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Objective: Recent preclinical and retrospective clinical evidence shows that androgen receptor (AR)-mediated signals have significant roles in development of non-muscle invasive bladder cancer (NMIBC). Here, we conducted a single-center, phase I study to assess the feasibility and efficacy of enzalutamide in patients having recurrent NMIBC with marker tumors. Patients with NMIBC who cannot achieve complete transurethral resection (TUR) or with recurrence within a year after the TUR, were enrolled. The patients were administered oral enzalutamide at 160 mg dose, once daily for four weeks. Clinical response at the end of the treatment was evaluated using cystoscopy. Results: Of the six patients enrolled, two experienced multiple recurrences. All the patients received the planned administration of enzalutamide. Enzalutamide was tolerable and all patients were able to complete the planed treatment, although four patients experienced mild treatment-related adverse events (AEs), but AEs with grade 2 or more were not observed. As for efficacy, three patients showed no change while the remaining three showed disease progression. Immunohistochemical analysis did not showed the strong staining of AR in the latest tumors. This is the first clinical study on enzalutamide treatment for NMIBC patients. In this study, four weeks of enzalutamide administration was well tolerated, however showed no clinical response for non-strong staining of AR. Trial registration: University Hospital Medical Information Network UMIN000026520 (date registration: 2017/3/13). [ABSTRACT FROM AUTHOR]

Background: The progression of bladder cancer (BC) from non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) significantly increases disease severity. Although the tumor microenvironment (TME) plays a pivotal role in this process, the heterogeneity of tumor cells and TME components remains underexplored. Methods: We characterized the transcriptomes of single cells from 11 BC samples, including 4 NMIBC, 4 MIBC, and 3 adjacent normal tissues. Bulk RNA-seq data were used to validate the clinical features of characteristic cells, and protein levels of these cells were further confirmed through immunohistochemistry (IHC) and multiplex immunofluorescence. Results: Bladder cancer progression was associated with distinct transcriptomic features in the TME. Tumor cells in MIBC displayed enhanced glycolytic activity and downregulation of chemokines and MHC-II molecules, reducing immune cell recruitment and facilitating immune evasion. This highlights glycolysis as a potential therapeutic target for disrupting tumor progression. We identified a T cell exhaustion pathway from naive CD8 + T cells (CD8 + TCF7) to terminally exhausted CD8 + STMN1 cells, with progressively declining immune surveillance. Targeting intermediate exhaustion states may restore T cell function and improve anti-tumor immunity. Macrophages polarized toward a pro-tumorigenic phenotype, while VEGFA + mast cells promoted angiogenesis in early-stage BC, suggesting their role as potential targets for therapeutic intervention in NMIBC. Furthermore, conventional dendritic cells (DCs) transformed into LAMP3 + DCs, contributing to an immunosuppressive microenvironment and enabling immune evasion. Conclusion: This study reveals dynamic changes in the TME during BC progression, including enhanced glycolysis, T cell exhaustion, and immune cell remodeling, which contribute to immune evasion and tumor progression. These findings identify critical pathways and cell populations as potential therapeutic targets, offering new strategies to improve treatment outcomes in BC patients. [ABSTRACT FROM AUTHOR]

Objective: This systematic review was conducted to synthesize current research on the role of repeated transurethral resection of the bladder (re-TURB) and the emerging use of magnetic resonance imaging (MRI) in discerning patient suitability for safely foregoing this procedure. Evidence acquisition: Employing a methodical literature search, we consulted several bibliographic databases including PubMed, Science Direct, Scopus, and Embase. The review process adhered strictly to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. Evidence synthesis: We evaluated data from 667 patients (mean age 65.8 years; age range 59–75 years) who underwent MRI prior to potential re-TURB. The gap between initial TURB and MRI was reported as 42 days in one study, while the interval between MRI and subsequent cystoscopy, with or without biopsy, varied from 21 days to 3 months. Initial TURB pathology for non-muscle invasive bladder cancer (NMIBC) patients identified stage Ta in 177 (42.5%) and T1 in 246 (57.5%) patients across three studies. High-grade and low-grade pathologic classifications were reported in 377 (64.5%) and 207 (35.5%) patients respectively in two studies. The VI-RADS scoring system's sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of bladder cancer recurrence were 89%, 85.5%, 82.7%, and 96%, respectively. A total of 365 patients (54.7%) underwent re-TUR. Among NMIBC patients, re-TUR pathology revealed Ta in 22 cases (5.4%) and pT1 in 179 cases (44%) with VI-RADS 1–2, while no cases of Ta (0%) and 37 cases of T1 (9%) were reported with VI-RADS 4–5, as documented in two studies. Notably, only 69 patients (10.7%) were identified as having MIBC across all studies. Conclusion: MRI is demonstrating reliability as a diagnostic tool for non-muscle invasive bladder cancers. The VI-RADS scoring system appears to be a promising approach in selecting patients for re-TURB. DW-MRI may serve as a primary diagnostic examination for patient follow-up post-TURB. [ABSTRACT FROM AUTHOR]

Objective: Given the increasing significance of digital health literacy (DHL) and health literacy (HL) in promoting informed decision-making and healthy behaviors, this study aimed to assess the influence of self-reported HL and DHL on treatment adherence and quality of life among patients who underwent transurethral resection of bladder tumors (TUR-BT) for primary non-muscle invasive bladder cancer (NMIBC). Materials & methods: This single-center observational study involved patients who underwent TUR-BT for NIMBC at a tertiary hospital from May 2022 to February 2024. Before the procedure, the patients' DHL and HL were evaluated using the European Health Literacy Survey Questionnaire short version and the eHealth Literacy Scale. Six months after surgery, we surveyed patients' QoL using the EORTC QLQ-C30. In line with recommendations from the European Association of Urology guidelines, adherence to the treatment plan was assessed along with a follow-up cystoscopy examination for each patient. Results: Multivariate analysis revealed that poorer DHL and HL were significantly associated with older age (p < 0.001), lower educational attainment (p < 0.001), and lack of internet access (p < 0.001). Conversely, higher DHL and HL levels were positively correlated with increased treatment adherence, as measured by cystoscopy completion (p < 0.001). Additionally, logistic regression analysis demonstrated significant associations between improved DHL and HL scores and better global health status (DHL, p = 0.022; HL, p = 0.008), higher emotional status (p < 0.001 for both), and social functioning (p < 0.001 for both). Notably, there were no significant differences in the symptom scale scores between the DHL and HL groups. Conclusion: To the best of our knowledge, this is the first study to explore the specific effect of HL/DHL on QoL and adherence in this patient population. Our research suggests that there may be a link between self-reported levels of DHL/HL and treatment adherence as well as QoL among patients with NIMBC. [ABSTRACT FROM AUTHOR]

Purpose: As Bladder EpiCheck® (BE) is a promising urinary biomarker for diagnosis and follow up of non-muscle-invasive bladder cancer (NMIBC), there are no studies evaluated this tool for second transurethral resection (TUR) indication. We aim to evaluate the performance of BE in predicting residual tumor before second TUR in NMIBC and its effects on clinical decision making. Methods: A total of 50 patients who were diagnosed with NMIBC and indicated for a second TUR were included in the study prospectively. The urine sample taken one day before the second TUR operation was evaluated with BE and the results were compared with second TUR pathologies. Results: The mean age was 65.3 and 45 of the patients were male. Specificity and negative predictive value of BE in primary tumor stage Ta were 100% and 87.5% while in primary tumor stage T1 were 71.4% and 68.2%, respectively. The specificity and negative predictive value of BE were 77.8% and 75%, respectively, in patients with high grade primary tumor. When all NMIBC were evaluated, the specificity and negative predictive value of BE were found to be 78.6% and 73.3% for second TUR, respectively. As an independent predictor of residual tumor in this group, positivity rates of BE were higher in T1 (p < 0.037) and high grade (p < 0.002) tumors. Conclusions: BE may be useful in detecting residual tumor before second TUR and benefit in clinical decision making with high specificity and negative predictive value. These results encourage the use of BE to reduce number of unnecessary second TUR procedures. It may improve cost effectivity and quality of life as high numbered studies are needed to support these views and to incorporate BE into clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective single-center study aimed to determine the correlation between The Paris System (TPS) urine cytology classification, cystoscopy findings, and non-muscle-invasive bladder cancer diagnosis. In addition, we sought to identify factors that might explain the abnormal cytology classification in cases in which no malignancy was detected. Methods: A Total of 855 patients evaluated with urine cytology between 2017 and 2020 at Kuopio University Hospital were included. Histological diagnoses and urinalysis results were correlated with cytology (TPS). Chi-squared and Fisher's exact tests were used to calculate statistical significance. Results: In the absence of exophytic tumors on cystoscopy, the risks of bladder cancer was 0.1% for NHGUC, 1.5% for AUC, 22.7% for SHGUC, and 83.3% for HGUC. Positive urinalysis corresponded to lower cytological diagnostic categories in both males and females. A statistically significant difference was observed in males with respect to moderate pyuria, hematuria, and higher cytological categories. Conclusions: This study provides evidence that a biopsy or follow-up may not be necessary for patients without a prior history of urothelial carcinoma and without exophytic tumors observed on cystoscopy, when the cytological diagnosis is NHGUC or AUC. Furthermore, concurrent hematuria and pyuria may result in a higher cytological classification. [ABSTRACT FROM AUTHOR]

