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Background: Enfortumab vedotin, a fully human monoclonal antibody-drug conjugate (ADC) directed to Nectin-4, prolonged overall survival (OS) versus standard chemotherapy in patients with previously treated locally advanced or metastatic urothelial carcinoma (mUC) previously receiving a programmed cell death protein 1/ligand 1 (PD-1/L1) inhibitor and platinum-based chemotherapy in the pivotal, phase 3 EV-301 clinical trial, supporting global approvals of enfortumab vedotin monotherapy. This bridging study was the first to evaluate enfortumab vedotin monotherapy in previously treated Chinese patients with locally advanced or mUC., Methods: EV-203 was a multicenter, open-label, phase 2 study (NCT04995419) assessing efficacy, safety/tolerability, pharmacokinetics (PK), and immunogenicity of enfortumab vedotin in 40 Chinese patients (PK analysis set, n = 13) with previously treated locally advanced or mUC. Patients received enfortumab vedotin 1.25 mg/kg (Days 1, 8, and 15). Primary endpoints included confirmed objective response rate (ORR) by the independent review committee (IRC) and PK parameters of ADC, total antibody (TAb), and free monomethyl auristatin E (MMAE). Secondary endpoints included investigator-assessed confirmed ORR; investigator-/IRC-assessed duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS); OS; immunogenicity; and safety/tolerability., Results: As of May 13, 2022, the median follow-up was 6.5 months. Confirmed ORR was 37.5% (n/N = 15/40; 95% CI: 22.7%-54.2%) by IRC and 42.5% (n/N = 17/40; 95% CI: 27.0%-59.1%) by investigator assessment. By IRC, DCR was 72.5% (n = 29), median DOR was not reached, and median PFS was 4.7 months. Median OS was not reached. Endpoints assessed by investigators were consistent with IRC assessments. Two patients discontinued treatment for treatment-related adverse events. No new safety signals were identified. ADC, TAb, and free MMAE were characterized in Chinese patients and consistent with previously characterized populations. The incidence of positive antitherapeutic antibodies postbaseline was 0%., Conclusion: Enfortumab vedotin demonstrated meaningful clinical activity with a manageable safety profile in Chinese patients with previously treated locally advanced or mUC., Trial Registration: ClinicalTrials.gov identifier: NCT04995419., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Small cell carcinoma of the bladder (SCCB) is a rare, highly malignant neuroendocrine tumor. This study attempted to analyze tumor characteristics, treatments and clinical outcomes in China. We conducted a retrospective analysis of patients diagnosed with non-metastatic SCCB at multi-institutions between January 2007 and January 2022. The Kaplan-Meier method was used to calculate survival. A total of 20 patients were included. 10 had localized disease (T1-2N0), and 10 had locally advanced disease (≥ T3 or N+). 13 received local treatment (partial cystectomy or transurethral resection of the bladder tumor) and 7 received radical treatment (radical cystectomy or radiotherapy). A total of 18 patients (90%) received chemotherapy (CT), either neoadjuvant CT (n = 5) or adjuvant CT (n = 13). The median OS for the receiving local treatment was 65.3 months (95% CI 0 to 138 months) and the corresponding 1-year, 2-year, and 3-year OS was 77%, 54%, and 54%, respectively. The median OS for the receiving radical treatment was not reached and the corresponding 1-year, 2-year, and 3-year OS was 100%, 100%, and 75%, respectively. The median PFS for receiving local treatment was 13.8 months (95% CI 9.3 to 18.3 months) and the corresponding 1-year, 2-year, and 3-year PFS was 46%, 31%, and 31%, respectively. The median PFS for the receiving radical treatment was not reached and the corresponding 1-year, 2-year, and 3-year PFS was 83%, 56%, and 56%, respectively. This study reported the largest cohort of non-metastatic SCCB among Chinese population. Given its metastatic potential, CT remained an essential part of the treatment. The survival outcomes of radical cystectomy and RT in non-metastatic SCCB were encouraging., (© 2024. The Author(s).)

Bladder cancer is one of the common malignant tumors in urology. According to statistics, there will be 613 791 new cases of bladder cancer in the world in 2022, and the number of new cases of bladder cancer in China will be approximately 92 900, accounting for approximately 15% of new cases of bladder cancer in the world, ranking 11th in the spectrum of malignant tumors in China, among which there are approximately 73 200 new cases in males, ranking 8th in the spectrum of male malignant tumors. Bladder urothelial cancer accounts for approximately 90% of all bladder malignant tumors. It can be divided into non-muscle-invasive bladder cancer and muscle-invasive bladder cancer according to whether it invades the bladder muscle layer. Radical cystectomy is the standard treatment for muscle invasive bladder cancer patients and bacillus calmette-guerin (BCG) unresponsive high-risk non-muscle invasive bladder cancer patients. Nevertheless, due to the patient's underlying diseases and the deterioration of the quality of life caused by surgery, many patients refused or are not suitable for radical cystectomy. Therefore, it is vital to find a bladder-preserving treatment that can achieve cure other than radical cystectomy. Bladder-preserving therapy that balances tumor control and quality of life serves as an alternative and supplement to radical cystectomy. This consensus is based on contemporary evidence-based medicine, combined with native clinical practice and experiences of bladder preservation in a multidisciplinary treatment manner. To some extent, this consensus serves as a guidance for bladder preservation of bladder cancer in China. The consensus aims to discuss issues including organizational structure and workflow of multidisciplinary treatment, the selection of patients for bladder-preserving therapy, treatment options and regimens, efficacy evaluation, follow-up, as well as regimen choices of recurrence after bladder-preserving therapy.

Objective: Small cell carcinoma of the bladder (SCCB) is a rare malignant tumor of the bladder. This study aims to explore its clinicopathological features and prognostic factors and to explore the role of perioperative treatment methods., Methods: The clinical data of SCCB patients admitted to West China Hospital, Sichuan University over 8 years from January 2016 to January 2024 were collected. The clinicopathological features of SCCB were summarized. The survival outcomes and prognostic factors were analyzed. The effect of perioperative treatment on the improvement in prognosis was explored., Results: A total of 31 confirmed cases of SCCB were enrolled. We observed a number of clinicopathologic features. All cases had advanced clinical staging, with the T staging status being above T2 in all cases, and distant metastasis was found in 23% of the newly diagnosed cases. A high proportion of the SCCB cases were combined with other histologic types, with 96% showing combination with urothelial carcinoma (UC). The SCCB patients had a poor prognosis, presenting a median survival of 12 months, 1-year overall survival (OS) of 57.9%, and 3-year OS of 27.6%. Patients with extensive-stage SCCB had a significantly worse prognosis than those with limited-stage SCCB did (median OS time of 17.0 months vs. 4.4 months, P <0.05). In limited-stage SCCB, the median OS of patients who underwent radical cystectomy (RC) was 19.9 months, while that of the patients who did not undergo RC was 15.2 months ( P <0.05). The OS of patients who received perioperative therapy in combination with RC had longer OS than those who received only RC did ( P <0.05). Among these, patients recevied neoadjuvant therapy (NAT) had a significantly longer OS than patients who didn't receive NAT ( P <0.05). Subgroup analysis revealed that patients who were responsive to neoadjuvant therapy had longer disease-free survival and longer OS than those who were not responsive did ( P <0.05). Lymph node metastasis was an independent factor of poor prognosis (hazard ratio [HR]=15.21, 95% confidence interval [CI]: 1.732-133.912, P =0.014). NAT prior to RS was an independent protective factor, significantly reducing the risk of death compared with RC alone (HR=0.03, 95% CI: 0.001-0.724, P =0.031)., Conclusion: RC is an effective treatment that prolongs the survival of patients with limited-stage SCCB. RS combined with NAT can further improve their survival., Competing Interests: 利益冲突　所有作者均声明不存在利益冲突, (© 2024《四川大学学报（医学版）》编辑部 版权所有Copyright ©2024 Editorial Office of Journal of Sichuan University (Medical Sciences).)

