Overall burden and impact on health-related quality of life associated with intravesical treatment of patients with non-muscle invasive bladder cancer in the United States.

BACKGROUND: This study aimed to describe the life impacts of intravesical therapies for non-muscle invasive bladder cancer (NMIBC) from a patient perspective. METHODS: A cross-sectional online survey design was used. Adults with NMIBC (and no other cancer) treated intravesically in the prior 12 months were recruited from US patient online communities. Individuals participating in a clinical trial or treated with erdafitinib were excluded. Participants' treatment experiences were evaluated using a questionnaire comprising (a) custom questions reported on 11-point numerical rating scales and (b) validated patient reported outcome (PRO) measures for bladder symptom burden and work productivity. RESULTS: Among 171 survey participants, most received bacillus Calmette-Guérin (BCG) (83%), intravesical gemcitabine (28%), or gemcitabine + docetaxel (13%) during the past year. Participants generally felt adequately informed about treatment, felt expectation of treatment matched actual experience, and expressed intent to complete the full treatment course and willingness to try different treatments if needed. Participants reported disease symptom burden of 42.6/72 on the NFBlSI-18 scale. Employed participants reported 51% work impairment and 59% overall work productivity loss due to NMIBC. CONCLUSIONS: Participants recently treated with intravesical therapies expressed intent to complete the full treatment course and willingness to try new therapies if needed. Participants reported high NMIBC symptom burden and work impairment negatively impacting their well-being, despite receiving intravesical treatment.

Does sheath size matter: benchtop comparison of flow and pressure across variety of continuous flow endoscopes.

INTRODUCTION: Laser enucleation utilizes purpose-built endoscopes for laser stabilization and continuous flow. No evaluation has been done with respect to flow or intravesical pressure with these scopes. We sought to evaluate the effect different endoscopes and sheath sizes on irrigation outflow and intravesical pressure. METHODS: Using a benchtop model using a silicone bladder model, five outer/inner sheath combinations were assessed: Storz 28/26Fr, Storz 26/26Fr, Wolf 26/24Fr, Wolf 26/22Fr, and Wolf 24/22Fr. A urodynamics pressure transducer was inserted alongside the scope for bladder pressure measurement and outflow from scope to drain was measured using uroflowmetry device. Four 1-minute trials were recorded for each sheath and the steady state flow and pressure was recorded. RESULTS: The Storz 28 F outer sheath and 26 F inner sheath had the highest outflow (12.4 ± 0.5 mL/s, p < 0.01). The Wolf 24 F outer and 22 F inner had the lowest outflow (7.0 ± 0.0 mL/s, p < 0.01). The steady state bladder pressure was the lowest in the Storz 28/26 (1.5 ± 1.7 cm H2O, p < 0.01)) and the greatest in the Storz 26/26 (24.2 ± 1.9 cm H2O, p < 0.01). CONCLUSION: The Storz 28/26 combination had best outflow rate and lowest intravesical pressures in our benchtop study. Flow rates generally decreased with smaller sheath sizes and steady state bladder pressures increased as the difference between the outflow and inflow sheath size narrowed. These findings provide initial parameters that could guide sheath selection in future to optimize visualization and success of voiding trials.

Strategies to Improve Clinical Outcomes and Patient Experience Undergoing Transurethral Resection of Bladder Tumor.

PURPOSE OF REVIEW: To describe patient experiences of transurethral resection of bladder tumor (TURBT) and review recent advances in enhancing clinical outcomes. RECENT FINDINGS: High rates of recurrence and progression of non-muscle invasive bladder tumors expose patients to multiple TURBT procedures throughout their disease process. Understanding the impact of TURBT on quality of life and patient experiences is crucial for shared decision-making, thus enhanced recovery protocol trials are being explored to improve patient outcomes. The variability in TURBT practices worldwide contributes to differing bladder tumor recurrence rates, prompting efforts to standardize practices by evaluating the impact of patient, hospital, and surgeon factors. For select cases, less intensive surveillance regimens have reduced toxicities and costs without compromising oncologic outcomes. New innovative approaches such as en bloc- and stratified resection techniques may reduce perioperative complications and improve clinical outcomes. Finally, neoadjuvant and ablative treatments have shown to be promising alternatives to TURBT, necessitating further investigation in this setting. TURBT is essential for diagnosing and treating bladder cancer. Reducing associated morbidities and improving surgical outcomes involve multifaceted approaches, including standardizing surgical practices, exploring innovative techniques, and optimizing surveillance regimens, all while promoting patient quality of life. Neoadjuvant therapies as alternative treatments are on the horizon and may ultimately change the landscape of bladder cancer care.

