Landscape of targeted therapies for advanced urothelial carcinoma.

Bladder cancer (BC) is the tenth most common malignancy globally. Urothelial carcinoma (UC) is a major type of BC, and advanced UC (aUC) is associated with poor clinical outcomes and limited survival rates. Current options for aUC treatment mainly include chemotherapy and immunotherapy. These options have moderate efficacy and modest impact on overall survival and thus highlight the need for novel therapeutic approaches. aUC patients harbor a high tumor mutation burden and abundant molecular alterations, which are the basis for targeted therapies. Erdafitinib is currently the only Food and Drug Administration (FDA)-approved targeted therapy for aUC. Many potential targeted therapeutics aiming at other molecular alterations are under investigation. This review summarizes the current understanding of molecular alterations associated with aUC targeted therapy. It also comprehensively discusses the related interventions for treatment in clinical research and the potential of using novel targeted drugs in combination therapy.

Trends in genitourinary cancer mortality in the United States: analysis of the CDC-WONDER database 1999-2020.

Introduction: Sociodemographic disparities in genitourinary cancer-related mortality have been insufficiently studied, particularly across multiple cancer types. This study aimed to investigate gender, racial, and geographic disparities in mortality rates for the most common genitourinary cancers in the United States. Methods: Mortality data for prostate, bladder, kidney, and testicular cancers were obtained from the Centers for Disease Control and Prevention (CDC) WONDER database between 1999 and 2020. Age-adjusted mortality rates (AAMRs) were analyzed by year, gender, race, urban-rural status, and geographic region using a significance level of p < 0.05. Results: Overall, AAMRs for prostate, bladder, and kidney cancer declined significantly, while testicular cancer-related mortality remained stable. Bladder and kidney cancer AAMRs were 3-4 times higher in males than females. Prostate cancer mortality was highest in black individuals/African Americans and began increasing after 2015. Bladder cancer mortality decreased significantly in White individuals, Black individuals, African Americans, and Asians/Pacific Islanders but remained stable in American Indian/Alaska Natives. Kidney cancer-related mortality was highest in White individuals but declined significantly in other races. Testicular cancer mortality increased significantly in White individuals but remained stable in Black individuals and African Americans. Genitourinary cancer mortality decreased in metropolitan areas but either increased (bladder and testicular cancer) or remained stable (kidney cancer) in non-metropolitan areas. Prostate and kidney cancer mortality was highest in the Midwest, bladder cancer in the South, and testicular cancer in the West. Discussion: Significant sociodemographic disparities exist in the mortality trends of genitourinary cancers in the United States. These findings highlight the need for targeted interventions and further research to address these disparities and improve outcomes for all populations affected by genitourinary cancers.

Temporal Trends in Urinary Diversion among Patients Undergoing Radical Cystectomy Between 1986 and 2022: Experience at the University Medical Center Mainz with 2224 Cases.

BACKGROUND: Analysis of temporal trends of urinary diversion (UD) and identification of predictive factors for continent urinary diversion (CUD) in patients with bladder cancer (BC) is scarce and data on large cohorts are missing. We aimed to describe longitudinal temporal trends and predictive factors for UD among patients with BC receiving radical cystectomy (RC). PATIENTS AND METHODS: We retrospectively analysed institutional data collected from patients undergoing RC from 1986 to 2022 to describe changes in patients' characteristics and UD. Primary end points were patients' characteristics associated with type of UD. Logistic regression analysis was used to determine predictive factors for CUD. RESULTS: In total, 2224 patients (77.16% male, 22.84% female) with a mean age of 66 years [standard deviation (SD), 10.64 years] were included. We observed an increase in mean age from 59.86 (10.8) years (1986-1990) to 69.85 (9.99) years (2016-2022) (p < 0.001). The proportion of CUD gradually declined from 43.72% (94/215; 1986-1990) to 18.38% (86/468; 2016-2022). Patients who were male [odds ratio (OR): 1.92, 95% confidence interval (CI): 1.43-2.57, p < 0.001), younger (OR: 0.88, 95% CI: 0.87-0.89, p < 0.001) and had no hydronephrosis prior to RC (OR: 2.2, 95% CI: 1.66-2.92, p < 0.001) were more likely to receive CUD. CONCLUSIONS: We report the largest European single-center cohort of UD after RC, demonstrating a significant shift from CUD to IUD, accompanied by an increasing age. Finally, our data mirrors the development and extensive experience with the Mainz Pouch-I in the 1980's and 1990's together with other colon pouches.