Objective: Most bladder cancers are nonmuscle invasive bladder cancer (NMIBC), and transurethral resection of bladder tumors (TURBT) is the standard treatment. However, postoperative recurrence remains a significant challenge, and the influence of bladder tumor location on prognosis is still unclear. This study aims to investigate how tumor location affects the prognosis of NMIBC patients undergoing TURBT and to identify the optimal surgical approach., Methods: A multicenter study was conducted, which included Chinese NMIBC data from 15 hospitals (1996-2019) and data from 17 registries of the Surveillance, Epidemiology, and End Results database (SEER) (2000-2020). Patients initially diagnosed with NMIBC and undergoing TURBT or partial cystectomy were analyzed, with cases lost to follow-up or with missing data excluded. The study investigated the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) among patients with different tumor locations. Kaplan-Meier, Cox regression, and propensity score matching methods were employed to explore the association between tumor location and prognosis. Stratified populations were analyzed to minimize bias., Results: This study included 118 477 NMIBC patients and highlighted tumor location as a crucial factor impacting post-TURBT prognosis. Both anterior wall and dome tumors independently predicted adverse outcomes in two cohorts. For anterior wall tumors, the Chinese cohort showed hazard ratios (HR) for OS of 4.35 ( P <0.0001); RFS of 2.21 ( P <0.0001); SEER cohort OS HR of 1.10 ( P =0.0001); DSS HR of 1.13 ( P =0.0183). Dome tumors displayed similar trends [Chinese NMIBC cohort OS HR of 7.91 ( P <0.0001); RFS HR of 2.12 ( P <0.0001); SEER OS HR of 1.05 ( P =0.0087); DSS HR of 1.14 ( P =0.0006)]. Partial cystectomy significantly improved the survival of dome tumor patients compared to standard TURBT treatment ( P <0.01)., Conclusion: This study reveals the significant impact of tumor location in NMIBC patients on the outcomes of TURBT treatment, with tumors in the anterior wall and bladder dome showing poor post-TURBT prognosis. Compared to TURBT treatment, partial cystectomy improves the prognosis for bladder dome tumors. This study provides guidance for personalized treatment and prognosis management for NMIBC patients., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: This study seeks to explore the impact of fast track surgery (FTS) with three-port in patients treated with laparoscopic radical cystectomy and ileal conduit on postoperative recovery, hospital stay and the complications., Methods: This retrospective study analyzed 230 patients with invasive bladder cancer who underwent laparoscopic radical cystectomy at the Second Hospital of Anhui Medical University between December 2011 to January 2023. 50 patients received conventional surgery (CS) and 180 patients received FTS with three-port. Patients were assessed for time to normal diet consumption, time to passing first flatus, number of postoperative recovery days and complications. Trends of serum C-reactive protein levels were monitored preoperatively and on postoperative days 1, 3 and 7., Results: Patients who underwent FTS with three-port had a shorter duration to first flatus (P < 0.05). And number of postoperative hospital days and the length of hospital stay were notably shorter in contrast to the CS group (P < 0.05). Serum CRP levels on postoperative day 7 were markedly reduced in those of the FTS group compared to the CS group (P < 0.05). Those of the CS group experienced more frequent rates of complications compared to those of the FTS with three-port group (P < 0.05)., Conclusion: Our findings demonstrate that the FTS with three-port program hastens postoperative recovery and reduces duration of hospital stay. It is safer and more effective than the CS program in the Chinese population undergoing laparoscopic radical cystectomy., (© 2024. The Author(s).)

Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P < 0.001) and between IC with membrane PD-L1 positivity and CD8+ T cells (0.44; P < 0.001). There is high prevalence of PD-L1 expression in Chinese patients with MIUBC, suggesting that a sizable subset of patients could benefit from immunotherapy. The correlation of PD-L1 expression with tumor biomarkers provide clues for mechanisms underlying the effects of biomarkers for predicting efficacy., (© 2024. The Author(s).)

Objectives: RC48 is an antibody-drug conjugate (ADC) that targets HER2. In China, RC48 is approved for patients with HER-2-positive metastatic urothelial carcinoma (mUC) who have failed at least platinum-based chemotherapy. This study aimed to evaluate RC48 for mUC in a cohort of real-world patients., Materials and Methods: We retrospectively collected data from 103 mUC patients from 12 centers between July 2021 and August 2023 in China. RC48 alone or with immunotherapy was administered until disease progression, intolerable toxicity, death, or other reasons. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and incidence of treatment-related adverse events (TRAEs) were evaluated., Results: The median age of the patients was 68 years, and 68.0% were men. Twenty-nine (28.2%) patients received RC48 alone; 73 (70.9%) received RC48 combination therapy. The response rates were as follows: complete response in 2 (1.9%) patients, partial response in 50 (48.5%) patients, stable disease in 30 (29.1%) patients. The ORR was 50.5%. In patients with ≥80 years, Eastern Cooperative Oncology Group (ECOG) performance status ≥2 and creatinine clearance rate (CCr) <30 mL/min, the ORR was 75%, 48.6%, and 40.0%, respectively. The median PFS was 6 (3.9-8.1) months, and the median OS was not reached. The most reported TRAEs were peripheral sensory neuropathy (53.4%), alopecia (42.7%), asthenia (38.8%), decreased appetite (35.9%) and weight loss (35.9%) and TRAE did not increase in patients with poor condition or impaired renal function., Conclusion: Administration of RC48 for real-world patients is both effective and safe. mUC patients can benefit from RC48-based therapy, regardless of their poor condition or impaired renal function., Competing Interests: Disclosure There are no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Bladder cancer (BCa) shows its potential immunogenity in current immune-checkpoint inhibitor related immunotherapies. However, its therapeutic effects are improvable and could be affected by tumor immune microenvironment. Hence it is interesting to find some more prognostic indicators for BCa patients concerning immunotherapies., Methods: In the present study, we retrospect 129 muscle-invasive BCa (MIBC) patients with radical cystectomy in Shanghai General Hospital during 2007 to 2018. Based on the results of proteomics sequencing from 9 pairs of MIBC tissue from Shanghai General Hospital, we focused on 13 immune-related differential expression proteins and their related genes. An immune-related prognostic signature (IRPS) was constructed according to Cancer Genome Atlas (TCGA) dataset. The IRPS was verified in ArrayExpress (E-MTAB-4321) cohort and Shanghai General Hospital (General) cohort, separately. A total of 1010 BCa patients were involved in the study, including 405 BCa patients in TCGA cohort, 476 BCa patients in E-MTAB-4321 cohort and 129 MIBC patients in General cohort., Result: It can be indicated that high IRPS score was related to poor 5-year overall survival and disease-free survival. The IRPS score was also evaluated its immune infiltration. We found that the IRPS score was adversely associated with GZMB, IFN-γ, PD-1, PD-L1. Additionally, higher IRPS score was significantly associated with more M2 macrophage and resting mast cell infiltration., Conclusion: The study revealed a novel BCa prognostic signature based on IRPS score, which may be useful for BCa immunotherapies., (© 2022. The Author(s).)

Choline metabolism alteration is considered as a metabolic hallmark in cancer, reflecting the complex interactions between carcinogenic signaling pathways and cancer metabolism, but little is known about whether genetic variants in the metabolism pathway contribute to the susceptibility of bladder cancer. Herein, a case-control study comprising 580 patients and 1,101 controls was carried out to analyze the association of bladder cancer with genetic variants on candidate genes involved in the choline metabolism pathway using unconditional logistic regression. Gene expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were applied for differential gene expression analysis. Cox regression was also applied to estimate the role of candidate genes on bladder cancer prognosis. Our results demonstrated that C allele of rs6810830 in ENPP6 was a significant protective allele of bladder cancer, compared to the T allele [Odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.64-0.86, P = 7.14 × 10 -5 in additive model]. Besides, we also found that the expression of ENPP6 remarkably decreased in bladder tumors compared with normal tissues. Moreover, high expression of ENPP6 was associated with worse overall survival (OS) in bladder cancer patients [hazard ratio (HR) with their 95% CI 1.39 (1.02-1.90), P = 0.039]. In conclusion, our results suggested that SNP rs6810830 (T > C) in ENPP6 might be a potential susceptibility loci for bladder cancer, and these findings provided novel insights into the underlying mechanism of choline metabolism in cancers., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite increasing evidence that dysbiosis of urinary microbiota is closely correlated with bladder cancer, the influence of the urinary microbiota on immune evasion and tumor growth in bladder cancer is unknown. This study investigated whether the urinary microbiota influences intratumoral infiltration of FoxP3+ regulatory T cells, expression of Ki-67 and clinical prognosis in non-muscle-invasive bladder cancer. Forty male patients, including 12 and 28 with or without recurrence, respectively, were retrospectively enrolled. Midstream urine samples were preoperatively collected. Urinary microbiota composition was analyzed by 16s rDNA sequencing. Alpha and beta diversities were measured. LEfSe analysis was employed to identify specific bacteria associated with recurrence. Intratumoral infiltration of FoxP3+ regulatory T cells and Ki-67 expression were evaluated by immunohistochemistry. Patients with recurrence had higher α-diversity compared to those without (Shannon Index, P = 0.0007, Simpson Index, P = 0.0004). Distinct beta diversity was observed between recurrence and non-recurrence groups (weighted Unifrac P = 0.02; unweighted Unifrac P = 0.001). LEfSe analysis showed that the recurrence group displayed marked enrichment of Pseudomonas, Staphylococcus, Corynebacterium, and Acinetobacter genera. Patients with higher alpha diversity had elevated Ki-67 expression than those with lower alpha diversity (P = 0.0194), although microbial diversity was unassociated with infiltration of FoxP3+ regulatory T cells (P = 0.1653). Patients with lower urinary microbial diversity had prolonged recurrence-free survival compared to those with higher diversity. Perturbation of urinary microbiota may induce immune evasion and tumor growth, eventually contributing to unfavorable outcomes. Additional study is warranted to confirm a causal role of urinary microbiota in modulating antitumor immune response and survival in bladder cancer., (© 2021. The Author(s) under exclusive licence to Japan Human Cell Society.)

