Advanced Stage Bladder Cancer Research Articles

Understanding symptom contribution to sex inequality in bladder and renal cancer stage at diagnosis.

Understanding sex-specific factors contributing to advanced-stage diagnosis can guide interventions to reduce sex inequality in patients with urological cancers. We used linked primary care and cancer registry data to examine associations between symptoms and advanced-stage in 1151 bladder cancer and 440 renal cancer patients diagnosed between January 2012 and December 2015 in England. We performed logistic regression, adjusting for sex, age, deprivation and routes to diagnosis, including interaction terms between symptoms and sex and symptoms and age. Female sex (OR vs. men 1.89 [1.28-2.79]; p = 0.001) and patients presenting with urinary tract infections (OR 2.22 [1.34-3.69]) and abdominal symptoms (OR 2.19 [1.30-3.70]) were associated with increased odds of advanced-stage bladder cancer (vs. haematuria, p = 0.016 for both). Women with haematuria and men with abdominal symptoms (compared with the opposite sex with the same presenting symptom) were more likely to have advanced-stage bladder cancer. Neither sex nor symptom associations were observed for renal cancer. Non-haematuria symptoms are associated with higher risk of advanced-stage bladder cancer. Greater risk of advanced-stage bladder cancer in women may reflect biological differences in haematuria onset and sex differences during diagnostic process. Identifying higher risk women with haematuria may reduce sex inequalities in bladder cancer outcomes.

Evidence-Based Analysis of the Critical Steps of Radical Cystectomy for Bladder Cancer.

Radical cystectomy (RC) is an integral part of the management of patients with advanced-stage bladder cancer. This major oncologic operation is prone to complications resulting in morbidity and mortality. We analyzed the critical steps of open RC, performed an evidence-based review of these steps, and discussed our experience and approach. We conducted a literature review of the open RC technique, identified the critical steps that consistently appeared across different sources, and organized these steps into a framework. PubMed was queried with the critical steps as keywords for relevant articles published from 1 January 2013 to 1 August 2023. We utilized this query to conduct a systematic review of the literature using the outcomes of overall survival and 90-day complication rate. We developed the "Summary for the 10 Critical Operative Steps of Radical Cystectomy", a concise guide to the approach to open RC. When available, an evidence-based analysis of each critical step was performed. We also included additional components of cystectomy optimization such as pre-habilitation in the preoperative phase, standard versus extended lymphadenectomy, the vaginal-sparing approach to female radical cystectomy, patient-reported outcomes following urinary diversion, the use of a mesh for stoma formation, and the use of the ERAS protocol for postoperative care. An evidence-based assessment of RC may help provide valuable information to optimize surgical techniques and patient outcomes.

Effective Antitumor Immunity Can Be Triggered by Targeting VISTA in Combination with a TLR3-Specific Adjuvant.

Resistance to anti-PD-1/PD-L1 treatment is often associated with accumulation of intratumoral inhibitory macrophages. V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a nonredundant immune checkpoint that can induce both T-cell and myeloid-cell immunosuppression. In this study, we found that high levels of VISTA+ immune cells were associated with advanced stage bladder cancer and predicted poor survival in patients. A combination of high infiltration of VISTA+ immune cells and PD-L1+ immune cells or PD-1+ T cells predicted the worst survival. Flow cytometry and multiplex immunofluorescence analyses confirmed that VISTA expression was higher in macrophages than in T cells or neutrophils, and only VISTA+CD163+ macrophage density predicted poor prognosis in patients with bladder cancer. Toll-like receptor (TLR) agonists are known to trigger the innate immune response in macrophages. We found that the VISTA-specific mAb 13F3 augmented the ability of a TLR3-specific adjuvant to induce macrophage activation in vitro. In the MB49 syngeneic mouse model of bladder cancer, treatment with 13F3 curbed tumor growth and prolonged survival when combined with a TLR3-specific adjuvant. The combination treatment reduced the intratumoral frequency of CD206+ anti-inflammatory macrophages and levels of the immunosuppressive molecule TGFβ1, but it upregulated expression of immunostimulatory molecules (Ifna, Ifnb, and Trail) and increased the CD8+ T cell/regulatory T-cell ratio. These findings indicate that elevated VISTA expression in immune cells, particularly macrophages, is associated with an unfavorable prognosis in patients with bladder cancer and suggest that targeting VISTA in combination with a TLR3-specific adjuvant has translational potential.