Successful pre-surgical treatment with carboplatin and gemcitabine chemotherapy for a patient with muscle-invasive bladder cancer and severe renal dysfunction.

Radical cystectomy is the standard treatment for muscle-invasive bladder cancer, and pre-surgical treatment can improve survival. Carboplatin and gemcitabine chemotherapy is considered an effective, safe treatment for patients ineligible for cisplatin-based chemotherapy owing to reduced renal function. However, there is limited evidence on pre-surgical treatment with carboplatin and gemcitabine chemotherapy with glomerular filtration rates < 30 mL/min. We discuss the treatment of a patient who did not undergo surgery owing to bladder tumor size of 12 cm (cT3bN0M1a) and severe renal dysfunction (serum creatinine: 2.57 mg/dL, estimated glomerular filtration rate: 20.2 mL/min/1.73 m2). After the patient received two courses of carboplatin and gemcitabine chemotherapy, the bladder tumor size had reduced by 60%. No nausea or renal dysfunction was observed; febrile neutropenia improved with antibiotic therapy and granulocyte colony-stimulating factor. Then, he could undergo robot-assisted radical cystectomy after the pre-surgical chemotherapy treatment. Pre-surgical treatment with carboplatin and gemcitabine chemotherapy is a viable treatment option for patients with muscle-invasive bladder cancer and severe renal dysfunction.

Identification and validation of sialyltransferase ST3Gal5 in bladder cancer through bioinformatics and experimental analysis.

BACKGROUND: Bladder cancer (BLCA) is one of the top ten most common cancers in the world. Aberrant sialylation is a common feature in tumorigenesis and tumor immunity. This study seeks to explore the potential impact of sialyltransferase ST3Gal5 on BLCA. METHODS: Initially, glycosyltransferase-related DEGs (GRDEGs) were identified using multiple bioinformatics approaches in TCGA-BLCA cohort and validated using GEO databases. Clinical prognosis integration facilitated the determination of ST3Gal5 as an independent prognostic factor in BLCA, employing univariate and multivariate Cox regression analyses. Immune cell infiltration was assessed via CIBERSORT and ssGSEA analyses, while HLA and immune checkpoint genes' levels, along with drug sensitivity, were evaluated in low- and high-ST3Gal5 groups. The TIDE and IPS scores were used to gauge the immune checkpoint blockade (ICB) response. Furthermore, functional experiments, both in vivo and in vitro, were conducted to elucidate the biological roles of ST3Gal5. RESULTS: In agreement with bioinformatics findings, ST3Gal5 expression was down-regulated in BLCA tissues and cells, correlating with poorer prognostic outcomes. The StromalScore, ImmuneScore, and ESTIMATEScore were significantly elevated in low-ST3Gal5 group. Moreover, the levels of HLA and immune checkpoint genes were upregulated in low-ST3Gal5 group. Down-regulated ST3Gal5 promoted the proliferation, migration, and invasion of BLCA cells in vivo and in vitro. CONCLUSION: Our findings demonstrated that low ST3Gal5 level promoted tumorigenesis and progression of BLCA, implying its potential as a predictive biomarker and therapeutic target.

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

The Prognostic Hub Gene POLE2 Promotes BLCA Cell Growth via the PI3K/AKT Signaling Pathway.