Background: Most patients initially diagnosed with non-muscle invasive bladder cancer (NMIBC) still have frequent recurrence after urethral bladder tumor electrodesiccation supplemented with intravesical instillation therapy, and their risk of recurrence is difficult to predict. Risk prediction models used to predict postoperative recurrence in patients with NMIBC have limitations, such as a limited number of included cases and a lack of validation. Therefore, there is an urgent need to develop new models to compensate for the shortcomings and potentially provide evidence for predicting postoperative recurrence in NMIBC patients. Methods: Clinicopathologic characteristics and follow-up data were retrospectively collected from 556 patients with NMIBC who underwent transurethral resection of bladder tumors by electrocautery (TURBT) from January 2014 to December 2023 at the Affiliated Hospital of Zunyi Medical University and 167 patients with NMIBC who underwent the same procedure from January 2018 to April 2024 at the Third Affiliated Hospital of Zunyi Medical University. Independent risk factors affecting the recurrence of NMIBC were screened using the least absolute shrinkage and selection operator (Lasso) and Cox regression analysis. Cox risk regression models and randomized survival forest (RSF) models were developed. The optimal model was selected by comparing the area under the curve (AUC) of the working characteristics of the subjects in both and presented as a column-line graph. Results: The study included data from 566 patients obtained from the affiliated hospital of Zunyi Medical University and 167 patients obtained from the third affiliated hospital of Zunyi Medical University. Tumor number, urine leukocytes, urine occult blood, platelets, and red blood cell distribution width were confirmed as independent risk factors predicting RFS by Lasso-Cox regression analysis. The Cox proportional risk regression model and RSF model were constructed based on Lasso, which showed good predictive efficacy in both training and validation sets, especially the traditional Cox proportional risk regression model. In addition, the discrimination, consistency, and clinical utility of the column-line graph were assessed using C-index, area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Patients at high risk of recurrence can be identified early based on risk stratification. Conclusion: Internal and external validation has demonstrated that the model is highly discriminative and stable and can be used to assess the risk of early recurrence in NMIBC patients and to guide clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: Non-muscle-invasive Bladder Cancer (NMIBC) is notorious for its high recurrence rate of 70-80%, imposing a significant human burden and making it one of the costliest cancers to manage. Current prediction tools for NMIBC recurrence rely on scoring systems that often overestimate risk and lack accuracy. Machine learning (ML) and artificial intelligence (AI) are transforming oncological urology by leveraging molecular and clinical data to enhance predictive precision. Methods: This comprehensive review critically examines ML-based frameworks for predicting NMIBC recurrence. A systematic literature search was conducted, focusing on the statistical robustness and algorithmic efficacy of studies. These were categorised by data modalities (e.g., radiomics, clinical, histopathological, genomic) and types of ML models, such as neural networks, deep learning, and random forests. Each study was analysed for strengths, weaknesses, performance metrics, and limitations, with emphasis on generalisability, interpretability, and cost-effectiveness. Results: ML algorithms demonstrate significant potential, with neural networks achieving accuracies of 65–97.5%, particularly with multi-modal datasets, and support vector machines averaging around 75%. Models combining multiple data types consistently outperformed single-modality approaches. However, challenges include limited generalisability due to small datasets and the "black-box" nature of advanced models. Efforts to enhance explainability, such as SHapley Additive ExPlanations (SHAP), show promise but require refinement for clinical use. Conclusion: This review illuminates the nuances, complexities and contexts that influence the real-world advancement and adoption of these AI-driven techniques in precision oncology. It equips researchers with a deeper understanding of the intricacies of the ML algorithms employed. Actionable insights are provided for refining algorithms, optimising multimodal data utilisation, and bridging the gap between predictive accuracy and clinical utility. This rigorous analysis serves as a roadmap to advance real-world AI applications in oncological care, highlighting the collaborative efforts and robust datasets necessary to translate these advancements into tangible benefits for patient management. [ABSTRACT FROM AUTHOR]

Simple Summary: We explored the symptoms and side effects that can result from using BCG (an immunotherapy agent) to treat bladder cancer. We concluded that when BCG was combined with chemotherapy and at lower doses, the symptoms and side effects were less reported. These findings allow clinicians to improve counselling of patients regarding the management course and side effects for treating NMIBC. Background/Objectives: Knowledge of the symptoms and side effects (SSEs) of Bacille Calmette–Guerin (BCG) therapy for non-muscle invasive bladder cancer (NMIBC) is critical when establishing selecting appropriate therapies for patients. The aim of our study was to systematically review the common patient-reported SSEs associated with BCG-based and other intravesical chemotherapy treatment options for NMIBC. Methods: A systematic search of AMED, MEDLINE, EMBASE, PsycINFO, Web of Knowledge, and Scopus was conducted from inception to July 2024. The PRISMA process was followed. Prospective studies with an adult cohort that assessed SSEs through direct patient reports with standardized patient-reported outcome measures were included in this study. A narrative synthesis was performed to compare the frequency of SSEs reported by treatment options. Statistical analysis was performed using chi square and Fisher's exact tests, with statistical significance at p < 0.05. Results: Thirty-four studies met the eligibility criteria. The main findings indicated that BCG induction is more toxic than BCG induction with maintenance; however, severe SSEs resulting in treatment cessation occurred almost twice as often in patients on BCG induction with maintenance. Patients who received full-dose BCG were more likely to have SSEs compared to those receiving a low dose. BCG monotherapy alone caused more SSEs compared to BCG with chemotherapy. Patients reported more SSEs with BCG compared to chemotherapy alone for induction with maintenance. Limitations of the study include the varied length of maintenance regimes affecting nature of data reported. Conclusions: The findings of this study allow for improved counselling of patients regarding expected side effects in accordance with their recommended treatment options for NMIBC. [ABSTRACT FROM AUTHOR]

The article discusses the importance of en bloc resection of bladder tumors (ERBT) in bladder cancer treatment, emphasizing precision and anatomical fidelity. A multicenter randomized controlled trial compared ERBT to conventional transurethral resection of bladder tumors (cTURBT) for non-muscle-invasive bladder cancer, highlighting higher bladder perforation rates in the ERBT group. The study faced limitations in recruitment, surgeon experience, tumor size, and standardization of variables, impacting the reliability of outcomes. Standardized protocols and technical precision are crucial for accurate assessment of ERBT benefits in bladder cancer management. [Extracted from the article]

Simple Summary: Bladder cancer is among the most common malignancies worldwide, often requiring radical cystectomy (RC) for muscle-invasive and high-risk non-muscle-invasive cases. While effective, this procedure frequently leads to significant functional impairments, including urinary incontinence and sexual dysfunction, adversely affecting quality of life. In response, sexual-sparing techniques in robot-assisted radical cystectomy (RARC) have emerged as a promising approach to improve functional outcomes without compromising oncological control. This review examines the latest evidence on sexual-sparing RARC, highlighting its potential to preserve sexual and urinary function in both male and female patients. Techniques such as nerve-sparing, capsule-sparing, and pelvic organ-preserving approaches show encouraging functional outcomes. In select patients, oncological outcomes align closely with those of standard RC. Careful patient selection remains crucial, favoring those with organ-confined disease and good baseline function. While early data is promising, further prospective studies and standardized protocols are needed to validate these findings and facilitate broader clinical adoption. Sexual-sparing RARC represents a step forward in balancing cancer control with improved postoperative quality of life. Background/Objectives: Radical cystectomy (RC) is the standard treatment for muscle-invasive and high-risk non-muscle-invasive bladder cancer, but it often results in significant functional impairments, including sexual and urinary dysfunction, adversely affecting quality of life (QoL). Sexual-sparing robotic-assisted radical cystectomy (RARC) has been introduced to mitigate these effects. This review evaluates the oncological and functional outcomes of sexual-sparing RARC in male and female patients. Methods: A systematic literature search identified 15 studies including 793 patients who underwent sexual-sparing RARC using techniques such as nerve-sparing, capsule-sparing, and pelvic organ-preserving approaches. Data on oncological and functional outcomes were analyzed. Results: Sexual-sparing RARC achieves oncological outcomes comparable to open RC, with negative surgical margin (NSM) rates exceeding 95% in most studies. RFS and CSS rates were robust, often surpassing 85% at intermediate follow-ups. Functional outcomes were also favorable, with continence rates exceeding 90% and erectile function recovery surpassing 70% in well-selected male patients. Female patients undergoing pelvic organ-preserving techniques demonstrated improved continence, preserved sexual function, and enhanced QoL. Patient selection emerged as critical, favoring those with organ-confined disease and good baseline function. Conclusions: Sexual-sparing RARC offers a promising balance between oncological control and functional preservation, making it an effective option for selected patients. Further research is needed to refine techniques and establish standardized protocols for broader adoption. [ABSTRACT FROM AUTHOR]

Background: While the clinical application of SII-ONCO-Bacillus Calmette–Guerin (BCG) for non-muscle-invasive bladder cancer (NMIBC) is well established in Greece, there is a lack of real-world data on its effectiveness and safety. This retrospective, observational, multicenter, chart-review study aims to provide real-life data on the effectiveness and safety of SII-ONCO-BCG in patients with intermediate- and high-risk NMIBC. Methods: From January 2016 to December 2023, medical records from six hospital centers were reviewed for adult patients with histologically confirmed stage Ta or T1 NMIBC (with or without carcinoma in situ [CIS]) who received at least one maintenance course of SII-ONCO-BCG after induction. Tumor recurrence and progression were monitored at scheduled time intervals. Primary outcomes included recurrence-free survival (RFS) and progression-free survival (PFS), while adverse events (AEs) constituted secondary outcomes. Results: A total of 162 patients receiving SII-ONCO-BCG were enrolled. Among all patients, 145 (89.5%) patients were men, 88 (54.3%) aged 70 years or older, 103 (63.6%) had T1, 43 (26.5%) Ta, and 21 (12.9%) concurrent CIS. The median follow-up duration was 28.9 months (range, 5–36) and the mean BCG intravesical instillation courses were 13.7 (range, 9–27). After 3-, 2-, and 1-year follow-up, RFS rates of 85.2% (95% CI, 79.7–90.7%), 85.8% (80.4–91.2%), and 87.0% (81.8–92.3%) were observed, respectively. The corresponding 3-, 2-, and 1-year PFS rates were 96.9% (94.2–99.6%), 96.9% (94.2–99.6%), and 97.5% (95.1–99.9%), respectively. During the whole follow-up period, 24 (14.8%) patients experienced at least one AE. Conclusions: This real-world study demonstrates that SII-ONCO-BCG is an effective and safe treatment for patients with intermediate- and high-risk NMIBC. [ABSTRACT FROM AUTHOR]