Short-term outcomes of intravesical gemcitabine for non-muscle-invasive bladder cancer after recent approval for use in Korea.

PURPOSE: In high-risk non-muscle-invasive bladder cancer (NMIBC), intravesical Bacillus Calmette-Guérin (BCG) is the standard adjuvant therapy post-transurethral resection of bladder tumor (TURBT). Intravesical gemcitabine, used as an alternative or second-line therapy amid BCG shortages, lacks outcome studies in the Korean population. MATERIALS AND METHODS: Patients who received weekly intravesical gemcitabine for 6 weeks after TURBT from 2019 to 2022 were retrospectively investigated. Based on the American Urological Association risk classification, patients with high- or very high-risk NMIBC who refused cystectomy were included. Maintenance treatment was performed depending on their risk. Recurrence was defined as histologic confirmation on subsequent cystoscopic biopsies or TURBT. Disease free survival (DFS) was evaluated by the Kaplan-Meier method. RESULTS: The study included 60 patients, comprising 45 high-risk (group 1) patients with a median age of 76 years and 15 very high-risk (group 2) patients with a median age of 68 years. Among them, 28 patients had previously received intravesical BCG. Over a median follow-up of 22 months, recurrence occurred in 31 patients in group 1 and 11 in group 2. The DFS rates of the high-risk group and the very high-risk group were 57.8% versus 40% at 1 year, 20.7% versus 21.3% at 2 years and 20.7% versus 21.3% at 3 years, respectively (p=0.831). Tis stage (p=0.042) and prostatic urethra invasion (p=0.028) were significant predictors of DFS. Cancer-specific mortality rates were 2.2% in group 1 and 6.7% in group 2 (p=0.441). CONCLUSIONS: Similar DFS outcome between high-risk and very high-risk patients were observed based on short-term results in Korea. This finding is crucial for clinical practice; however, studies analyzing more patients and long-term outcomes are needed.

Comparative Effectiveness of Bacillus Calmette-Guérin and Sequential Intravesical Gemcitabine and Docetaxel for Treatment-naïve Intermediate-risk Non-muscle-invasive Bladder Cancer.

BACKGROUND AND OBJECTIVE: Sequential intravesical gemcitabine/docetaxel (Gem/Doce) has emerged as a potential alternative to bacillus Calmette-Guérin (BCG) for the treatment of non-muscle-invasive bladder cancer (NMIBC). Our aim was to determine the comparative effectiveness of BCG and Gem/Doce for patients with intermediate-risk (IR) NMIBC, composed mainly of high-grade (HG) Ta disease. METHODS: Patients with IR-NMIBC who received either BCG or Gem/Doce during 2013-2023 were included. Maintenance BCG (as per the Southwest Oncology Group protocol) and monthly Gem/Doce maintenance for 1 yr were offered to patients with no evidence of recurrence after induction. Routine surveillance with cystoscopy was performed according to the American Urological Association guidelines. The Kaplan-Meier method was used to assess high-grade and any-grade recurrence-free survival (RFS). Cox regression analysis was performed to find predictors of recurrence. KEY FINDINGS AND LIMITATIONS: Of 483 patients, 127 had IR-NMIBC; 66 patients received BCG and 61 received Gem/Doce. Median age was 69 yr (interquartile range [IQR] 61-76) for the BCG group and 72 yr (IQR 62-76) for the Gem/Doce group. Median follow-up was 53.1 mo (IQR 25.3-71.2) for the BCG group and 20.2 mo (IQR 8.28-33.1) for the Gem/Doce group. The 2-yr high-grade RFS rates for primary high-grade tumors for BCG versus Gem/Doce groups were 81% versus 61%, with corresponding any-grade RFS rates of 60% versus 41%. Induction with Gem/Doce predicted any-grade recurrence (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.1-3.2) and high-grade recurrence for primary high-grade tumors (HR 3.4 95% CI 1.27-9.13), while receipt of maintenance therapy decreased the risk of any-grade recurrence (HR 0.4, 95% CI 0.22-0.72). This study is limited by its retrospective design. CONCLUSIONS AND CLINICAL IMPLICATIONS: For patients with IR-NMIBC, BCG was associated with superior any-grade RFS and high-grade RFS for primary high-grade tumors. Maintenance therapy was associated with better RFS when receiving Gem/Doce. Standardization and longer maintenance therapy protocols should be considered for Gem/Doce treatment. PATIENT SUMMARY: We compared outcomes for patients who received two different in-bladder treatments for intermediate-risk bladder cancer. Bacillus Calmette-Guérin (BCG) led to better outcomes than gemcitabine + docetaxel (Gem/Doce). Monthly maintenance therapy improved recurrence-free survival for patients who received Gem/Doce. We conclude that maintenance therapy is essential for patients receiving Gem/Doce to avoid bladder cancer recurrence after treatment.