Synthetic lethality in human bladder cancer cells by curcumin via concurrent Aurora A inhibition and autophagy induction

Combination therapies to induce mixed-type cell death and synthetic lethality have the potential to overcome drug resistance in cancer. In this study, we demonstrated that the curcumin-enhanced cytotoxicity of cisplatin/carboplatin in combination with gemcitabine was associated with Aurora A suppression-mediated G2/M arrest, and thus apoptosis, as well as MEK/ERK-mediated autophagy in human bladder cancer cells. Animal study data confirmed that curcumin combined with cisplatin/gemcitabine reduced tumorigenesis of xenograft in mice and this phenomenon was associated with elevated expressions of p-ERK and reduced p-Aurora A in tumors. Gene analyses using data repositories further revealed that reduced Aurora A expression alone did not significantly elevate the sensitivity of human bladder carcinoma cells to these anticancer drugs. Unlike other major cancer types, human bladder urothelial carcinoma tissue coexpressed higher AURKA and lower MAP1LC3B than normal tissue, and reduced Aurora A and induction of autophagy have been clinically associated with a better prognosis in patients with early but not advanced stage bladder cancer. Therefore, our results suggest that treatment strategies can utilize the synthetic lethal pair to concurrently suppress oncogenic Aurora A and induce autophagy by coadministrating curcumin with anticancer drugs for early-stage bladder cancer with high expression of Aurora A.

Expression-based subtypes define pathologic response to neoadjuvant immune-checkpoint inhibitors in muscle-invasive bladder cancer

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced-stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identify five distinctive genetic and transcriptomic programs and validate these in an independent neoadjuvant CPI trial to identify the features of response or resistance to CPI. By modeling the regulatory network, we identify the histone demethylase KDM5B as a repressor of tumor immune signaling pathways in one resistant subtype (S1, Luminal-excluded) and demonstrate that inhibition of KDM5B enhances immunogenicity in FGFR3-mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy.

