Outcomes In Bladder Cancer Patients Research Articles

Abstract A021: The role of MGAT5 in sex-dependent regulation of CD8+ T cells in muscle-invasive bladder cancer

Abstract Biological sex significantly affects bladder cancer incidence and outcome. Although men have much greater incidence of bladder cancer than women, females tend to be diagnosed with more advanced tumors and have worse outcomes. The mechanisms driving these differences are likely multifactorial, with biological factors playing an important role, however, much of the biology underlying these differences is unknown. The immune system is a critical regulator of cancer biology, and immune features have been associated with bladder cancer grade, stage, progression, and response to therapies. Sex dramatically affects the immune system including anti-tumor immunity. However, how sex and immunity intersect to affect clinical outcomes in bladder cancer patients remains unclear. CD8+ T cells are a key part of anti-tumor immune responses and the importance of inhibitory receptors such as programmed cell death-1 (PD-1), is now well established as a mechanism restricting T cell responses in MIBC. However, there are a variety of other regulatory pathways that restrict their anti-tumor function, which have yet to be investigated. One such pathway involves alterations in protein glycosylation, which can affect T cell function at many levels. The activity of the glycosyltransferase N-acetylglucosaminyltransferase V (MGAT5), responsible for complex N-glycan branching, has been shown to regulate T cell function in autoimmunity and chronic viral infections, however, its role in regulating anti-tumor CD8+ T cell responses has yet to be explored. We assessed the activity of MGAT5 in circulating and tumor-infiltrating CD8+ T cells in mice using a panel of cell lines in a syngeneic orthotopic model of muscle-invasive bladder cancer (MIBC). We found that in all tumor models, MGAT5 activity was upregulated in tumor infiltrating CD8+ T cells compared with circulating cells. Furthermore, using high parameter flow cytometry, we assessed the activity of MGAT5 in CD8+ T cells from mice with bladder cancer induced by the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), and in patients with MIBC. In both mice and humans, we found that sex affects MGAT5 activity in memory CD8+ T cells, with females exhibiting decreased MGAT5 activity in these cells compared to males. The functional significance of altering MGAT5 activity in T cells was also assessed in vivo. To do this, chimeric mice were generated by mixed bone-marrow transplant resulting in mice with loss of Mgat5 in T cells. Bladder cancer was then induced using BBN, and morbidity (defined as either 10% weight loss in one week, 10% weight loss post-BBN, or humane endpoint), as a proxy for mortality, was assessed over time. In this model, male mice were protected from BBN-induced morbidity compared to female mice, and this protection was abrogated by homozygous or heterozygous loss of Mgat5 in T cells. Overall, our data suggest that sex-dependent regulation of MGAT5 activity in CD8+ T cells may be an important underlying factor affecting outcomes in bladder cancer. Citation Format: Morgan E. Roberts, Igor Moskalev, Peter C. Black. The role of MGAT5 in sex-dependent regulation of CD8+ T cells in muscle-invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A021.

Breaking Barriers: Modulation of Tumor Microenvironment to Enhance Bacillus Calmette–Guérin Immunotherapy of Bladder Cancer

Breaking Barriers: Modulation of Tumor Microenvironment to Enhance Bacillus Calmette–Guérin Immunotherapy of Bladder Cancer

Poorer Outcomes in Bladder Cancer Patients With Diabetes: A Systematic Review and Meta-analysis Addressing Over 226,472 Bladder Cancer Patients

Purpose: Diabetes mellitus, a frequent comorbid condition in cancer patients, has been shown to increase risk of all-site cancer mortality. This relationship has not been systematically studied in bladder cancer patients. This systematic review and meta-analysis aimed to identify, evaluate, and synthesize available evidence on the relationship between history of diabetes and outcomes in bladder cancer patients.Materials and Methods: Systematic searches interrogated OVID MEDLINE, Embase, Web of Science, Google Scholar, and Cochrane Library to identify scholarly reports relating diabetes to all-cause mortality, bladder cancer-specific mortality, recurrence, and progression in bladder cancer patients. After critical review, meta-analysis was used to quantitively synthesize qualifying data and assess potential influence of publication bias, clinical heterogeneity, and residual confounding.Results: We synthesized data on over 226,472 patients treated with curative intent uniquely represented in 28 studies that met quality metrics. Having diabetes was positively associated with each outcome. Hazard ratio estimates were indistinguishable for mortality from any cause, 1.22 (95% confidence interval [CI], 1.12–1.33) and bladder cancer-specific mortality, 1.28 (95% CI 1.17–1.41) and notably stronger in patients with muscle-invasive and high-risk non–muscle-invasive bladder cancer, 1.32 (95% CI, 1.15–1.50) and 1.48 (95% CI, 1.06–2.06). Neither publication bias, systematic error, nor confounding by factors such as smoking or obesity is likely to explain the observed associations.Conclusions: Bladder cancer patients with diabetes experience elevated mortality that is not explained by diabetes-related comorbidities or complications. Future research should explore type, severity, and duration of diabetes in relation to unfavorable bladder cancer outcomes.

