treatment options. We assessed the escalating costs and economic viability of mUC treatment guidelines in Europe. We used a pragmatic approach that involved: (1) collection of the costs of the recommended medications in the five most populous European countries; (2) conversion of the costs into international dollars to account for differences in purchasing power parity among countries; (3) evaluation of the cost trends over time; and (4) comparison of the medication costs to World Health Organization thresholds. Introduction of ICIs in European guidelines substantially increased the cost of medications for mUC. Intriguingly, important differences across European countries emerged: the annual cost of medications was twofold higher in Italy than in France and the UK. Despite limitations, our study sheds light on the escalating costs and economic challenges of mUC treatment, and highlights the need for assessments of sustainable and cost-effective management approaches. PATIENT SUMMARY: We looked at the costs of treatments for metastatic bladder cancer and found that costs have been rising over time, especially with the introduction of new immune therapies, with notable differences among European countries. While these new treatments improve patient outcomes, they also come with a high price tag, which could strain health care budgets. Our results suggest that cost-effectiveness studies will be essential in determining the best and most sustainable treatment strategies in the future.

The Utility of Inflammatory Serum Markers in the Assessment of Perioperative Morbidity after Radical Cystectomy for Bladder Cancer.

Background and Objectives: To date, sparse evidence exists about the impact of inflammatory serum markers in predicting perioperative complications after radical cystectomy (RC) for bladder cancer (BC). Here, we evaluated the role of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), C-reactive protein (CRP), and plasma fibrinogen in predicting perioperative morbidity and unplanned 30-days readmission after RC for BC. Materials and methods: We relied on a collaborative database of 271 patients who underwent open RC for cT1-4a N0 M0 BC between January 2012 and December 2022. Univariable and multivariable binomial logistic regression analyses were performed to assess the odds ratio (OR) with 95% confidence intervals (CI) testing the ability of each serum marker to predict postoperative complications (any-grade and major complications), and 30-days unplanned readmission. Results: The median age at RC was 73 yr (IQR 67-79). A total of 182 (67.2%) patients were male and the median BMI was 25.2 (IQR 23.2-28.4). Overall, 172 (63.5%) patients had a Charlson Comorbidity Index (CCI) greater than 2 points and 98 (36.2%) were current smokers at the time of RC. Overall, 233 (86.0%) patients experienced at least one complication after RC. Of these, 171 (63.1%) patients had minor complications (Clavien-Dindo grade 1-2) while 100 (36.9%) experienced major complications (Clavien-Dindo grade ≥ 3). According to multivariable analysis, current smoking status, high plasma fibrinogen, and preoperative anemia were independently associated with major complications (OR 2.10, 95%CI 1.15-4.90, p = 0.02), (OR 1.51, 95%CI 1.26-1.98, p = 0.09), and (OR 1.35, 95%CI 1.17-2.57, p = 0.03), respectively. Overall, 56 (20.7%) patients experienced a 30-days unplanned readmission. According to univariable analysis, high preoperative CRP and hyperfibrinogenemia were significantly associated with an increased risk of unplanned readmission (OR 2.15, 95%CI 1.15-4.16, p = 0.02; OR 2.18, 95%CI 1.13-4.44, p = 0.02, respectively). Conclusions: In our study, the preoperative immune-inflammation signature described by NLR, PLR, LMR, SII, and CRP showed a low reliability in predicting perioperative course after RC. Preoperative anemia and hyperfibrinogenemia were independent predictors of major complications. Further studies are pending in order to draw definitive conclusions.

Assessment of Predictive Genomic Biomarkers for Response to Cisplatin-based Neoadjuvant Chemotherapy in Bladder Cancer.

Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy is recommended for patients with muscle-invasive bladder cancer (MIBC). It has been shown that somatic deleterious mutations in ERCC2, gain-of-function mutations in ERBB2, and alterations in ATM, RB1, and FANCC are correlated with pathological response to NAC in MIBC. The objective of this study was to validate these genomic biomarkers in pretreatment transurethral resection material from an independent retrospective cohort of 165 patients with MIBC who subsequently underwent NAC and radical surgery. Patients with ypT0/Tis/Ta/T1N0 disease after surgery were defined as responders. Somatic deleterious mutations in ERCC2 were found in nine of 68 (13%) evaluable responders and two of 95 (2%) evaluable nonresponders (p = 0.009; FDR = 0.03). No correlation was observed between response and alterations in ERBB2 or in ATM, RB1, or FANCC alone or in combination. In an exploratory analysis, no additional genomic alterations discriminated between responders and nonresponders to NAC. No further associations were identified between the aforementioned biomarkers and pathological complete response (ypT0N0) after surgery. In conclusion, we observed a positive association between deleterious mutations in ERCC2 and pathological response to NAC, but not overall survival or recurrence-free survival. Other previously reported genomic biomarkers were not validated. PATIENT SUMMARY: It is currently unknown which patients will respond to chemotherapy before definitive surgery for bladder cancer. Previous studies described several gene mutations in bladder cancer that correlated with chemotherapy response. This study confirmed that patients with bladder cancer with a mutation in the ERCC2 gene often respond to chemotherapy.

