A population-based registry cohort study on the correlation between bladder-intact event-free survival and overall survival in cystectomy-ineligible/refusal muscle-invasive bladder cancer patients in Sweden.

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Global burden of benign prostatic hyperplasia, urinary tract infections, urolithiasis, bladder cancer, kidney cancer, and prostate cancer from 1990 to 2021.

BACKGROUND: The burden of common urologic diseases, including benign prostatic hyperplasia (BPH), urinary tract infections (UTI), urolithiasis, bladder cancer, kidney cancer, and prostate cancer, varies both geographically and within specific regions. It is essential to conduct a comprehensive and precise assessment of the global burden of urologic diseases. METHODS: We obtained data on incidence, prevalence, mortality, and disability-adjusted life-years (DALYs) for the aforementioned urologic diseases by age, sex, location, and year from the Global Burden of Disease (GBD) 2021. We analyzed the burden associated with urologic diseases based on socio-demographic index (SDI) and attributable risk factors. The trends in burden over time were assessed using estimated annual percentage changes (EAPC) along with a 95% confidence interval (CI). RESULTS: In 2021, BPH and UTI were the leading causes of age-standardized incidence rate (ASIR) and age-standardized prevalence rate (ASPR), with rates of 5531.88 and 2782.59 per 100,000 persons, respectively. Prostate cancer was the leading cause of both age-standardized mortality rate (ASMR) and age-standardized DALYs rate (ASDR), with rates of 12.63 and 217.83 per 100,000 persons, respectively. From 1990 to 2021, there was an upward trend in ASIR, ASPR, ASMR, and ASDR for UTI, while urolithiasis showed a downward trend. The middle and low-middle SDI quintile levels exhibited higher incidence, prevalence, mortality, and DALYs related to UTI, urolithiasis, and BPH, while the high and high-middle SDI quintile levels showed higher rates for the three cancers. The burden of these six urologic diseases displayed diverse age and sex distribution patterns. In 2021, a high body mass index (BMI) contributed to 20.07% of kidney cancer deaths worldwide, while smoking accounted for 26.48% of bladder cancer deaths and 3.00% of prostate cancer deaths. CONCLUSIONS: The global burden of 6 urologic diseases presents a significant public health challenge. Urgent international collaboration is essential to advance the improvement of urologic disease management, encompassing the development of effective diagnostic screening tools and the implementation of high-quality prevention and treatment strategies.

Prognostic value of nucleotide excision repair and translesion DNA synthesis proteins in muscle-infiltrating bladder carcinoma.

BACKGROUND: Cisplatin (CDDP) remains a key agent in the treatment of muscle-infiltrating bladder carcinoma (MIBC). However, a proportion of MIBC patients do not respond to chemotherapy, which may be caused by the increased repair of CDDP-induced DNA damage. The purpose of this study was to explore the prognostic value of proteins involved in nucleotide excision repair (NER) and translesion DNA synthesis (TLS) in MIBC patients. METHODS: This is a retrospective analysis of 86 MIBC patients. The XPA, XPF, XPG, ERCC1, POLI, POLH and REV3L proteins were stained in primary bladder tumors and their levels were analyzed both in the total cohort and in a subgroup with metastatic urothelial carcinoma (mUC) that received gemcitabine and CDDP as a first-line therapy. Both cohorts were divided by percentage of cancer cells stained positive for each protein into subgroups with high and low expression. In the same manner, the combined expression of NER (XPA + ERCC1 + XPF + XPG) and TLS (POLI + POLH + REV3L), as the whole pathways, was analyzed. RESULTS: Mortality was 89.5% at the median follow-up of 120.2 months. In the total cohort, patients with tumors stained positive for XPA, XPG and POLI had significantly worse overall survival (OS) compared to those with negative staining [hazard ratio (HR) = 0.60, 0.62 and 0.53, respectively]. Both XPG and POLI were independent prognostic factors in multivariate analyses (MVA). In addition, an increase in NER and TLS pathway expression was significantly associated with worse OS in the total cohort (HR = 0.54 and 0.60, respectively). In the mUC subgroup, high POLI expression was associated with significant deterioration of OS (HR = 0.56) in univariate analyses, and its independent prognostic value was shown in MVA. CONCLUSIONS: Our study showed significant correlations between the tumor expression of XPG and POLI, as well as NER and TLS as the whole pathways, and inferior OS. Hence, they could constitute prognostic biomarkers and potentially promising therapeutic targets in MIBC. However, a prospective trial is required for further validation, thereby overcoming the limitations of this study.