Identification of RNA methylation-related lncRNAs for prognostic assessment and immunotherapy in bladder cancer-based on single cell/Bulk RNA sequencing data.

Bladder cancer is a malignancy characterized by significant heterogeneity. RNA methylation has received an increasing amount of attention in recent years. RNA data were collected from the GEO database, and cell subsets were classified according to specific cell markers. Epithelial, immunological, and fibroblast cells were clustered individually to explore the tumor heterogeneity. To distinguish between malignant and benign cells, the InferCNV R package was employed. The monocle2 R package was used for pseudotime analysis. The Decouple R package was used for transcription factor analysis of each cell subgroup, and PROGENy was used to predict the activity of pathways related to tumors. The target lncRNA was screened for model construction. In addition, the qPCR experiment was used to detect the transcription level of lncRNA. Epithelial cells, fibroblasts, and T cells significantly differ in tumor and normal tissues. The lncRNAs related to m6A/m5C/m1A were intersected to construct the model. Finally, six model lncRNAs (PSMB8-AS1, THUMPD3-AS1, U47924.27, XXbac-B135H6.15, MIR99AHG, and C14orf132) were screened. High-risk individuals were shown to have a better prognosis. qPCR experiments showed that the model lncRNA was differentially expressed between normal and tumor cells. Immunotherapy will be more effective in treating individuals with lower risk than those with higher risk using 4 candidate drugs. The prognostic m6A/m5C/m1A-related lncRNA model was constructed for evaluating the clinical outcomes of bladder cancer patients and guiding clinical medication.

CircRNA TATA-box binding protein associated factor 15 acts as an oncogene to facilitate bladder cancer progression through targeting miR-502-5p/high mobility group box 3.

Circular RNAs (circRNAs) are key in regulating bladder cancer progression. This study explored the effects of circRNA TATA-box binding protein associated factor 15 (circTAF15) on bladder cancer progression. We enrolled 80 bladder cancer patients to examine the relationship between circTAF15 expression and clinical features. The function of circTAF15 on bladder cancer cell viability, proliferation, migration, invasion, and glycolysis was monitored by cell counting kit-8 assay, 5-Ethynyl-2'-deoxyuridine experiment, Transwell experiment, and glycolysis analysis. Dual luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation assay were used to verify the binding between circTAF15 and miR-502-5p or between miR-502-5p and high mobility group box 3 (HMGB3). circTAF15 effect on in vivo growth of bladder cancer was investigated by xenograft tumor experiment. Quantitative real-time polymerase chain reaction, Western blot, and immunohistochemistry were implemented to investigate the expression levels of genes. circTAF15 was upregulated in bladder cancer patients, associated with unfavorable outcomes. circTAF15 knockdown attenuated bladder cancer cell viability, proliferation, migration, invasion, epithelial-mesenchymal transition, and glycolysis. circTAF15 suppressed miR-502-5p expression, and miR-502-5p inhibited HMGB3 expression. Low miR-502-5p expression was associated with unfavorable outcomes in bladder cancer patients. miR-502-5p silencing and HMGB3 overexpression counteracted the inhibition of circTAF15 knockdown on the malignant phenotype of bladder cancer cells. circTAF15 knockdown attenuated the in vivo growth of bladder cancer cells. circTAF15 enhanced the progression of bladder cancer through upregulating HMGB3 via suppressing miR-502-5p. circTAF15 may be a novel target to treat bladder cancer in the future.