Background: In Japan, the authorized period (2–4 h) between oral administration of 5-aminolevulinic acid hydrochloride (5-ALA) and transurethral resection for non-muscle invasive bladder cancer (NMIBC) may restrict photodynamic diagnosis (PDD) usage. Therefore, this prospective, single-arm, phase III study aimed to evaluate the diagnostic accuracy and safety of PDD at an extended administration period (4–8 h). Methods: From January 2022 to May 2023, 161 patients with NMIBC were enrolled from eight hospitals. The primary endpoint was the blue light (BL) sensitivity of pathologically positive biopsies. The secondary endpoints were a comparison of the specificity and positive and negative prediction rates under BL and white light (WL) conditions. Results: A total of 1242 specimens comprising 337 histological NMIBC specimens were analyzed. BL-sensitivity was 95.3%. Its lower limit of 95% confidence interval (92.4–97.3%) exceeded the threshold (70%) of non-inferiority to authorized usage. Sensitivity and specificity were significantly higher and lower for BL than those for WL (95.3% vs. 61.1%, P < 0.001; 52.7% vs. 95.2%, P < 0.001), respectively. The positive and negative predictive rates were significantly lower and higher for BL than those for WL (42.9% vs. 82.7%, P < 0.001; 96.8% vs. 86.8%, P < 0.001), respectively. Of the 145 patients receiving 5-ALA, 136 (93.8%) and 75 (51.7%) experienced 377 adverse events and 95 adverse reactions, respectively, most of which were grade 1 or 2. Conclusion: For extended period, the efficacy of PDD for NMIBC was similar to that of authorized period, in terms of higher sensitivity and lower specificity compared with WL, and the safety was acceptable. [ABSTRACT FROM AUTHOR]

Purpose: Up to 50% of high-risk non-muscle invasive bladder cancer (HR-NMIBC) patients fail Bacillus Calmette-Guérin (BCG) treatment, resulting in a high risk of progression and poor clinical outcomes. Biomarkers that predict outcomes after BCG are lacking. The antitumor effects of BCG are driven by a cytotoxic T cell response, which may be controlled by immune checkpoint proteins like Programmed Death Ligand 1 (PD-L1). Here, we hypothesized that PD-L1 protein expression could serve as a biomarker for BCG-failure. Methods: HR-NMIBC patients who received ≥ 5 BCG instillations were included. Tissue microarrays were constructed from BCG-naïve tumors and recurrences and stained with the PD-L1 (SP142) antibody. PD-L1 status was defined as ≥ 5% tumor-infiltrating immune cells with membrane staining in the tumor area. Clinicopathological associations with PD-L1 positive tumors were investigated, and time-to-event analyses were performed comparing PD-L1 positive vs. negative tumors. Results: 432 BCG-naïve tumors and 160 recurrences were included, and 91% of patients received adequate BCG. In BCG-naïve tumors, PD-L1 was expressed in 7% of patients and PD-L1 expression was associated with stage T1 versus Ta disease (p = 0.015). PD-L1 expression was not associated with treatment failure after adequate BCG (p = 0.782) nor with progression-free survival (p = 0.732). Testing cut-offs of ≥ 1% and ≥ 10% PD-L1 positivity did not alter results. High PD-L1 expression was more frequent in tumor recurrences (14%) as compared to BCG-naïve tumors (p = 0.012). Conclusion: PD-L1 expression in HR-NMIBC is not a biomarker of response to BCG. However, PD-L1 is higher in a subset of tumors that failed BCG treatment. More research is needed to determine the role of PD-L1 in tumors where BCG treatment failed. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to identify factors that predict recurrence by comparing low-dose and standard-dose Bacillus Calmette-Guérin (BCG) induction therapy in patients with non-muscle invasive bladder cancer (NMIBC). Methods: A total of 273 consecutive NMIBC patients who received low-dose (40 mg) or standard-dose (80 mg) BCG intravesical instillation therapy between January 2004 and December 2023 were analyzed. Recurrence-free survival (RFS) rates were assessed using the Kaplan–Meier method with the log-rank test. Univariate and multivariate Cox proportional hazards regression analyses were used to identify independent predictors of recurrence based on the Club Urológico Español de Tratamiento Oncológico (CUETO) criteria. Results: The log-rank test showed that older age, low BCG dose, number of tumors, and a history of recurrence increased the risk of recurrence significantly. Regarding older patients, recurrence rates were similar between the two dose groups. However, younger patients had significantly lower recurrence rates with standard-dose BCG compared to low-dose BCG. Multiple Cox regression analysis confirmed that older age, low-dose BCG, greater than three tumors, and a history of recurrence were significant predictors of recurrence. Conclusions: In this study, we found that low-dose BCG induction therapy was associated with higher relapse rates compared with standard doses, especially in younger patients. Age-related differences in the immune response to BCG may influence these relapse patterns. [ABSTRACT FROM AUTHOR]

Background: Immunotherapy is gaining great relevance in both non-muscle-invasive bladder cancer (NMIBC), with the use of bacille Calmette–Guerin (BCG), and in muscle-invasive BC (MIBC) with anti-checkpoint therapies blocking PD-1/PD-L1, CTLA-4/CD80-CD86, and, more recently, NKG2A/HLA-E interactions. Biomarkers are necessary to optimize the use of these therapies. Methods: We evaluated killer-cell immunoglobulin-like receptors (KIRs) and HLA-I genotyping and the expression of NK cell receptors in circulating T and NK lymphocytes at diagnosis in 325 consecutive BC patients (151 treated with BCG and 174 treated with other therapies), as well as in 648 patients with other cancers and 973 healthy donors as controls. The proliferation and production of cytokines and cytotoxicity were evaluated in peripheral blood mononuclear cells, stimulated in vitro with anti-CD3/CD28 or BCG, from selected patients based on HLA-B −21M/T dimorphism (NKG2A ligands). Results: The HLA-B −21M/T genotype showed opposing results in BC patients treated with BCG or other therapies. The MM genotype, compared to MT and TT, was associated with a longer 75th-percentile overall survival (not reached vs. 68.0 ± 13.7 and 52.0 ± 8.3 months, p = 0.034) in BCG, but a shorter (8.0 ± 2.4 vs. 21.0 ± 3.4 and 19.0 ± 4.9 months, p = 0.131) survival in other treatments. The HLA-B −21M/T genotype was an independent predictive parameter of the progression-free survival (HR = 2.08, p = 0.01) and the OS (HR = 2.059, p = 0.039) of BC patients treated with BCG, together with age and tumor histopathologic characteristics. The MM genotype was associated with higher counts of circulating CD56bright, fewer KIR2DL1/L2+ NK cells, and lower NKG2A expression, but not with differential in vitro NK cell functionality. Conclusions: The HLA-B −21M/T is independently associated with BC patient outcomes and can help to optimize the use of new immunotherapies in these patients. [ABSTRACT FROM AUTHOR]