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

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

The disease burden of bladder cancer and its attributable risk factors in five Eastern Asian countries, 1990-2019: a population-based comparative study.

BACKGROUNDS: The study aimed to estimate bladder cancer burden and its attributable risk factors in China, Japan, South Korea, North Korea and Mongolia from 1990 to 2019, to discuss the potential causes of the disparities. METHODS: Data were obtained from the Global Burden of Disease Study 2019. The annual percent change (APC) and average annual percent change (AAPC) were calculated by Joinpoint analysis, and the independent age, period and cohort effects were estimated by age-period-cohort analysis. RESULTS: In 2019, the highest incidence (7.70 per 100,000) and prevalence (51.09 per 100,000) rates of bladder cancer were in Japan, while the highest mortality (2.31 per 100,000) and DALY rates (41.88 per 100,000) were in South Korea and China, respectively. From 1990 to 2019, the age-standardized incidence and prevalence rates increased in China, Japan and South Korea (AAPC > 0) and decreased in Mongolia (AAPC < 0), while mortality and DALY rates decreased in all five countries (AAPC < 0). Age effects showed increasing trends for incidence, mortality and DALY rates, while the prevalence rates increased first and then decreased in older groups. The cohort effects showed downward trends from 1914-1918 to 2004-2008. Smoking was the greatest contributor and males had the higher burden than females. CONCLUSION: Bladder cancer was still a major public health problem in East Asia. Male and older population suffered from higher risk, and smoking played an important role. It is recommended that more efficient preventions and interventions should be operated among high-risk populations, thereby reduce bladder cancer burden in East Asia.

LIG1 is a novel marker for bladder cancer prognosis: evidence based on experimental studies, machine learning and single-cell sequencing.

Background: Bladder cancer, a highly fatal disease, poses a significant threat to patients. Positioned at 19q13.2-13.3, LIG1, one of the four DNA ligases in mammalian cells, is frequently deleted in tumour cells of diverse origins. Despite this, the precise involvement of LIG1 in BLCA remains elusive. This pioneering investigation delves into the uncharted territory of LIG1's impact on BLCA. Our primary objective is to elucidate the intricate interplay between LIG1 and BLCA, alongside exploring its correlation with various clinicopathological factors. Methods: We retrieved gene expression data of para-carcinoma tissues and bladder cancer (BLCA) from the GEO repository. Single-cell sequencing data were processed using the "Seurat" package. Differential expression analysis was then performed with the "Limma" package. The construction of scale-free gene co-expression networks was achieved using the "WGCNA" package. Subsequently, a Venn diagram was utilized to extract genes from the positively correlated modules identified by WGCNA and intersect them with differentially expressed genes (DEGs), isolating the overlapping genes. The "STRINGdb" package was employed to establish the protein-protein interaction (PPI) network.Hub genes were identified through the PPI network using the Betweenness Centrality (BC) algorithm. We conducted KEGG and GO enrichment analyses to uncover the regulatory mechanisms and biological functions associated with the hub genes. A machine-learning diagnostic model was established using the R package "mlr3verse." Mutation profiles between the LIG1^high and LIG1^low groups were visualized using the BEST website. Survival analyses within the LIG1^high and LIG1^low groups were performed using the BEST website and the GENT2 website. Finally, a series of functional experiments were executed to validate the functional role of LIG1 in BLCA. Results: Our investigation revealed an upregulation of LIG1 in BLCA specimens, with heightened LIG1 levels correlating with unfavorable overall survival outcomes. Functional enrichment analysis of hub genes, as evidenced by GO and KEGG enrichment analyses, highlighted LIG1's involvement in critical function such as the DNA replication, cellular senescence, cell cycle and the p53 signalling pathway. Notably, the mutational landscape of BLCA varied significantly between LIG1high and LIG1low groups.Immune infiltrating analyses suggested a pivotal role for LIG1 in immune cell recruitment and immune regulation within the BLCA microenvironment, thereby impacting prognosis. Subsequent experimental validations further underscored the significance of LIG1 in BLCA pathogenesis, consolidating its functional relevance in BLCA samples. Conclusions: Our research demonstrates that LIG1 plays a crucial role in promoting bladder cancer malignant progression by heightening proliferation, invasion, EMT, and other key functions, thereby serving as a potential risk biomarker.