PD26-04 COMPARISON OF SEXUAL FUNCTION IN FEMALES AFTER REPRODUCTIVE ORGAN SPARING VERSUS NON-REPRODUCTIVE ORGAN SPARING RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 Apr 2023PD26-04 COMPARISON OF SEXUAL FUNCTION IN FEMALES AFTER REPRODUCTIVE ORGAN SPARING VERSUS NON-REPRODUCTIVE ORGAN SPARING RADICAL CYSTECTOMY Sajya Singh, Natasha Gupta, Shirley Wang, Isabella Florissi, Max Kates, Trinity Bivalacqua, and Sunil Patel Sajya SinghSajya Singh More articles by this author , Natasha GuptaNatasha Gupta More articles by this author , Shirley WangShirley Wang More articles by this author , Isabella FlorissiIsabella Florissi More articles by this author , Max KatesMax Kates More articles by this author , Trinity BivalacquaTrinity Bivalacqua More articles by this author , and Sunil PatelSunil Patel More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003304.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Given recent data, reproductive organ sparing (ROS) radical cystectomy is a safe and effective treatment for bladder cancer in select women. In this study, we sought to better understand sexual function outcomes in females who underwent a ROS versus a non-reproductive organ sparing (non-ROS) radical cystectomy for the treatment of bladder cancer. METHODS: A cross-sectional questionnaire was administered in April 2022 to eligible participants selected from a retrospective single-institution cohort of female patients with a primary bladder malignancy who underwent radical cystectomy between 2016-2020. The study questionnaire included the short form of the Female Sexual Function Index (FSFI-6), a validated evaluation tool for diagnosing female sexual dysfunction (FSD) (score ≤19). Satisfaction with sex life was reported on a Likert scale with 5=dissatisfied and 1=satisfied. Bother with lack of sexual activity was reported as 4=a lot and 1=not at all. RESULTS: Among eligible patients (n=70), 45 women (64%) completed the questionnaire on average 3.1±1.0 and 3.4±1.4 years post-cystectomy for the ROS and non-ROS groups, respectively (p=0.59). Advanced-stage bladder cancer (≥pT3) was not statistically more prevalent in non-ROS (36%) compared to ROS patients (19%, p=0.25). Before surgery, significantly more women were sexually active in the ROS group (61%) than non-ROS (21%, p=0.01); however, post-cystectomy, this difference was not observed (29% vs. 21%, p=0.59). There was a trend towards more FSD among ROS patients by FSFI-6 (57% vs. 33%, p=0.49). In both the ROS and non-ROS groups, patients who were not sexually active reported low levels of bother regarding the absence of sexual activity (1.8±1.0 vs. 1.8±1.1, p=0.86). CONCLUSIONS: Within our limited cross-sectional cohort, we identified a higher prevalence of FSD in the ROS group, although this finding was not statistically significant. Consideration of patient-specific values when discussing post-operative sexual function is essential as most non-sexually active patients denied feeling concerned by a lack of sexual activity. Further research is needed to better understand the factors impacting post-cystectomy sexual function in women and to investigate interventions targeting the psychoeducational components of sexual health. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e736 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sajya Singh More articles by this author Natasha Gupta More articles by this author Shirley Wang More articles by this author Isabella Florissi More articles by this author Max Kates More articles by this author Trinity Bivalacqua More articles by this author Sunil Patel More articles by this author Expand All Advertisement PDF downloadLoading ...

Intravesical VAX014 Synergizes with PD-L1 Blockade to Enhance Local and Systemic Control of Bladder Cancer.

Emerging clinical evidence indicates that the combination of local administration of immunotherapy with systemic immune-checkpoint blockade targeting the PD-1/PD-L1 pathway improves response rates in select solid tumor indications; however, limited clinical experience with this approach exists in advanced bladder cancer patients. VAX014 is a novel bacterial minicell-based, integrin-targeted oncolytic agent undergoing clinical investigation for intravesical (IVE) treatment of nonmuscle-invasive bladder cancer. Here, we demonstrated that the antitumor activity of VAX014 following IVE administration was dependent upon CD4+ and CD8+ T cells in two syngeneic orthotopic bladder tumor models (MB49 and MBT-2). PD-L1 upregulation was found to be an acquired immune-resistance mechanism in the MB49 model, and the combination of VAX014 with systemic PD-L1 blockade resulted in a significant improvement in bladder tumor clearance rates and development of protective antitumor immunologic memory. Combination treatment also led to enhanced systemic antitumor immune responses capable of clearing distal intradermal tumors and controlling pulmonary metastasis. Distal tumors actively responding to combination therapy demonstrated a phenotypic shift from regulatory T cell to Th1 in intratumoral CD4+ T cells, which was accompanied by a higher percentage of activated CD8+ T cells and higher IFNγ. Finally, VAX014's target integrins α3β1 and α5β1 were overexpressed in tumor biopsies from advanced-stage bladder cancer patients, as well as in both the MB49 and MBT-2 orthotopic mouse models of bladder cancer. These collective findings provide a rationale for the clinical investigation of VAX014 and systemic PD-1/PD-L1 blockade in advanced-stage bladder cancer.

Patterns of treatment in older patients with newly diagnosed advanced bladder cancer: A SEER dataset analysis.