Abstract B051: GSTT2 modulates the bladder tumor environment and response to BCG Immunotherapy

Abstract The purpose of this study was to elucidate the impact of Glutathione -S-transferase Theta 2 (GSTT2) loss on the response of bladder tumors to Mycobacterium Bovis, Bacillus Calmette Guerin (BCG) immunotherapy. GSTT2 gene expression is controlled by a promoter deletion that occurs frequently in 25-29% of Asians and 41% of Caucasians. The GSTT2 promoter deletion correlated with better response to BCG therapy in a retrospective analysis of patients who received less BCG therapy. To understand this response, we generated GSTT2 knockout mice to elucidate the role of GSTT2 in BCG immunotherapy. Female C57BL/6J mice from GSTT2 wildtype (WT) and KO backgrounds were orthotopically implanted with MB49-PSA cells (murine MB49 cells secreting human PSA). To view the impact of GSTT2 loss on BCG immunotherapy, mice were treated with only 4 instillations of BCG Tokyo. This therapeutic schedule would not result in a high cure rate and but was chosen as we expected it to provide insights into the anti-tumor response. Mice were treated weekly with intravesical BCG Tokyo instillations and tumor growth was monitored by urinary PSA secretion. Final tumor presence was confirmed by real-time PCR analysis of PSA gene expression. One day after the last instillation the bladders (n=7) were harvested for single cell RNA sequencing (Parse Biosciences). Cell clusters were identified by their gene expression profiles. The response to BCG in terms of the cure rate was similar in KO and WT mice (cure rate of 18-20%) but several genes were differentially expressed. Genes with a Log2FC value of +1.5 in KO mice (Peak1, Rpph1, Gphn and Gm19551) and -1.5 in KO (Rora, Tshz2, Sh3gl2, Ankfn1, Rbms3, Naaladl2, Prkn, Mecom, Fmo5, Saa3, Tmprss2, C3, Gm10800 and Gm10801) relative to WT mice were examined. Based on the literature, these genes either block tumor progression (Rora, Tshz2, Sh3gl2 and Gphn); promote tumor progression (Ankfn1, Rbms3, Naaladl2, Prkn, Mecom, Fmo5, Tmprss2, Saa3, C3, Peak1, Rpph1) or modulate immune cells (C3, Saa3 and Rpph1). The majority of these genes were not previously associated with bladder cancer. Interrogation of the TCGA database showed that high expression of Gphn, Peak1 and GSTT2 correlated with poorer outcomes in bladder cancer patients in terms of disease-free survival (HR=1.9 log rank p=0.00038). While expression of the genes downregulated in KO mice and GSTT2 resulted in better outcomes with lower expression of all the genes (HR=1.4, log rank p=0.042). This data indicates that the loss of GSTT2 expression impacts the response of tumors to BCG immunotherapy, primarily by modulating the expression of genes associated with cancer progression and the expression of genes in multiple cell types. Given the common loss of GSTT2 expression in man this gene may be a parameter that should be evaluated in further detail in patients receiving BCG immunotherapy. Citation Format: Ratha Mahendran, Mugdha Vijay Patwardhan, Qin Kane Toh, Edmund Chiong. GSTT2 modulates the bladder tumor environment and response to BCG Immunotherapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor Immunology and Immunotherapy; 2023 Oct 1-4; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2023;11(12 Suppl):Abstract nr B051.

Cluster of differentiation 147 (CD147) as potential membrane protein biomarker for bladder cancer cells

Studies reveal that alterations in membrane protein (MP) patterns are associated with underlying drug resistance to chemotherapy. Therefore, the tryptic-digested MPs from the bladder cancer cell line were subjected to global proteomics using LC-MS/MS to identify the highly expressed potential MPs in bladder cancer cells. Our findings revealed the identification of MP biomarkers, CD147, and caveolin-1. Immunocytochemistry analysis confirmed the presence of CD147 on the cell membrane, while caveolin-1 showed positive signals without apparent staining on the membrane, suggesting its existence in multiple locations. Western blot analysis confirmed the higher expression of CD147 in non-invasive (RT 112) and metastatic (UM-UC-13) bladder cancer cells compared to invasive bladder cancer cells (5637 and J82), suggesting its potential as an MP biomarker for both of the former subtypes. The identified MPs could be used as drug therapy targets aimed at improving drug sensitivity and enhancing treatment outcomes in bladder cancer patients. SignificanceIdentification of the membrane proteins associated with bladder cancer recurrence is crucial to understanding the mechanisms underlying the drug resistance to chemotherapy.