Development of prognostic model incorporating a ferroptosis/cuproptosis-related signature and mutational landscape analysis in muscle-invasive bladder cancer.

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a prevalent and aggressive malignancy. Ferroptosis and cuproptosis are recently discovered forms of programmed cell death (PCD) that have attracted much attention. However, their interactions and impacts on MIBC overall survival (OS) and treatment outcomes remain unclear. METHODS: Data from the TCGA-BLCA project (as the training set), cBioPortal database, and GEO datasets (GSE13507 and GSE32894, as the test sets) were utilized to identify hub ferroptosis/cuproptosis-related genes (FRGs and CRGs) and develop a prognostic signature. Differential expression analysis (DEA) was conducted, followed by univariate and multivariate Cox's regression analyses and multiple machine learning (ML) techniques to select genetic features. The performance of the ferroptosis/cuproptosis-related signature was evaluated using Kaplan-Meier (K-M) survival analysis and receiver-operating characteristics (ROC) curves. Mutational and tumour immune microenvironment landscapes were also explored. Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) experiments confirmed the expression patterns of the hub genes, and functional assays assessed the effects of SCD knockdown on cell viability, proliferation, and migration. RESULTS: DEA revealed dysregulated FRGs and CRGs in the TCGA MIBC cohort. SCD, DDR2, and MT1A were identified as hub genes. A prognostic signature based on the sum of the weighted expression of these genes demonstrated strong predictive efficacy in the training and test sets. Nomogram incorporating this signature accurately predicted 1-, 3-, and 5-year survival probabilities in the TCGA cohort and GSE13507 dataset. Copy number variation (CNV) and tumour immune microenvironment analysis revealed that high risk score level groups were associated with immunosuppression and lower tumour purity. The associations of risk scores with immunotherapy and chemical drugs were also explored, indicating their potential for guiding treatment for MIBC patients. The dysregulated expression patterns of three hub genes were validated by RT-qPCR experiments. CONCLUSIONS: Targeting hub FRGs and CRGs could be a promising therapeutic approach for MIBC. Our prognostic model offers a new framework for MIBC subtyping and can inform personalized therapeutic strategies.

Impact of intra-tumoral immunity on predicting response and survival after neoadjuvant cisplatin-based chemotherapy in patients with muscle invasive bladder cancer.

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy (NAC) followed by cystectomy is the standard of care for patients with muscle-invasive bladder cancer (MIBC). Pathologic complete response (pCR) is associated with favorable outcomes, but only 30%-40% of patients achieve that response. The aim of this study is to investigate the role played by the Tumor and Immune Microenvironment (TIME) in association with the clinical outcome of patients with MIBC undergoing NAC. METHODS: Nineteen patients received NAC and were classified as pCR (n = 10) or non-pCR (n = 9). Bulk RNA-seq and immune protein evaluations using Digital Spatial Profiling (DSP) were performed on formalin-fixed paraffin-embedded (FFPE) tumor biopsies collected before NAC (baseline). Immunohistochemistry (IHC) evaluation focused on CD3 and CD20 expression was performed on baseline and end-of-treatment (EOT) FFPEs. Baseline peripheral blood was assessed for lymphocyte and neutrophil counts. Kaplan-Meier analyses and Cox PH regression models were used for survival analyses (OS). RESULTS: In the periphery, pCR patients showed lower neutrophil counts, and neutrophil/ lymphocyte ratio (NLR) when compared to non-pCR patients. In the tumor microenvironment (TME), gene expression analysis and protein evaluations highlighted an abundance of B cells and CD3+ T cells in pCR versus non-pCR patients. On the contrary, increased protein expression of ARG1+ cells, and cells expressing immune checkpoints such as LAG3, ICOS, and STING were observed in the TME of patients with non-pCR. CONCLUSIONS: In the current study, we demonstrated that lower NLR levels and increased CD3+ T cells and B cell infiltration are associated with improved response and long-term outcomes in patients with MIBC receiving NAC. These findings suggest that the impact of immune environment should be considered in determining the clinical outcome of MIBC patients treated with NAC.

Advancing bladder cancer management: development of a prognostic model and personalized therapy.