Bladder cancer is one of the top 10 cancers diagnosed in Americans with a median age of 73. This is the patient population that tends to be older with multiple medical conditions, and previously described variability in treatment in the earlier stages of the disease. This study aimed to evaluate the first-line therapeutic choices for older adults newly diagnosed with advanced bladder cancer. In addition, this work evaluated predictors of response as well as the role of events of functional importance in relation to treatment assignment. A population-based cohort study was conducted using the SEER-Medicare database of patients with advanced stage bladder cancer not eligible for curative intent therapy between 2010 and 2013. Patient groups of interest were compared via univariate and multivariate associations. Additionally, a latent class analysis was applied to identify classes with similar features in reference to events of functional importance-events linked to the maintenance or improvement of physical function status. Within the sample, we noted that a minority of patients received a standard cisplatin-containing regimen (14.77%) and a majority did not receive any chemotherapy (59.69%). Most patients were over age 75. The adjusted odds ratio of no chemo versus cisplatin in patients aged 76 and older compared to patients 66-75 was 6.61 (4.79-9.13; p < 0.0001). We applied latent class analysis methods to the dataset, and three classes demonstrated very low and moderate levels of functional events in the 12 months prior to a person's first outpatient visit for advanced bladder cancer care. Patients with new diagnosis of advanced bladder cancer largely do not receive the recommended first-line systemic therapy of cisplatin chemotherapy, and a significant majority does not receive any treatment. When evaluating the association between class assignment and predictors of chemotherapy use, such as comorbidity and age, patients with "low usage overall" were more likely to receive chemotherapy. Yet even patients who received chemotherapy had some events of functional importance.

Does neoadjuvant chemotherapy diminish the sex disparity in bladder cancer survival after radical cystectomy?

Sex-specific survival disparities for bladder cancer outcomes after radical cystectomy (RC) have been demonstrated in several studies. However, these studies predate the widespread adoption of neoadjuvant chemotherapy (NAC). We evaluated the differences in sex-specific survival between patients who received NAC with those who did not, using a contemporary national outcomes database.The National Cancer Data Base was queried from 2004 to 2015 to identify subjects who underwent RC. Kaplan-Meier method with log-rank test was performed to compare all-cause mortality between men and women at each pathologic (p) TNM stage group: T1-4N0, N+ and M+ disease. Associations for all-cause mortality were identified using an adjusted Cox regression analysis, and our findings were confirmed with a subgroup analysis.A total of 9,835 subjects (7,483 men and 2,532 women) were included in the analysis. Kaplan-Meier survival curves and Cox regression analysis demonstrated female sex was not associated with worse overall survival compared to males (HR 0.947, 95%CI 0.852-1.053, P = 0.947) in the overall cohort. Stratified by pT stage and node positivity, worse overall survival was seen in women with pT4 disease who did not receive NAC compared to men (5-year OS 9.6% women vs. 15.2% men, P < 0.001), but no sex-specific difference was seen across all groups in patients who received NAC. Subgroup multivariable analysis showed that female sex conferred a survival disadvantage for pT4 (HR 1.369, P = 0.026) disease only in patients who did not receive NAC.In a contemporary cohort of subjects who underwent RC, administration of NAC narrows the sex survival-gap in advanced stage bladder cancer. Strategies to improve NAC usage in women should be adopted to overcome potential sex-specific differences such as delayed diagnosis, anatomic differences in higher stage disease, or altered tumor biology which may contribute to differences in oncologic outcomes.

Superselective vesical artery embolization versus intravesical formalin for intractable hematuria in patients with bladder cancer

