Muscle-invasive Bladder Cancer Research Articles

Single-cell RNA sequencing analysis reveals the dynamic changes in the tumor microenvironment during NMIBC recurrence.

Due to the clinical characteristic of frequent recurrence in urothelial bladder cancer (UBC), patients face significant health impacts and economic burdens. Therefore, understanding the molecular mechanisms involved in UBC recurrence is crucial for reducing its recurrence rate. The aim of our study is to help urologists and clinical researchers gain a deeper understanding of the changes in the tumor microenvironment (TME) during UBC recurrence. We collected 10 samples from primary and recurrent non-muscle-invasive bladder cancer (NMIBC) and performed single-cell RNA sequencing. By distinguishing and annotating cell subpopulations, we identified tissue preferences of some novel cell subgroups. Next, pseudotime trajectory analysis, cell-cell communication analysis, and function enrichment analysis were applied to evaluate the dynamic changes in the TME and biological functions. Finally, we validated the distribution of some of these cell subgroups using multiplex immunofluorescence experiments. We identified a tumor-associated fibroblast (CAF) subtype with high COL18A1 expression that is highly expressed in recurrent NMIBC, suggesting that the stromal component of the tumor may play a crucial role in the recurrence process. Additionally, pseudotime trajectory analysis revealed a macrophage subtype with high IL-6 expression at the terminal stage of macrophage differentiation, exhibiting significant immunosuppressive features. This indicated the presence of immune exhaustion during NMIBC recurrence. Lastly, we found an upregulation of estrogen in recurrent urothelial cancer cells, which may partially explain the gender disparity observed in UBC. This study identified several cell subpopulations influencing NMIBC recurrence, which were heavily infiltrated in the TME of recurrent NMIBC. Additionally, the enrichment of estrogen in urothelial cancer cells from various sources suggested a role of sex hormones in NMIBC recurrence.

The impact of positive surgical margins after cystectomy on oncological outcomes: a nationwide study.

To evaluate whether surgical margin status, alongside existing postoperative risk indicators, improves the identification of bladder cancer patients who may benefit from adjuvant therapy following radical cystectomy (RC). In this nationwide cohort study, patients aged ≥18 years diagnosed with muscle-invasive bladder cancer(MIBC) without nodal or distant metastasis (cT2-4aN0/xM0) between November 2017 and December 2020 who underwent RC were selected from the Netherlands Cancer Registry. Detailed information on surgical margin status was obtained through linkage with the Dutch central pathology database, Palga. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to assess the independent prognostic effect of positive surgical margins (carcinoma in situ (CIS)] only or invasive carcinoma) on PFS and OS. We identified 1445 MIBC patients treated by RC (53% open, 47% robot-assisted), of whom 135 (9.3%) had positive surgical margins (10.7% in the open and 7.7% in the robot-assisted cohort). In the entire cohort, OS was 79% and 60% at 12 and 48 months after RC, respectively. PFS was 70% and 61% at 12 and 24 months, respectively. Multivariable Cox regression showed worse PFS (hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.67-2.72) and OS (HR 2.02, 95% CI 1.58-2.58) in patients with surgical margins with invasive carcinoma vs patients with negative margins. Patients with only CIS in the margins also appeared to have worse PFS (HR 1.60, 95% CI 1.00-2.58) but these results were not statistically significant. No difference was found for OS (HR 1.30, 95% CI 0.80-2.12). Positive margins should be considered a 'high risk feature, as they result in increased risk of disease progression and impaired survival outcomes. These findings support further investigation of the potential efficacy of adjuvant therapy (i.e., radiotherapy and systemic therapy) among patients with positive surgical margins.