Thermoresponsive mucoadhesive hydrogel based on Pluronic F127/thiolated glycol chitosan for intravesical administration of celecoxib/gemcitabine

In recent years, mucoadhesivein situ gelling formulations for intravesical application have been studied to improve the therapeutic outcomes of bladder cancer patients. Here, we carefully tuned a Pluronic F127-based thermoresponsive gel using two mucoadhesive thiolated derivatives of glycol chitosan, S-preactivated N-acetylcysteine (NAC)- and glutathione (GSH)-glycol chitosan (GC). The gel was loaded with a combination of Gemcitabine (GEM) and Celecoxib (CEX), and the aqueous solubility of the latter was increased for a synergic influence between Pluronic and the inclusion complex of 2-Hydroxypropyl-β-cyclodextrin/CEX. The effect of the inclusion complex of two mucoadhesive polymers on rheological features of Pluronic based gels was highlighted to select the best performance. Finally, ex-vivo retention studies, mucosal penetration and in-vitro drug release of the selected systems were monitored for 24 h, providing enhanced retention properties (50% after 6h) and continued drug release.

Body composition as a predictor of oncological outcome in patients with non-muscle-invasive bladder cancer receiving intravesical instillation after transurethral resection of bladder tumor.

Body status, categorized as sarcopenia or obesity and assessed using body mass index and body composition, affects the outcome of bladder cancer patients. However, studies comparing disease progression, recurrence, or overall survival in patients with non-muscle-invasive bladder cancer (NMIBC) with different body compositions are lacking. Therefore, we conducted a retrospective study to identify the impact of body composition, sarcopenia, and obesity on the oncological prognosis of patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) with Bacillus Calmette-Guerin (BCG) intravesical instillation (IVI). Patients with NMIBC who had undergone TURBT with adjuvant IVI with BCG from March 2005 to April 2021 were included. Body composition parameters were evaluated using computed tomography images of the third lumbar vertebrae and further categorized by sarcopenia and obesity. Oncological outcomes including recurrence-free survival (RFS), progression-free survival, and overall survival (OS) after treatment were analyzed. A total of 269 patients were enrolled. Subcutaneous adipose tissue (SAT) density was a significant predictor of RFS, whereas psoas muscle density was a significant predictor of OS in the multivariate analysis. Patients with sarcopenia but without obesity tolerated significantly fewer BCG IVIs than patients without sarcopenia or obesity. Patients with sarcopenia had poorer RFS and OS than those without sarcopenia. In contrast, patients with obesity had better OS than those without obesity. Body composition parameters, including SAT density and psoas muscle density, emerged as significant predictors of OS and RFS, respectively. Hence, our findings indicate that body composition is a helpful measurement to assess the oncological outcomes of patients with NMIBC.

MicroRNA-30c-5p arrests bladder cancer G2/M phase and suppresses its progression by targeting PRC1-mediated blocking of CDK1/Cyclin B1 axis

BackgroundMicroRNAs (miRNAs) play a critical role in cancer development and progression, the dis-regulation of miR-30c-5p has been observed in various malignant tumors but no research was done in bladder cancer (BCa). This study aims to investigate the downregulation of miR-30c-5p in BCa, and examine its mechanism and prognostic significance. MethodsBioinformatics analyses and clinical specimens were employed to investigate the relationship between miR-30c-5p and clinical information in BCa patients. The expression levels of miR-30c-5p and its target gene were assessed by real-time PCR and western blot. Cell viability was evaluated through clonogenic capacity, CCK-8, and EdU assays. Cell cycle distribution and cell apoptosis were determined by flow cytometry. The anti-tumor effect of miR-30c-5p was also validated in animal models. ResultsThe expression levels of miR-30c-5p were significantly decreased in both bladder tumor tissue and BCa cell lines. Low miR-30c-5p expression was found to be correlated with unfavorable TNM stages and poor prognosis. Over-expressing miR-30c-5p was observed to hinder BCa cell growth, migration, and invasion abilities and causing cell cycle arrest. Mechanistically, miR-30c-5p directly binds and suppresses PRC1, thereby blocking the CDK1/Cyclin B1 axis in BCa, thus impairing BCa cell viability and inducing cell cycle arrest at G2/M phase. ConclusionDown-regulated miR-30c-5p promotes BCa through its target gene PRC1, miR-30c-5p is a favorable biomarker for predicting clinical outcomes in BCa patients and has the potential to be a therapeutic target.

A novel genes-based signature with prognostic value and predictive ability to select patients responsive to Atezolizumab treatment in bladder cancer: an analysis on data from real-world studies.