Background: Intravesical bacillus Calmette-Guérin (BCG) fails in a considerable proportion of non-muscle invasive bladder cancer (NMIBC) patients despite treatment per recommended protocol. This real-world study aimed to understand the current patterns of treatment and disease management for the broad BCG-unresponsive NMIBC patient population, alongside collecting sufficient data on patients who do not undergo cystectomy., Methods: This was a multicenter, retrospective survey of physicians treating BCG-unresponsive NMIBC patients. Data were collected in eight countries - France, Germany, Spain, Italy, United Kingdom, United States, China, and Japan - between January and May 2019. The study consisted of a short online physician survey and a retrospective chart review of eligible BCG-unresponsive NMIBC patients. Physicians abstracted chart data for the last 10 (five patients in Japan) eligible BCG-unresponsive NMIBC patients meeting the inclusion criteria, and the data were analysed for all countries combined using descriptive statistics. Country-specific analyses were also carried out, as appropriate., Results: Overall, 508 physicians participated in the study. Almost one-quarter (22.9%) of physicians' current NMIBC patient caseload was BCG-unresponsive, whereby BCG therapy was no longer considered an option. Half of physicians (49.4%) did not regularly use biomarker tests in their practice, with particularly few physicians undertaking biomarker testing in Spain and Japan. Biomarker testing varied considerably, with the proportions of physicians selecting 'none' ranging from 11.4% in China to 70.3% in Japan. Physicians reported transurethral resection of the bladder tumor (TURBT) and BCG as the most common current treatments received by their patients. Chemotherapy and anti-PD-L1 treatment options were considered impactful new therapies by 94.7% and 90.0% of physicians surveyed in this study, respectively., Conclusions: The most common treatments received by patients in this study were TURBT and BCG. Emerging new treatments are driven by exploring biomarkers, but in real-world clinical practice only half of physicians or fewer regularly tested their NMIBC patients for biomarkers; PD-1/PD-L1 was the most common biomarker test used. Most physicians reported that, in addition to chemotherapy, anti-PD-L1 was an impactful new therapy., (© 2022. The Author(s).)

Background: Reliable molecular markers are much needed for early prediction of recurrence in muscle-invasive bladder cancer (MIBC) patients. We aimed to build a long-noncoding RNA (lncRNA) signature to improve recurrence prediction and lncRNA-based molecular classification of MIBC., Methods: LncRNAs of 320 MIBC patients from the Cancer Genome Atlas (TCGA) database were analyzed, and a nomogram was established. A molecular classification system was created, and immunotherapy and chemotherapy response predictions, immune score analysis, immune infiltration analysis, and mutational data analysis were conducted. Survival analysis validation was also performed., Results: An eight-lncRNA signature classifed the patients into high- and low-risk subgroups, and these groups had significantly different (disease-free survival) DFS. The ability of the eight-lncRNA signature to make an accurate prognosis was tested using a validation dataset from our samples. The nomogram achieved a C-index of 0.719 (95% CI, 0.674-0.764). Time-dependent receiver operating characteristic curve (ROC) analysis indicated the superior prognostic accuracy of nomograms for DFS prediction (0.76, 95% CI, 0.697-0.807). Further, the four clusters (median DFS = 11.8, 15.3, 17.9, and 18.9 months, respectively) showed a high frequency of TTN (cluster 1), fibroblast growth factor receptor-3 (cluster 2), TP53 (cluster 3), and TP53 mutations (cluster 4), respectively. They were enriched with M2 macrophages (cluster 1), CD8 + T cells (cluster 2), M0 macrophages (cluster 3), and M0 macrophages (cluster 4), respectively. Clusters 2 and 3 demonstrated potential sensitivity to immunotherapy and insensitivity to chemotherapy, whereas cluster 4 showed potential insensitivity to immunotherapy and sensitivity to chemotherapy., Conclusions: The eight-lncRNA signature risk model may be a reliable prognostic signature for MIBC, which provides new insights into prediction of recurrence of MIBC. The model may help clinical decision and eventually benefit patients., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Conflicting results exist between the potential protective effects of metformin and the prognosis of urologic cancers. This meta-analysis summarized the effects of metformin exposure on the recurrence, progression, cancer-specific survival (CSS), and overall survival (OS) of the three main urologic cancers (kidney cancer, bladder cancer, and prostate cancer)., Methods: We systematically searched PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases (January 2010 to December 2019), which identified studies regarding metformin users and nonusers with urologic cancers and extracted patient data. A random effect model or fixed effect model was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs)., Results: Among the 1883 confirmed studies, 27 eligible studies were identified, including 123,212 participants. In prostate cancer, patients using metformin have significant benefits for recurrence (HR = 0.74; 95% CI: 0.61-0.90; P = 0.007; I 2 = 56%), CSS (HR = 0.74; 95% CI: 0.61-0.91; P = 0.002; I 2 = 79%), and OS (HR = 0.76; 95% CI: 0.65-0.90; P < 0.001; I 2 = 86%). Moreover, further subgroup analysis showed that the beneficial effects of metformin may be more significant for patients receiving radical radiotherapy. For kidney cancer, metformin was beneficial for progression (HR = 0.80; 95% CI: 0.65-0.98; P = 0.14; I 2 = 46%). Analysis revealed that the effect of metformin on the overall survival of kidney cancer patients may be related to nationality (American: HR = 0.76; 95% CI: 0.59-0.98; P = 0.88; I 2 = 0%). For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a median follow-up time of more than 4 years (HR = 0.43; 95% CI: 0.28-0.67; P = 0.61; I 2 = 0%)., Competing Interests: The authors have declared that there is no competition of interests., (Copyright © 2021 Xiangyang Yao et al.)

Introduction: It's widely reported the "writer" enzymes mediated RNA adenosine modifications which is known as a crucial mechanism of epigenetic regulation in development of tumor and the immunologic response in many kinds of cancers. However, the potential roles of these writer genes in the progression of bladder cancer (BLCA) remain unclear., Materials and Methods: We comprehensively described the alterations of 26 RNA modification writer genes in BLCA from the genetic and transcriptional fields and identified writer-related genes from four independent datasets. Utilizing least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression, we constructed a ten writer-related gene signature. After that, we confirmed the predictive and prognostic value of this signature on another six independent datasets and established a nomogram to forecast the overall survival (OS) and mortality odds of BLCA patients clinically., Results: The writer-related genes signature showed good performance in predicting the OS for BLCA patients. Moreover, the writer-related gene signature was related to EMT-related pathways and immune characteristics. Furthermore, the immune cell infiltration levels of CD8 T cells, cytotoxic cells, M1/2 macrophage cells and tumor mutation burden might be able to predict which patients will benefit from immunotherapy. This could also be reflected by the writer-related gene signature., Conclusions: This signature might play an important role in precision individualized immunotherapy. The present work highlights the crucial clinical implications of RNA modifications and may help developing individualized therapeutic strategies for patients with BLCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Liu, Wang, Li, Xing and Xiao.)

Background: Bladder cancer (BLCA) is one of the most common urinary malignancies with poor prognosis. There is an unmet need to develop novel robust tools to predict prognosis and treatment efficacy for BLCA., Methods: The hypoxia-related genes were collected from the Molecular Signatures Database. The TCGA-BLCA cohort was downloaded from the Cancer Genome Atlas and then was randomly divided into training and internal validation sets. Two external validation cohorts were gathered from Gene Expression Omnibus. Also, another independent validation cohort (Xiangya cohort) was collected from our hospital. The Cox regression model with the LASSO algorithm was applied to develop the hypoxia risk score. Then, we correlated the hypoxia risk score with the clinical outcomes, the tumor microenvironment (TME) immune characteristics, and the efficacy prediction for several treatments, which included cancer immunotherapy, chemotherapy, radiotherapy, and targeted therapies., Results: Hypoxia risk score was an independent prognostic factor. A high-risk score indicated an inflamed TME based on the evidence that hypoxia risk score positively correlated with the activities of several cancer immunity cycles and the infiltration levels of many tumor-infiltrating immune cells, such as CD8 + T cells, Dendritic cells, and NK cells. Consistently, the hypoxia risk score was positively related to the expression of several immune checkpoints, such as PD-L1, PD-1, CTLA-4, and LAG-3, as well as the T cell inflamed score. Furthermore, the hypoxia risk score positively correlated with the enrichment scores of most immunotherapy-positive gene signatures. Therefore, patients with higher risk score may be more sensitive to cancer immunotherapy. Meanwhile, the hypoxia risk score was positively related to the sensitivities of several chemotherapeutic drugs, including Cisplatin, Docetaxel, Paclitaxel, Bleomycin, Camptothecin, and Vinblastine. Similarly, the enrichment scores for radiotherapy-predicted pathways and EGFR ligands were higher in the high-risk score group. Conversely, the enrichment scores of several immunosuppressive oncogenic pathways were significantly higher in the low-risk score group, such as the WNT-β-catenin network, PPARG network, and FGFR3 network., Conclusions: We developed and validated a new hypoxia risk score, which could predict the clinical outcomes and the TME immune characteristics of BLCA. In general, the hypoxia risk score may aid in the precision medicine for BLCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Tang, Qi, Othmane, Yang, Chen, Hu and Zu.)