Mycobacteria Treatment Inhibits Bladder Cancer Cell Migration, Invasion, and Anchorage-Independent Growth

Bladder cancer (BC) is a highly recurrent and invasive malignancy, with Mycobacterium bovis BCG serving as the primary immunotherapy, particularly for non-muscle-invasive bladder cancer (NMIBC). However, the mechanisms underlying BCG’s antitumor effects and the potential of non-tuberculous mycobacteria like Mycobacterium brumae remain unclear. This study investigates the antitumor effects of M. bovis BCG and M. brumae on BC cell migration, invasion, and anchorage-independent growth. BC cell lines representing different stages of tumor differentiation were treated with either M. bovis BCG or M. brumae. Cell migration was assessed through wound healing and transwell assays, invasiveness by transwell invasion assays, MMP-9 production by gelatin zymography, and anchorage-independent growth via soft agar colony formation. Both mycobacteria inhibited individual cell migration across all BC lines, while collective migration was only reduced in intermediate-grade cells. Both treatments also reduced invasiveness, associated with decreased MMP-9 production. Furthermore, M. brumae inhibited anchorage-independent growth across all BC lines, while M. bovis BCG had a more selective effect, primarily inhibiting growth in high-grade cells. In conclusion, both mycobacteria reduce migration, invasion, and anchorage-independent growth of BC cells, with their effectiveness varying by species and tumor differentiation grade.

Loss of NUMB drives aggressive bladder cancer via a RHOA/ROCK/YAP signaling axis

Advances in bladder cancer (BCa) treatment have been hampered by the lack of predictive biomarkers and targeted therapies. Here, we demonstrate that loss of the tumor suppressor NUMB promotes aggressive bladder tumorigenesis and worsens disease outcomes. Retrospective cohort studies show that NUMB-loss correlates with poor prognosis in post-cystectomy muscle-invasive BCa patients and increased risk of muscle invasion progression in non-muscle invasive BCa patients. In mouse models, targeted Numb ablation induces spontaneous tumorigenesis and sensitizes the urothelium to carcinogenic insults, accelerating tumor onset and progression. Integrative transcriptomic and functional analyses in mouse and human BCa models reveal that upregulation of YAP transcriptional activity via a RHOA/ROCK-dependent pathway is a hallmark of NUMB-deficient BCa. Pharmacological or genetic inhibition of this molecular pathway selectively inhibits proliferation and invasion of NUMB-deficient BCa cells in 3D-Matrigel organoids. Thus, NUMB-loss could serve as a biomarker for identifying high-risk patients who may benefit from targeted anti-RHOA/ROCK/YAP therapies.

The role of autophagy dysregulation in low and high-grade nonmuscle invasive bladder cancer: A survival analysis and clinicopathological association

IntroductionBladder cancer disproportionately affects men and often presents as nonmuscle-invasive bladder cancer (NMIBC). Despite initial treatments, the recurrence and progression of NMIBC are linked to autophagy. This study investigates the expression of autophagy genes (mTOR, ULK1, Beclin1, and LC3) in low and high-grade NMIBC, providing insights into potential prognostic markers and therapeutic targets. Material and methodsA total of 115 tissue samples (n = 85 NMIBC (pTa, pT1, and CIS) and n = 30 control from BPH patients) were collected. The expression level of autophagy genes (mTOR, ULK1, Beclin1, and LC3) and their proteins were assessed in low and high-grade NMIBC, along with control tissue samples using quantitative real-time polymerase chain reaction and western blotting. Association with clinicopathological characteristics and autophagy gene expression was analyzed by multivariate and univariate survival analysis using SPSS. ResultIn high-grade NMIBC, ULK1, P = 0.0150, Beclin1, P = 0.0041, and LC3, P = 0.0014, were substantially downregulated, whereas mTOR, P = 0.0006, was significantly upregulated. The KM plots show significant survival outcomes with autophagy genes. The clinicopathological characters, high grade (P = 0.019), tumor stage (CIS P = 0.039, pT1 P = 0.018, P = 0.045), male (P = 0.010), lymphovascular invasion (P = 0.028) and autophagy genes (ULK1 P = 0.002, beclin1 (P = 0.010, P = 0.022) were associated as risk factors for survival outcome in NMIBC patients. ConclusionThe upregulated mTOR, downregulated ULK1, and beclin1 expression is linked to a high-grade, CIS and pT1 stage, resulting in poor recurrence-free survival and progression-free survival and highlights the prognostic significance of autophagy gene in nonmuscle-invasive bladder cancer.