ObjectiveIntractable hematuria is a leading critical problem occurring in patients with advanced stage bladder cancer (BCa) that are not suitable for radical cystectomy. The present study, for the first time in the literature, aimed to compare the effectiveness of intravesical formalin (IF) and superselective vesical artery embolization (SVAE) in the management of intractable and life-threatening hematuria in BCa patients. MethodsThe retrospective study included 40 BCa patients who underwent SVAE or IF treatment due to intractable hematuria after failure of other methods. Patients were divided into two groups based on the procedures administered: SVEA Group (n = 24) and IF Group (n = 16). ResultsThe success rate at first-line therapy was 50% (12/24) in SVAE Group and 82% (13/16) in IF Group (p = 0.046). Based on the success rates at first- and second-line therapies, the overall success rate in SVAE Group was 75% and this rate was similar to that of IF Group (p = 0.439). Complication rate was significantly higher in IF patients than in SVAE patients (37.5% vs. 8.3; p = 0.024), whereas duration of postoperative hospital stay was significantly longer in SVAE Group (15.8 vs. 6 days; p = 0.041). ConclusionThe advantages of IF appear to include shorter postoperative hospital stays and higher success rates at a single session, while the advantages of SVAE seem to include non-requirement of spinal/general anesthesia, easy repeatability, and low complication rates. In the management of patients with intractable hematuria, patients’ general condition, comorbidities, and anesthesia-related risks should be taken into consideration.

Embolización vesical supraselectiva versus formalina intravesical para la hematuria intratable en pacientes con cáncer de vejiga

ObjectiveIntractable hematuria is a leading critical problem occurring in patients with advanced stage bladder cancer (BCa) that are not suitable for radical cystectomy. The present study, for the first time in the literature, aimed to compare the effectiveness of intravesical formalin (IF) and superselective vesical artery embolization (SVAE) in the management of intractable and life-threatening hematuria in BCa patients. MethodsThe retrospective study included 40 BCa patients who underwent SVAE or IF treatment due to intractable hematuria after failure of other methods. Patients were divided into two groups based on the procedures administered: SVEA Group (n=24) and IF Group (n=16). ResultsThe success rate at first-line therapy was 50% (12/24) in SVAE Group and 82% (13/16) in IF Group (p=0.046). Based on the success rates at first- and second-line therapies, the overall success rate in SVAE Group was 75% and this rate was similar to that of IF Group (p=0.439). Complication rate was significantly higher in IF patients than in SVAE patients (37.5% vs. 8.3; p=0.024), whereas duration of postoperative hospital stay was significantly longer in SVAE Group (15.8 vs. 6 days; p=0.041). ConclusionThe advantages of IF appear to include shorter postoperative hospital stays and higher success rates at a single session, while the advantages of SVAE seem to include non-requirement of spinal/general anesthesia, easy repeatability, and low complication rates. In the management of patients with intractable hematuria, patients’ general condition, comorbidities, and anesthesia-related risks should be taken into consideration.

Tertiary lymphoid structures marker CXCL13 is associated with better survival for patients with advanced-stage bladder cancer treated with immunotherapy

IntroductionImmune checkpoint inhibitors (ICIs) have proved to be an effective treatment for up to 40% of muscle-invasive bladder cancer (MIBC), but there is still a need for better performing biomarkers allowing to improve prediction of response to ICI. Response to immunotherapy in soft-tissue sarcoma, melanoma and renal cell carcinoma have been recently linked to the presence of tertiary lymphoid structures (TLS) in the tumour. TLS are organised aggregates of T, B and dendritic cells, participating in adaptive antitumor immune response. The chemokine CXCL13 is involved in the formation of TLS, and is reported as a reliable transcriptomic marker of TLS. ObjectivesIn this study, we sought to assess whether CXCL13 transcript expression can be a prognostic biomarker for ICI-treated MIBC patients and also investigated whether it can serve a biomarker of TLS in MIBC. MethodsWe analysed transcriptomic data from three publicly available MIBC cohorts and evaluated pathological slides from the TCGA-BLCA cohort for TLS presence and stage of maturation. ResultsWe showed that CXCL13 was independently associated with both prolonged survival (HR = 0.8, 95% CI [0.68–0.94]) and objective response (p < 0.0001) in patients treated with ICI, at the difference of others immunological signatures. However, it was not a predictor for non–ICI-treated MIBC, suggesting a predictive effect of ICI efficacy. Finally, we validated that CXCL13 expression was correlated with tumour TLS in TCGA data set (p < 0.001), and can serve as a marker of TLS in bladder cancer. ConclusionThese results support that CXCL13 expression, as a surrogate for tumour TLS, is a relevant candidate predictive biomarker of response to ICI for patients with advanced-stage bladder cancer.