Pharmacological Inhibition of Endogenous Hydrogen Sulfide Production Slows Bladder Cancer Progression in an Intravesical Murine Model.

Present bladder cancer therapies have relatively limited therapeutic impact and account for one of the highest lifetime treatment costs per patient. Therefore, there is an urgent need to explore novel and optimized treatment strategies. The present study investigated the effects of inhibiting endogenous hydrogen sulfide (H2S) production on bladder cell viability and in vivo tumor progression. We targeted the H2S-producing enzyme, cystathionine γ-lyase, in 5637 cells using propargylglycine (H2S inhibitor) and performed cytofluorimetric analysis to evaluate cell viability. We then tested the efficacy of propargylglycine alone or in combination with gemcitabine (conventional chemotherapy) in an intravesical murine model of bladder cancer. Magnetic resonance imaging and immunohistochemical staining for cell proliferation, apoptosis, immune-cell infiltration, and neovascularization were performed to evaluate tumor response. Compared to control conditions or cohorts, propargylglycine administration significantly attenuated bladder cancer cell viability in vitro (p < 0.0001) and tumor growth (p < 0.002) and invasion in vivo. Furthermore, propargylglycine enhanced the anti-cancer effects of gemcitabine, resulting in tumor regression (p < 0.0001). Moreover, propargylglycine induced cleaved PARP-1-activated apoptosis (p < 0.05), as well as intratumoral CD8+ T cell (p < 0.05) and F4/80+ macrophage (p < 0.002) infiltration. Propargylglycine also reduced intratumoral neovascularization (p < 0.0001) and cell proliferation (p < 0.0002). Importantly, the pro-apoptotic and anti-neovascularization effects of gemcitabine were enhanced by propargylglycine co-administration. Our findings suggest that inhibition of endogenous H2S production can be protective against bladder cancer by enhancing the chemotherapeutic action of gemcitabine and may be a novel pharmacological target and approach for improved bladder cancer diagnosis and treatments in the future.

Recent Advances in Drug Delivery Strategies for High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: A Brief Review from 2018 to 2024.

High-risk BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) is a condition that is typically treated with Bacillus Calmette-Guérin (BCG) therapy. Unfortunately, NMIBC is characterized by high recurrence, with a significant percentage of BCG patients ultimately requiring radical cystectomy. As a consequence, the development of effective new therapies to avoid RC has become a rapidly evolving field to address this unmet clinical need. To date, three biologics-Keytruda, Adstiladrin, and Anktiva-have been approved by the FDA, and multiple drug modalities, particularly gene therapies, have shown promising results in clinical trials. Advances in drug delivery strategies, such as targeted delivery, sustained release, and permeabilization of protective layers, are critical in overcoming the challenges posed by therapeutic intervention in bladder cancer. This review focuses on high-risk BCG-unresponsive NMIBC therapies that have been or are currently being investigated in clinical trials, offering a broad overview of the delivery system designs and up-to-date clinical outcomes that have been reported as of July 2024. It aims to inform the development of future drug delivery systems for second-line therapies in high-risk BCG-unresponsive NMIBC.