Oncological outcomes of patients with muscle-invasive bladder cancer treated with trimodal strategy: A French multicentric study

PurposeTrimodal therapy, an organ-sparing alternative, may be proposed for selected patients with muscle-invasive bladder cancer instead of radical cystectomy. In this multicentre retrospective study, we aimed to assess the oncological outcomes of patients who had trimodal therapy for a muscle-invasive bladder cancer. Materials and methodsSeventy-three patients from four centres treated who had trimodal therapy (maximal transurethral resection of bladder tumour and concomitant chemoradiotherapy) for localized muscle-invasive bladder cancer were included. Patients meeting the optimal trimodal therapy eligibility criteria as per the European Association of Urology guidelines were identified. Overall survival, recurrence-free survival and cancer-specific survival were assessed using the Kaplan–Meier method. The cumulative incidence of recurrence was estimated using the Kalbfleisch–Prentice method. ResultsMedian overall survival was 27.0 months (95 % confidence interval [CI]: 20.3–58.3 months), 5-years overall-, cancer-specific- and recurrence-free survival rates were 37.5% (95 % CI: 25.5–49.5 %), 60 % (95 % CI: 48.3–72.0 %), and 17.9 % (95 % CI: 9.3–28.8 %), respectively. There was no significant difference in 5-year overall survival and recurrence-free survival between the trimodal therapy-eligible and non-eligible patients (hazard ratio [HR]: 1.38, P=0.30 and HR: 0.96, P=0.90, respectively). The univariate analysis did not reveal any significant prognostic factors associated with recurrence-free or overall survival. ConclusionTrimodal therapy offers encouraging specific survival, the prognosis remains poor. Our study highlights the low number and high frailty of patients to whom trimodal therapy is offered in clinical practice.

Performance of urinary markers in patients with suspicious cystoscopy during follow-up of recurrent non-muscle invasive bladder cancer: BTA stat®, NMP22® BladderChek®, UBC® Rapid Test, CancerCheck® UBC® rapid VISUAL, and uromonitor® in comparison to cytology

ObjectivesTo compare all available rapid tests on a large cohort of recurrent bladder cancer during follow-up in this multicentre-study is the first study. BTA stat®, NMP22® BladderChek®, UBC® Rapid Test CancerCheck® UBC® rapid VISUAL, and uromonitor® are urinary based rapid tests for bladder cancer detection. MethodsIn total 187 urine samples were analysed from patients with suspected recurrent non-muscle invasive urothelial bladder cancer on cystoscopy during follow-up in a real-world assessment. All suspicious lesions were resected with 110 samples showing recurrent urothelial cancer. Urine samples were analysed by the BTA stat®, NMP22® BladderChek®, UBC® Rapid Test, CancerCheck® UBC® rapid VISUAL, uromonitor®, and cytology. Sensitivities and specificities were calculated by contingency analyses. ResultsAll investigated urinary markers could detect a higher percentage of pathological results in urine of bladder cancer patients compared to urine of tumor free patients. The calculated diagnostic sensitivities for BTA stat®, NMP22® BladderChek®, UBC® Rapid Test, CancerCheck® UBC® rapid VISUAL, uromonitor®, and cytology were 60.0%, 10.0%, 58.0%, 32.0%, 54.5%, and 41.5% for non-muscle invasive low-grade, and 64.0%, 40.0%, 77.8%, 50.0%, 56.0%, and 65.5% for non-muscle invasive high-grade bladder cancer. The specificity was 51.3%, 94.8%, 66.2%, 89.5%, 94.9%, and 66.2%, respectively. ConclusionsDuring follow-up sensitivities and specificities of most urinary markers are higher compared to cytology for the detection of recurrent bladder cancer. BTA stat®, UBC® Rapid Test, and uromonitor® appear useful in this setting.