There is a lack of molecular markers that effectively predict response to treatment with immune checkpoint inhibitors in patients with uroepithelial bladder carcinoma. The purpose of this study was to explore molecular markers that effectively predict the efficacy of Atezolizumab in the treatment of uroepithelial bladder carcinoma based on real-world clinical trial data. Gene expression and clinical information of two groups of patients in two datasets, IMvigor210 and GSE176307, who were treated effectively and ineffectively with the programmed cell death 1 ligand 1 (PD-L1) inhibitor Atezolizumab, were obtained. Bioinformatic methods were used to screen out differentially expressed genes and detect the correlation between their expression and immune-related indicators. Subsequently, we assessed the ability of differentially expressed genes to predict the therapeutic response and prognosis of bladder cancer patients following Atezolizumab treatment. A total of 2 differentially expressed genes, CXC motif chemokine ligand 9 (CXCL9) and CXC motif chemokine ligand 10 (CXCL10) [all P<0.05, log|fold change (FC)| >1], which were co-upregulated, were screened as study targets. In The Cancer Genome Atlas (TCGA) database, CXCL9/10 mRNA expression was positively correlated with both PD-L1 and tumor mutation burden (TMB) (all P<0.05). In the IMvigor210 dataset, the area under the receiver operating characteristic (ROC) curve for CXCL9, CXCL10 and PD-L1 mRNA expression to predict response to treatment with Atezolizumab were 0.645, 0.636 and 0.566, respectively; And CXCL9/10 mRNA was effective in predicting overall survival in patients receiving treatment (all P<0.05). In the GSE176307 dataset, the area under the ROC curve for CXCL9, CXCL10 and PD-L1 mRNA expression to predict response to treatment with Atezolizumab were 0.829, 0.829 and 0.765, respectively; And CXCL9/10 mRNA was not effective in predicting overall survival in patients receiving treatment (all P>0.05). The mRNA expression levels of CXCL9/10 have the potential to serve as a molecular marker for predicting the therapeutic response and overall survival outcomes of bladder cancer patients treated with Atezolizumab.

Clinical Outcomes of Pelvic Lymph Node Dissection Before Versus After Robot-Assisted Laparoscopic Radical Cystectomy.

Objective: The purpose of this study was to compare the clinical outcomes of bladder cancer patients treated with extended pelvic lymph node dissection (ePLND) before or after cystectomy under robotic-assisted radical cystectomy (RARC). Methods: A retrospective study to identify 348 patients with bladder cancer who underwent RARC was performed. Of the patients, 152 (42.8%) underwent ePLND before radical cystectomy (RC) (group A) and 196 (56.3%) underwent ePLND after RC (group B). The clinical, pathological, and overall survival were compared. Results: The total and RC operation time in Group A (total: 130.68 ± 29.25 minutes, RC: 59.45 ± 28.63 minutes) were both shorter than Group B (total: 154.17 ± 38.18 minutes, RC: 94.81 ± 41.21 minutes) (P < .05). However, no significant difference in time of ePLND. The estimate blood loss (EBL) of RC part and total operation (RC+ePLND) in group A was less than group B (both P < .05), while the ePLND part did not show significance. The result of vascular and nerve injury and surgical drain withdrawal time were similar in two groups. The total number of lymph nodes in group A was fewer than group B (16 versus 26; P < .05). Moreover, the number of bilateral internal iliac and presacral lymph nodes of group A was fewer than group B significantly, whereas the number of bilateral external iliac, common iliac, and obturator lymph nodes was similar in two groups. The lymph node density of group A was significantly lower than group B. The median follow-up of all patients was 33.0 months. Importantly, the survival of group B was better than group A (hazard ratio: 1.412; 95% confidence interval: 1.004-1.987; P = .048). Conclusions: Performing ePLND before RC reveals better result on operation time and EBL, while, when ePLND after RC, the total number of lymph nodes dissected is more and the survival is better. It recommended ePLND be performed before RC, and it is necessary to recheck the internal iliac and presacral area after cystectomy.

LncRNA-mediated ceRNA network in bladder cancer.

Bladder cancer is a common disease associated with high rates of morbidity and mortality. Although immunotherapy approaches such as adoptive T-cell therapy and immune checkpoint blockade have been investigated for the treatment of bladder cancer, their off-target effects and ability to affect only single targets have led to clinical outcomes that are far from satisfactory. Therefore, it is important to identify novel targets that can effectively control tumor growth and metastasis. It is well known that long noncoding RNAs (lncRNAs) are powerful regulators of gene expression. Increasing evidence has shown that dysregulated lncRNAs in bladder cancer are involved in cancer cell proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). In this review, we focus on the roles and underlying mechanisms of lncRNA-mediated competing endogenous RNA (ceRNA) networks in the regulation of bladder cancer progression. In addition, we discuss the potential of targeting lncRNA-mediated ceRNA networks to overcome cancer treatment resistance and its association with clinicopathological features and outcomes in bladder cancer patients. We hope this review will stimulate research to develop more effective therapeutic approaches for bladder cancer treatment.