Background: Bladder cancer (BLCA) was recognized as a significant public health challenge due to its high incidence and mortality rates. The influence of molecular subtypes on treatment outcomes was well-acknowledged, necessitating further exploration of their characterization and application. This study was aimed at enhancing the understanding of BLCA by mapping its molecular heterogeneity and developing a robust prognostic model using single-cell and bulk RNA sequencing data. Additionally, immunological characteristics and personalized treatment strategies were investigated through the risk score. Methods: Single-cell RNA sequencing (scRNA-seq) data from GSE135337 and bulk RNA-seq data from several sources, including GSE13507, GSE31684, GSE32894, GSE69795, and TCGA-BLCA, were utilized. Molecular subtypes, particularly the basal-squamous (Ba/Sq) subtype associated with poor prognosis, were identified. A prognostic model was constructed using LASSO and Cox regression analyses focused on genes linked with the Ba/Sq subtype. this model was validated across internal and external datasets to ensure predictive accuracy. High- and low-risk groups based on the risk score derived from TCGA-BLCA data were analyzed to examine their immune-related molecular profiles and treatment responses. Results: Six molecular subtypes were identified, with the Ba/Sq subtype being consistently associated with poor prognosis. The prognostic model, based on basal-squamous subtype-related genes (BSSRGs), was shown to have strong predictive performance across diverse clinical settings with AUC values at 1, 3, and 5 years indicating robust predictability in training, testing, and entire datasets. Analysis of the different risk groups revealed distinct immune infiltration and microenvironments. Generally higher tumor mutation burden (TMB) scores and lower tumor immune dysfunction and exclusion (TIDE) scores were exhibited by the low-risk group, suggesting varied potentials for systemic drug response between the groups. Finally, significant differences in potential systemic drug response rates were also observed between risk groups. Conclusions: The study introduced and validated a new prognostic model for BLCA based on BSSRGs, which was proven effective in prognosis prediction. The potential for personalized therapy, optimized by patient stratification and immune profiling, was highlighted by our risk score, aiming to improve treatment efficacy. This approach was promised to offer significant advancements in managing BLCA, tailoring treatments based on detailed molecular and immunological insights.

Results from a real-world study: a novel glycosyltransferase risk score for prognosis, tumor microenvironment phenotypes and immunotherapy in bladder cancer.

BACKGROUND: Although immunotherapy shows tremendous potential in the treatment of bladder cancer (BLCA), the overall prognosis and response rates to immunotherapy in BLCA remain suboptimal. METHODS: We performed an extensive evaluation of glycosyltransferase expression patterns in BLCA patients by analyzing 210 glycosyltransferase-related genes. Subsequently, we established correlations between these glycosyltransferase patterns, prognosis, and tumor microenvironment (TME) phenotypes. To offer personalized patient assessments, we developed a glycosyltransferase risk score that accurately predicts prognosis, TME phenotypes, and molecular subtypes. Importantly, we developed a RNA-seq cohort, named Xiangya cohort, to validate our results. RESULTS: Two distinct patterns of glycosyltransferase expression were identified, corresponding to inflamed and noninflamed TME phenotypes, and demonstrated the potential to predict prognosis. We developed and validated a comprehensive risk score that accurately predicted individual patient prognosis in the TCGA-BLCA cohort. Additionally, we constructed a nomogram that integrated the risk score with several key clinical factors. Importantly, this risk score was successfully validated in external cohorts, including the Xiangya cohort and GSE48075. Furthermore, we discovered a positive correlation between this risk score and tumor-infiltrating lymphocytes in both the TCGA-BLCA and Xiangya cohorts, suggesting that patients with a higher risk score exhibited an inflamed TME phenotype and were more responsive to immunotherapy. Finally, we observed that the high and low risk score groups were consistent with the luminal and basal subtypes of BLCA, respectively, providing further validation of the risk score's role in the TME in terms of molecular subtypes. CONCLUSIONS: Glycosyltransferase patterns exhibit distinct TME phenotypes in BLCA. Our comprehensive risk score provides a promising approach for prognostic prediction and assessment of immunotherapy efficacy, offering valuable guidance for precision medicine.

Monopolar versus bipolar transurethral resection of bladder Tumour: post-hoc analysis of a prospective trial.