BACKGROUND: BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear. AIMS: This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA). OBJECTIVE: The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease. METHODS: We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays. RESULTS: In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels. CONCLUSION: In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.

The therapeutic effect of baicalin in the treatment of bladder cancer: a mini-review.

Bladder cancer (BC) is one of the most common challenges endangering public health worldwide. Therefore, finding effective ways to prevent and treat this disease can significantly reduce the detrimental effects of BC. Baicalein is a compound derived from the root of Scutellaria baicalensis. This compound possesses anticancer potential because numerous studies have confirmed its effectiveness in improving breast, liver, colon, leukaemia, skin, and lung cancers. In this study, we focused on reviewing the latest research on the therapeutic effects of baicalein in treating BC. According to our findings in this review, baicalein, by affecting various signalling pathways such as AKT, MAPK, Survivin/CDC2, MMP, Bax/Bcl2, NF-kB, and Drp1, inducing cell death, and halting cellular growth in cancer cells, can be an appealing therapeutic approach in treating BC.

N-803 Plus BCG Treatment for BCG-Naïve or -Unresponsive Non-Muscle Invasive Bladder Cancer: A Plain Language Review.

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

Addition of the IL-15 superagonist N-803 to BCG therapy produces a high rate of success in eliminating non-muscle invasive bladder cancer in both BCG-naive and BCG-unresponsive patients, with long-lasting effects that allow patients to avoid surgical removal of the bladder.

Factors influencing health-related quality of life in patients with bladder or kidney cancer: a prospective cohort study of the impact of nutritional status and frailty phenotype.

PURPOSE: This study aimed to investigate the impact of nutritional status and frailty phenotype and the predictors of temporal changes on health-related quality of life (HRQoL) of patients with bladder or kidney cancer. METHODS: Frailty phenotype, Patient-Generated Subjective Global Assessment, and Quality-of-life questionnaire Core-30 were applied twice to patients diagnosed with bladder or kidney cancer. Patients also completed a sociodemographic questionnaire, and clinical data were collected from records. RESULTS: Sixty-two individuals completed the study, mostly male, with a mean age of 62.5 (± 11.4) years. The median time of follow-up was 14.5 months. Role functioning, emotional functioning, and fatigue improved over time (p < 0.05). The factors that negatively affected the long-term quality of life summary score were being female, malnourished, pre-frail and frail, cancer treatment, performance status, and lower income. Using the multivariate model, being malnourished (ß = - 7.25; 95% CI, - 10.78 to - 3.71; p < 0.001), frail (ß = - 7.25; 95% CI, - 13.39 to - 1.11; p = 0.021), and each one-point increase in performance status (ß = - 6.9; 95% CI, - 9.54 to - 4.26; p < 0.001), were the ones that most negatively impacted the HRQoL between the two assessments. CONCLUSION: This study confirmed that frailty, nutritional status, and performance status are the main predictors of HRQoL of patients with bladder or kidney cancer over time. IMPLICATIONS FOR CANCER SURVIVORS: These findings may be the first step towards highlighting the importance of preventing malnutrition and frailty, in favor of a better long-term QoL for cancer patients.

Cisplatin eligibility in the neoadjuvant setting of patients with muscle-invasive bladder cancer undergoing radical cystectomy.

