Anti-CV2 Antibody-Positive Sensorimotor Polyneuropathy Following Bacillus Calmette-Guérin Intravesical Infusion Therapy.

Bacillus Calmette-Guérin (BCG) intravesical infusion therapy is widely used to control recurrence after transurethral resection of bladder tumors. Herein, we report a case of polyneuropathy with transiently positive onconeural antibodies after BCG bladder infusion therapy. A man in his 70s presented with upper and lower extremity weakness 11 weeks after BCG intravesical infusion therapy, a postoperative therapy for superficial bladder cancer. Nerve conduction studies revealed findings that were consistent with demyelinating sensorimotor polyneuropathy. Anti-CV2 antibody was positive; however, contrast-enhanced computed tomography and positron emission tomography revealed no malignancy. The patient's symptoms improved with immunoglobulin therapy. Contrast-enhanced computed tomography showed no malignancy, and the anti-CV-2 antibody test result was negative six months after discharge. The immune response to BCG bladder infusion therapy may have caused the transient CV2 antibody positivity and polyneuropathy. The possibility of transiently positive onconeural antibodies after BCG intravesical infusion therapy should be considered.

Comparative Effectiveness of Bacillus Calmette-Guérin and Sequential Intravesical Gemcitabine and Docetaxel for Treatment-naïve Intermediate-risk Non-muscle-invasive Bladder Cancer.

BACKGROUND AND OBJECTIVE: Sequential intravesical gemcitabine/docetaxel (Gem/Doce) has emerged as a potential alternative to bacillus Calmette-Guérin (BCG) for the treatment of non-muscle-invasive bladder cancer (NMIBC). Our aim was to determine the comparative effectiveness of BCG and Gem/Doce for patients with intermediate-risk (IR) NMIBC, composed mainly of high-grade (HG) Ta disease. METHODS: Patients with IR-NMIBC who received either BCG or Gem/Doce during 2013-2023 were included. Maintenance BCG (as per the Southwest Oncology Group protocol) and monthly Gem/Doce maintenance for 1 yr were offered to patients with no evidence of recurrence after induction. Routine surveillance with cystoscopy was performed according to the American Urological Association guidelines. The Kaplan-Meier method was used to assess high-grade and any-grade recurrence-free survival (RFS). Cox regression analysis was performed to find predictors of recurrence. KEY FINDINGS AND LIMITATIONS: Of 483 patients, 127 had IR-NMIBC; 66 patients received BCG and 61 received Gem/Doce. Median age was 69 yr (interquartile range [IQR] 61-76) for the BCG group and 72 yr (IQR 62-76) for the Gem/Doce group. Median follow-up was 53.1 mo (IQR 25.3-71.2) for the BCG group and 20.2 mo (IQR 8.28-33.1) for the Gem/Doce group. The 2-yr high-grade RFS rates for primary high-grade tumors for BCG versus Gem/Doce groups were 81% versus 61%, with corresponding any-grade RFS rates of 60% versus 41%. Induction with Gem/Doce predicted any-grade recurrence (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.1-3.2) and high-grade recurrence for primary high-grade tumors (HR 3.4 95% CI 1.27-9.13), while receipt of maintenance therapy decreased the risk of any-grade recurrence (HR 0.4, 95% CI 0.22-0.72). This study is limited by its retrospective design. CONCLUSIONS AND CLINICAL IMPLICATIONS: For patients with IR-NMIBC, BCG was associated with superior any-grade RFS and high-grade RFS for primary high-grade tumors. Maintenance therapy was associated with better RFS when receiving Gem/Doce. Standardization and longer maintenance therapy protocols should be considered for Gem/Doce treatment. PATIENT SUMMARY: We compared outcomes for patients who received two different in-bladder treatments for intermediate-risk bladder cancer. Bacillus Calmette-Guérin (BCG) led to better outcomes than gemcitabine + docetaxel (Gem/Doce). Monthly maintenance therapy improved recurrence-free survival for patients who received Gem/Doce. We conclude that maintenance therapy is essential for patients receiving Gem/Doce to avoid bladder cancer recurrence after treatment.

Assessing muscle invasion in bladder cancer via virtual biopsy: a study on quantitative parameters and classical radiomics features from dual-energy CT imaging.