Comprehensive genetic profile of Chinese muscle-invasive bladder cancer cohort

ObjectiveThe aim of our study was to characterize the spectrum of mutations in muscle-invasive bladder cancer (MIBC) in the Chinese population, identifying mutational features and exploring potential therapeutic targets. MethodsWe collected samples from 62 Chinese patients with MIBC. For each patient, tumor tissues or blood samples were collected and sequenced by whole exome sequencing. ResultsOur findings revealed the most frequently mutated genes included TP53 (41%), TTN (41%), HYDIN (34%), FRG1 (33%), ZNF717 (23%), AHNAK2 (21%), MUC4 (21%), KMT2D (20%), CDC27 (18%) and IGSF3 (18%). The most frequently mutated DNA damage repair (DDR) genes were TP53 (49%), SMARCA4 (10%), ERCC2 (8%), BRAC2 (6%), HERC2 (6%), HLTF (6%), PALB2 (6%) and POLG (6%). Additionally, our analysis confirmed an association between DDR mutations and high TMB (P = 0.022). Significant differences in MSI were observed between smokers and nonsmokers (P = 0.022), drinkers and nondrinkers (P = 0.018). By analyzing the data of 323 white MIBC samples from TCGA database, we identified frequently mutated driver genes in both our cohort and TCGA white cohort, including TP53, KMT2D, KMT2C, and FGFR3. Our study also revealed genes with distinct mutation frequencies compared to the TCGA white cohort, including FRG1, CDC27, IGSF3, MUC16, and ARID1A. ConclusionsOur study provided comprehensive insights into genomic alterations in a cohort of Chinese MIBC, which could provide potential clues for clinical applications. MicroAbstractThis study aimed to characterize mutations in muscle-invasive bladder cancer (MIBC) in the Chinese population, identifying mutational features and potential therapeutic targets. Samples from 62 Chinese MIBC patients were sequenced using whole exome sequencing, revealing frequent mutations in genes like TP53, TTN, and HYDIN. The study also found associations between DNA damage repair mutations and high tumor mutational burden, as well as differences in mutational profiles between Chinese and white MIBC cohorts. These findings offer valuable insights for clinical applications in Chinese MIBC patients.

High-Risk Non-Muscle Invasive Bladder Cancer: outcomes of patients who cannot benefit from Standard of Care

Introduction: High grade non-muscle invasive bladder cancer (HG-NMIBC) exposes to a high risk of recurrence and progression. Standard of care includes repeated trans-urethral resection of bladder tumor (reTURBT) and bacillus Calmette-Guérin (BCG) therapy. Not following Standard of care (SOC) may be associated with a worse prognosis. We aimed to compare prognosis outcomes of patients with primary HG-NMIBC according to the respect of the SOC or not.Materials & Methods: We conducted an eleven-year retrospective observational study including all patients undergoing initial bladder resection for de novo HG-NMIBC at our institution. Exclusion criteria were prior urothelial carcinoma histology, low grade NMIBC or ≥ T2 staging. Four groups were formed according to the treatment received.Results: Among 164 patients, 44.5% received standard of care, 18.3% received only BCG-therapy, 16.5% benefited only from reTURBT and 20.7% did not receive treatment. Upstaging to T2 tumor was found in 6% of reTURBT specimens. Presence of residual tumor (RT) on re-TURBT (p < 10-4) and having benefited from SOC (p=0.016) impacted recurrence-free survival. Progression-free survival was impacted by presence of RT (p=0.001) but not by SOC (p=0.284).Conclusion: Performing standard of care on patients with HG-NMIBC is associated with a lower risk of recurrence. We believe SOC should be provided for all HG-NMIBC patients, especially those with poor prognostic factors such as T1 tumor, or multiplicity or largeness of the bladder tumor.

Mitomycin C vs. Bacillus Calmette–Guerin for treatment of intermediate-risk nonmuscle invasive bladder cancer patients—A comparative analysis from a single center