Objective: The intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) prognostic group is heterogeneous. Growing evidence supports the role of active surveillance (AS) for patients with low-risk NMIBC, however, no clear data exists considering IR-NMIBC. The aim of the study was to assess the risk of recurrence of patients eligible for AS based on the International Bladder Cancer Group (IBCG) stratification. Methods: We retrospectively evaluated 174 LG IR-NMIBC patients who underwent transurethral resection of bladder tumor (index TURBT) from 2012 to 2023 at a tertiary referral center and fulfilled the inclusion criteria for enrollment in AS protocols at the index TURBT (≤ 5 suspicious lesions, no macrohematuria, negative urine cytology, lesions ≤ 1 cm). Patients were then stratified according to the International Bladder Cancer Group (IBCG) risk factors: frequent recurrence, early recurrence, previous instillation, and multifocality. Kaplan Meier plots and multivariable Cox regression analysis (MVA) were used to assess the risk of any and high-grade (HG) recurrence according to the number of risk factors. Results: Overall, 168 (97%) patients had a Ta low grade bladder tumor. After a median follow-up of 36 months [Interquartile range (IQR) 20–54], 75 (43%) and 32 (18%) patients experienced any- and HG recurrence, respectively. The 3-year recurrence free-survival (RFS) was 86% [95% Confidence Interval (CI) 76–98%] for patients with 0, 76% (95% CI 68–84%) for those with 1–2, and 54% (95% CI 34–84%) for those with ≥ 3 risk factors. The 3-year HG-RFS was > 90% for patients with 0 and 1–2 risk factors, compared to 76% (95% CI 58–99%) for those with ≥ 3 risk factors. At MVA, the presence of ≥ 3 risk factors was associated with a higher risk of recurrence [hazard ratio: 4.74, 95% CI 1.75–12.8, p = 0.002]. Conclusion: Among patients with LG IR-NMIBC eligible for AS, those with more than 2 IBCG risk factors may not be suitable candidates due to a higher risk of developing HG recurrence. Randomized controlled trials with standardized AS protocols are necessary to validate these findings and optimize patient selection for AS in LG IR-NMIBC. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to comprehensively evaluate the prognostic value of T1 histo-anatomic substaging (T1a/T1b) for high grade (HG) non-muscle invasive bladder cancer (NMIBC) over a large single-centre cohort. Materials and methods: Patients with primary HG T1 NMIBC were identified from our Institutional database, between 2011 and 2022. Data from diagnosis to repeated transurethral resection of bladder tumour (RE-TURBT), bacillus Calmette-Guérin (BCG) treatment and follow-up were collected. Patients were stratified based on histo-anatomic landmark into T1a (invasion above the Muscularis Mucosa-MM) and T1b (into/beyond MM). Kaplan-Meier curves and multivariate Cox regression analyses were used to assess the impact of histo-anatomic substaging on recurrence-free survival (RFS), cancer-specific survival (CSS), and progression-free survival (PFS). Results: Substaging was feasible in 88% of cases. The median (IQR) follow-up was 40 (17–72) months. T1b patients had larger initial tumours (> 3 cm: 43.2% vs. 26.1%, p < 0.001), while upstaging to muscle-invasive bladder cancer (MIBC) at RE-TURBT was more frequent in T1b than in T1a (5.9% vs. 1.5%, p = 0.02). T1b patients without BCG induction had worse RFS and PFS (all p ≤ 0.02) compared to T1a, while no differences were observed in patients who received complete BCG induction. At Multivariate analysis, completing at least a BCG induction course was associated with better outcomes across all endpoints. Conclusions: Invasion of the MM in primary T1 NMIBC is associated with a higher risk of upstaging to MIBC. Patients who received full BCG induction had similar outcomes regardless of substaging, whereas T1b patients without BCG induction experienced higher recurrence and progression rates. [ABSTRACT FROM AUTHOR]

Uromonitor and urinary telomerase reverse transcriptase promoter mutation droplet digital PCR (uTERTpm ddPCR) are non-invasive tests designed to detect bladder cancer in urine. We aimed to compare the diagnostic performance of uTERTpm ddPCR, Uromonitor and urine cytology in detecting bladder cancer. Urine samples were collected prospectively from patients diagnosed with primary (n = 74) and recurrent bladder cancer (n = 20) or benign urological conditions (n = 48) prior to surgical resection. The samples were tested for bladder cancer via uTERTpm ddPCR, Uromonitor and urine cytology. The sensitivity, specificity, and predictive values were calculated for each test, including confidence intervals. The results were stratified by low-grade non-muscle-invasive bladder cancer, high-grade non-muscle-invasive bladder cancer and muscle-invasive bladder cancer. Compared with urine cytology (59.5%, p = 0.005) and Uromonitor (56.8%, p = 0.001), the uTERTpm ddPCR test had the highest sensitivity (79.7%) for the detection of primary bladder cancer. Specificity did not significantly differ. The uTERTpm ddPCR test exhibited superior diagnostic performance over urine cytology and Uromonitor, highlighting its potential for non-invasive primary bladder cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: Urine biomarkers are crucial for monitoring patient responses in treating urological pathologies, including non-muscle invasive bladder cancer (NMIBC). Yet, analysing urine biomarkers poses several challenges, including ensuring specimen stability during transportation and analytical processing. This prospective feasibility study aimed to investigate how urinary leukocytes and proteins are impacted by storing and refrigerating urine. Methods: Stability of leukocytes from four healthy donors (HD) spiked into urine supernatants was analyzed for up to 72 h at 4°C. Urine samples from five NMIBC patients undergoing BCG treatment were divided into two portions, followed by either immediate processing or overnight refrigeration. Urinary cell content and soluble factors were analyzed by multiparameter flow cytometry and Luminex®, respectively. Results: We confirmed the stability of healthy donor peripheral blood leukocytes spiked into cell-free urine supernatants from healthy donors or untreated bladder cancer patients for up to 72 h under refrigeration at + 5℃. Additionally, we conducted immune cell and proteomic analysis from urine samples obtained from five NMIBC patients receiving Bacillus Calmette-Guérin (BCG) therapy either processed immediately or after overnight refrigeration. We successfully demonstrated that leukocyte and protein composition remain stable in refrigerated urine from BCG-treated NMIBC for 24 h. This included granulocytes, monocytes, and T cells, as well as total protein, creatinine and 46 additional individual immune-related mediators. Conclusions: This work demonstrates the compatibility of refrigerated urine shipment from the collection sites to analytical laboratories with both immunophenotyping and proteomic analysis and establishes clear logistical benefits for numerous clinical settings focused on monitoring patient immune responses in the urine matrix. [ABSTRACT FROM AUTHOR]

Simple Summary: We conducted an updated systematic review and meta-analysis of observational cohort studies and randomized clinical trials published between 2009 and 2022 that evaluated the efficacy of and outcomes after treatment with mitomycin C, gemcitabine, and docetaxel for non-muscle invasive bladder cancer recurrence and progression. Compared to other treatments, both gemcitabine and mitomycin C showed statistically significant risk reductions of 24% and 37% for tumor recurrence, respectively. Fewer studies examined the risk of progression, with large variability and inconclusive results. Our findings corroborate the current guidelines indicating that both gemcitabine and mitomycin C are effective treatments that reduce tumor recurrence and improve survival of non-muscle-invasive bladder cancer, although with large variability across studies. Given that women and minorities were generally underrepresented, our results highlight the importance of including a broader patient population in future clinical trials. Background: Non-muscle-invasive bladder cancer (NMIBC) comprises about 75% of all bladder cancers. Although NMIBC is treatable, it poses significant costs and burdens to patients due to high recurrence rates. We conducted an updated meta-analysis of studies that evaluated the efficacy of and outcomes after treatment with mitomycin C (MMC), gemcitabine (GEM), and docetaxel (DOCE) for NMIBC recurrence and progression. Methods: We searched the PubMed and Cochrane databases for observational cohort studies and randomized clinical trials (RCT) conducted between 2009 and 2022 that assessed the efficacy of GEM, DOCE, or MMC, alone or in combination, regarding NMIBC outcomes. A total of 49 studies that met the inclusion criteria were reviewed for their quality, sample size, outcomes, and potential for bias, and relevant data were extracted for the meta-analysis. Separate meta-analyses were performed to assess the risks of recurrence or progression when comparing GEM/DOCE or MMC vs. other treatments. Study heterogeneity was assessed by I2 statistics. Results: Among 31 studies comparing GEM or MMC to other treatments for NMIBC recurrence, there were statistically significant risk reductions of 24% for GEM (pooled relative risk (RR) of 0.76; 95% confidence interval (CI) 0.64–0.87) and 37% for MMC (pooled RR = 0.63; 95% CI 0.58–0.68). Recurrence-free survival (RFS) for GEM or MMC alone was 69.5% (95% CI 66.6–72.3%) and 67.2% (95% CI 66.2–68.2%), respectively. Studies assessing the combination of treatments had a pooled RFS of 44.6% (95% CI 40.4–48.7%). Fewer studies examined the risk of NMIBC progression, with large variability and inconclusive results across them. Conclusions: Our findings corroborate recent guidelines indicating that both GEM and MMC are effective treatments that reduce tumor recurrence and improve survival of NMIBC, although with large variability across the studies. Fewer studies evaluated DOCE treatment, with inconclusive results. Women and minorities were generally underrepresented, raising concerns about the generalizability of the findings and highlighting the importance of including a broader patient population in future RCTs. [ABSTRACT FROM AUTHOR]

Bladder cancer (BC) is an epidemiological urologic malignancy that continues to increase each year. Early diagnosis and prognosis monitoring is always significant in clinical practice, especially in distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC), due to the various depths of tumor invasion related to different therapeutic schedules and recurrence rates. Common diagnostic approaches are too invasive or generally inefficient in accuracy and specificity. In this work, a totally non-invasive and cost-effective method is established by investigating urine samples using surface-enhanced Raman spectroscopy (SERS) and multivariate statistical analysis. The comparison of urine SERS spectra shows the intensities of characteristic peaks for DNA/RNA, hypoxanthine, albumin, D-(+)-galactosamine, fatty acids, and some amino acids are distinguishable in BC occurrence and invasion progression. A PLS-LDA-based two-step binary classification scheme is performed on urine SERS spectra and the diagnostic accuracies were 97.7% and 96.3% for healthy individuals versus BC patients and NMIBC versus MIBC patients, respectively. Moreover, the impact of urine SERS spectral lengths in reaching high-precision recognition of BC is investigated. The results show that the Raman peaks at 803, 893, 1139, 1375, and 1466 cm−1 play an essential role in correctly categorizing healthy control, NMIBC, and MIBC patients, and SERS spectra ranges from 400 to 1600 cm−1 are enough for this identification task. These findings provide a sensitive, label-free, rapid, and totally non-invasive way for assessment of invasion depth of BC to its early diagnosis and prognosis monitoring, as well as valuable insights for selecting reasonable spectral range to enhance the measurement efficiency especially in large-scale sample datasets. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsEndoglin/CD105-microvessel density (CD105-MVD) is identified as one of the most potential methods for semi-quantification of angiogenesis in human cancer tissues. Present study aimed to examine the diagnosticand prognostic value of CD105-MVD in two clinically distinct subtypes of urothelial carcinoma of bladder (UCB) namely non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) patients.Message expression of endoglin was analysed by real-time quantitative polymerase chain reaction (RT-qPCR) and MVD measurement was done by immunohistochemical staining in 90 UCB [NMIBC: 60; MIBC: 30] patients. SEM studies were carried out to examine tumor vasculature and extent of neoangiogenesis in NMIBC and MIBC patients.Elevated message expression of CD105 showed statistical significance with tumor stage, grade, smoking/tobacco chewing history in NMIBC andage in MIBC cohort. Higher values of CD105-MVD showed statistical relevance with tumor stage, grade, size, smoking/tobacco chewing history in NMIBC cohort. Kaplan Meier test identified high CD105-MVD as strong predictor of poor RFS in NMIBC patients.Association of CD105 expression and MVD with the clinicohistopathological features as well as poor survival outcomes potentially identify it as a preferred marker of clinical significance in a given cohort of UCB patients.Clinical significanceStrong association of CD105 at message level with the demographics of UCB patients identifies it as a marker of diagnosis in a given cohort of patients.Survival analysis examined CD105-MVD as an independent strong predictor of poor recurrence free survival in NMIBC patients.Present study provides clear evidence of increased vascular density, vascular sprouts proliferation and new blood vessel formation with disease aggressiveness indicating CD105 as a preferred marker of neoangiogenesis in the given cohort of patients.The study describes CD105-MVD as a biomarker of diagnosis and prognosis with the sensitivity of 91.67% and 93.33% in a given cohort of NMIBC and MIBC patients.Strong association of CD105 at message level with the demographics of UCB patients identifies it as a marker of diagnosis in a given cohort of patients.Survival analysis examined CD105-MVD as an independent strong predictor of poor recurrence free survival in NMIBC patients.Present study provides clear evidence of increased vascular density, vascular sprouts proliferation and new blood vessel formation with disease aggressiveness indicating CD105 as a preferred marker of neoangiogenesis in the given cohort of patients.The study describes CD105-MVD as a biomarker of diagnosis and prognosis with the sensitivity of 91.67% and 93.33% in a given cohort of NMIBC and MIBC patients. [ABSTRACT FROM AUTHOR]