INTRODUCTION: Previously, in a randomised trial we demonstrated bipolar transurethral resection of bladder tumor (TURBT) could achieve a higher detrusor sampling rate than monopolar TURBT. We hereby report the long-term oncological outcomes following study intervention. METHODS: This is a post-hoc analysis of a randomized phase III trial comparing monopolar and bipolar TURBT. Only patients with pathology of non-muscle invasive bladder cancer (NMIBC) were included in the analysis. Per-patient analysis was performed. Primary outcome was recurrence-free survival (RFS). Secondary outcomes included progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: From the initial trial, 160 cases were randomised to receive monopolar or bipolar TURBT. 24 cases of non-urothelial carcinoma, 22 cases of muscle-invasive bladder cancer, and 9 cases of recurrences were excluded. A total of 97 patients were included in the analysis, with 46 in the monopolar and 51 in the bipolar group. The median follow-up was 97.1 months. Loss-to-follow-up rate was 7.2%. Regarding the primary outcome of RFS, there was no significant difference (HR = 0.731; 95%CI = 0.433-1.236; P = 0.242) between the two groups. PFS (HR = 1.014; 95%CI = 0.511-2.012; P = 0.969), CSS (HR = 0.718; 95%CI = 0.219-2.352; P = 0.584) and OS (HR = 1.135; 95%CI = 0.564-2.283; P = 0.722) were also similar between the two groups. Multifocal tumours were the only factor that was associated with worse RFS. CONCLUSION: Despite the superiority in detrusor sampling rate, bipolar TURBT was unable to confer long-term oncological benefits over monopolar TURBT.

The clinical significance and anti-tumor role of PRKG1 in bladder cancer.

Introduction: cGMP-dependent protein kinase 1 (PRKG1) has shown to be associated with some tumorigenesis, while the role of PRKG1 in bladder cancer is unclear. Methods: To investigate the biological and clinical significance of PRKG1 in bladder cancer, we detected the expression of PRKG1 and explored the function of PRKG1 in bladder cancer cells. The PRKG1 transcripts data was downloaded from The Cancer Genome Atlas (TCGA) database, and immunohistochemistry staining was conducted on formalin-fixed paraffin-embedded (FFPE) sample tissues. Relationship between clinical characteristics of patients and expression of PRKG1 was analyzed in FFPE samples, TCGA database, and GSE19423 dataset. PRKG1 was over-expressed, and cell proliferation, migration, invasion, apoptosis, and spheroidizing ability were then detected. Chemosensitivity to cisplatin was detected with cell viability, and half-maximal drug inhibitory concentration (IC50) was calculated. In addition, the relation between PRKG1 expression and the infiltration level of tumor immune cells in tumor microenvironment were analyzed. Results: The results showed expression of PRKG1 was lower in bladder cancer, compared with normal tissues both at protein and transcript levels. Lower PRKG1 expression was related to higher tumor grade, T stage, and muscle invasion, also predicted worse overall survival and recurrence free survival in patients treated with Bacillus Calmette-Guerin (BCG) intravesical immunotherapy. Analysis of tumor immune cells infiltration showed lower PRKG1 was associated with non-inflamed tumor microenvironment. Conclusion: The present study firstly identified the anti-tumor role and tumor immune regulatory role of PRKG1, also found loss of PRKG1 could be used as a prognosis factor. The present study provided a potential biomarker and therapy target to bladder cancer.

Amino-truncated NOV expression and its correlation with clinicopathologic features, prognosis, metastasis, and chemoresistance in bladder cancer.

Nephroblastoma, an overexpressed gene (NOV) protein, plays an important role in proliferation, differentiation, angiogenesis, adhesion, invasion and tumorigenesis, but the function of amino-truncated NOV is different. This study is to investigate the role of amino-truncated NOV in the progression of bladder cancer. Using immunohistochemistry and Western blot analysis, we detected the amino-truncated NOV in bladder cancer, and statistical analysis was performed to estimate the association between the expression of amino-truncated NOV and the patient's prognosis by SPSS 19.0. With transduction of amino-truncated NOV, we evaluated alteration for proliferation, migration, invasion and chemoresistance in bladder cancer cells, as well as some proteins related to Wnt/ß-catenin pathway and epithelial-mesenchymal transition. The truncated variant of the NOV protein was located in a nucleus other than the cytoplasm and highly expressed in bladder cancer, which was also linked to higher pathological grade and positive lymph node metastasis as well as recurrence. The exact sequence of this truncated protein was confirmed, and it was a 26-kDa splicing. The truncated NOV protein found in bladder cancer was cut at the 187th amino acid of the full-length protein. It was also involved in bladder cancer progression and chemoresistance through a mechanism involving epithelial-mesenchymal transition (EMT) and the Wnt/ß-catenin signaling pathway. Our findings provide experimental evidence that the nuclear NOV protein expression is a potential biomarker in the prognostic evaluation of bladder cancer and enhanced amino-truncated NOV expression is potentially important for bladder cancer cell invasion, metastasis and chemoresistance during progression.