Risk Stratification Tools and Prognostic Models in Non-muscle-invasive Bladder Cancer: A Critical Assessment from the European Association of Urology Non-muscle-invasive Bladder Cancer Guidelines Panel.

CONTEXT: This review focuses on the most widely used risk stratification and prediction tools for non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To assess the clinical use and relevance of risk stratification and prediction tools to enhance clinical decision making and counselling of patients with NMIBC. EVIDENCE ACQUISITION: The most frequent, currently used risk stratification tools and prognostic models for NMIBC patients were identified by the members of the European Association of Urology (EAU) Guidelines Panel on NMIBC. EVIDENCE SYNTHESIS: The 2006 European Organization for Research and Treatment of Cancer (EORTC) risk tables are the most widely used and validated tools for risk stratification and prognosis prediction in NMIBC patients. The EAU risk categories constitute a simple alternative to the EORTC risk tables and can be used for comparable risk stratification. In the subgroup of NMIBC patients treated with a short maintenance schedule of bacillus Calmette-Guerin (BCG), the Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model is more accurate than the EORTC risk tables. Both the EORTC risk tables and the CUETO scoring model overestimate the recurrence and progression risks in patients treated according to current guidelines. The new concept of conditional recurrence and progression estimates is very promising during follow-up but should be validated. CONCLUSIONS: Risk stratification and prognostic models enable outcome comparisons and standardisation of treatment and follow-up. At present, none of the available risk stratification and prognostic models reflects current standards of treatment. The EORTC risk tables and CUETO scoring model should be updated with previously unavailable data and recalculated. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is a heterogeneous disease. A risk-based therapeutic approach is recommended. We present available risk stratification and prediction tools and the degree of their validation with the aim to increase their use in everyday clinical practice.

Microhematuria assessment an IBCN consensus-Based upon a critical review of current guidelines.

RATIONALE: Assessment of patients with asymptomatic microhematuria (aMh) has been a challenge to urologists for decades. The aMh is a condition with a high prevalence in the general population and also an established diagnostic indicator of bladder cancer. Acknowledging aMh needs to be assessed within a complex context, multiple guidelines have been developed to identify individuals at high risk of being diagnosed with bladder cancer. MATERIAL & METHODS: This structured review and consensus of the International Bladder Cancer Network (IBCN) identified and examined 9 major guidelines. These recommendations are partly based on findings from a long-term study on the effects of home dipstick testing, but also on the assumption that early detection of malignancy might be beneficial. RESULTS: Despite similar designs, these guidelines differ in a variety of parameters including definition of aMh, rating of risks, use of imaging modalities, and the role of urine cytology. In addition, recommendations for further follow-up after negative initial assessment are controversial. In this review, different aspects for aMh assessment are analyzed based upon the evidence currently available. DISCUSSION: We question whether adherence to the complicated algorithms as recommended by most guidelines is practical for routine use. Based upon a consensus, the authors postulate a need for better tools. New concepts for risk assessment permitting improved risk stratification and prepone cystoscopy before refined imaging procedures (computed tomography scan and magnetic resonance imaging) are suggested.

Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy.

CONTEXT: This review focuses on the prediction of recurrence and progression in non-muscle invasive bladder cancer (NMIBC) and the treatments advocated for this disease. OBJECTIVE: To review the current status of epidemiology, recurrence, and progression of NMIBC and the state-of-the art treatment for this disease. EVIDENCE ACQUISITION: A literature search in English was performed using PubMed and the guidelines of the European Association of Urology and the American Urological Association. Relevant papers on epidemiology, recurrence, progression, and management of NMIBC were selected. Special attention was given to fluorescent cystoscopy, the new World Health Organisation 2004 classification system for grade, and the role of substaging of T1 NMIBC. EVIDENCE SYNTHESIS: In NMIBC, approximately 70% of patients present as pTa, 20% as pT1, and 10% with carcinoma in situ (CIS) lesions. Bladder cancer (BCa) is the fifth most frequent type of cancer in western society and the most expensive cancer per patient. Recurrence (in < or = 80% of patients) is the main problem for pTa NMIBC patients, whereas progression (in < or = 45% of patients) is the main threat in pT1 and CIS NMIBC. In a recent European Organisation for Research and Treatment of Cancer analysis, multiplicity, tumour size, and prior recurrence rate are the most important variables for recurrence. Tumour grade, stage, and CIS are the most important variables for progression. Treatment ranges from transurethral resection (TUR) followed by a single chemotherapy instillation in low-risk NMIBC to, sometimes, re-TUR and adjuvant intravesical therapy in intermediate- and high-risk patients to early cystectomy for treatment-refractory high-risk NMIBC. CONCLUSIONS: NMIBC is a heterogeneous disease with varying therapies, follow-up strategies, and oncologic outcomes for an individual patient.