BackgroundInduction followed by 1 year maintenance instillation of intravesical Bacillus Calmette–Guerin (BCG) is the standard treatment for intermediate-risk (IR) nonmuscle invasive bladder cancer (NMIBC) patients. Few data exist on the efficacy of Mitomycin C (MMC) instillation in this setting. MethodsWe retrospectively analyzed 226 IR-NMIBC patients classified by the International Bladder Cancer Group (IBCG) and 250 IR-NMIBC intravescical treatment-naïve patients classified by the European Association of Urology (EAU). All patients received either a full induction course of BCG or 40 mg/40 ml MMC from 2012 to 2022. Optimal treatment was defined as 1-year maintenance for BCG and 11 monthly maintenance instillations for MMC. Kaplan–Meier analysis estimated recurrence-free survival (RFS) before and after inverse probability of treatment-weighting (IPTW) and progression-free survival (PFS). Multivariable Cox regression was used to evaluate difference in recurrence after adjustment for clinically relevant variables before and after IPTW. ResultsOptimal BCG and MMC courses were administered to 21% of IR-IBCG and 23% of IR-EAU patients. At 4-years, patients treated with optimal MMC and BCG treatment had similar RFS and PFS in both EAU and IBCG groups. Patients receiving nonoptimal BCG compared to optimal MMC exhibited lower 4-year RFS after IPTW (82% vs. 68% in EAU and 82% vs. 65% in IBCG). At 4-year optimal MMC had greater PFS non optimal BCG. Optimal MMC treatment predicted recurrence in EAU (adjusted and weighted HR 0.33, 95% CI, 0.11-0.98) and IBCG (adjusted and weighted HR 0.29, 95% CI, 0.08-0.97) groups compared to nonoptimal BCG. ConclusionsOptimal 40 mg/40 ml MMC treatment was as effective as optimal BCG in IR-IBCG and IR-EAU NMIBC patients, reducing both recurrence and progression compared to nonoptimal BCG. MMC could be a valid first line alternative to BCG for both IR-EAU and IR-IBCG intravescical treatment-naïve patients, during BCG shortages.

Robot-assisted, laparoscopic and open radical cystectomy for bladder cancer: A systematic review and network meta-analysis.

To evaluate the safety and effectiveness of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC), and open radical cystectomy (ORC) in bladder cancer. A literature search for network meta-analysis was conducted using international databases up to February 29, 2024. Outcomes of interest included baseline characteristics, perioperative outcomes and oncological outcomes. Forty articles were finally selected for inclusion in the network meta-analysis. Both LRC and RARC were associated with longer operative time, smaller amount of estimated blood loss, lower transfusion rate, shorter time to regular diet, fewer incidences of complications, and fewer positive surgical margin compared to ORC. LRC had a shorter time to flatus than ORC, while no difference between RARC and ORC was observed. Considering lymph node yield, there were no differences among LRC, RARC and ORC. In addition, there were statistically significant lower transfusion rates (OR=-0.15, 95% CI=-0.47 to 0.17), fewer overall complication rates (OR=-0.39, 95% CI=-0.79 to 0.00), fewer minor complication rates (OR=-0.23, 95% CI=-0.48 to 0.02), fewer major complication rates (OR=-0.23, 95% CI=-0.68 to 0.21), fewer positive surgical margin rates (OR=0.22, 95% CI=-0.27 to 0.68) in RARC group compared with LRC group. LRC and RARC could be considered as a feasible and safe alternative to ORC for bladder cancer. Notably, compared with LRC, RARC may benefit from significantly lower transfusion rates, fewer complications and lower positive surgical margin rates. These data thus showed that RARC might improve the management of patients with muscle invasive or high-risk non-muscle invasive bladder cancer.

Clinical performance of Bladder EpiCheck™ versus voided urine cytology for detecting recurrence of nonmuscle invasive bladder cancer: Systematic review and meta-analysis