This study aimed to highlight the critical knowledge of bladder cancer education using UROPEDIA videos, an e-learning platform developed by the Society of Urological Surgery in Turkiye. We analyzed 90 educational videos on bladder cancer uploaded on UROPEDIA between January 2016 and October 2023. Two experienced urologists independently reviewed the videos, focusing on the essential information presented. Of the 90 videos, 43 (47.8%) addressed non-muscle-invasive bladder cancer, 39 (43.3%) focused on muscle-invasive bladder cancer, and 8 (8.9%) covered both. Key topics included Bacillus Calmette-Guerin (BCG) therapy, treatment options following BCG failure, and cystectomy procedures. UROPEDIA is an invaluable resource for urology residents and specialists, providing up-to-date information and expert insights. [ABSTRACT FROM AUTHOR]

Non-muscle invasive bladder cancer (NMIBC) accounts for approximately 70–75% of all bladder cancer cases. The standard treatment for high-risk NMIBC involves transurethral tumour resection followed by intravesical Bacillus Calmette–Guerin (BCG) immunotherapy. While BCG immunotherapy is both safe and effective, it frequently leads to the development of lower urinary tract symptoms (LUTS) such as urinary urgency, frequency, dysuria, and pelvic discomfort. These symptoms can significantly diminish patients' quality of life and may result in the discontinuation of BCG treatment, adversely affecting oncological outcomes. Despite the considerable clinical impact of BCG-induced LUTS, the underlying mechanisms remain unclear, hindering the implementation or development of effective treatments. This review provides novel insights into the potential mechanisms underlying BCG-induced LUTS, focusing on the integrated roles of afferent and efferent nerves in both normal and pathological bladder sensation and function. Specifically, this review examines how the body's response to BCG—through the development of inflammation, increased urothelial permeability, and altered urothelial signalling—might contribute to LUTS development. Drawing from known mechanisms in other common urological disorders and data from successful clinical trials involving NMIBC patients, this review summarises evidence supporting the likely changes in both sensory nerve signalling and bladder muscle function in the development of BCG-induced LUTS. However, further research is required to understand the intricate mechanisms underlying the development of BCG-induced LUTS and identify why some patients are more likely to experience BCG intolerance. Addressing these knowledge gaps could have profound implications for patients' quality of life, treatment adherence, and overall outcomes in NMIBC care. [ABSTRACT FROM AUTHOR]

Bladder cancer is a prevalent and highly recurrent malignancy within the urinary tract. The accurate segmentation of the bladder wall and tumor in magnetic resonance imaging (MRI) is a crucial step in distinguishing between non-muscle-invasive and muscle-invasive types of bladder cancer, which plays a pivotal role in guiding clinical treatment decisions and influencing postoperative quality of life. The performance of data-driven methods is highly dependent on the quality of the annotations and datasets, however the amount of high-quality annotated data is very limited given the difficulty of professional radiologists to distinguish the mixed regions between the bladder wall and the tumor. The performance of the data-driven approach is highly dependent on the quality of the annotation and datasets, Therefore, in order to alleviate these problems and take full advantage of the potential of limited annotated and unlabeled data, we designed a semi-supervised multi-region framework for bladder wall and tumor segmentation. Our framework incorporates wall-enhanced self-supervised pre-training, designed to enhance discrimination of the bladder wall, and a semi-supervised segmentation network that utilizes both limited high-quality annotated data and unlabeled data. Contrast consistency and reconstruction observation losses are introduced to constrain the model to enhance the bladder walls, and adaptive learning rate and post-processing techniques are implemented to further improve segmentation performance. Extensive experimental validation demonstrated that our proposed method achieves promising results in the segmentation of both the bladder wall and the tumor. The average Dice Similarity Coefficients (DSCs) of the proposed method for the bladder wall and tumor were 0.8351 and 0.9175, respectively. Visualization results indicated that our method can effectively reduce excessive segmentation artifacts outside the bladder, and improve the clinical significance of the segmentation results. [ABSTRACT FROM AUTHOR]

The Vesical Imaging-Reporting and Data System (VI-RADS) is a standard magnetic resonance imaging (MRI) and diagnostic method for muscle-invasive bladder cancer that was published in 2018. Several studies have demonstrated that VI-RADS has high diagnostic power and reproducibility. However, reading VI-RADS requires a certain amount of expertise, and radiologists need to be aware of the various pitfalls. MRI of the bladder includes T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced imaging (DCEI). T2WI is excellent for understanding anatomy. DWI and DCEI show high contrast between the tumor and normal anatomical structures and are suitable for staging local tumors. Bladder tumors are classified into five categories according to their size and morphology and their positional relationship to the bladder wall based on the VI-RADS diagnostic criteria. If the T2WI, DWI, and DCEI categories are the same, the category is the VI-RADS category. If the categories do not match, the DWI category is the VI-RADS category. If image quality of DWI is not evaluable, the DCEI category is the final category. In many cases, DWI is dominant, but this does not mean that T2WI and DCEI can be omitted from the reading of the bladder. In this educational review, typical and atypical teaching cases are demonstrated, and how to resolve misdiagnosis and the limitations of VI-RADS are discussed. The most important aspect of VI-RADS reading is to practice multiparametric reading with a solid understanding of the characteristics and role of each sequence and an awareness of the various pitfalls. [ABSTRACT FROM AUTHOR]

Introduction: Non-muscle invasive bladder cancer (NMIBC) represents a significant portion of bladder cancer cases and imposes a substantial economic burden, stemming from both direct treatment costs and long-term surveillance. As the treatment landscape evolves with advances in immunotherapy and targeted therapies, a multidisciplinary approach to management is increasingly crucial for optimizing patient outcomes and resource utilization. Areas covered: A PubMed search from 2010 to 15 June 2024 was conducted. This review examines the evolving role of multidisciplinary team (MDT) care in NMIBC management. It explores the potential benefits of MDT care, including improved risk stratification and personalized treatment plans, while acknowledging the challenges to implementation and proposing strategies to overcome them. Expert opinion: With a growing understanding of NMIBC and expanding therapeutic options, MDT care is pivotal in navigating patient care and maximizing outcomes. Strategic planning and collaborative efforts will facilitate the broader adoption of MDT care, enhancing the value of NMIBC treatment. MDT care holds promise for personalized, effective, and cost-efficient care for patients with NMIBC in the future. [ABSTRACT FROM AUTHOR]

Abstract Background Urine biomarkers are crucial for monitoring patient responses in treating urological pathologies, including non-muscle invasive bladder cancer (NMIBC). Yet, analysing urine biomarkers poses several challenges, including ensuring specimen stability during transportation and analytical processing. This prospective feasibility study aimed to investigate how urinary leukocytes and proteins are impacted by storing and refrigerating urine. Methods Stability of leukocytes from four healthy donors (HD) spiked into urine supernatants was analyzed for up to 72 h at 4°C. Urine samples from five NMIBC patients undergoing BCG treatment were divided into two portions, followed by either immediate processing or overnight refrigeration. Urinary cell content and soluble factors were analyzed by multiparameter flow cytometry and Luminex®, respectively. Results We confirmed the stability of healthy donor peripheral blood leukocytes spiked into cell-free urine supernatants from healthy donors or untreated bladder cancer patients for up to 72 h under refrigeration at + 5℃. Additionally, we conducted immune cell and proteomic analysis from urine samples obtained from five NMIBC patients receiving Bacillus Calmette-Guérin (BCG) therapy either processed immediately or after overnight refrigeration. We successfully demonstrated that leukocyte and protein composition remain stable in refrigerated urine from BCG-treated NMIBC for 24 h. This included granulocytes, monocytes, and T cells, as well as total protein, creatinine and 46 additional individual immune-related mediators. Conclusions This work demonstrates the compatibility of refrigerated urine shipment from the collection sites to analytical laboratories with both immunophenotyping and proteomic analysis and establishes clear logistical benefits for numerous clinical settings focused on monitoring patient immune responses in the urine matrix.