Propofol‑based anesthesia has been reported to reduce the recurrence and metastasis of a number of cancer types following surgical resection. However, the effects of propofol in bladder cancer (BC) are yet to be fully elucidated. The aim of the present study was to investigate the functions of propofol in BC and their underlying mechanisms. In the study, the expression of microRNA (miR)‑145‑5p in BC tissues and cell lines was evaluated using reverse transcription‑quantitative PCR, and the effects of propofol on BC cells were determined using cell viability, wound healing and Transwell cell invasion assays, bioinformatics analysis, western blotting, immunohistochemistry and in vivo tumor xenograft models. It was found that propofol significantly suppressed the proliferation, migration and invasion of BC cells in vitro . In addition, propofol induced miR‑145‑5p expression in a time‑dependent manner, and miR‑145‑5p knockdown attenuated the inhibitory effects of propofol on the proliferation, migration and invasion of BC cells. Topoisomerase II α (TOP2A) was a direct target of miR‑145‑5p, and silencing TOP2A reversed the effects of miR‑145‑5p knockdown in propofol‑treated cells. Furthermore, propofol suppressed tumor xenograft growth, which was partially attenuated by miR‑145‑5p knockdown. The present study provided novel insight into the advantages of surgical intervention with propofol anesthesia in patients with BC.

Rationale: Siglec15 is an emerging target for normalization cancer immunotherapy. However, pan-cancer anti-Siglec15 treatment is not yet validated and the potential role of Siglec15 in bladder cancer (BLCA) remains elusive. Methods: We comprehensively evaluated the expression pattern and immunological role of Siglec15 using pan-cancer analysis based on RNA sequencing data obtained from The Cancer Genome Atlas. We then systematically correlated Siglec15 with immunological characteristics in the BLCA tumor microenvironment (TME), including immunomodulators, cancer immunity cycles, tumor-infiltrating immune cells (TIICs), immune checkpoints, and T cell inflamed score. We also analyzed the role of Siglec15 in predicting the molecular subtype and the response to several treatment options in BLCA. Our results were validated in several public cohorts as well as our BLCA tumor microarray cohort, the Xiangya cohort. We developed an immune risk score (IRS), validated it, and tested its ability to predict the prognosis and response to cancer immunotherapy. Results: We found that Siglec15 was specifically overexpressed in the TME of various cancers. We hypothesize that Siglec15 designs a non-inflamed TME in BLCA based on the evidence that Siglec15 negatively correlated with immunomodulators, TIICs, cancer immunity cycles, immune checkpoints, and T cell inflamed score. Bladder cancer with high Siglec15 expression was not sensitive to cancer immunotherapy, but exhibited a higher incidence of hyperprogression. High Siglec15 levels indicated a luminal subtype of BLCA characterized by lower immune infiltration, lower response to cancer immunotherapy and neoadjuvant chemotherapy, but higher response to anti-angiogenic therapy and targeted therapies such as blocking Siglec15, β-catenin, PPAR-γ, and FGFR3 pathways. Notably, a combination of anti-Siglec15 and cancer immunotherapy may be a more effective strategy than monotherapy. IRS can accurately predict the prognosis and response to cancer immunotherapy. Conclusions: Anti-Siglec15 immunotherapy might be suitable for BLCA treatment as Siglec15 correlates with a non-inflamed TME in BLCA. Siglec15 could also predict the molecular subtype and the response to several treatment options., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Objective: To investigate the efficacy and safety of transurethral holmium laser resection (THOLR) and transurethral electrocision (TUR) combined with intravesical epirubicin within 24 hours postoperatively for treatment of non-muscular invasive bladder cancer., Methods: A total of 218 consecutive patients who were newly diagnosed with bladder cancer were enrolled in this prospective study from July 2014 to December 2017. The patients were randomly divided into THOLR and TUR groups. All patients received intravesical epirubicin (30 mg dissolved in 5% glucose solution) within 24 hours postoperatively. The operation time, blood loss, rate of obturator reflex, hospitalization time, catheterization time, complications, and recurrence were analyzed., Results: Operation, hospitalization, and catheterization times were significantly greater in the TUR group than in the THOLR group. The rates of blood loss and intraoperative obturator reflex were also significantly greater in the TUR group. There were no significant differences in complications, recurrence rate survival, or recurrence-free survival between the two groups, with the exception of bladder perforation rate., Conclusions: THOLR and TUR combined with intravesical epirubicin within 24 hours postoperatively were both safe and effective for treatment of bladder tumor; however, patients who undergo THOLR might experience more rapid recovery.

BACKGROUND Orientin is a flavone isolated from medicinal plants used in traditional Chinese medicine (TCM), which suppresses the growth of cancer cells in vitro. The effects of orientin in bladder cancer cells remains unknown. This study aimed to investigate the effect of orientin on proliferation and apoptosis of T24 human transitional cell bladder carcinoma cells in vitro in the presence of an agonist and an inhibitor of nuclear factor-kappaB (NF-kappaB). MATERIAL AND METHODS T24 cells were cultured and divided into four study groups: an untreated control group; a group treated with 100 μM orientin; a group treated with 100 μM orientin with NF-kappaB agonist, phorbol 12-myristate 13-acetate (PMA); and a group treated with 100 μM orientin and the NF-kappaB inhibitor, IkappaBalpha. The MTT assay was performed to assess cell viability, and flow cytometry evaluated the cell cycle. The expression of proteins in the Hedgehog signaling pathway and inflammatory cytokines were determined by Western blot and enzyme-linked immunosorbent assay (ELISA). RESULTS Orientin inhibited the proliferation of T24 cells, caused cell cycle arrest, reduced cell viability, and inhibited the expression of inflammatory mediators. Treatment of T24 cells with orientin inhibited the expression of NF-kappaB and components of the Hedgehog signaling pathway, and the NF-kappaB agonist, PMA, reversed these effects. CONCLUSIONS Treatment of T24 human bladder carcinoma cells in vitro with orientin inhibited cell proliferation and promoted cell apoptosis by suppressing the Hedgehog signaling pathway and NF-kappaB.

BACKGROUND Testis-specific gene antigen 10 (TSGA10) is a tumor suppressor in several types of human malignancy. However, there have been few studies that have investigated the role of TSGA10 in bladder cancer. This study aimed to investigate the expression of TSGA10 in human bladder cancer cell lines and bladder cancer tissues and its effects on patient prognosis. MATERIAL AND METHODS The expression of TSGA10 in 40 tissue samples of bladder cancer and matched normal adjacent bladder tissue, and five human bladder cancer cell lines was assessed by immunohistochemistry, Western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and flow cytometry. The correlation between the expression level of TSGA10 and the clinicopathological features of patients with bladder cancer was analyzed and overall survival (OS) in patients with bladder cancer was determined by Kaplan-Meier curves. RESULTS Upregulation of TSGA10 expression in tissues from patients with bladder cancer was compared with normal adjacent bladder tissue and was significantly correlated with gender, metastasis, lymphovascular invasion, and tumor stage in bladder cancer. In bladder cancer cell lines, down-regulation of TSGA10 reduced cell apoptosis and increased cell migration, and resulted in the formation of an epithelial-mesenchymal transition (EMT) phenotype. Overexpression of TSGA10 resulted in an increased apoptosis rate of tumor cells, reduced cell migration, and contributed to the reversal of the EMT phenotype. CONCLUSIONS These findings support that TSGA10 deserves further study as a potential novel prognostic biomarker in bladder cancer.