Expression-Based Subtypes Define Pathologic Response to Neoadjuvant Immune-Checkpoint Inhibitors in Muscle-Invasive Bladder Cancer

Checkpoint immunotherapy (CPI) has increased survival for some patients with advanced stage bladder cancer (BCa). However, most patients do not respond. Here, we characterized the tumor and immune microenvironment in pre- and post-treatment tumors from the PURE01 neoadjuvant pembrolizumab immunotherapy trial, using a consolidative approach that combined transcriptional and genetic profiling with digital spatial profiling. We identified five distinctive genetic and transcriptomic programs associated with resistance and response to CPI and validated these in an independent neoadjuvant CPI trial. By modeling the regulatory network, we identified histone demethylase KDM5B as a repressor of tumor immune signaling pathways and demonstrated that inhibition of KDM5B enhances immunogenicity in FGFR3- mutated BCa cells. Our study identifies signatures associated with response to CPI that can be used to molecularly stratify patients and suggests therapeutic alternatives for subtypes with poor response to neoadjuvant immunotherapy.

Clinical Value of C-reactive Protein and Erythrocyte Sedimentation Rate in Advanced Bladder Cancer

Background: The identification of biomarkers would improve the management of advanced urinary bladder carcinoma. Aim: The current study assessed the potential prognostic role of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in advanced stage bladder cancer. Methods: Forty-six patients with advanced urinary bladder carcinoma were included in the study. After consent, CRP and ESR were measured before treatment, after 2 cycles of chemotherapy and at the end of treatment. The relation between CRP and ESR serum measurements and patients' characteristics and treatment response were assessed. Results: Both CRP and ESR were elevated in all included patients with mean values ± standard deviation: 35.43 ± 12.65 and 57.17 ± 18.15, respectively. The baseline CRP level was higher in patients with metastatic disease. ESR was significantly elevated in association with squamous cell carcinoma pathology and hydronephrosis and in patients who died within one year of diagnosis (p = 0.003, 0.001 and 0.03; respectively). Patients who experienced disease progression after 2 cycles of platinum-based chemotherapy had higher levels of CRP and ESR. Serial measurements during the course of treatment revealed that both CRP and ESR levels declined significantly during treatment mainly among responding patients (p = 0.001). Conclusion: CRP and ESR might be useful noninvasive biomarkers in advanced urinary bladder carcinoma.

Perioperative and long-term outcomes after radical cystectomy in hemodialysis patients

PurposePatients on hemodialysis have an increased risk of developing advanced stage bladder cancer. They also have a significant risk of noncancer–related mortality. Radical cystectomy (RC) is the standard of care for nonmetastatic muscle–invasive bladder cancer, however little is known regarding outcomes in this population. Materials and methodsThe United States Renal Disease System database was used to identify all patients on hemodialysis who underwent RC for bladder cancer in the United States between 1984 and 2013. A total of 985 patients were identified for analysis. Perioperative outcomes were evaluated. Competing risks analysis was used to estimate overall and cancer-specific mortality along with factors associated with death. ResultsMedian hospital length of stay was 10 days and 43.1% of patients experienced a complication. Mortality within 30 days was 9.3%. Overall mortality at 1, 3, and 5 years was 51.7%, 77.3%, and 87.9%, respectively. Cancer-specific mortality at 1, 3, and 5 years was 12.3%, 18.4%, and 19.7%, respectively. Age, diabetes, and cerebrovascular disease were independently associated with overall mortality, while performance of urinary diversion was associated with a protective effect. Active smoking was the sole risk factor for cancer-specific mortality. ConclusionsRC in dialysis patients is associated with significant morbidity and mortality, with less than 15% overall survival at 5 years. Older patients, and those with a history of diabetes or cerebrovascular disease, are at an increased risk of mortality.