BackgroundNonmuscle invasive bladder cancer (NMIBC) has a favorable prognosis but has high propensity for recurrence. Recent development in one of the urinary biomarker tests, Bladder EpiCheck™, offers a noninvasive and accurate method to detect NMIBC recurrence. In this study, we aimed to compare the diagnostic performance of Bladder EpiCheck™ with urine cytology to detect NMIBC recurrence. MethodsWe performed a systematic review search through PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to July 2023. Diagnostic accuracy was defined by sensitivity, negative predictive value (NPV), specificity, and positive predictive value (PPV). ResultsA total of 6 studies involving 1588 patients were included. Bladder EpiCheck™ has a sensitivity and specificity of 0.81 (95% CI: 0.63–0.91; I2: 43%) and 0.87 (95% CI: 0.83–0.91; I2: 20%), respectively. On the other hand, urine cytology has a sensitivity and specificity of 0.63 (95% CI: 0.29–0.87; I2: 61%) and 0.97 (95% CI: 0.78–1.00; I2: 79%), respectively. EpiCheck™ has a higher NPV (0.94 (95% CI: 0.87–0.97) vs. 0.84 (95% CI: 0.80–0.87) though a lower PPV (0.62 (95% CI: 0.45–0.76) vs. 0.87 (95% CI: 0.56–0.97) than urine cytology. In our subgroup analysis, the sensitivity of Bladder EpiCheck™ for detecting high-grade tumors improved to 0.90 (95% CI: 0.83–0.94) while that for urine cytology improved to 0.72 (95% CI: 0.50–0.87). ConclusionBladder EpiCheck™ has a high sensitivity and NPV for detecting recurrence among patients with NMIBC.

Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment: Erratum.

Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline: 2024 Amendment: Erratum.

The Emerging Treatment of BCG (Bacillus Calmette-Guérin)-Unresponsive Non–Muscle-Invasive Bladder Cancer

Bacillus Calmette-Guérin (BCG) remains the cornerstone in the treatment of high-risk non-muscle-invasive bladder cancer (NMIBC), effectively preventing recurrence and progression. Unfortunately, a significant proportion of patients are classified as BCG-unresponsive, and there have been no definite alternative treatments for these disease group except for radical cystectomy, which is still challenging and sometimes not applicable. Therefore, there has been a need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. Intravesical therapies, such as gemcitabine, mitomycin C and docetaxel, are mostly studied approaches, showing some promising results. However, no definitive conclusion has be drawn because of the heterogeneity of the studies and protocols and the limited number of patients enrolled in most of these studies. Immunotherapy and anti-inflammatory agents, though promising, require further validation through ongoing clinical trials to ensure their safety and efficacy. Gene therapy is also being explored, though it is in its early stages, with challenges in gene delivery and immune regulation still to be addressed. Photodynamic therapy and hyperthermia, particularly in combination with other treatments like intravesical chemotherapy, have shown potential in improving outcomes for BCG-unresponsive patients, though they are not yet considered first-line treatments. While these novel approaches hold promise, more robust data and clinical trial results are necessary to guide treatment protocols. In conclusion, ongoing research and clinical trials will continue to shape the future of NMIBC management, with the aim of providing more effective and bladder-preserving options for patients.

Identification of tumor-antigen signatures and immune subtypes for mRNA vaccine selection in muscle-invasive bladder cancer

BackgroundMuscle-invasive bladder cancer continues to lack reliable diagnostic and prognostic biomarkers. Recently, tumor vaccines targeting specific molecules have emerged as a promising treatment in inhibiting tumor progression, which was rekindled under the background of coronavirus disease-2019 pandemic. However, the application of mRNA vaccine targeting muscle-invasive bladder cancer–specific antigens remains limited, and there has been a lack of comprehensive studies or validations to identify suitable patient subgroups for vaccination. This study aims to explore novel muscle-invasive bladder cancer antigen signatures to identify patients most likely to benefit from vaccination. MethodsGene expression profiles of muscle-invasive bladder cancer samples, along with corresponding clinical data, were retrieved from the Cancer Genome Atlas Program. The least absolute shrinkage and selection operator model was applied to develop signatures for stratifying muscle-invasive bladder cancer patients. Prognostic accuracy of each factor was assessed using receiver operating characteristic analysis. Tumor Immune Estimation Resource was employed to visualize the relationship between the proportion of antigen-presenting cells and the expression of selected genes. The CIBERSORT and WGCNA R packages were used to identify differences in immune infiltration levels across muscle-invasive bladder cancer subgroups. Additionally, the STRING database and Cytoscape were used to construct the protein-protein interaction network. CCK-8 and colony formation assays were employed in invitro experiments. ResultsA total of 49 potential tumor antigens were identified. Using least absolute shrinkage and selection operator Cox regression, 14 tumor antigens were selected to develop a risk evaluation signature. The risk score signature can serve as a valuable tool for predicting the outcomes of muscle-invasive bladder cancer patients. Based on differential clinical, molecular, and immune-related gene profiles, muscle-invasive bladder cancer patients were classified into 2 subtypes: the immune “cold” subtype (immune score 1) and the immune “hot” subtype (immune score 2). The immune score signature, developed using a logistic score model, effectively distinguishes between patients more likely to belong to immune score 1 or 2. Notably, patients with a high risk score exhibited a higher proportion of immune score 2 compared to those with a low risk score. Additionally, the prognostic accuracy was significantly enhanced when the risk score and immune score were combined. Different tumor subtypes displayed distinct immune landscapes and signaling pathways. Moreover, novel tumor antigens associated with oxidative stress were identified. ConclusionThe risk score and immune score signatures based on tumor antigens have identified potential effective neo-antigens for the development of mRNA vaccines targeting muscle-invasive bladder cancer. Patients with low risk score and immune score 1 subtype are more likely to benefit from mRNA vaccination. Additionally, this study highlights the critical role of oxidative stress in modulating the efficacy of the mRNA vaccine.