BACKGROUND: To examine the agreement of different calculated estimated glomerular filtration rate (eGFR) formulas and measured creatinine clearance (CrCI) at the primary diagnosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We performed a multicenter analysis of patients with MIBC, treated with cisplatin-based neoadjuvant chemotherapy (NAC) and radical cystectomy (RC), or with RC alone, between 2011 and 2021. Baseline eGFR was computed using 4 calculated serum equations including Cockcroft-Gault (CG), MDRD, CKD-EPI 2009, and race-free CKD-EPI 2021. To examine the association between calculated eGFR and measured CrCI, subgroup analyses were performed among patients in whom measured 24-hour urine CrCl was determined. Cisplatin-ineligibility was defined as CrCI and/or eGFR < 60 mL/minute per 1.73 m2. RESULTS: Of 956 patients, 30.0%, 33.3%, 31.9%, and 27.7% were found to be cisplatin-ineligible by the CG, MDRD, CKD-EPI, and race-free CKD-EPI equations (P = .052). The concordance between calculated eGFR formulas was rated substantial (Cohen's kappa (k): 0.66-0.95). Among the subgroup (n = 245) with measured CrCl, 37 (15.1%) patients had a CrCI less than 60 mL/minute. Concordance between measured CrCl and calculated eGFR was poor (ĸ: 0.29-0.40). All calculated eGFR formulas markedly underestimated the measured CrCI. Specifically, 78%-87.5% of patients with a calculated eGFR between 40 and 59 mL/minute exhibited a measured CrCI ≥ 60 mL/minute. CONCLUSIONS: Comparing calculated eGFR formulas, similar percentages of patients with MIBC were deemed cisplatin-ineligible. However, a significant number of patients could be upgraded by being cisplatin-fit based on measured CrCI, particularly when the calculated eGFR was falling within the gray range of 40-59 mL/minute.

SLC16A3 is a Prognostic Marker and Affects Immune Regulation in Bladder Cancer.

BACKGROUND: Overexpression of SLC16A3 can contribute to the development of various tumors by regulating metabolism, but a systematic analysis of SLC16A3 in bladder cancer (BC) has been rarely reported. METHODS: We used the BC datasets from public databases to investigate SLC16A3 expression in BC. We first analysed the relationship between SLC16A3 expression and clinical characteristics of 412 bladder cancer patients. After that, gene function analyses and immunocorrelation analyses of SLC16A3 were conducted with the R package. For immunotherapy effect and drug sensitivity analysis, we also used the R package. We also analysed the relation between SLC16A3 expression and 20 m6A modification key genes. Finally, we determined the expression localization of SLC16A3 in bladder cancer by single-cell sequencing analysis using 3,115 BC cells. We further detected the expression of SLC16A3/MCT4 on BC samples by reversed transcriptionquantitative polymerase chain reaction and immunohistochemistry. RESULTS: The SLC16A3 was overexpressed in BC cells, including epithelial cells (p＜0.001). The high SLC16A3 expression level of patients with BC was significantly related to poor prognosis (p＝0.044), and we established a reliable prognosis model for BC patients. Statistically significant associations between SLC16A3 and m6A modification (ALKBH5) gene (p＜0.001), key genes in aerobic glycolysis, M2 macrophage infiltration (p＝0.0058), and immune checkpoint regulation were observed. CONCLUSION: Overexpression of SLC16A3 is an independent prognostic factor in patients with BC. SLC16A3 may influence the immune infiltration of BC by regulating BC metabolism and m6A methylation, which ultimately can lead to the progress of BC. For the detection and therapy of BC, SLC16A3 may be a potent therapeutic target for BC.

Gut microbiota Parabacteroides distasonis enchances the efficacy of immunotherapy for bladder cancer by activating anti-tumor immune responses.