Apoptosis related genes mediated molecular subtypes depict the hallmarks of the tumor microenvironment and guide immunotherapy in bladder cancer

Apoptosis has been discovered as a mechanism of cell death. The purpose of this study is to identify the diagnostic signature factors related to bladder cancer (BLCA) through apoptosis related genes (ARGs). Clinicopathological parameters and transcriptomics data of 1,440 BLCA patients were obtained from 7 datasets (GSE13507, GSE31684, GSE32548, GSE32894, GSE48075, TCGA-BLCA, and IMvigor210). We first identified prognosis-related ARGs in BLCA and used them to construct two ARGs molecular subtypes by using consensus clustering algorithm. By using principal component analysis algorithms, a ARGscore was constructed to quantify the index of individualized patient. High ARGscore correlated with progressive malignancy and poor outcomes in BLCA patients. High ARGscore was associated with higher immune cell, higher estimate scores, higher stromal scores, higher immune scores, higher immune checkpoint, and lower tumor purity, which was consistent with the “immunity tidal model theory”. Preclinically, BLCA immunotherapy cohorts confirmed patients with low ARGscore demonstrated significant therapeutic advantages and clinical benefits. These findings contribute to our understanding of ARGs and immunotherapy in BLCA. The ARGscore is a potentially useful tool to predict the prognosis and immunotherapy in BLCA.

V08-03 INDIANA POUCH CONTINENT CUTANEOUS URINARY DIVERSION AFTER ROBOTIC-ASSISTED RADICAL CYSTECTOMY: A 16-YEAR EXPERIENCE

You have accessJournal of UrologyCME1 Apr 2023V08-03 INDIANA POUCH CONTINENT CUTANEOUS URINARY DIVERSION AFTER ROBOTIC-ASSISTED RADICAL CYSTECTOMY: A 16-YEAR EXPERIENCE Albert Kim and Kevin Chan Albert KimAlbert Kim More articles by this author and Kevin ChanKevin Chan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003306.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Continent urinary diversion after radical cystectomy is an underutilized option even at high-volume centers with studies demonstrating socio-economic, geographical, and gender disparities. Efforts to optimize utilization of continent diversion must concentrate on changing perceptions regarding feasibility and accurate reporting of complications.The objective of this study is to report long-term clinical outcomes in bladder cancer patients receiving an Indiana pouch continent cutaneous urinary diversion (CCUD) after robot-assisted radical cystectomy. METHODS: After Institutional Review Board approval, a prospectively maintained bladder cancer database was queried for patients with T1-T4, N0-N1, M0 bladder cancer undergoing radical cystectomy with CCUD at a tertiary referral center from 2004 to 2020. Complications at 30- and 90-days were recorded according to the Clavien-Dindo classification. Continence rates were recorded by manual chart review. RESULTS: A total of 97 patients were included with a median follow-up of 93 months. Clinically, 91.8% had £T2 disease and 29.9 % received neoadjuvant chemotherapy. The median length of surgery was 8.0 hours, length of hospital stay was 8.3 days, and urinary continence rate was 99.0%. The overall complication rate was 73.2% and 76.5% at 30- and 90-days respectively. Most complications were low grade (Clavien I or II). Acute blood loss anemia and symptomatic urinary tract infection were the most common low grade complications. The major complication rate was 17.5% at 30-days and 22.7% at 90-days. The most common major complications were abdominal infection requiring percutaneous drain placement, Clavien Grade III, and uretero-colonic stricture requiring percutaneous nephrostomy tube placement and surgical revision, Clavien Grade III. The readmission rate was 21.4% and median overall survival was 108 months. CONCLUSIONS: CCUD provides exceptional functional outcomes with acceptable complication rates compared to other diversion types. Source of Funding: NONE Disclosures: NONE © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e749 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Albert Kim More articles by this author Kevin Chan More articles by this author Expand All Advertisement PDF downloadLoading ...