Purpose: We sought to identify the method that could obtain the best survival rate for AJCC stage IV bladder cancer (BCa) patients., Methods: Patients with AJCC stage IV BCa diagnosed between 2004 and 2015 were identified using the Surveillance, epidemiology and end results (SEER) database. Kaplan-Meier curves and log-rank test were used for overall survival (OS) and cancer-specific survival (CSS). Multivariable Cox regression was used to determine factors associated with all-cause mortality (ACM) and cancer-specific mortality (CSM)., Results: We found that among the 11824 patients, the number of patients who received chemotherapy (CT), radiotherapy (RT) and radical cystectomy (RC) was 6243 (52.8%), 2005 (17.0%) and 4987 (42.2%), respectively. Patients who received CT or RC had improved OS (26.4% vs. 11.7%, p < 0.001 and 27.3% vs. 13.7%, p < 0.001, respectively), but patients who underwent RT alone had lower OS (14.4% vs. 20.5%, p < 0.001). Furthermore, CT combined with RC was associated with the lowest ACM (hazard ratio (HR) = 0.26, 95% CI 0.24-0.28, p < 0.001) and the lowest CSM (HR = 0.24, 95% CI 0.22-0.26, p < 0.001). Patients who only received RT had the highest ACM (HR = 0.84, 95% CI 0.77-0.92, p < 0.001) and the highest CSM (HR = 0.85, 95% CI 0.77-0.94, p = 0.002)., Conclusions: We concluded that CT combined with RC was the best method with the highest survival rate for patients with AJCC stage IV BCa and that CT combined with RC had more benefits in improving OS and CSS than did RT alone.

Background: Oncostatin M receptor (OSMR) represents a part of the interleukin-six (IL6) cytokine group that was discovered recently to be closely associated with cell's growth and differentiation, inflammation, and enhancement of metastatic capacity. A comprehensive study suggests a close relationship between OSMR and papillary thyroid cancer, colorectal cancer, breast cancer, and other tumors. However, the relationship between OSMR and bladder cancer has yet to be determined., Methods: Three hundred six patients (including 142 patients with muscle-invasive bladder cancer and 164 patients with non-muscle-invasive bladder cancer) as well as 459 normal controls were included in this study. Two tag SNPs of OSMR, rs2278329, and rs2292016 were genotyped by TaqMan® SNP Genotyping Assay method and then the associations with bladder cancer were analyzed, as well as risk factors and prognosis., Results: Patients with bladder cancer and controls did not differ significantly in terms of genotype frequencies and allele frequency distribution of rs2278329 (P = 0.77, OR = 0.97) and rs2292016 (P = 0.39, OR = 1.20) respectively. For rs2278329, no differences were found in terms of risk factors in stratified analyses. However, rs2292016 was associated with recurrence and tumor grade. GT/TT was found to increase the risk of relapse compared to the patients without allele T (GG genotype) (P = 0.016, OR = 1.878, 95% CI = 1.12-3.14) with the T allele of rs2292016 being a risk factor for recurrence (P = 0.032, OR = 0.67, 95% CI = 0.47-0.97). Besides, patients with GT genotype often present with high-grade bladder cancer (P = 0.003, OR = 2.33, 95% CI = 1.32-4.17). Multiple Cox regression analysis showed that rs2278329 and rs2292016 were related to the recurrence-free survival and overall survival in non muscle invasive bladder cancer (NMIBC) patients. For rs2278329, GA genotype could affect recurrence-free survival (P = 0.01, OR = 2.16, 95% CI = 1.17-3.98). For rs2292016, TT/GT genotype had a lower risk of death compared with GG homozygote genotype, and T was a protective factor for overall survival in bladder cancer (P = 0.029, OR = 0.22, 95% CI = 0.06-0.86)., Conclusions: OSMR genotype frequencies were found to be associated with higher recurrence in bladder cancer, and it may serve as a biomarker candidate gene to predict prognosis of this disease. Further validation of OSMR as biomarker is required.

Bladder cancer is one of the common malignant tumors in China. Three-quarter bladder cancer is non-muscle invasive bladder cancer with a high recurrence rate. Intravesical therapy can reduce the risk of recurrence and progression in bladder cancer. According to the recent updates of evidence-based medical evidence at home and abroad, as well as the deepening of domestic experts' research on the diagnosis and treatment of bladder cancer, the consensus has summarized the current intravesical therapy for non-muscle invasive bladder cancer in China, including the indications, contraindications and methods for intravesical therapy, as well as commonly used drugs in bladder cancer.

Purpose: To investigate the effects of intra-arterial chemotherapy on T1 stage bladder cancer (Bca) and evaluate patient outcome with bladder-preserving treatment approaches., Materials and Methods: A total of 238 patients with T1 stage Bca were retrospectively analyzed. Among them, 35 patients were categorized into the subgroup of highest-risk T1 stage according to the European Association of Urology guidelines and received immediate radical cystectomy (RC group), whereas 62 were classified as being highest-risk T1 patients but were unwilling to undergo RC and were treated with gemcitabine plus cisplatin intra-arterial chemotherapy (GC group). There were 141 T1 patients who had bladder-preserving surgery with intravesical chemotherapy (IVC group)., Results: For patients with T1 stage Bca, the GC group had a higher estimated recurrence-free survival rate (44.4 vs. 13.9%, P = 0.087), progression-free survival rate (75.4 vs. 32.8%, P = 0.006), and cancer-specific survival (CSS) rate (78.7 vs. 67.5%, P = 0.399) when compared with the IVC group, respectively. Using the multivariable regression model, the GC intra-arterial chemotherapy was significantly related to bladder preservation (P = 0.004), lower recurrence (P = 0.012), and less progression (P = 0.004). For patients with the highest-risk T1 stage, GC group did not have a poorer CSS rate in comparison with the RC group (P = 0.383). Moreover, immediate RC did not confer a survival benefit in terms of CSS when compared with those who underwent deferred RC after failing GC intra-arterial chemotherapy (P = 0.283)., Conclusions: Gemcitabine plus cisplatin intra-arterial chemotherapy may be an effective bladder-preserving alternative adjuvant treatment for patients with T1 stage Bca with oncologic benefits, good compliance, and low toxicity.

Mounting evidence indicates that microbiome plays an important role in the development and progression of cancer. The dogma that urine in healthy individuals must be sterile has been overturned. Dysbiosis of the urinary microbiome has been revealed responsible for various urological disorders, including prostate cancer. The link between chronic inflammation, microbiome and solid tumors has been established for various neoplastic diseases. However, a detailed and comprehensive analysis of urinary microenvironment of bladder cancer has not been yet reported. We performed this study to characterize the potential urinary microbial community possibly associated with bladder cancer. Mid-stream urine was collected from 31 male patients with bladder cancer and 18 non-neoplastic controls. DNA was extracted from urine pellet samples and processed for high throughput 16S rRNA amplicon sequencing of the V4 region using Illumina MiSeq. Sequencing reads were filtered using QIIME and clustered using UPARSE. We observed increased bacterial richness (Observed Species, Chao 1 and Ace indexes; cancer vs. control; 120.0 vs. 56.0; 134.5 vs. 68.3; and 139.6 vs. 72.9, respectively), enrichment of some bacterial genera (e.g., Acinetobacter, Anaerococcus, and Sphingobacterium ) and decrease of some bacterial genera (e.g., Serratia, Proteus , and Roseomonas ) in cancer group when compared to non-cancer group. Significant difference in beta diversity was found between cancer and non-cancer group, among different risk level, but not among different tumor grade. Enrichment of Herbaspirillum, Porphyrobacter , and Bacteroides was observed in cancer patients with high risk of recurrence and progression, which means these genera maybe potential biomarkers for risk stratification. The PICRUSt showed that various functional pathways were enriched in cancer group, including Staphylococcus aureus infection, glycerolipid metabolism and retinol metabolism. To our knowledge, we performed the most comprehensive study to date to characterize the urinary microbiome associated with bladder cancer. A better understanding of the role of microbiome in the development and progression of bladder cancer could pave a new way for exploring new therapeutic options and biomarkers.

Background: The expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC)., Methods: There were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients' clinical characteristics, and clinical results., Results: B4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm 2 ) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression., Conclusions: Our evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.

Background: N-acetyltransferase 2 (NAT2) is involved in both carcinogen detoxification through hepatic N-acetylation and carcinogen activation through local O-acetylation. NAT2 slow acetylation status is significantly associated with increased bladder cancer risk among European populations, but its association in Asian populations is inconclusive., Methods: NAT2 acetylation status was determined by both single nucleotide polymorphisms (SNPs) and caffeine metabolic ratio (CMR), in a population-based study of 494 bladder cancer patients and 507 control subjects in Shanghai, China., Results: The CMR, a functional measure of hepatic N-acetylation, was significantly reduced in a dose-dependent manner among both cases and controls possessing the SNP-inferred NAT2 slow acetylation status (all P-values<5.0×10-10). The CMR-determined slow N-acetylation status (CMR<0.34) was significantly associated with a 50% increased risk of bladder cancer (odds ratio = 1.50, 95% confidence interval = 1.10-2.06) whereas the SNP-inferred slow acetylation statuses were significantly associated with an approximately 50% decreased risk of bladder cancer. The genotype-disease association was strengthened after the adjustment for CMR and was primarily observed among never smokers., Conclusions: The apparent differential associations for phenotypic and genetic measures of acetylation statuses with bladder cancer risk may reflect dual functions of NAT2 in bladder carcinogenesis because the former only measures the capacity of carcinogen detoxification pathway while the latter represents both carcinogen activation and detoxification pathways. Future studies are warranted to ascertain the specific role of N- and O-acetylation in bladder carcinogenesis, particularly in populations exposed to different types of bladder carcinogens., Competing Interests: The authors declare no competing interests.