Preoperative neutrophil-to-lymphocyte ratio (NLR) value as a predictor of recurrence of non-muscle-invasive bladder cancer.

To predict oncological outcomes and select appropriate treatments for non-muscle-invasive bladder cancer (NMIBC), pre-treatment predictors such as neutrophil-to-lymphocyte ratio (NLR) are being used. This study aims to evaluate whether NLR is an independent predictor of disease and disease recurrence in NMIBC patients. In this prospective clinical study, from March 2018 to March 2023, preoperative NLR values were monitored in 99 patients newly diagnosed with NMIBC, who were initially treated with trans-urethral resection of bladder tumor (TURBT) and adjuvant intravesical therapy. To evaluate the best NLR cutoff points to predict recurrence, the ROC (receiver operating characteristic) curve and the Youden index were used. The monitoring period was 24 months. With the cutoff value of NLR = 1.73, there is a statistically significant correlation (p = 0.008) between the NLR value and the increased risk of recurrence. Univariate and multivariate Cox regression analyses show the significant prognostic impact of NLR on the recurrence of the disease. The value of NLR > 1.73 is a significant preoperative predictor in risk assessment and will help with proper selection of treatment in the high- and intermediate-risk groups of patients.

Do we need group and save for trans-urethral resection of bladder tumour and trans-urethral resection of the prostate procedures?

Background: Trans-urethral resection of the prostate (TURP) and trans-urethral resection of bladder tumour (TURBT) are urological procedures essential for treating benign prostatic hyperplasia (BPH) and non-muscle invasive bladder cancer, respectively, these procedures may result in post-operative bleeding. In our hospital, pre-operative blood group and save is a routine to enhance patient safety. This study aims to evaluate transfusion rates and the potential cost benefits of limiting routine blood group and save. Methods: We conducted a retrospective audit of patients undergoing TURP and TURBT between October 2018 and October 2020. Data was collected using theatre system records and blood bank information regarding transfusions. Results: Out of 233 patients (average age 74), 141 underwent TURBT, 89 underwent TURP, and 3 underwent both simultaneously. Historical group and save were found in 214 (91.84%) patients, and 162 (69.5%) had same-day group and save. Only 2 patients (0.85%) necessitated transfusions. Conclusions: The necessity for blood transfusion after TURP and TURBT is low, indicating that routine pre-operative group and save may not be essential for all patients. Tailoring this practice to high-risk individuals may reduce costs and relieve workloads. Enhanced surgical techniques and tools are likely contributors to these improved outcomes.