MP22-10 IMPACT OF SMOKING ON LONGITUDINAL HEALTH RELATED QUALITY OF LIFE MEASURES AMONG BLADDER CANCER SURVIVORS

You have accessJournal of UrologyCME1 Apr 2023MP22-10 IMPACT OF SMOKING ON LONGITUDINAL HEALTH RELATED QUALITY OF LIFE MEASURES AMONG BLADDER CANCER SURVIVORS Hannah Kay, Sarah Silver, Ram Basak, Kimberly Shoenbill, Deborah Usinger, Adam Goldstein, Angela Smith, Richard Matulewicz, Ronald C. Chen, and Marc Bjurlin Hannah KayHannah Kay More articles by this author , Sarah SilverSarah Silver More articles by this author , Ram BasakRam Basak More articles by this author , Kimberly ShoenbillKimberly Shoenbill More articles by this author , Deborah UsingerDeborah Usinger More articles by this author , Adam GoldsteinAdam Goldstein More articles by this author , Angela SmithAngela Smith More articles by this author , Richard MatulewiczRichard Matulewicz More articles by this author , Ronald C. ChenRonald C. Chen More articles by this author , and Marc BjurlinMarc Bjurlin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003247.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cigarette smoking is the most common risk factor for the development of bladder cancer. However, there is a paucity of data characterizing the relationship between smoking status and longitudinal Health Related Quality of Life (HRQoL) outcomes in bladder cancer patients. We sought to examine the association between current smoking status and HRQoL measures among bladder cancer patients following their cancer diagnosis. METHODS: We performed a longitudinal, prospective study on a sample of patients aged ≥18 years diagnosed with bladder cancer in North Carolina from 2014-2015. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire core instrument (QLQ-C30) was administered at 3, 12, and 24 months after bladder cancer diagnosis. This questionnaire has been validated in diverse samples of cancer patients. The main exposure variable was current smoking status, assessed at 3, 12, and 24 months after bladder cancer diagnosis. We analyzed mean differences for each outcome between exposure groups with linear regression using Generalized Estimating Equations (GEE). RESULTS: A total of 167 bladder cancer patients completed at least one survey. Of those, 154 participated in later surveys. A total of 125 patients who did not smoke completed surveys at 3, 108 at 12, and 86 at 24 months. A total of 28 patients who smoked completed surveys at 3, 23 at 12, and 25 at 24 months. Bladder cancer patients who smoked had significantly worse HRQoL measures in the domains of physical function (mean difference (MD) = 6.78, p < .05), emotional function (MD = 6.06, p < .05), fatigue (MD = -7.68, p < .05), and financial difficulties (MD = -10.20, p < .05). When controlling for time, stage, demographic covariates, and treatment type, emotional function (MD = 6.00) and fatigue (MD = -6.98) remained significantly different (Table 1). CONCLUSIONS: Bladder cancer patients who smoke have significantly worse HRQoL scores in the domains of physical function, emotional function, and fatigue. These results underscore the need to treat smoking as an essential component of bladder cancer care. Future work should implement smoking interventions that are directed at patient goals with respect to their unique values regarding life quality. Source of Funding: UNC Lineberger Comprehensive Cancer Center University Cancer Research Fund © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e300 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hannah Kay More articles by this author Sarah Silver More articles by this author Ram Basak More articles by this author Kimberly Shoenbill More articles by this author Deborah Usinger More articles by this author Adam Goldstein More articles by this author Angela Smith More articles by this author Richard Matulewicz More articles by this author Ronald C. Chen More articles by this author Marc Bjurlin More articles by this author Expand All Advertisement PDF downloadLoading ...

Optimizing surgical outcomes in bladder cancer patients undergoing radical cystectomy.

To evaluate predictors of high-quality surgery and their effect on surgical outcomes in patients with bladder cancer undergoing radical cystectomy. A systematic and thorough review was performed to identify the most recent literature on current optimal management and predictors of high-quality surgery for patients undergoing radical cystectomy. Muscle-invasive bladder cancer is an aggressive cancer requiring efficient and high-quality surgery in order to achieve the best oncological outcomes. Negative surgical margins, number of lymph nodes resected, lymph node dissection template, and surgical volume have been associated with improved oncologic outcomes. Robotic radical cystectomy continues to evolve and recent randomized controlled trials have shown that oncological outcomes are non-inferior when compared to the open technique. Regardless of approach, surgical technique should continually be evaluated and refined to optimize outcomes in patients undergoing radical cystectomy.

Depletion of PSMD14 suppresses bladder cancer proliferation by regulating GPX4.