Introduction Distant recurrence of non‐muscle invasive bladder cancer is a rare condition that is poorly understood and difficult to detect in follow‐up protocols. Case presentation A 73‐year‐old female with a history of T1N0M0 bladder cancer 8 years ago suffered from a left axillary tumor, a left lung tumor, left mediastinal lymph node swelling, and bilateral adrenal gland tumors. Initially, she was diagnosed with metastatic left breast cancer of the left accessory mamma by needle biopsy of an axillary tumor. Subsequent bronchoscopic biopsy of the mediastinal lymph node revealed metastatic urothelial carcinoma, although no recurrence was detected in the urinary tract. She underwent systemic therapy, and all regions shrank without reprogression. Conclusion Non‐muscle invasive bladder cancer should be managed considering distant metastasis. If the origin of the metastatic lesions is unknown, this disease should be considered as a possible origin, even in the absence of urinary tract recurrence.

Abstract No pan‐India‐specific guidelines exist for the management of urological cancers. Although western guidelines are useful for informing management strategies, they do not account for the nuances of management in the Indian context. A modified Delphi method was used to provide a framework for the systematic development of India‐centric guidelines for the management of three uro‐oncology disease states: small renal masses, non‐muscle invasive bladder cancer and high‐risk/locally advanced prostate cancer.

Abstract Background Detecting carcinoma prostate (CaP) after intravesical Bacillus Calmette Guerin (BCG) immunotherapy for non‐muscle invasive bladder cancer (NMIBC) poses diagnostic challenges. Granulomatous prostatitis (GP) has an incidence of 0.8%–3.3% in post‐intravesical BCG patients and 6% incidence in a PIRADS 5 lesion on multiparametric MRI (mpMRI). Patients with GP after intravesical BCG may have clinical, biochemical, and radiological features similar to CaP. In our study, we evaluate the reliability of mpMRI in diagnosing CaP after intravesical BCG therapy. Materials and Methods We reviewed the NMIBC patients treated with intravesical BCG therapy between 2017 and 2023 and investigated those who underwent mpMRI and MR fusion biopsy in suspicion of CaP. A total of 120 patients had intravesical BCG immunotherapy, and 10 patients met our selection criteria. We performed a descriptive analysis of these patients and assessed the sensitivity and specificity of mpMRI in diagnosing CaP. Results The sensitivity of mpMRI in detecting CaP was 100%, and the specificity was 28.6%. Similarly, the negative predictive value for detecting CaP was 100%, and the positive predictive value was 37.5%. Among patients evaluated with mpMRI, a PIRADS 4 or 5 lesion was seen in 8 (80%) patients, and there was no lesion in 2 (20%) patients. The mpMRI detected 1 lesion in 6 patients (60%) and 2 (20%) in 2 patients. The lesions had a PIRADS score of 4 and 5 in 6 (60%) and 2 (20%) patients, respectively. Among these lesions, 8 (80%) were in the peripheral zone and 2 (20%) in the transition zone. In the MR fusion biopsy of these 10 patients, 7 (70%) had granulomatous prostatitis, and 3 (30%) had CaP. Conclusion In our study on evaluating the reliability of mpMRI in diagnosing CaP among post‐intravesical BCG patients, we noted that although PIRADS in mpMRI had high sensitivity in identifying prostate lesions, its specificity for detecting CaP is limited.

The main purpose of this study was to construct two nomograms to predict all-cause mortality (ACM) and cause-specific mortality (CSM) in non-muscle-invasive bladder cancer (NMIBC) patients after transurethral resection of bladder tumors (TURBTs). We selected NMIBC patients who underwent TURBT between 2004 and 2017 from the Surveillance, Epidemiology, and End Results database. The patients were randomly divided into a training set and a validation set at a ratio of 7:3. The independent influencing factors of ACM and CSM in the training set were determined by univariate and multivariate Cox regression analyses. We then integrated those independent influencing factors to construct nomograms. These prediction nomograms were further verified in the validation set. The C-index, calibration curve, receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve were used to evaluate the identification, calibration, predictive ability and clinical effectiveness of the nomograms. A total of 28,086 cases were ultimately included in this study, which were divided into a training set (19,661 individuals) and a validation set (8425 individuals). Nine variables, including age at diagnosis, race, marital status, tumor grade, T stage, tumor size, number of tumors, and primary site, were obtained via multivariate Cox regression of the training set and used to construct two nomograms prediction model. The C-index values for the ACM nomogram were 0.743 and 0.741 for the training and validation sets, respectively. Moreover, the corresponding values of the C-index for the CSM nomogram were 0.785 and 0.786, respectively. The ROC curves, calibration curves, and DCA curves showed good predictive performance. The nomograms can assist clinicians in identifying high-risk populations and devising more individualized treatment strategies for NMIBC patients. [ABSTRACT FROM AUTHOR]

What is this summary about? This is a summary of two studies that looked at the safety and effectiveness of a potential new treatment, N-803 (Anktiva), in combination with a standard treatment bacillus Calmette-Guerin (BCG) for people with non-muscle invasive bladder cancer (NMIBC). One study was a Phase 1b study that tested increasing doses of N-803 in combination with the same dose of BCG in people with NMIBC who had never received BCG previously (BCG-naive). The other study is a Phase 2/3 study of N-803 and BCG in people with NMIBC whose cancer wasn't eliminated by BCG alone (BCGunresponsive). What happened in the studies? In the Phase 1b study, the nine participants were split into three groups of 3 participants who received a dose of 100, 200, or 400 μg N-803 along with a standard 50 mg dose of BCG. In the Phase 2/3 study, one group (cohort A) of participants with carcinoma in situ (CIS) disease and another group (cohort B) with papillary disease were treated with 400 μg N-803 plus 50 mg BCG. There was also a cohort C that received only 400 μg N-803. Treatments were delivered directly into the bladder once a week for 6 weeks in a row. What were the key takeaways? N-803 plus BCG eliminated NMIBC in all nine BCG-naive participants and the effects were long-lasting, with participants remaining NMIBC-free for a range of 8.3 to 9.2 years. As reported in 2022, cancer was eliminated in 58 of 82 (71%) participants with BCG-unresponsive CIS disease and the effect was also long-lasting. Importantly, approximately 90% of the successfully treated participants avoided surgical removal of the bladder. In cohort B participants with papillary disease, 40 of 72 (55.4%) were cancer-free 12 months after treatment. N-803 used alone was only effective in 2 of 10 participants. In both studies, the combination of N-803 and BCG was found to be associated with very few adverse events. Based on results from the Phase 2/3 study, the U.S. Food and Drug Association (FDA) approved the use of N-803 plus BCG for the treatment of BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease. Clinical Trial Registration:NCT02138734 (Phase 1b study), NCT03022825 (Phase 2/3 study) Tweetable Abstract Addition of the IL-15 superagonist N-803 to BCG therapy produces a high rate of success in eliminating non-muscle invasive bladder cancer in both BCG-naive and BCG-unresponsive patients, with long-lasting effects that allow patients to avoid surgical removal of the bladder [ABSTRACT FROM AUTHOR]

Background: Chat Generative Pre-Trained Transformer (ChatGPT) has previously been shown to accurately predict colon cancer screening intervals when provided with clinical data and context in the form of guidelines. The National Comprehensive Cancer Network® (NCCN®) guideline on non-muscle invasive bladder cancer (NMIBC) includes criteria for risk stratification into low-, intermediate-, and high-risk groups based on patient and disease characteristics. The aim of this study is to evaluate the ability of ChatGPT to apply the NCCN Guidelines to risk stratify theoretical patient scenarios related to NMIBC. Methods: Thirty-six hypothetical patient scenarios related to NMIBC were created and submitted to GPT-3.5 and GPT-4 at two separate time points. First, both models were prompted to risk stratify patients without any additional context provided. Custom instructions were then provided as textual context using the written versions of the NMIBC NCCN® Guidelines, followed by repeat risk stratification. Finally, GPT-4 was provided with an image of the NMIBC risk groups table, and the risk stratification was again performed. Results: GPT-3.5 correctly risk stratified 68% (24.5 of 36) of scenarios without context, slightly increasing to 74% (26.5 of 36) with textual context. Using GPT-4, the model had accuracy of 83% (30 of 36) without context, reaching 100% (36 of 36) with textual context (P =.025). GPT-4 with image context maintained similar accuracy to GPT-4 without context, with accuracy 81% (29 of 36). ChatGPT generally performed poorly when stratifying intermediate risk NMIBC (33%-63%). When risk stratification was incorrect, most responses were overestimations of risk. Conclusions: GPT-4 can accurately risk stratify patients with respect to NMIBC when provided with context containing guidelines. Overestimation of risk is more common than underestimation, and intermediate risk NMIBC is most likely to be incorrectly stratified. With further validation, GPT-4 can become a tool for risk stratification of NMIBC in clinical practice. [ABSTRACT FROM AUTHOR]