Bladder cancer is one of the most common malignancies worldwide and the stage pT1nonmuscle invasive bladder cancer (NMIBC) has a high probability of recurrence after initial diagnosis and treatment. However, risk factors predictive of repeated recurrence and progression of pT1 bladder tumors after primary relapse have not been uncovered. Thus, we conducted the retrospective study.A total of 418 patients who suffered initial recurrence after transurethral resection (TUR) of pT1 bladder tumor were selected for the analyses. Clinic information of the patients was retrieved from their medical records. Recurrence-free survival (RFS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. The probability of recurrence and progression by multivariate analyses was used as a surrogate marker to construct receiver operating curve (ROC).Results showed that variables including time to prior recurrence time, prior treatment, number of tumor, tumor size, tumor grade, and time of instillation after surgery were associated with the repeated recurrence of pT1 bladder tumor (P < 0.05). The variables including time to prior recurrence time, tumor size, tumor grade, carcinoma in situ (CIS), and time of instillation after surgery were associated with progression of pT1 bladder tumor (P < 0.05). In the present study, the multivariate model showed an area under ROC (AUC) value of 0.754 and 0.798 for tumor recurrence and progression, respectively, which was more effective in prediction than a single risk factor.In conclusion, we have identified several risk factors relevant to RFS and PFS for patients who have had a history of recurrence of pT1 bladder tumor after TUR. These predictive factors may help urologists to stratify patients into distinct risk groups of recurrence and progression, which probably contributes to the individualized treatment for patients.

Lactate dehydrogenase-A(LDH-A) is an important rate-limiting enzyme in the Warburg effect. Survival analysis indicated poor clinical outcomes in MIBC with high LDH-A expression. The results of in vitro experiment indicated that LDH-A promotes MIBC cells proliferation, invasion and migration. The positive relationship between LDH-A expression and CSC/EMT markers was confirmed both in invasive bladder cell line and in 136 MIBC specimens. Thus, we conclude that LDH-A may be a promising target for MIBC., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Long noncoding RNAs (lncRNAs) have been implicated playing important roles in human urologic cancers. In the present study, microarray analysis was initially performed to screen the differentially expressed lncRNAs between bladder cancer tissues and paired adjacent non-cancerous tissues (n = 3). Subsequent qRT-PCR validation was conducted using tissue samples from 95 patients with bladder cancer. Results showed that the expression level of lncRNA-n336928 (noncode database ID: n336928) was significantly higher in bladder cancer tissues compared to that in adjacent noncancerous tissues (P < 0.001). Chi-square test showed that expression of lncRNA-n336928 was positively correlated with bladder tumor stage and histological grade (P < 0.001). Kaplan-Meier survival analysis revealed that patients with bladder cancer with high expression of lncRNA-n336928 had shorter overall survival time compared to the patients with low expression of lncRNA-n336928. Multivariate analysis indicated that lncRNA-n336928 was an independent prognostic factor for overall survival for bladder cancer patients. Collectively, our study shows that high expression of lncRNA-n336928 is associated with the progression of bladder cancer, and that lncRNA-n336928 might serve as a biomarker for prognosis of bladder cancer., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: Oxidative stress is believed to be one of the important etiologies in carcinogenesis that has not been systemically investigated in urothelial carcinoma (UC). Through data mining from a published transcriptomic database of UC of urinary bladders (UBUCs) (GSE31684), glutathione peroxidase 2 (GPX2) was identified as the most significant downregulated gene among those response to oxidative stress (GO:0006979). We therefore analyze GPX2 transcript and protein expressions and its clinicopathological significance., Methods: Real-time RT-PCR assay was used to detect GPX2 mRNA level in 20 fresh UBUC specimens. Immunohistochemistry was used to determine GPX2 protein expression in 340 urothelial carcinomas of upper tracts (UTUCs) and 295 UBUCs with mean/median follow-up of 44.7/38.9 and 30.8/23.1 months, respectively. Its expression status was further correlated with clinicopathological features and evaluated for its impact on disease-specific survival and metastasis-free survival (MeFS)., Results: Decrease in GPX2 transcript level was associated with both higher pT and positive nodal status in 20 UBUCs (all p < 0.05). GPX2 protein underexpression was also significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs (all p < 0.05). GPX2 underexpression not only predicted dismal DDS and MeFS at univariate analysis, but also implicated worse DDS (UTUC, p = 0.002; UBUC, p = 0.029) and MeFS (UTUC, p = 0.001; UBUC, p = 0.032) in multivariate analysis., Conclusions: GPX2 underexpression is associated with advanced tumor status and implicated unfavorable clinical outcome of UCs, suggesting its role in tumor progression and may serve as a theranostic biomarker of UCs.

Purpose: To explore the characteristics, predictive risk factors, and prognostic effect of concomitant non-muscle-invasive bladder cancer (NMIBC) in patients with upper tract urothelial carcinoma (UTUC)., Methods: We evaluated 727 consecutive UTUC patients treated with radical resection between 2000 and 2012 in a high-volume center of China. Preoperative cystoscopy was performed in all patients. Patients with previous or concomitant total cystectomy were excluded., Results: Overall, 73 patients (10.0 %) had NMIBC. Concomitant NMIBC was associated with previous bladder cancer (p = 0.003), tumor located in ureter (p = 0.008), multifocality (p < 0.001), and preoperative renal insufficiency (p = 0.023). The presence of concomitant NMIBC was predictive for lower tumor stage (p = 0.019), papillary architecture (p = 0.023), and organ-confined disease (pT < 3 and N-, p = 0.006). The median follow-up duration was 57 months. The presence of concomitant NMIBC was a risk factor for bladder recurrence (p < 0.001), and particularly in patients with non-muscle-invasive UTUCs, it affects cancer-specific survival (odds ratio 1.614, p = 0.030) and contralateral recurrence (odds ratio, 1.907, p = 0.016). Most concomitant NMIBC were found at the lateral wall or bladder neck, while most intravesical recurrences occurred near the site of surgery or posterior wall., Conclusions: The most common site for concomitant NMIBC was lateral wall and bladder neck, and previous bladder cancer, tumor located in ureter, tumor multifocality, and preoperative renal insufficiency were risk factors for concomitant NMIBC. The presence of concomitant NMIBC is predictive for relative better pathologic outcomes but higher rate of bladder recurrence, while the effect on postoperative survival was limited with patients early-stage UTUCs. The potential mechanisms need further investigation.

Purpose: CD8(+) TILs at different tumor sites have diverse clinical attributes, which might result from distinct tumor microenvironments that promote differentiation into distinct subsets. However, only a few markers have been identified that can define CD8(+) T-cell subsets. CD103 is a marker of tissue resident memory CD8(+) T cells. In this retrospective study we investigated the cellular source and clinical significance of CD103 expression in urothelial cell carcinoma of bladder tissues in situ., Materials and Methods: Immunohistochemistry and immunofluorescence were used to identify the cellular source of CD103 in bladder urothelial cell carcinoma tissues. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall and recurrence-free survival in 302 patients with bladder urothelial cell carcinoma., Results: CD8(+) T cells but not natural killer cells accounted for most CD103 expressing cells in bladder urothelial cell carcinoma tissues. Notably CD103(+) cells were predominantly located in intratumor regions rather than in associated stroma (p < 0.0001). The density of intratumor CD103(+) TILs was inversely associated with tumor size (p < 0.0001) and could represent a favorable prognostic predictor of overall and recurrence-free survival (p = 0.002 and 0.011, respectively). Moreover, intratumor CD103(+) TILs were positively associated with the expression of cognate ligand E-cadherin in intratumor regions of bladder urothelial cell carcinoma tissues (p = 0.008)., Conclusions: Our findings suggest that CD8(+) T cells might have a significant role in tumor immunity by expressing CD103 in intratumor regions of bladder urothelial cell carcinoma tissues. Intratumor CD103(+) TILs could potentially serve as a prognostic marker in patients with bladder urothelial cell carcinoma., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the impact of body mass on recurrence and progression in patients with Ta, T1 urothelial bladder cancer., Methods: Data from 469 patients with Ta, T1 bladder cancer who were treated with transurethral resection of bladder tumor at our center during 2006-2014 were retrospectively studied. According to body mass index (BMI), patients were divided into three groups: normal weight (BMI < 24 kg/m(2)), overweight (24 kg/m(2) ≤ BMI < 28 kg/m(2)) and obesity (BMI ≥ 28 kg/m(2)). Clinicopathologic features were compared across groups. Kaplan-Meier curves and Cox proportional hazards regression analyses were employed to assess the association between body mass and oncologic outcomes., Results: Compared with patients with normal weight, overweight and obese counterparts showed significantly shorter recurrence-free or progression-free survival. In multivariate analyses, being overweight was an independent factor for recurrence and obesity was for both recurrence and progression. The presence of diabetes mellitus (DM) was not a strong risk factor for the entire cohort, while it became a significant predictor for both recurrence and progression in the subgroup of overweight and obese patients., Conclusion: Excessive body mass seems to act as independent risk factors for worse oncologic outcomes of Ta, T1 bladder cancer. Further studies should be carried out to elucidate the exact impact of obesity, DM or even other metabolic disorders.