OBJECTIVE: To evaluate the prediction value of Dual-energy CT (DECT)-based quantitative parameters and radiomics model in preoperatively predicting muscle invasion in bladder cancer (BCa). MATERIALS AND METHODS: A retrospective study was performed on 126 patients with BCa who underwent DECT urography (DECTU) in our hospital. Patients were randomly divided into training and test cohorts with a ratio of 7:3. Quantitative parameters derived from DECTU were identified through univariate and multivariate logistic regression analysis to construct a DECT model. Radiomics features were extracted from the 40, 70, 100 keV and iodine-based material-decomposition (IMD) images in the venous phase to construct radiomics models from individual and combined images using a support vector machine classifier, and the optimal performing model was chosen as the final radiomics model. Subsequently, a fusion model combining the DECT parameters and the radiomics model was established. The diagnostic performances of all three models were evaluated through receiver operating characteristic (ROC) curves and the clinical usefulness was estimated using decision curve analysis (DCA). RESULTS: The normalized iodine concentration (NIC) in DECT was an independent factor in diagnosing muscle invasion of BCa. The optimal multi-image radiomics model had predictive performance with an area-under-the-curve (AUC) of 0.867 in the test cohort, better than the AUC = 0.704 with NIC. The fusion model showed an increased level of performance, although the difference in AUC (0.893) was not statistically significant. Additionally, it demonstrated superior performance in DCA. For lesions smaller than 3 cm, the fusion model showed a high predictive capability, achieving an AUC value of 0.911. There was a slight improvement in model performance, although the difference was not statistically significant. This improvement was observed when comparing the AUC values of the DECT and radiomics models, which were 0.726 and 0.884, respectively. CONCLUSION: The proposed fusion model combing NIC and the optimal multi-image radiomics model in DECT showed good diagnostic capability in predicting muscle invasiveness of BCa.

The prognostic significance of circulating tumor DNA in patients with positive lymph node disease after robotic-assisted radical cystectomy: A contemporary analysis.

BACKGROUND AND OBJECTIVE: Neoadjuvant therapy followed by radical cystectomy with lymphadenectomy remains the gold standard of treatment in patients with muscle-invasive bladder cancer. Pathologically positive lymph node (pN+) disease is known to convey a poor prognosis. Tumor-informed circulating tumor DNA (ctDNA) has emerged as a possible novel prognostic biomarker in the field. We seek to assess recurrence-free survival (RFS) for patients undergoing robotic-assisted radical cystectomy (RARC) with extended pelvic lymphadenectomy (ePLND) and to assess whether ctDNA status can be a prognostic marker for RFS outcomes in patients with pN+ disease. METHODS: Patients who underwent RARC + ePLND during 2015 to 2023 were included. A sub-group analysis (n = 109) of patients who had prospectively collected serial-longitudinal tumor-informed ctDNA analyses during 2021-2023 was performed. Survival analysis and Cox-regression models were conducted. RESULTS: Included were 458 patients with a median age of 69 (IQR 63-76), and a median follow-up time of 20 months (IQR 10-37). RFS for pN0 (n = 353) and pN+ (n = 105) at 12, 24 and 36 months were 87% vs. 54%, 80% vs. 39%, and 74% vs. 35%, respectively (log-rank, P < 0.0001). On Cox multivariate analysis ≥pT3 disease (Hazzard ratio [HR] = 3.36 [2.18-5.18], P < 0.001), pN+ disease (HR = 2.39 [1.55-3.7], P < 0.001), and recipients of neoadjuvant treatment (HR = 1.61 [1.11-2.34], P = 0.013) were predictive of disease relapse. Patients with pN+ disease and undetectable precystectomy or postcystectomy ctDNA status had similar RFS to patients with pN0 with undetectable ctDNA. On Cox-regression multivariate sub-group analysis, detectable precystectomy ctDNA status (HR = 3.89 [1.32-11.4], P = 0.014), detectable ctDNA status in the minimal residual disease window ([MRD], HR = 2.89 [1.12-7.47], P = 0.028), and having ≥pT3 with pN+ disease (HR = 4.2 [1.43-12.3], P = 0.009) were predictive of disease relapse. CONCLUSIONS: Patients with pN+ .after RARC had worse oncological outcomes than patients with pN0 disease. Undetectable ctDNA status was informative of RFS regardless of nodal status at both the precystectomy and the MRD window. Patients with undetectable ctDNA status and pN+ disease may benefit from treatment de-escalation.

Radical cystectomy versus trimodal therapy for muscle-invasive bladder cancer: Analysis of an other-cause mortality matched cohort.

OBJECTIVE: Comparative effectiveness studies comparing trimodal therapy (TMT) to radical cystectomy (RC) are typically hindered by selection bias where TMT is usually reserved to patients with poor overall health status. We developed a novel approach by matching patients based on their calculated other-cause mortality (OCM) risk. Using this homogeneous cohort, we tested the impact of TMT vs RC on cancer-specific mortality (CSM). MATERIALS AND METHODS: The Surveillance, Epidemiology and End Results (SEER) 2004-2018 database was queried to identify patients diagnosed with cT2-4N0M0 muscle-invasive bladder cancer (MIBC). A Fine-Gray competing-risk regression model calculating the 5-year OCM risk was used to create a 1:1 propensity-score matched-cohort of patients treated with RC or TMT. Cumulative incidence and competing-risk regression analyses tested the impact of treatment type (RC vs TMT) on CSM. Patients were further stratified according to clinical T stage (cT2 vs cT3-4) in sensitivity analyses. RESULTS: We identified 6,587 patients (76%) treated with RC and 2,057 (24%) with TMT. The median follow-up was 3.0 years. In the unmatched-cohort, 5-year OCM and CSM rates were 14% and 40% for RC vs 23% and 47% in TMT group, respectively (all P < 0.001). Our matched-cohort included 4,074 patients, equally distributed for treatment type, with no difference in 5-year OCM (HR: 0.98, 95% CI: 0.86-1.11, P = 0.714). In clinical-stage specific sensitivity analyses, 5-year CSM rate was significantly worse for cT2N0M0 patients treated with TMT (HR: 1.52, 95% CI: 1.21-1.91, P < 0.001) than those treated with RC. For cT3-4N0M0 patients, there was no difference in CSM among the 2 approaches (HR: 0.98, 95% CI: 0.63-1.52, P = 0.900). CONCLUSIONS: Our findings demonstrate an oncologic advantage of RC over TMT for cT2 MIBC patients. Conversely, we did not find a cancer-specific survival difference for cT3-T4 MIBC patients, regardless of treatment.