OBJECTIVE: Bladder cancer(BCa) was a disease that seriously affects patients' quality of life and prognosis. To address this issue, many researches suggested that the gut microbiota modulated tumor response to treatment; however, this had not been well-characterized in bladder cancer. In this study, our objective was to determine whether the diversity and composition of the gut microbiota or the density of specific bacterial genera influence the prognosis of patients with bladder cancer. METHODS: We collected fecal samples from a total of 50 bladder cancer patients and 22 matched non-cancer individuals for 16S rDNA sequencing to investigate the distribution of Parabacteroides in these two groups. Further we conducted follow-up with cancer patients to access the impact of different genera of microorganisms on patients survival. We conducted a Fecal Microbiota Transplantation (FMT) and mono-colonization experiment with Parabacteroides distasonis to explore its potential enhancement of the efficacy of anti-PD-1 immunotherapy in MB49 tumor-bearing mice. Immunohistochemistry, transcriptomics and molecular experiment analyses were employed to uncover the underlying mechanisms. RESULTS: The 16S rDNA showed that abundance of the genus Parabacteroides was elevated in the non-cancer control group compared to bladder cancer group. The results of tumor growth curves showed that a combination therapy of P. distasonis and ICIs treatment significantly delayed tumor growth and increased the intratumoral densities of both CD4+T and CD8+T cells. The results of transcriptome analysis demonstrated that the pathways associated with antitumoral immune response were remarkably upregulated in the P. distasonis gavage group. CONCLUSION: P. distasonis delivery combined with α-PD-1 mAb could be a new strategy to enhance the effect of anti-PD-1 immunotherapy. This effect might be achieved by activating immune and antitumor related pathways.

A histopathological and epidemiological study of urothelial carcinoma at a tertiary care centre in Peshawar, Pakistan.

Bladder cancer is the ninth leading cause of death worldwide and 14th leading cause of death in Pakistan. The objective of this study was to determine the frequency of urothelial carcinoma in various age groups, its gender distribution, and grades. A total of 131 cases of urothelial carcinoma, received at Department of Pathology, Peshawar Medical College, Peshawar, between January 2017 to December 2022, were included in the study; of them 107 (81.6%) were males while 24 (18.3%) were females with a mean age of 62±13 years. The most common histological subtype was papillary urothelial carcinoma in 117(89.3%) cases, followed by Squamous and Glandular in 5(3.8%) cases. Majority of the urothelial carcinoma with high grade showed a statistically significant relation with muscle invasion 38 (50.66%). Males were four times more likely to have urothelial carcinoma while older age groups were more likely to have high grade urothelial carcinoma.

Urinary exosomes: Potential diagnostic markers and application in bladder cancer.

Background: The exosome is a critical component of the intercellular communication., playing a vital role in regulating cell function. These small vesicles contain proteins, mRNAs, miRNAs, and lncRNAs, surrounded by lipid bilayer substances. Most cells in the human body can produce exosomes, released into various body fluids such as urine, blood, and cerebrospinal fluid. Bladder cancer is the most common tumor in the urinary system, with high recurrence and metastasis rates. Early diagnosis and treatment are crucial for improving patient outcomes. Methods: This study employed the PubMed search engine to retrieve publicly accessible data pertaining to urinary exosomes. Results: We summarize the origins and intricate biological characteristics of urinary exosomes, the introduction of research methodologies used in basic experiments to isolate and analyze these exosomes, the discussion of their applications and progress in the diagnosis and treatment of bladder cancer, and the exploration of the current limitations associated with using urinary exosomes as molecular biomarkers for diagnosing bladder cancer. Conclusion: Exosomes isolated from urine may be used as molecular biomarkers for early detection of bladder cancer.

Metastatic Urothelial Carcinoma With Sarcomatoid Subtype After Robot-Assisted Radical Cystectomy Successfully Treated With Pembrolizumab.