A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery.

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.

Efficacy and tolerance of hyperthermic intravesical chemotherapy (HIVEC) according to the number of instillations administered.

PURPOSE: To report the oncological outcomes and the tolerance between 6 instillations and more than 6 cycles of hyperthermic intravesical chemotherapy(HIVEC) in patients with non-muscle invasive bladder cancer(NMIBC). METHODS: This is a multicenter retrospective study from a national database including 9 expert centers. All patients treated with HIVEC between 2016 and 2023 for NMIBC were included. Patients were classified into two groups according to the total number of HIVEC instillations, including induction plus maintenance. Kaplan-Meier curves were computed to present survival outcomes. RESULTS: 261 patients with a median follow-up of 25.5 months were included. 199(76.2%) and 62(23.8%) were treated by 6 and more than 6 cycles of HIVEC, respectively. The 2-years RFS(40.2% vs. 34.4%,p = 0.3) and the 2-years PFS(86% vs. 87%,p = 0.85) were similar between group treated with 6 and more than 6 instillations. 2-years CSS and OS were also similar between both groups. Univariate Cox regression showed no association between the number of bladder instillation and RFS (HR = 1.2 95%CI[0.8-1.84], p = 0.3) or PFS (HR = 0.8 95%CI[0.29-2.02], p = 0.2). In the group treated with more than 6 cycles, 2-years RFS and 2-years PFS were similar between patients who received induction plus maintenance compared to those treated with induction only. Finally, hematuria and urinary burning were significantly higher in the group treated by more than 6 cycles (21% vs. 8.5%(p < 0.01),and 29% vs. 17% (p = 0.03), respectively). Serious side effects(grade ≥ 3) are rare(3.1%) and similar in both groups. CONCLUSIONS: Results show no significant difference in two years RFS, PFS, CSS and OS according to number of instillations received, while toxicity profile seems better in the group receiving six instillations only.

[New therapeutic approaches for non-muscle invasive bladder cancer-is organ preservation also possible after BCG (Bacillus Calmette Guérin)?] / Neue Therapieansätze beim nicht-muskelinvasiven Urothelkarzinom der Harnblase ­ Ist der Organerhalt auch nach BCG (Bacillus Calmette-Guérin) möglich?

Bacillus Calmette-Guérin (BCG) therapy is the standard of care in the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). In the absence of a response to BCG and persistent high-grade disease, cystectomy is recommended depending on the clinical risk. A variety of targeted therapy approaches, which aim at immune- and gene-based molecular targets, such as PD-(L)1 and FGFR, are currently being investigated in randomized studies for BCG-unresponsive NMIBC. Furthermore, novel forms of application for instillation therapy, such as the TAR device, in combination with gemcitabine or erdafitinib are being investigated in clinical trials in order to extend the duration of action of the active substance on the urothelium. Thus, there are now many developments that could make bladder-preserving therapy with comparable survival data possible as an alternative to BCG or in the event of BCG failure. In the future, it will be necessary to clarify how BCG response can be predicted by using molecular markers and how to define risk groups that should primarily be given an alternative therapy to BCG.

Adverse drug reactions of intravesical instillation therapy for bladder cancer: based on FDA adverse event reporting system.

BACKGROUND: Intravesical chemotherapy and immunotherapy are common adjuvant treatments for non-muscle invasive bladder cancer post-surgery. Analyzing adverse events linked to these therapies, can assist in clinical decision-making and risk assessment. STUDY DESIGN AND METHODS: Disproportionality analysis was conducted to analyze data from the Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the first quarter of 2024, exploring potential positive signals between Bacillus Calmette-Guérin, mitomycin-C, epirubicin, gemcitabine, and adverse events. RESULTS: The database retrieved 2018, 140, 31, and 85 adverse event reports associated with Bacillus Calmette-Guérin, mitomycin-C, epirubicin, and gemcitabine, respectively. Adverse reactions not mentioned in the label, such as aortic aneurysm and ocular congestion, were observed in preferred term level related to Bacillus Calmette-Guérin. Mitomycin-C exhibited specificity in skin and subcutaneous tissue diseases not reflected in the package insert. Gemcitabine-induced adverse drug reactions showed signals in vascular and lymphatic diseases meeting the screening criteria of all 4 indicators, with capillary leakage syndrome being the preferred term with the highest signal intensity. CONCLUSION: This study observed new adverse event signals, providing important assistance for drug selection in adjuvant therapy for non-muscle invasive bladder cancer postoperatively.