Quantifying treatment burden: the patient burden score a study of 758 patients across three clinical urologic scenarios

ObjectivesTo develop a comprehensive scale that measures the three burden types of any treatment, including expected, unexpected (complications), and need for ancillary procedures.MethodsA panel of experts created a scale that assessed the burden of all aspects of treatment, including hospitalization, anesthesia, surgery, and follow-up. The total score is defined as the burden score (BS). BS was calculated retrospectively for patients in three clinical scenarios in urology, each with two acceptable treatment options: patients with a small renal mass (T1a) treated with either partial nephrectomy (PN, 139 patients) or percutaneous ablation (PA, 83 patients), patients with bladder cancer (stages T2-4a, N0, M0) treated with radical cystectomy (RC, 162 patients) or trimodal therapy (TMT, 88 patients), and patients with upper ureteral stones ≤ 10 mm treated with either ureteroscopy (137 patients) or extracorporeal shock-wave lithotripsy (SWL, 150 patients).ResultsBoth PN and PA provided excellent oncological results (5-year recurrence-free survival ≥ 97%) and low complication rates. However, the BS of PN was more than twice that of PA (27.3 ± 7.7 vs. 12.5 ± 6.4, p < 0.01). RC and TMT showed identical 3-year disease-specific survival rates (73%), but the BS of TMT was significantly lower (53.8 ± 11.1 vs. 42.0 ± 11.6, p < 0.01). Both ureteroscopy and SWL have achieved high stone-free rates (≥ 97%) and low complication rates. However, the BS of ureteroscopy was significantly lower (7.8 ± 3 vs. 9.0 ± 3.5, p < 0.01).ConclusionPA treatment for small renal masses, TMT for muscle-invasive bladder cancer, and ureteroscopy for upper ureteral stones provided similar success rates to those of PN, RC, and SWL, but with significantly lower BS. This tool can assist in patient consultation when multiple treatment options are available. The concept of BS can be extended to other fields of medicine.

E2F8 facilitates malignant phenotypes of muscle-invasive bladder cancer via increasing MCM7 expression.

E2F transcription factor 8 (E2F8) is an important regulator of the cell cycle. In this study, we first assessed the expression of E2F8 in bladder cancer and examined its effects in the malignant phenotypes of bladder cancer cell lines. We found that E2F8 was upregulated in bladder cancer tissues, and the increased expression was positively associated with higher clinical stage. E2F8 knockdown suppressed bladder cancer cell proliferation, accompanied by the performance of G1 phase arrest and the upregulated Cyclin D1 protein expression. The migrative and invasive capability was reduced in E2F8-depleted bladder cancer cells. Cisplatin resistance is an important cause of bladder cancer relapse. E2F8 downregulation facilitated cisplatin-induced apoptosis of bladder cancer cells. MCM7 is regulated by E2F and has been shown to participate in bladder cancer. There was a positive correlation between E2F8 and MCM7 expression in bladder cancer. We confirmed that E2F8 bound to the promoter region of MCM7 and activated MCM7 transcription. MCM7 overexpression abrogated the suppressive effects of E2F8 knockdown on malignant phenotypes of bladder cancer cells. We also demonstrated that E2F8 knockdown suppressed bladder cancer progression in vivo. In conclusion, we verify that E2F8 functioned in bladder cancer, and might exert its function via MCM7.

Epigenetic Biomarkers as a New Diagnostic Tool in Bladder Cancer—From Early Detection to Prognosis

Bladder cancer (BC) currently ranks as the 9th most common cancer worldwide. It is characterised by very high rates of recurrence and metastasis. Most cases of BC are of urothelial origin, and due to its ability to penetrate muscle tissue, BC is divided into non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). The current diagnosis of BC is still based primarily on invasive cystoscopy, which is an expensive and invasive method that carries a risk of various complications. Urine sediment cytology is often used as a complementary test, the biggest drawback of which is its very low sensitivity concerning the detection of BC at early stages, which is crucial for prompt implementation of appropriate treatment. Therefore, there is a great need to develop innovative diagnostic techniques that would enable early detection and accurate prognosis of BC. Great potential in this regard is shown by epigenetic changes, which are often possible to observe long before the onset of clinical symptoms of the disease. In addition, these changes can be detected in readily available biological material, such as urine or blood, indicating the possibility of constructing non-invasive diagnostic tests. Over the past few years, many studies have emerged using epigenetic alterations as novel diagnostic and prognostic biomarkers of BC. This review provides an update on promising diagnostic biomarkers for the detection and prognosis of BC based on epigenetic changes such as DNA methylation and expression levels of selected non-coding RNAs (ncRNAs), taking into account the latest literature data.