A 76-year-old man who was diagnosed with urothelial carcinoma (UC) in the bladder diverticulum was referred to our institution. The patient was diagnosed with muscle-invasive bladder cancer, which was confirmed by magnetic resonance imaging that showed tumor invasion into the fatty tissue surrounding the diverticulum. After two cycles of neoadjuvant gemcitabine and cisplatin, he underwent robot-assisted radical cystectomy (RARC) with pelvic lymph node dissection followed by intracorporeal ileal conduit. The histopathologic diagnosis of the bladder tumor was UC with squamous differentiation and sarcomatoid subtype and ypT3bN0M0 without positive surgical margins. The patient refused any adjuvant therapy. Six months after RARC, the patient visited our institution with a complaint of suddenly occurring generalized pain. Because 18F-fluorodeoxyglucose positron emission tomography-CT showed multiple metastases, including bone, para-aortic lymph nodes, and pleura, pembrolizumab was initiated as a second-line treatment. After two courses of pembrolizumab, the patient's symptoms remarkably improved, and the abnormal systemic accumulation on PET-CT almost disappeared. After 26 months of continuous treatment with pembrolizumab, the patient remains disease-free. Several studies have been reported that focused on tumor subtypes and programmed cell death ligand 1 (PD-L1)-positive tumor cells as candidate biomarkers in relation to the efficacy of pembrolizumab. The higher proportion of PD-L1-positive cells in the sarcomatoid subtype may have resulted in favorable oncological outcomes compared with pure UC.

Machine learning-based CT radiomics enhances bladder cancer staging predictions: A comparative study of clinical, radiomics, and combined models.

BACKGROUND: Predicting the accurate preoperative staging of bladder cancer (BLCA), which markedly affects treatment decisions and patient outcomes, using traditional clinical parameters is challenging. Nevertheless, emerging studies in radiomics, especially machine learning-based computed tomography (CT) image-based radiomics, hold promise in improving stage prediction accuracy in various tumors. However, the comparative performance and clinical utility of models for BLCA are under investigation. PURPOSE: We aimed to investigate the application value of machine learning-based CT radiomics in preoperative staging prediction by comparing the performance of clinical, radiomics, and clinical-radiomics combined models. METHODS: A retrospective cohort of 105 patients with initial BLCA was randomized into training (70%) and testing (30%) cohorts. Radiomics features were extracted from CT images using the optimal feature filter, followed by the application of the least absolute shrinkage and selection operator algorithm for optimum feature selection. Furthermore, machine learning algorithms were used to establish a radiomics model within the training cohort. Independent risk factors for muscle-invasive BLCA (MIBC) obtained by multivariate logistic regression (LR) analysis were separately used to construct a clinical model. For a clinical-radiomics fusion model, radiomics features were combined with clinical parameters. Performance was evaluated based on receiver operating characteristic curves, calibration curves, decision curve analysis (DCA), and standard performance metrics. RESULTS: Patients exhibited a significantly higher age (p = 0.029), larger tumor size (p = 0.01), and an increased neutrophil-to-lymphocyte ratio (NLR; p = 0.045) in the MIBC group than in the NMIBC group. LR analysis revealed age (p = 0.026), tumor size (p = 0.007), and NLR (p = 0.019) as significant predictors for constructing the clinical model. In the testing cohort, the radiomics model, which used an Support Vector Machine classifier, achieved the highest area under the curve (AUC) value of 0.857. The clinical-radiomics model outperformed the remaining two models, with AUC values of 0.958 and 0.893 in the training and testing cohorts, respectively. DeLong's test indicated significant differences between the three models. Calibration curves showed good agreement, and DCA confirmed the superior clinical utility of the clinical-radiomics model. CONCLUSIONS: Machine learning-based CT radiomics combined with clinical parameters was a promising approach in staging BLCA accurately, which outperformed the individual models. Integrating radiomics features with clinical information holds the potential to improve personalized treatment planning and patient outcomes in BLCA.

An immune biomarker associated with EMT serves as a predictor for prognosis and drug response in bladder cancer.