Intravesical Agents for Prevention of Recurrent Urinary Tract Infections.

Recurrent urinary tract infections (rUTIs) are common and can significantly impact a patient's quality of life. The mainstay of treatment is antibiotic-based, which contributes to the global problem of antibiotic resistance among urinary pathogens, so many alternative therapies have been explored. In this mini-review we evaluate evidence for intravesical agents that prevent rUTI, including antibiotic and nonantibiotic options. The current evidence supports the use of intravesical agents that replenish the glycosaminoglycan layer and of aminoglycoside antibiotics as safe and effective therapies to prevent rUTI. PATIENT SUMMARY: We reviewed evidence on the use of bladder instillations to treat repeated urinary infections. Studies have shown that agents that improve the bladder surface and one specific antibiotic class are effective and safe treatments for prevention of recurrent infections.

Differential effect of surgical technique on intravesical recurrence after radical nephroureterectomy in patients with upper tract urothelial cancer: a systematic review and Meta-analysis.

CONTEXT: Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC. OBJECTIVE: To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients. EVIDENCE ACQUISITION: Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU. EVIDENCE SYNTHESIS: Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44-0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06-1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51-0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15-2.34, p = 0.006, respectively). CONCLUSIONS: EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy.

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.

Long-term outcomes of bladder-sparing therapy vs radical cystectomy in BCG-unresponsive non-muscle-invasive bladder cancer.

OBJECTIVE: To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). PATIENTS AND METHODS: Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. RESULTS: Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). CONCLUSION: In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

Developments in conservative treatment for BCG-unresponsive non-muscle invasive bladder cancer.

INTRODUCTION: To reduce the risk of disease recurrence and progression of intermediate and high-risk Non-Muscle Invasive Bladder Cancers (NMIBCs), intravesical adjuvant treatment with Bacillus Calmette-Guerin (BCG) represents the standard of care, although up to 50% of patients will eventually recur and up to 20% of them will progress to Muscle Invasive Bladder Cancer (MIBC). Radical Cystectomy (RC) is the treatment of choice in this setting; however, this represents a major and morbid surgery, thus meaning that not all NMIBCs patient could undergo or may refuse this procedure or may refuse. The search for effective bladder sparing strategies in NMIBCs BCG-unresponsive patients is a hot topic in the urologic field. AREAS COVERED: We aimed to review the most important bladder-preserving strategies for BCG unresponsive disease, from those used in the past, even though rarely used nowadays (intravesical chemotherapy with single agents), to current available therapies (e.g. intravesical instillation with Gemcitabine-Docetaxel), and to future upcoming treatments (Oportuzumab Monatox). EXPERT OPINION: At present, bladder-preserving treatments in BCG-unresponsive patients are represented by the use of intravesical instillations, systemic immunotherapies, both with good short-term and modest mid-term efficacy, and numerous clinical trials ongoing, with encouraging initial results, in which patients could be recruited.

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.

Update on the Mechanism of Action of Intravesical BCG Therapy to Treat Non-Muscle-Invasive Bladder Cancer.