Background/Objectives: Bladder cancer (BC) is a highly heterogeneous disease, presenting clinical challenges, particularly in predicting patient outcomes and selecting effective treatments. Molecular subtyping has emerged as an essential tool for understanding the biological diversity of BC; however, its implementation in clinical practice remains limited due to the high costs and complexity of genomic techniques. This review examines the role of immunohistochemistry (IHC) as a surrogate marker for molecular subtyping in BC, highlighting its potential to bridge the gap between advanced molecular classifications and routine clinical application; Methods: We explore the evolution of taxonomic classification in BC, with a particular focus on cytokeratin (KRT) expression patterns in normal urothelium, which are key to identifying basal and luminal subtypes. Furthermore, we emphasise the need for consensus on IHC markers to reliably define these subtypes, facilitating wider and standardised clinical use. The review also analyses the application of IHC in both muscle-invasive (MIBC) and non-muscle-invasive bladder cancer (NMIBC), with particular attention to the less extensively studied NMIBC cases. We discuss the practical advantages of IHC for subtyping, including its cost effectiveness and feasibility in standard pathology laboratories, alongside ongoing challenges such as the requirement for standardised protocols and external validation across diverse clinical settings; Conclusions: While IHC has limitations, it offers a viable alternative for laboratories lacking access to advanced molecular techniques. Further research is required to determine the optimal combination of markers, establish a consensus diagnostic algorithm, and validate IHC through large-scale trials. This will ultimately enhance diagnostic accuracy, guide treatment decisions, and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Most non-muscle invasive bladder cancers have been treated by transurethral resection and following intravesical injection of immunotherapeutic agents. However, the delivery efficiency of therapeutic agents into bladder wall is low due to frequent urination, which leads to the failure of treatment with side effects. Here, we report a urease-powered nanomotor containing the agonist of stimulator of interferon genes (STING) for the efficient activation of immune cells in the bladder wall. After characterization, we perform in vitro motion analysis and assess in vivo swarming behaviors of nanomotors. The intravesical instillation results in the effective penetration and retention of nanomotors in the bladder. In addition, we confirm the anti-tumor effect of nanomotor containing the STING agonist (94.2% of inhibition), with recruitment of CD8+ T cells (11.2-fold compared with PBS) and enhanced anti-tumor immune responses in bladder cancer model in female mice. Furthermore, we demonstrate the better anti-tumor effect of nanomotor containing the STING agonist than those of the gold standard Bacille Calmette-Guerin therapy and the anti-PD-1 inhibitor pembrolizumab in bladder cancer model. Taken together, the urease-powered nanomotor would provide a paradigm as a next-generation platform for bladder cancer immunotherapy. Self-propelling micro/nanomotors represent a therapeutic option for drug delivery. Here the authors report the design and characterization of a biodegradable urease-powered nanomotor containing STING agonist, promoting anti-tumor immune responses in bladder cancer models. [ABSTRACT FROM AUTHOR]

Urothelial carcinoma (UC) of the urinary bladder has significant challenges in treatment due to its diverse genetic landscape and variable response to systemic therapy. In recent years, patient-derived organoids (PDOs) emerged as a novel tool to model primary tumors with higher resemblance than conventional 2D cell culture approaches. However, the potential of organoids to predict therapy response in a clinical setting remains to be evaluated. This study explores the clinical feasibility of PDOs for pharmacotyping in UC. Initially, we subjected tumor tissue specimens from 50 patients undergoing transurethral resection or radical cystectomy to organoid propagation, of whom 19 (38%) yielded PDOs suitable for drug sensitivity assessment. Notably, whole transcriptome-based analysis indicated that PDOs may show phenotypes distinct from their parental tumor tissue. Pharmacotyping within a clinically relevant timeframe [mean of 35.44 and 55 days for non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), respectively] was achieved. Drug sensitivity analyses revealed marked differences between NMIBC and MIBC, with MIBC-derived organoids demonstrating higher chemosensitivity toward clinically relevant drugs. A case study correlating organoid response with patient treatment outcome illustrated the complexity of predicting chemotherapy efficacy, especially considering the rapid acquisition of drug resistance. We propose a workflow of prospective organoid-based pharmacotyping in UC, enabling further translational research and integration of this approach into clinical practice. [ABSTRACT FROM AUTHOR]

Background: Non-muscle-invasive bladder cancer (NMIBC) is renowned for its high recurrence, invasiveness, and poor prognosis. Consequently, developing new biomarkers for risk assessment and investigating innovative therapeutic targets postoperative in NMIBC patients are crucial to aid in treatment planning. Approaches: Differential gene expression analysis was performed using multiple Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between NMIBC and normal tissue, as well as between NMIBC and muscle-invasive bladder cancer (MIBC). Functional enrichment analysis was conducted based on the DEGs identified. Subsequently, prognosis-related genes were selected using Kaplan–Meier (KM) analysis and Cox regression analysis. The Boruta algorithm was utilized to further screen for core DEGs related to postoperative progression in NMIBC based on the aforementioned prognosis-related genes. Single-cell and clinical correlation studies were performed to verify their expression across various stages of bladder cancer. To investigate the link between core genes and the immune microenvironment, single-sample gene set enrichment analysis (ssGSEA) was utilized, and Receiver Operating Characteristic (ROC) and KM analyses were performed to confirm predictive power for immune therapy outcomes. Machine learning (ML) models were constructed using the DepMap dataset to predict the efficacy of core gene inhibitors in treating bladder cancers. The prognostic performance of the core genes was evaluated using ROC curve analysis. An online prediction tool was developed based on the core genes to provide prognostic predictions. Finally, RT-qPCR, CCK-8, and Transwell assays were used to verify the pro-tumor effects of the GINS2 in bladder cancer. Results: A total of 70 DEGs were identified, among which 11 prognostic genes were obtained through KM analysis, and an additional 8 prognostic genes were obtained through COX analysis. The Boruta algorithm selected AURKB, GINS2, and UHRF1 as the three core DEGs. Single-cell and clinical variable correlation analyses indicated that the core genes promoted the progression of bladder cancer. The analysis of immune infiltration revealed a strong positive association between the core genes and both activated CD4 T cells and Type 2 helper T cells. Two random forest (RF) models were constructed to effectively predict the treatment effect of bladder cancer after targeted inhibition of AURKB and GINS2. In addition, an online nomogram tool was developed to effectively predict the risk of postoperative progression in NMIBC patients undergoing TURBT. Finally, RT-qPCR, CCK8, and Transwell assays showed that GINS2 promoted the growth and progression of bladder cancer. Conclusion: AURKB, GINS2, and UHRF1 have the potential to enhance postoperative management of NMIBC patients undergoing transurethral resection of bladder tumor (TURBT) and can predict immunotherapy response, establishing them as promising therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Follow-up protocols for non-muscle-invasive bladder cancer (NMIBC) include mainly cystoscopy and urinary cytology. However, the role of urine cytology during follow-up for low-grade (LG) NMIBC is not entirely known, and studies assessing adherence to guideline recommendations have revealed an overuse of urinary cytology. Our aim with this study was to evaluate the impact of urine cytology as a complementary method to cystoscopy during follow-up for LG NMIBC. We found that performing urine cytology during follow-up for primary LG non-muscle-invasive bladder cancer is only useful to detect recurrences when suspicious lesions are seen during cystoscopic evaluation. Nevertheless, a positive cytology alerts to the risk of progression to high-grade disease during surveillance. Background and Objective: The role of urine cytology during follow-up for low-grade (LG) non-muscle-invasive bladder cancer (NMIBC) is not well established, although cytology has low sensitivity in detecting LG recurrences. Our study aims to evaluate the impact of urine cytology as a complementary method to cystoscopy during follow-up for LG NMIBC. Methods: Patients diagnosed with primary LG TaT1 bladder cancer (BC) between 2010 and 2020 were included. Patients were stratified according to the EAU NMIBC scoring model. Urine cytology was performed during follow-up cystoscopy. The outcomes of the study were BC recurrence and upgrading to high-grade (HG). Cytology utility was established by assessing whether its result led to management change. Results: We included 337 patients with LG TaT1 BC. EAU risk group distribution was low in 262 (77.7%), intermediate in 57 (16.9%), and high-risk in 18 (5.3%) cases. With a median follow-up of 5 years, 166 (49.3%) patients experienced recurrence. Cystoscopy was positive in 154 (92.8%) and suspicious in 12 (7.2%) cases. Urine cytology was positive in 33 (19.9%) cases but only changed management in 3 (0.89%), all with suspicious cystoscopy. Positive cytology at first recurrence was associated with higher risk of upgrading during follow-up (HR 2.781, p = 0.006) and lower upgrading-free survival (p = 0.001). Conclusions: The role of urine cytology to detect first recurrences during follow-up for primary LG TaT1 NMIBC might be limited to patients with non-conclusive lesions in the cystoscopy. A positive cytology at first recurrence is associated with a higher risk of upgrading to HG BC during follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Bladder cancer is the ninth most commonly diagnosed form of cancer in both sexes worldwide and the fifth in Europe. The most common form, non-muscle-invasive bladder cancer, is highly prevalent with high recurrence rates and has wide range of outcomes that is partially due to the variability in the treatment delivered. Therefore, some recommendations have been done by the European Association of Urology to standardize their management. Several quality control indicators have been proposed to monitor the adherence of urologists and hospitals to these recommendations. A quality control indicator program has been initiated in the hospitals that are a part of the Flemish Hospital Network in June 2013 using a specific prospective registry. We have recently published the first analysis of these quality control indicators, which showed significant differences between the hospitals. Before publishing the second analysis with more patients and additional quality control indicators, we aimed to describe the characteristics of the cohort in this study. Purpose: Bladder cancer (BC) is a heterogeneous disease with varying outcomes, influenced by disease heterogeneity and variability in treatment and follow-up. Risk groups have been established for non–muscle-invasive BC (NMIBC) to standardize therapy, and several quality control indicators (QCIs) monitor adherence to these risk group-based guidelines. However, controversial results had been obtained regarding the oncological benefits of these QCIs until recent high-quality studies from large registries showed their usefulness. To improve adherence to the European Association of Urology (EAU) Guidelines and benchmark current care in Flemish hospitals within Vlaams Ziekenhuisnetwerk–KU Leuven (VZNKUL), a QCI program for NMIBC was initiated in 2013. This study aims to describe the demographic, clinical, and treatment data of patients enrolled in this program. Participants: The VZNKUL–NMIBC Quality Indicators Program Registry is a prospective cohort including patients treated and followed up with at seven academic and non-academic Flemish hospitals since June 2013. Data collection includes patient characteristics, tumor data, treatment, and oncological outcomes. Findings to date: From June 2013 to December 2020, 4744 transurethral resections of bladder tumors (TURBTs) from 2237 unique patients were analyzed. Most patients (80%) were men with a median age of 73. The median time from diagnosis to TURBT was 19 days. A single tumor was detected in 37% of TURBTs. Tumors larger than 3 cm were found in 20.8% of cases. In 46% of TURBTs, a reTURBT was scheduled according to guidelines. The complication rates were 7.5% and 2.4% for bladder perforation and bleeding, respectively. Postoperative single intravesical instillation of chemotherapy (SIVIC) was administered to 56.9% of 1533 indicated patients with a median time to administration of 4.7 h. Among the cohort, 60.4% had NMIBC, and 9.3% had muscle-invasive BC. Of 972 high-risk patients, 60.7% received adequate BCG induction, while 39.4% received adequate maintenance. After BCG induction ± maintenance, 39.7% were tumor-free, with 17.7% recurrence and 4% progression to muscle-invasive BC. BCG treatment was terminated early for 17% of patients due to intolerance. Early cystectomy was performed for 2.4% of the BCG-naïve patients, and 27.7% of patients with BCG failure underwent a BCG rechallenge. For intermediate-risk patients, 2.1% received adequate BCG, and 23% received intravesical chemotherapy. The median follow-up was 57 months. Five-year recurrence-free, progression-free, cancer-free, overall, and cancer-specific survival rates were 53%, 91.6%, 89%, 70.6%, and 95.6%, respectively, for the NMIBC patients. Of 400 non-metastatic MIBC patients, 217 (54.3%) underwent radical cystectomy (RC), of whom 46% received neoadjuvant chemotherapy, while 18 (4.5%) refused RC, and 74 (18.5%) were considered unfit for the surgery. Future plans: The VZNKUL–NMIBC Quality Indicators Program Registry will continue collecting data to evaluate QCIs and monitor treatment quality, enabling hospitals to benchmark their performance and improve patient care. Additionally, the registry's real-world data can support research and international collaboration. Trial registration: The study was registered on ClinicalTrials.gov (NCT04167332). [ABSTRACT FROM AUTHOR]