BACKGROUND: Bladder cancer (BLCA), which develops from the upper endometrial of the bladder, is the sixth most prevalent cancer across the globe. WDHD1 (WD repeat and HMG-box DNA binding protein 1 gene) directly affects signaling, the cell cycle, and the development of the cell skeleton. Uncertainty surrounds WDHD1's function in BLCA immunity and prognosis, though. MATERIALS AND METHODS: Using weighed gene co-expression network analysis (WGCNA), initially, we first identified 32 risk factors in genes with differential expression for this investigation. Then, using a variety of bioinformatic techniques and experimental validation, we examined the connections between WDHD1 and BLCA expression, clinical pathological traits, WDHD1-related proteins, upper-skin-intermediate conversion (EMT), immune cell immersion, convergence factors, immune markers, and drug sensitivity. RESULT: The findings demonstrated that we constructed a 32-gene risk-predicting model where WDHD1 was elevated as a representative gene expression in BLCA and related to a range of clinical traits. Furthermore, high WDHD1 expression was a standalone predictor associated with a worse survival rate. The most commonly recruited cells and their evolutionary patterns were highlighted to better comprehend WDHD1's function in cancer. High WDHD1 expression was associated with many aspects of immunology. Finally, the study found that individuals with high expression of WDHD1 were drug-sensitive to four different broad-spectrum anti-cancer drugs. CONCLUSION: These results describe dynamic changes in the tumor microenvironment in BLCA and provide evidence for the hypothesis that WDHD1 is a novel biomarker of tumor development. WDHD1 may therefore be a useful target for the detection and management of BLCA.

Utilization of neoadjuvant chemotherapy for muscle-invasive bladder cancer in elderly patients: a retrospective cohort study.

Neoadjuvant chemotherapy (NAC) improves overall survival in muscle-invasive bladder cancer (MIBC). Older patients often do not receive NAC due to its potential toxicities. We examined treatment patterns of elderly MIBC patients as well as impact of NAC on survival in this population. The National Cancer Database was queried from 2006 to 2019 for stage T2-T4a MIBC patients ≥ 80 years old. Treatment exposures (extirpative surgery; chemotherapy; radiation) were ascertained. Kaplan-Meier survival curves were generated based on treatment modalities (no treatment; radiation only; chemotherapy only; chemoradiation; surgery only; NAC with surgery). Multivariable Cox proportional hazards regression assessed associations with overall survival (OS). The cohort included 16,391 patients (mean age 86 years); 51% received treatment. MIBC treatment was less common with advancing age; patients receiving NAC then surgery were younger and had lower comorbidity scores. From 2006 to 2019, more patients received chemoradiation, while rates of NAC rose modestly. Median OS for the NAC with surgery group was 48 months versus 9 months for the no treatment group. Log-rank tests showed significantly improved survival in the NAC with surgery group compared to the surgery only group, while Cox proportional hazards regression analysis showed highest survival benefit in the NAC with surgery group. Only half of elderly MIBC patients received treatment, with fewer undergoing curative intent. NAC with surgery was associated with the greatest survival benefit. While our findings should be taken in the context of potential selection bias and patient preferences, they support NAC as part of shared-decision making regardless of age.

Comparative analysis of adverse events among intravesical drugs in bladder cancer: a real-world study on FAERS database.

BACKGROUND: Intravesical therapy is a commonly utilized treatment for non-muscle invasive bladder cancer (NMIBC). This study focuses on summarizing the signals of all intravesical drugs and aims to highlight the comprehensive differences in adverse events (AEs) between these drugs. RESEARCH DESIGN AND METHODS: We conducted pharmacovigilance data analysis based on the real-world big data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. RESULTS: We elucidated all signals compared with the overall FAERS database or other administration routes for Bacillus Calmette-Guerin (BCG), mitomycin, gemcitabine, valrubicin, and epirubicin. Notably, the distribution of reported AEs associated with intravesical therapy exhibited a noticeable inclination toward male patients. Furthermore, all five drugs demonstrated a disproportionate distribution in local AEs, particularly in renal and urinary disorders. Additionally, specific signals and findings were summarized for each individual drug. Finally, we highlighted the AEs that resulted in serious outcomes for each drug. CONCLUSION: We have compiled an overview of the AEs tied to intravesical drugs whilst considering their individual distinctions. These insightful findings serve to enrich our comprehension of the safety profiles and potential risks linked to intravesical therapy.