Treatment Options for Signet Ring Cell Carcinoma of the Urinary Bladder: A Population-Based Study.

OBJECTIVES: Signet ring cell carcinoma (SRCC) of the urinary bladder is a rare and highly aggressive form of bladder cancer, with no widely agreed-upon treatment strategy. The aim of this study was to identify important factors influencing patient prognosis and to assess how various treatment approaches affect survival outcomes. METHODS: A retrospective study was conducted using data from the Surveillance, Epidemiology, and End Results (SEER) Program, including patients with bladder primary SRCC who were presented between 2000 and 2017. Univariate and multivariate Cox regression models were used to examine the impact of various factors on cancer-specific survival (CSS) and overall survival (OS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to homogenize both groups. The impact of different treatment regimens on patient CSS and OS was analyzed using the Kaplan-Meier method. RESULTS: A total of 33 cases of non-muscular invasive SRCC and 210 cases of muscular invasive SRCC were included in this study. Multivariate analysis identified race, TNM stage, and surgical method as independent variables influencing both OS and CSS. In non-muscle invasive bladder SRCC patients, radical cystectomy showed no CSS benefit compared to transurethral resection of bladder tumors (P = 0.304). For muscle invasive SRCC, patients who underwent partial cystectomy had better OS and CSS compared to those who underwent radical cystectomy (P = 0.019, P = 0.024). However, after conducting a PSM analysis, the differences between the two surgical outcomes were not statistically significant (P = 0.504, P = 0.335). Lymphadenectomy, chemotherapy, and radiation did not show any benefit to the prognosis of patients. CONCLUSION: This study identified race, TNM stage, and surgical approach as significant independent predictors for SRCC outcomes. Simple radical cystectomy and partial cystectomy proved to be effective treatments for SRCC. The optimal treatment option still needs to be supported by a number of prospective research trials.

Multiple omics integrative analysis identifies GARS1 as a novel prognostic and immunological biomarker: from pan-cancer to bladder cancer.

Glycyl-tRNA synthetase (GARS1) is differentially expressed across cancers. In this study, the value of GARS1 in the diagnosis and prognosis of various cancers was comprehensively evaluated by multiple omics integrative pan-cancer analysis and experimental verification. Through Kaplan-Meier, ROC and multiple databases, we explored GARS1 expression and prognostic and diagnostic patterns across cancers. The GARS1 relative reaction network was identified in PPI, GO, KEGG, methylation models and the genetic mutation atlas. Further research on the GARS1 value in bladder urothelial carcinoma (BLCA) was conducted by regression and nomogram models. We further analyzed the correlation between GARS1 and immune markers and cells in BLCA. Finally, in vitro experiments were used to validate GARS1 the oncogenic function of GARS1 in BLCA. We found that GARS1 was highly expressed across cancers, especially in BLCA. GARS1 expression was correlated with poor survival and had high diagnostic value in most tumor types. GARS1 is significantly associated with tRNA-related pathways whose mutation sites are mainly located on tRNA synthetase. In addition, Upregulation of GARS1 was connected with immune cell infiltration and five key MMR genes. M2 macrophages, TAMs, Th1 and T-cell exhaustion, and marker sets associated with GARS1 expression indicated specific immune infiltration in BLCA. Finally, in vitro experiments validated that GARS1 expression promotes BLCA cell proliferation and metastasis and inhibits apoptosis. Overall, GARS1 can be a novel prognostic and immunological biomarker through multiple omics integrative pan-cancer analysis. The expression of GARS1 in BLCA was positively correlated with specific immune infiltration, indicating that GARS1 might be related to the tumor immune microenvironment.

Predicting prognosis and drug sensitivity in bladder cancer: an insight into Pan-programmed cell death patterns regulated by M6A modifications.