Papillary urothelial neoplasm of low malignant potential (PUNLMP) had the incidence of low and definitive recurrence. Therefore, few studies showed that the relationship between pathological factors and the prognosis of patients with PUNLMP. The aim of this study assessed the linkage of pathological factors and prognosis of patients with PUNLMP including the presence or absence of mitoses and the thickness of urothelium. A retrospective analysis of 71 patients with PUNLMP was enrolled between January 2007 and June 2013. The clinicopathological factors consisting of tumor diameter, multifocality, the presence or absence of mitoses and cell thickness of urothelium were retrieved, Log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses to evaluate the associations of these factors with recurrence-free survival (RFS) and progression-free survival (PFS).The incidence of recurrence and progression for PUNLMP was 19.7% and 16.9%, respectively. Patients with grade progression represented 85.7% in the recurrent patients. No patients had stage progression and no cases died from invasive urothelial carcinoma. Univariate analysis showed that the presence of mitoses, tumor diameter greater than or equal to 0.8 cm, multifocality were significantly correlated with worse RFS (P<0.05) and PFS (P<0.05). Multivariate analysis demonstrated that the presence of mitoses, tumor multifocality were significantly independent biomarkers for worse RFS (P<0.05) and PFS (P<0.05). Although the rare and infrequent mitoses were found for PUNLMP, the presence of mitoses and tumor multifocality were still the independent and poor predictors for the prognosis of PUNLMP. In addition, once the PUNLMP appeared to the recurrence, the inevitable grade progression could be determined, herein, long-term follow-up was necessary to be warranted, especially for patients with multiple lesions and the presence of mitoses.

Objective: The risk factors of bladder cancer recurrence after transurethral resection of bladder tumor (TURBt) were poorly understood, especially in Chinese population. This study evaluated the potential risk factors of recurrence based on a Chinese population., Materials and Methods: A total of 698 patients that received TURBt procedure in our institute from 2000 to 2012 were recruited in this study. Clinical information was collected. The patients were followed up according to the schedule recommended by Chinese guideline., Results: A total of 583 males (83.5%) and 115 females (16.5%) were enrolled in our study. The median follow-up duration was 51.5 months. Gender, chief complain, tumor size, number of lesions, histological grade and chemotherapeutic agents were found significantly associated with patients' short-term recurrence (less than 1 year) (All p<0.05). In the multivariate analysis, tumor size, number of lesions, histological grade and chemotherapeutic agents were significantly related to patients' short-term recurrence (less than 1 year) (All p<0.05). A multivariate model based on tumor size, number of lesions, histological grade and chemotherapeutic agents had an AUC of 0.697, which significantly improved the prediction utility for bladder cancer short-term recurrence (less than 1 year) than any single factor In the multivariate Cox regression, tumor size greater than 3 cm, multifocal lesions, worsen histological grade and non-urothelial carcinoma was related to time to recurrence (TR)., Conclusion: Patients with larger tumor size, multifocal number of lesions, higher tumor grade and who received chemotherapeutic agents other than Epirubicin and Pirarubicin might have higher risks of recurrence less than 1 year. Tumor size, number of lesions, pathology and histological grade might be associated with TR. As Bacille Calmette-Guerin (BCG) is currently not approved for bladder cancer in China, Epirubicin and Pirarubicin might be considered prior to other chemotherapy medications when providing post-operative instillation of chemotherapy.

Bladder cancer is the ninth most frequent malignancy in China. Toll-like receptor 4 (TLR4) is expressed on various cells and greatly involves in immune responses. Genetic polymorphism may affect the pathogenesis of diseases through various pathways. In the current study, we evaluated the association between genetic polymorphisms in TLR4 and risk of bladder cancer. We also examined the effect of the polymorphisms on gene expression. The TLR4 -729G/C and -260G/C polymorphisms were genotyped in 282 bladder cancer patients and 298 healthy controls in the Chinese population. Results showed that subjects with -729GC genotype are at significantly higher risk of bladder cancer than those with GG genotype [odds ratio (OR) = 2.50, 95% confidence interval (CI) = 1.39-4.48, P = 0.002]. Similarly, TLR4 -729C allele revealed a positive association with the disease (OR = 2.39, P = 0.002). The other polymorphism, TLR4 -260G/C, did not present clear correlations with bladder cancer. To understand the function of the polymorphisms, we evaluated TLR4 messenger RNA (mRNA) and protein levels in CD4+ T cells, CD8+ T cells, and monocytes from subjects carrying different TLR4 genotypes. Results revealed that subjects carrying -729GC genotype had significantly downregulated mRNA and protein levels of TLR4 in CD4+ T cells, CD8+ T cells, and monocytes compared to those carrying GG genotype. However, subjects with -260G/C polymorphism did not show any differences in gene expression from immune cells These data suggest that TLR4 polymorphism is associated with increased susceptibility to bladder cancer possibly by downregulating gene expression in various immune cells.

The TERT promoter and FGFR3 gene mutations are two of the most common genetic events in urothelial bladder cancer (UBC), and these mutation assays in patient urine have been shown to be promising biomarkers for UBC diagnosis and surveillance. These results were obtained mainly from studies of patients with UBC in Western countries, and little is known about such information in Han Chinese patients with UBC. In the present study, we addressed this issue by analyzing tumors from 182 Han Chinese patients with UBC and urine samples from 102 patients for mutations in the TERT promoter and FGFR3 and TERT mRNA expression in tumors and/or urine. TERT promoter and FGFR3 mutations were identified in 87 of 182 (47.8%) and 7 of 102 (6.7%) UBC cases, respectively. In 46 urine samples from patients with TERT promoter mutation-carrying tumors, the mutant promoter was detected in 24 (52%) prior to operation and disappeared in most examined urine samples (80%) taken 1 week after operation. TERT mRNA was detected in urine derived from 46 of 49 patients (94%) that was analyzed before operation independently of the presence of TERT promoter mutations. Collectively, FGFR3 mutations occur at a very low rate in Han Chinese UBC and cannot serve as diagnostic markers for Chinese patients. Han Chinese patients with UBC have relatively low TERT promoter mutation frequency compared with patients in Western countries, and simultaneous detection of both mutant TERT promoter and TERT mRNA improves sensitivity and specificity of urine-based diagnosis., (©AlphaMed Press.)

Purpose: To evaluate the clinical value of fluorescence in situ hybridization (FISH) for diagnosis and surveillance of bladder urothelial carcinoma (BUC)., Materials and Methods: Between November 2010 and December 2013, patients suspected of having BUC were examined using urine cytology and FISH assay. Based on histopathological examination results, FISH results were com­pared with urine cytology. In addition, patients with a history of non-muscle invasive BUC were also examined using urine cytology and FISH assay at the first time of visit and then monitored with cystoscopy during follow-up period., Results: A total of 162 patients included in this study and 12 patients were excluded due to uninformative FISH assays. The remaining 150 patients consisted of 108 patients suspected for BUC and 42 patients with a history of non-muscle invasive BUC. The sensitivities of FISH analysis and urine cytology were 72.8% and 27.2%, respectively, and the difference was statistically significant (P <.05). Difference between specificity of urine cytology (100%) and FISH assay (85%) was not statistically significant (P >.05). At the first visit, of 42 patients, one patient had positive cystoscopy, and FISH assay was positive in 26 of 41 patients with negative cystoscopy. During the follow-up period (mean, 29.5 months), 18 of 26 patients developed recurrence, and recurrence occurred in only one of 15 patients with negative FISH analysis., Conclusion: Our results suggest that FISH analysis can be used as a non-invasive diagnostic tool for patients suspect­ed of having new BUC. In addition, FISH analysis may provide important prognostic information to better define the individual risk for BUC recurrence.& nbsp;

Background/purpose: There is currently no consensus about the pattern and risk factors of bladder recurrence after nephroureterectomy, especially in the Chinese population. We evaluated the pattern and risk factors based on data from a large Chinese center., Methods: The clinical and pathological data of 438 patients with upper tract urothelial carcinoma (UTUC), who underwent nephroureterectomy at Peking University First Hospital, Beijing, China between 2000 and 2010, was retrospectively analyzed. Univariate analysis by log-rank test and multivariate analysis by Cox proportional hazards regression model were used to determine the independent risk factors., Results: A total of 135 patients (30.8%) developed intravesical recurrence within a median follow-up of 45 months (range: 12-144 months). The median interval of bladder recurrence was 15 months (range: 2.0-98.0 months), and the two peaks for recurrence were 4-6 months and 17-19 months. Lower tumor grade, tumor multifocality, concomitant carcinoma in situ (CIS) and tumors located in the lower ureter were significant risk factors by univariate and multivariate analysis. A risk-scoring system was developed and a significant difference was found between different risk evaluations. Patients with concomitant CIS tended to develop a late bladder recurrence. One hundred and eighteen patients (87.4%) received transurethral resection after bladder tumor recurrence., Conclusion: Lower tumor grade, tumor multifocality, concomitant CIS and tumors located in the lower ureter tend to be predictive for bladder recurrence after nephroureterectomy, although the underlying mechanism is not fully elucidated, and the scoring system could help risk stratification. Most recurrent tumors could be treated by transurethral resection and there were two peaks for recurrence, which is probably related to the mechanisms and may be unique to the Chinese population., (Copyright © 2013. Published by Elsevier B.V.)