Discrepancies in staging, treatment, and delays to treatment may explain disparities in bladder cancer outcomes: An update from the National Cancer Data Base (2004–2013)

IntroductionWe sought to characterize national disparities in the diagnosis of advanced stage bladder cancer. Among patients with advanced disease, we explored disparities in overall survival, treatment, and time to treatment. Methods and materialsWe queried the National Cancer Data Base for patients diagnosed with bladder urothelial carcinoma. We used multivariable logistic regression to assess the association between covariates and diagnosis of advanced disease (AJCC stage III–IV). We used Kaplan-Meier, log-rank, and Cox proportional analyses to evaluate disparities in overall survival for patients with advanced disease. Receipt of treatment and delays to treatment were compared between subgroups. ResultsAmong our cohort of 328,560 patients, 7.6% were diagnosed with advanced disease. Female sex, black race, Hispanic ethnicity, and living in a region of lower income and education were all associated with increased odds of advanced disease. Female sex (HR = 1.16; 95% CI: 1.12–1.20; P<0.001), black race (HR = 1.10; 95% CI: 1.04–1.18; P = 0.002), and lower regional income levels (fourth quartile compared to first: HR = 1.08; 95% CI: 1.02–1.16; P = 0.016) portended worse overall survival. Chemotherapy (HR = 0.55, 95% CI: 0.53–0.57; P<0.001) and radical cystectomy (HR = 0.61; 95% CI: 0.59–0.64, P<0.001) improved survival. Females, black patients, and patients from regions of lower income and education were less likely to receive treatment and less likely to receive treatment within 12 weeks of diagnosis. ConclusionThere are several disparities in the diagnosis and treatment of advanced bladder cancer. Overall survival for certain groups may benefit from earlier diagnosis and improved timely access to potentially life prolonging treatment.

Sexual Problems of Patients with Urostomy: A Qualitative Study

Urostomy is a surgical procedure that creates a stoma for the treatment of advanced stage bladder cancer, which is more common among males. It is performed mandatorily by attaching ureters to the abdominal wall directly or indirectly via a stoma after a cystectomy. This study was designed and conducted in order to identify experiences, views, and problems of patients who had urostomy due to bladder cancer, regarding the effects of urostomy on their and their spouse/partner’s sexual life. This phenomelogical qualitative study was conducted with 10 volunteer male patients with urostomy and their spouses/partners. The data were collected using an interview form which had open-ended questions about the effects of urostomy on sexual life. The obtained data were coded, and themes were formed using content analysis methods. Content analysis results revealed the following themes: change in body image, problems experienced during sexual activity, spouse’s response to the problems experienced, and receiving help and support about the problems experienced. This study revealed that urostomy affected the patients’ sexual functions in a negative way, and they did not receive any professional help or support for the solutions to their problems. In the care and treatment of patients with urostomy, health professionals should be aware that these patients might experience sexual problems during their care and treatment, and they should encourage and guide patients and their spouses/partners about receiving help and support and telling about their sexual problems.

Concurrent Autophagy Inhibition Overcomes the Resistance of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Human Bladder Cancer Cells.