While more than four decades have elapsed since intravesical Bacillus Calmette-Guérin (BCG) was first used to manage non-muscle invasive bladder cancer (NMIBC), its precise mechanism of anti-tumor action remains incompletely understood. Besides the classic theory that BCG induces local (within the bladder) innate and adaptive immunity through interaction with multiple immune cells, three new concepts have emerged in the past few years that help explain the variable response to BCG therapy between patients. First, BCG has been found to directly interact and become internalized within cancer cells, inducing them to act as antigen-presenting cells (APCs) for T-cells while releasing multiple cytokines. Second, BCG has a direct cytotoxic effect on cancer cells by inducing apoptosis through caspase-dependent pathways, causing cell cycle arrest, releasing proteases from mitochondria, and inducing reactive oxygen species-mediated cell injury. Third, BCG can increase the expression of programmed death ligand 1 (PD-L1) on both cancer and infiltrating inflammatory cells to impair the cell-mediated immune response. Current data has shown that high-grade recurrence after BCG therapy is related to CD8+ T-cell anergy or 'exhaustion'. High-field cancerization and subsequently higher neoantigen presentation to T-cells are also associated with this anergy. This may explain why BCG therapy stops working after a certain time in many patients. This review summarizes the detailed immunologic reactions associated with BCG therapy and the role of immune cell subsets in this process. Moreover, this improved mechanistic understanding suggests new strategies for enhancing the anti-tumor efficacy of BCG for future clinical benefit.

[Transrectal ultrasonography of intravesical prostatic protrusion and the detection rate of clinically significant prostate cancer].

OBJECTIVE: To investigate the value of transrectal ultrasonography (TRUS) in the detection of clinically significant prostate cancer (CsPCa) in patients with intravesical prostatic protrusion (IPP). METHODS: We retrospectively analyzed the data on 128 patients undergoing TRUS-guided prostate biopsy in the General Hospital of Eastern Theater Command and Jiangsu Province Hospital from January 2019 to December 2022. We measured the size of and graded IPP, compared the clinicopathological and ultrasonographic features of the patients in the CsPCa group (Gleason score ≥7) and those in the control group (Gleason score <7), and analyzed the correlation of the IPP grades with the detection rate of CsPCa by multivariate logistic regression analysis. RESULTS: The prostate volume was significantly higher in the CsPCa group than in the control (ï¼»51.3±12.1ï¼½ vs ï¼»43.5±11.3ï¼½ ml, P< 0.05), while the PSA density (PSAD) remarkably lower in the former than in the latter (ï¼»0.45±1.92ï¼½ vs ï¼»0.59±2.14ï¼½ ng/ml, P< 0.05) and so was the detection rate of CsPCa in the patients with IPP grade 3 than in those with IPP grades 0, 1 and 2 (56.0% vs 85.4%, 87.1% and 80.6%, P< 0.05). Spearman correlation analysis showed that the Gleason score was correlated positively with the prostate volume (r = 0.612) but negatively with PSAD (r = －0.735) and the IPP grade (r = －0.619) (P< 0.05). Logistic regression analysis indicated that IPP grade 3 (OR: 0.690, 95% CI: 0.380－0.995, P = 0.032) was an independent protective factor for CsPCa. CONCLUSION: CsPCa is significantly correlated with the IPP grade, and the detection rate of CsPCa by TRUS-guided biopsy is lower in patients with IPP grade 3 than in those with IPP grades 0－2. Therefore, special attention should be paid to false negative probability in case of high-grade IPP.

A Self-Induced Foreign Body in the Urinary Bladder of an Adolescent Female.

In the pediatric population, foreign bodies within the urinary bladder are uncommon, typically resulting from urethral insertion out of curiosity. Other etiologies include sexual assault, iatrogenic factors, or migration from adjacent sites. Symptoms such as urinary retention, dysuria, increased frequency, decreased volume, nocturia, hematuria, painful erections, and pelvic pain are common. Radiographic imaging in the form of pelvic X-rays, ultrasound and CT scans often aids in diagnosis and making an action plan. Management depends on the object type, size, location and available expertise, often starting with a transurethral approach and resorting to open surgery if necessary. This case report describes a 13-year-old female presenting with severe dysuria and visible hematuria. Initially reporting the accidental insertion of a scarf pin into her vagina, she later admitted to intentionally inserting it. A pelvic radiograph revealed a needle-like object in the pelvis but its location and position were more convincing of its presence in the urinary bladder. A diagnostic cystoscopy was performed which confirmed a scarf pin in the urinary bladder, embedded in its wall. The pin was successfully removed transurethrally using endoscopic forceps.