The team aimed to explore the possible functional significance of M6A regulation in Pan-programmed cell death (PCD) among patients with bladder cancer (BLCA). In BLCA patients, the analysis was conducted on the13 patterns of programmed cell death (PCD) and the regulation of M6A. Transcriptome, genomics, and clinical data were collected from TCGA-BLCA, GEO32548, and IMvigor210. Consensus clustering analysis, functional enrichment analysis, and other prognostic tools were used to validate the Pan-PCD. Finally, in vitro experiments and transcription sequencing were performed to understand the potential influence of the PI3K pathway on Pan-PCD in BLCA patients. Diverse PCD patterns were simultaneously activated, and M6A regulators exhibited significant variability in bladder malignant tissues. The machine learning algorithm established an 8-gene M6A-related Pan-PCD signature. This signature was validated in three independent datasets, and BLCA patients with higher risk scores had worse prognosis. An unsupervised clustering approach identified activated and suppressed Pan-PCD subgroups of BLCA patients, with distinct responses to immunotherapy and drug sensitivity. In addition, the PI3K pathway was identified as a key mechanism for various forms of programmed cell death, encompassing apoptosis, pyroptosis, autophagy, and cell death dependent on lysosomes. This research revealed that the Pan-PCD model was a more promising approach for BLCA patients under M6A regulation. A new signature from M6A-related Pan-PCD was proposed, with prognostic value for survival or drug sensitivity. The PI3K pathway was a key mechanism for multiple PCDs in BLCA patients.

Observational study of in-hospital mortality risk from bladder cancer: Five years of experience at a tertiary referral hospital in Indonesia.

Bladder cancer (BC) is a neoplasm arising from the bladder. It requires appropriate management and its prognosis depends on many factors. This study aimed to analyze the factors that influence outcomes in BC management. This was a retrospective study. Data were collected at one of Indonesia's largest tertiary referral hospitals. All patients diagnosed with BC from January 2019 to December 2023 were included. The outcome measured was survival or death. Statistical analysis was conducted using SPSS version 26.0 software. The study included 219 patients with a median age of 57.97 years, of which 99 (45.2 %) patients died. In a bivariate analysis, sex, active smoking status, Karnofsky score, metastasis status, chronic kidney disease, type 2 diabetes mellitus, chemotherapy, radiotherapy, and alternative medicine were found to affect mortality status. Based on multivariate analysis, the route of admission (odds ratio [OR] 0.19), irregular visit (OR 6.21), metastasis (OR 3.58), radiotherapy (OR 21.12), and traditional medicine (OR 0.21) were independent factors of in-hospital mortality. The mortality rate for BC was considerably high. Irregular visits, metastasis, type 2 diabetes, and radiotherapy were independent risk factors for mortality.

Pelvic organ-preserving radical cystectomy versus standard radical cystectomy in female patients diagnosed with bladder cancer.

BACKGROUND: Pelvic organ-preserving radical cystectomy (POPRC) has been reported to result in a better postoperative quality of life in female with bladder cancer compared to standard radical cystectomy (SRC). However, its oncological outcomes remain a concern. PATIENTS AND METHODS: Female patients with bladder cancer who underwent POPRC or SRC were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Logistic regression was used to identify predictors of POPRC usage. To avoid the potential impact of baseline differences between groups on survival, a 1:2 propensity score matching (PSM) was implemented. After that, Kaplan-Meier curves and Log-rank tests were used to determine the significance of overall survival (OS) differences between patients in the SRC group and POPRC group. Finally, subgroup analysis based on predetermined indicators was performed. RESULTS: A total of 2193 patients were included with a median follow-up of 53 months, of whom 233 (10.6%) received POPRC and 1960 (89.4%) received SRC. No definitive predictors of POPRC were identified. Before PSM, POPRC resulted in comparable OS to SRC (HR = 1.09, p = 0.309), while after PSM, POPRC was associated with significantly worse OS (HR = 1.23, p = 0.038). In subgroup analyses, POPRC led to non-inferior OS (HR = 1.18, 95%CI 0.71-1.95, p = 0.531) in patients with non-muscle invasive bladder cancer (NMIBC) and T2 patients (HR = 1.07, p = 0.669), but significantly worse OS in T3 patients (HR = 1.41, p = 0.02). CONCLUSION: Currently, patients undergoing POPRC have not undergone strict screening, and candidates for POPRC should have more stringent criteria in the future to achieve satisfactory oncological outcomes. However, flaws in the study make more evidence needed to support our findings.

Radiotherapy plus pembrolizumab for advanced urothelial carcinoma: results from the ARON-2 real-world study.

The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.