Fast-track surgery (FTS), which combines various techniques with evidence-based adjustments, is aimed to reduce postoperative morbidity, attenuate surgical stress response, thereby accelerating recovery and shorting length of stay. To further investigate the effectiveness of fast-track surgery, we compared the short-term outcomes of laparoscopic radical cystectomy and ileal conduit diversion for Chinese bladder cancer patients with FTS or with CS in our hospital. Patients with bladder cancer were included and divided into two consecutive groups: CS group and FTS group. Duration to first flatus and regular diet, postoperative hospital days, hospital expense, incidence of complications and postoperative surgical stress response were compared. There was no significant difference between the two groups in age, sex, BMI and postoperative TNM classification. Compared with the CS group, the FTS group had significantly shorter duration to first flatus, time to regular diet, postoperative hospital days and hospital expense, less complications, lower white blood count (WBC) and serum of C-reactive protein (CRP) on postoperative day 5 and 7. Our study indicates that FTS program is safe and efficacious for Chinese patients undergoing laparoscopic radical cystectomy and ileal conduit diversion. It can accelerate recovery, reduce stress action, shorten postoperative hospitals days and reduce hospital expenses.

Genome-wide association studies (GWAS) have identified a number of genetic variants associated with risk of bladder cancer in populations of European descent. Here, we assessed association of two of these variants, rs11892031 (2q37.1 region) and rs401681 (5p15.33 region) in a Chinese case-control study, which included 367 bladder cancer cases and 420 controls. We found that the AC genotype of rs11892031 was associated with remarkably decreased risk of bladder cancer (adjusted odds ratio (OR), 0.27; 95% confidence interval (CI), 0.09-0.81; p=0.019), compared with the AA genotype of rs11892031; and that CT/CC genotypes of rs401681 were associated with significantly increased risk of bladder cancer (adjusted OR, 1.79; 95% CI, 1.10-2.91; p=0.02), compared with the TT genotype of rs401681. We further conducted stratification analysis to examine the correlation between single nucleotide polymorphism (SNP) rs11892031/rs401681 and tumor grade/stage. Results showed that heterogeneity in ORs of tumor categories was not significant for either rs11892031 or rs401681 (p>0.05), indicating that the two SNPs seemingly do not associate with tumor grade and stage of bladder cancer in our study population. The present study suggests that the SNPs rs11892031 and rs401681 are associated with bladder cancer risk in a Chinese population. Future analyses will be conducted with more participants recruited in a case-control study.

Thrombospondin-1 (TSP-1) is a glycoprotein that plays a major role in bladder cancer. We investigated the relationship between the distribution of the TSP-1 -696 C/T polymorphism (rs2664139) and the clinical features of bladder cancer. TaqMan assay was used to determine the genotype among the 609 cases and 670 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk. Compared with the CT/TT genotypes, the CC genotype was associated with a significantly increased risk of bladder cancer (adjusted odds ratio [OR] 1.43, 95% CI 1.01-2.04), which was more prominent among the male participants (OR 1.82, 95% CI 1.20-2.76). The polymorphism was associated with a higher risk of developing grade 3 (OR 1.84, 95% CI 1.00-3.36), multiple-tumor (OR 1.81, 95% CI 1.08-3.02), and large-tumor (OR 1.94, 95% CI 1.22-3.10) bladder cancers. These observations suggest that the TSP-1 -696 C/T polymorphism may contribute to bladder cancer susceptibility in the Chinese population., (Copyright © 2014. Published by Elsevier Inc.)

Interleukin-17 (IL-17) has been shown to play an important role in the pathogenesis of inflammation and autoimmune disorders, and to be elevated in several types of cancer. The present study analyzed polymorphisms in IL-17 gene and their impact on the pathogenesis of bladder cancer. The TaqMan® SNP Genotyping Assay was used to genotype the SNP rs2275913 of IL-17A and SNP rs763780 of IL-17F in 301 bladder cancer patients and 446 ethnicity-matched healthy controls. The frequencies of AA genotype and A allele of rs2275913, as well as TT genotype and T allele of rs763780 in the bladder cancer patients were significantly higher than that of controls, indicating that both of these two SNPs were associated with bladder cancer (P = 0.003, OR = 1.37, 95% CI = 1.12-1.69 for allele A of rs2275913, and P = 0.018, OR = 1.46, 95% CI = 1.07-2.00 for allele T of rs763780, respectively). Results of stratified analysis revealed that rs2275913 was associated with male, non-smokers, and invasion of bladder cancer, while rs763780 was associated with invasion of bladder cancer. Our results suggested that the SNP rs2275913 of IL-17A and SNP rs763780 of IL-17F were associated with the development, as well as gender, smoking status and tumor stage of bladder cancer., (© 2012 Wiley Periodicals, Inc.)

Recently, genome-wide association studies (GWAS) have identified over 12 single-nucleotide polymorphisms (SNPs) associated with bladder cancer risk in populations of European descent. However, effects of these SNPs in bladder cancer have not been systemically evaluated in the Chinese population. We conducted association studies of 12 SNPs in a Chinese population of 184 cases and 962 controls. These SNPs were previously identified in European GWAS and a fine mapping study. The reported risk alleles of rs798766 on TACC3 at 4p16 and rs9624880 on MYC at 8q24 were significantly associated with increased bladder cancer risk with P-values of 0.003 and 0.03, respectively. Next, we performed a meta-analysis, by combining our study with previous association studies performed in Chinese. In the meta-analysis, the reported risk allele for four SNPs were significantly associated with increased bladder cancer risk, including rs798766 on TACC3 at 4p16, rs9624880 on MYC at 8q24, rs2294008 on PSCA at 8q24, and rs2736100 on TERT at 5p15. The meta-analysis P-values for the four SNPs ranged from 0.017 to 5.52E-05. The results from our study suggest that a sub-set of bladder cancer risk-associated SNPs identified from the European population are also associated with bladder cancer risk in the Chinese population. Additional studies with larger sample sizes are needed to further confirm our results., (© 2012 Wiley Periodicals, Inc.)

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. After investigation, it was confirmed that there were considerably fewer cases with modified U-shaped ileal neobladder at the research institution than was written about in the manuscript., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to retrospectively analyze the clinicopathological features and prognosis of Chinese patients diagnosed with sarcomatoid carcinoma (SC) of the bladder., Methods: 13 patients admitted to the General Hospital of People's Liberation Army (PLA) between 1999 and 2010 (study group) and 74 Chinese patients diagnosed between 1994 and 2010 and reported in one of two Chinese databases (literature group)., Results: The two groups were similar in all demographic and clinical characteristics except depth of tumor invasion. SC of the bladder was most common in older males and most patients had high-grade or late-stage disease at diagnosis. The 6-month, 1-year, 2-year, and 5-years survival rates were 78.9%, 42.7%, 28.0%, and 21.0%, respectively. Analysis of the association of demographic and clinical characteristics with prognosis indicated no significant effect of sex, age, lesion location, tumor diameter, tumor type, depth of invasion, type of surgery, gross hematuria, and urinary tract infection., Conclusions: Our results suggest that the pathologic tumor stage was unrelated to prognosis. Early diagnosis and surgical intervention are preferred strategies for improvement of prognosis. The association between clinical stage and survival time requires further analysis.

Background: A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer., Materials and Methods: TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression., Results: Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR) = 1.92, 95% confidence interval (CI) = 1.42-2.59]. The increased risk was more prominent among subjects over 65 years old (OR = 2.37, 95% CI= 1.52-3.70), male subjects (OR = 1.97, 95% CI = 1.40-2.79) and subjects with self-reported family history of cancer (OR = 3.59, 95% CI = 1.19-10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR= 2.07, 95% CI= 1.51-2.85), grade 1 bladder cancer (OR = 2.40, 95% CI = 1.68-3.43), single tumor bladder cancer (OR = 2.04, 95% CI = 1.48-2.82) and smaller tumor size bladder cancer (OR = 2.10, 95% CI= 1.51-2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele., Conclusions: In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population.