Despite the potential therapeutic efficacy of epithelial growth factor receptor (EGFR) inhibitors in the treatment of advanced stage bladder cancer, there currently is no clear evidence to support this hypothesis. In this study, we investigate whether the concurrent treatment of autophagy-blocking agents with EGFR inhibitors exerts synergistic anti-cancer effects in T24 and J82 human bladder cancer cells. Lapatinib and gefitinib were used as EGFR inhibitors, and bafilomycin A1 (BFA1), chloroquine (CQ) and 3-methyladenine (3-MA) were used as the pharmacologic inhibitors of autophagy activities. To assess the proliferative and self-renewal capabilities, the Cell Counting Kit-8 (CCK-8) assay and a clonogenic assay were performed, respectively. To examine apoptotic cell death, flow cytometry using annexin-V/propidium iodide (PI) was used. To measure the autophagy activities, the expression levels of LC3I and II was determined by Western blot analysis. To validate the synergistic effects of autophagy inhibition with EGFR inhibitors, we specifically blocked key autophagy regulatory gene ATG12 by transfection of small interference RNA and examined the phenotypic changes. Of note, lapatinib and gefitinib triggered autophagy activities in T24 and J82 human bladder cancer cells, as indicated by upregulation of LC3II. More importantly, inhibiting autophagy activities with pharmacologic inhibitors (BFA1, CQ or 3-MA) remarkably reduced the cell viabilities and clonal proliferation of T24 and J82 cells, compared to those treated with either of the agents alone. We also obtained similar results of the enhanced anti-cancer effects of EGFR inhibitors by suppressing the expression of ATG12. Notably, the apoptotic assay showed that synergistic anti-cancer effects were induced via the increase of apoptotic cell death. In summary, concomitant inhibition of autophagy activities potentiated the anti-cancer effects of EGFR inhibitors in human bladder cancer cells, indicating a novel therapeutic strategy to treat advanced bladder cancer.

Characteristic of advanced stage bladder cancer managed with radiotherapy

Characteristic of advanced stage bladder cancer managed with radiotherapy

Association between the metabolic syndrome and T1 high grade urothelial carcinoma of the bladder

Objective To summarize the relationship between metabolic syndrome(MS), its components and T1 stage with high grade urothelial carcinoma (HGUC) of the Bladder. Methods The clinical data of 200 patients with T1 high grade bladder cancer who were admitted to our hospital from January 2010 to June 2014 were retrospectively analyzed, including 155 males and 45 females. Ages were 24 to 86 years old, average 66 years old. Based on the history or blood glucose levels, patients were divided into diabetic group (n = 41) (20.5%) and non diabetes group 159 cases (79.5%); According to the body mass index (BMI) were divided into obese group (≥25 kg / m2) of 98 cases (49.0%) and non obese group (< 25 kg / m2) of 102 cases (51.0%). According to the blood pressure level, 71 cases (35.5%) were divided into hypertension group and 129 cases of non hypertension group (64.5%). MS and its components and the relationship between the recurrence and progress of bladder cancer were analyzed. The Kaplan Meier method was used to assess MS and its components division of tumor progression free survival (progress-free survival, PFS) and recurrence free survival (recurrence-free survival, RFS) influence. Cox regression model of multi factor analysis were used to evaluate the PFS and RFs of MS and its components with bladder cancer. Results Of the 200 cases, 16 cases (8.0%) were MS. Tumor recurrence occurred in 121 cases (60.5%), and 84 patients (42.0%) were in progress. Diabetes and non diabetes groups the average RFs were 21.7 and 29.3 months respectively, and the difference was statistically significant (χ2=10.115, P=0.001); The median PFS were 32.8 and 39.8 months respectively, the difference has statistical significance (χ2=14.760, P<0.001). Obese group and non obese group average RFs were 34.7 and 42.0 months respectively, and the difference were statistically significant (χ2=16.077, P<0.001); The median PFS were 22.8 and 32.6 months respectively, the difference was statistically significant (χ2=16.174, P<0.001). The average RFS of MS group and non MS group were 21.5 and 28.4 months respectively, the difference was statistically significant (χ2=5.429, P=0.02); the average PFS was 35.1 and 38.7 months respectively, and the difference was statistically significant (χ2=3.854, P<0.05). Cox multivariate survival analysis showed that diabetes and obesity can increase the risk of recurrence and progression of T1 advanced stage bladder cancer (HR=1.792, P=0.013, HR=2.498, P<0.001; HR=0.559, P<0.001; HR=0.492, P<0.001). Conclusions Diabetes mellitus and obesity are high risk factors for the recurrence and progression of T1 advanced stage bladder cancer, but MS is not related to the prognosis of T1 patients with advanced bladder cancer. Key words: Metabolic syndrome; Urothelial carcinoma; Diabetes mellitus; Hypertension; Obesity