The aim of this study was to investigate the role of deubiquitinase (DUB) 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in patients with bladder cancer. From 2016 to 2018, 181 patients diagnosed with primary bladder cancer at the Affiliated Hospital of Qingdao University were recruited. The expression of PSMD14 in bladder cancer tissues was tested by immunochemistry. The association between PSMD14 expression and clinical and pathological data and outcomes of bladder cancer patients was determined. Overexpression and knockdown cells were constructed to evaluate the effects of PSMD14 on proliferation of bladder cancer cells. Our results showed that PSMD14 was significantly overexpressed in bladder cancer tissues compared to adjacent non-tumor tissues (76.24% vs 23.76%, P = 0.02). The expression of PSMD14 was significantly higher in patients with larger tumor diameters (85.14% vs 70.09%, P = 0.019) and patients with a family history of cancer (92.16% vs 70.00%, P = 0.002). Patients with high expression of PSMD14 had poor disease-free survival (DFS) (HR = 2.89, 95% CI [1.247-6.711], P = 0.013). Gain and loss of function experiments demonstrated that PSMD14 deficiency inhibited bladder cancer cell proliferation. Additionally, depletion of PSMD14 suppressed bladder cancer cell growth via down-regulation of GPX4, and the promotion of PSMD14-induced cell growth was observably reversed by the GPX4 inhibitor RSL3. We determined that PSMD14 is highly expressed in bladder cancer tissues, and that PSMD14 expression correlated with poor disease-free survival. Depletion of PSMD14 could inhibit the proliferation of bladder cancer cells through the downregulation of GPX4. Therefore, PSMD14 may be an effective target for the treatment of bladder cancer.

AB0 blood groups and oncological and functional outcomes in bladder cancer patients treated with radical cystectomy.

We investigated AB0 blood groups prevalence according to preoperative and pathological tumor characteristics, and their association with oncological outcomes, and renal function decline in a contemporary large cohort of bladder cancer (BCa) patients, who underwent radical cystectomy (RC) at a tertiary referral center. We retrospectively evaluated data of patients with histologically confirmed and clinically non metastatic BCa, who underwent RC between 2014 and 2021 at our Institution. Kaplan-Meier (KM) plots and Cox regression (CR) models tested the relationship between AB0 blood groups and local recurrence-, metastasis-, cancer specific mortality-, and overall mortality-free survival. Logistic regression (LR) models tested the association between AB0 blood groups and renal function decline, defined as an estimated Glomerular Filtration Rate (eGFR) < 60 mL/min, at post-operative day 1, discharge and 6- months of follow-up. Of 301 included patients, 128 (42.5%) had group A, 126 (41.9%) had group 0, 28 (9.3%) had group B, and 19 (6.3%) had group AB. Patients with group 0 developed higher rates of muscle- invasive BCa (p = 0.028) with high-grade features (p = 0.005) at last bladder resection, and less frequently received preoperative immunotherapy with Bacillus of Calmette-Guerin (p = 0.044), than their non-0 counterparts. Additionally, these patients harbored more advanced pathologic tumor stage at RC (p = 0.024). KM plots showed no differences among all tested cancer control outcomes between AB0 blood groups (p > 0.05 in all cases). Patients with group AB presented the lowest median eGFR at each time point. In multivariable LR analyses addressing renal function decline, group AB was independently associated with eGFR< 60 mL/min at discharge (Odds Ratio: 4.28, p = 0.047). Among AB0 blood groups, patients with group 0 exhibited the most aggressive tumor profile. However, no differences were recorded in recurrence or survival rates. Group AB independently predicted renal function decline at discharge.

Fibronectin 1 as a Key Gene in the Genesis and Progression of Cadmium-Related Bladder Cancer.

Exposure to cadmium (Cd), a non-essential heavy metal, leads to the malignant transformation of urothelial cells and promotes bladder cancer (BC) development, but the mechanisms are unclear. Therefore, we aimed to explore the possible molecules associated with Cd-related BC. By analyzing and mining biological big data in public databases, we screened genes associated with the malignant transformation of uroepithelial cells caused by Cd and further screened the key gene associated with BC prognosis from these genes. The possible roles of the key gene in BC progression were then further explored through biological big data analysis and cellular experiments. Data mining yielded a total of 387 malignant transformation-related genes, which were enriched in multiple cancer-related signaling pathways, such as cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, and Jak-STAT signaling pathway. Further screening identified Fibronectin 1 (FN1) as the key gene. High expression of FN1 was associated with the advanced pathologic stage, T stage, N stage, and M stage and predicted an unfavorable outcome in BC patients. FN1 expression was positively associated with the infiltration of several types of immune cells, particularly tumor-associated macrophages and cancer-associated fibroblasts. Overexpression of FN1 could be detected in Cd-treated urothelial cells and BC cell lines. Interestingly, silencing of FN1 impaired the proliferation and invasive capacity of BC cells. In conclusion, the present study provides new insight into the mechanism of Cd-related BC. FN1 might be a prognostic marker and therapeutic target for BC. Future studies are needed to confirm these results.