Purpose: The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity. Methods: The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues. Results: The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%. Conclusion: CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer is still the most common cancer of the bladder tract and the ninth most common cancer in the world. Most people who get bladder cancer have nonmuscle invasive bladder cancer (NMIBC), which has a much lower death rate than muscle invasive bladder cancer. Urologists are now more interested in enbloc removal of bladder tumor (ERBT), but there are only a few small studies that look at hydrodissemination during ERBT. ERBT gives a lot of detrusor muscle samples (more than 95%) and good samples for figuring out what's wrong. So far, it hasn't been looked into whether second resections can be avoided. All energy tools, like lasers and electric cautery, have been used to do ERBT with the same positive effects on the patient and the cancer. Conclusions: The numbers show that there isn't a big difference between normal and perioperative morbidity transurethral resection of bladder tumors, but only a few of the papers used a structured way to group them. There are no conclusions that can be made about how ERBT affects recurrence. [ABSTRACT FROM AUTHOR]

Purpose: To compare the oncological outcomes between standard radical cystectomy (SRC) and organ-sparing cystectomy (OSC) in male patients diagnosed with bladder cancer. Methods: Patients with stage Ta-T3 bladder cancer who underwent OSC or SRC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The association between preoperative factors and the implementation of OSC was analyzed using logistic regression. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Patients' overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method. Subgroup analyses based on the T stage were also conducted. Results: A total of 7264 patients were included, with 96.8% (7033 patients) receiving SRC and 3.2% (231 patients) receiving OSC. Patients with higher T stages and high-grade tumors were less likely to undergo OSC. After PSM, OSC was associated with significantly worse OS and CSS than SRC. Subgroup analysis revealed that OSC did not lead to worse OS and CSS in non-muscle invasive bladder cancer and T2 stage patients, but it resulted in significantly worse outcomes in T3 stage patients. Conclusion: Our study indicates that OSC is associated with poorer oncological outcomes compared to SRC, particularly in patients with advanced-stage tumors. These findings suggest the need for stringent selection criteria for OSC in bladder cancer patients. Given the negative impact on prognosis, stage T3 should potentially be considered a contraindication for OSC. Further evidence is required to confirm these assertions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The ability of the Veterans Health Administration System to care for veterans with bladder cancer is influenced by the increased complexity of both veterans and the system's capacity to do so, which is determined by personnel and equipment allocation. Herein, we review the guidelines for bladder cancer management in the context of this population and highlight unique veteran characteristics that impact the delivery of bladder cancer care within the Veterans Health Administration System. There are opportunities for standardization and implementation, which can improve the quality of this care, and we summarize the questions for which coordinated research efforts may provide answers. [ABSTRACT FROM AUTHOR]

To investigate the cadence of recurrence in patients with low grade intermediate-risk non-muscle invasive bladder cancer (LG IR-NMIBC) based on clinical determinants. We aim to describe patterns in rates of recurrence to better inform surveillance regimens for this chronic, burdensome, and costly disease. Using baseline and follow-up data from participants in the West Midlands' (United Kingdom, UK) Bladder Cancer Prognosis Programme (BCPP), we assessed overall recurrence rate and recurrence-free intervals throughout the follow-up period for IR-NMIBC participants. Recurrence-free intervals were calculated using the Kaplan-Meier method. We identified 379 patients with G1/G2 pTa tumors classified as intermediate risk. Median age was 70 and 284/379 (75%) were male. The median follow-up time was 4.2 years (95% CI: 3.9-4.8). After 5 years of follow-up, 53% of patients had at least one recurrence. One-year recurrence-free survival (RFS) was 75% and 4-year RFS was 50%. The median time to or between 1st, 2nd, 3rd, 4th, and 5th sequential recurrences was 49, 19, 12, 14, and 10 months, respectively. Over half of patients with IR-NMIBC are destined to recur. Our data suggest that a subset of patients experience acceleration of recurrence over time and that this acceleration may serve as a potential kinetic biomarker for these individuals that could inform surveillance intervals and future treatment strategies. [ABSTRACT FROM AUTHOR]

Background: The predictive accuracy of the preoperative neutrophil-to-lymphocyte ratio (NLR) on the prognosis of patients with non-muscle-invasive bladder cancer (NMIBC) with intravesical Bacillus Calmette–Guérin immunotherapy (BCG) after transurethral resection of the bladder tumor (TURBT) remains unknown. Therefore, the current study performed a systematic review and meta-analysis to examine the relationship between preoperative NLR and the prognosis of patients with NMIBC with intravesical BCG immunotherapy. Methods: For this systematic review and meta-analysis, articles were retrieved from PubMed, Cochrane Library, Web of Science, and Embase databases from their inception to 14 May 2024. The role of NLR in predicting recurrence and progression in NMIBC was determined using pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Seven articles were included in this meta-analysis, involving 4,187 patients. An elevated NLR was significantly associated with recurrence (HR = 2.67, 95% CI = 1.34–5.32, P < 0.001) and progression (HR = 1.72, 95% CI = 1.13–2.60, P = 0.004) in patients with NMIBC with intravesical BCG immunotherapy. Conclusion: This meta-analysis demonstrated that elevated preoperative NLR levels were significantly associated with recurrence and disease progression in patients with NMIBC who underwent intravesical BCG immunotherapy after TURBT. Systematic review registration: https://inplasy.com/inplasy-2024-7-0058/ , identifier 202470058. [ABSTRACT FROM AUTHOR]

BCG is the standard of care for non-muscle invasive high-risk bladder cancer. Notwithstanding the high rate of cure, cancer may recur. A non-muscle invasive high-risk recurrence may be defined as BCG refractory or naïve. BCG refractory patients have been further divided into BCG unresponsive and BCG exposed. A recurrent high-risk bladder cancer within 1 year after BCG induction plus maintenance or two courses of BCG induction defines an unresponsive disease. Any recurrence after 24 months since induction and maintenance should be considered as BCG naïve. The remaining cases are BCG exposed. The standard of care for BCG exposed and naïve patients is another cycle of BCG in the first place, while radical cystectomy should be discussed as alternative with the patient. The preferred therapy for BCG unresponsive patients is radical cystectomy according to AUA or EAU guidelines. However, systemic immunotherapy with pembrolizumab or gene therapy with intravesical nadofaragene firadenovec may be administered for patients unfit or unwilling to undergo radical cystectomy with outcomes superior to intravesical docetaxel, gemcitabine or valrubicin. Our narrative review tries to elucidate BCG refractory definition and treatment specifically regarding alternative therapies to radical cystectomy yet approved or under investigation. The last years have been exciting regarding new developments in this field after a long period of stagnation. Unfortunately, data available on some alternative therapies are mainly limited mainly to Phase I or II studies with a lack of robust evidence, but a clear trend in future treatments has just been drawn. [ABSTRACT FROM AUTHOR]