Impact of Age, Period, Cohort, Region, Race, and Health Services on Bladder Cancer Mortality in Brazil: A 23-Year Ecological Study.

Bladder cancer is one of the most economically costly types of cancer, but few studies have evaluated its mortality considering the factors that impact this outcome. This study aimed to investigate the impact of sociodemographic factors, period, cohort, and health services on bladder cancer mortality. This ecological study analyzed bladder cancer mortality data in Brazil from 2000 to 2022 and evaluated sociodemographic variables (race, region of residence), socioeconomic variables (gross domestic product per capita, Gini index of household income per capita, number of health professionals per inhabitant, expenditure on public health services, and consultations per inhabitant), and bladder cancer diagnosis and treatment procedures. These data were subjected to statistical analysis, which revealed that after the age of 50, there was a progressive increase in the risk of bladder cancer. Indigenous people had the lowest mortality rate, while white people had a significantly greater mortality rate than black and brown people. The North Region and Northeast Region presented the lowest mortality rates, whereas the South Region presented the highest mortality rates. In the South and Southeast Regions, a higher GDP was related to lower mortality. In the South, higher mortality was associated with a lower number of consultations per inhabitant per region. Fewer bladder punctures/aspirations and bladder biopsies were associated with higher mortality rates. In oncology, more procedures, such as total cystectomy, cystoenteroplasty, and total cystectomy with a single shunt, do not reduce the mortality rate. These results can serve as guidelines for adjusting public health policies.

Immunophenotypic and molecular changes during progression of papillary urothelial carcinoma.

PURPOSE: Urothelial carcinoma has various molecular subtypes, each with different tumor characteristics. Although it is known that molecular changes occur during tumor progression, little is known about the specifics of these changes. In this study, we performed transcriptional analysis to understand the molecular changes during tumor progression. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tumor tissues were obtained from 12 patients with muscle-invasive bladder cancer (MIBC). The invasive and non-invasive papillary areas were identified in papillary urothelial carcinoma specimens. Immunohistochemistry (IHC) and mRNA sequencing were performed for each tumor area. RESULTS: Patients with CK5/6-negative and CK20-positive non-invasive papillary areas were selected and classified into the IHC switch subgroup (CK5/6-positive and CK20-negative in the invasive area) and the IHC unchanged subgroup (CK5/6-negative and CK20-positive in the invasive area) according to the IHC results of the invasive area. We identified differences in the mRNA expression between the non-invasive papillary and invasive areas of the papillary MIBC tissue samples. In both the non-invasive papillary and invasive areas, the IHC switch subgroup showed basal subtype gene expression, while the IHC unchanged subgroup demonstrated luminal subtype gene expression. CONCLUSIONS: The non-invasive papillary area showed a gene expression pattern similar to that of the invasive area. Therefore, even if the non-invasive papillary area exhibits a luminal phenotype on IHC, it can have a basal subtype gene expression depending on the invasive area.

Immune checkpoint gene signature assesses immune infiltration profiles in bladder cancer and identifies KRT23 as an immunotherapeutic target.

BACKGROUND: In the past few decades, researchers have made promising progress, including the development of immune checkpoint inhibitors (ICIs) in the therapy of bladder cancer (BLCA). Existing studies mainly focus on single immune checkpoint inhibitors but lack relevant studies on the gene expression profiles of multiple immune checkpoints. METHODS: RNA-sequencing profiling data and clinical information of BLCA patients and normal human bladder samples were acquired from the Cancer Genome Atlas and Gene Expression Omnibus databases and analyzed to identify different expression profiles of immune checkpoint genes (ICGs) after consensus clustering analysis. Based on the 526 intersecting differentially expressed genes, the LASSO Cox regression analysis was utilized to construct the ICG signature. RESULTS: According to the expression of ICGs, BLCA patients were divided into three subtypes with different phenotypic and mechanistic characteristics. Furthermore, the developed ICG signature were independent predictors of outcome in BLCA patients, and was correlated with the immune infiltration, the expression of ICGs and chemotherapeutic effect. CONCLUSIONS: This study systematically and comprehensively analyzed the expression profile of immune checkpoint genes, and established the ICG signature to investigate the differences in ICGs expression and tumor immune microenvironment, which will help risk stratification and accelerate precision medicine. Finally, we identified KRT23 as the most critical model gene, and highlighted KRT23 as a potential target to enhance immunotherapy against BLCA.

Reevaluating the role of platinum-based chemotherapy in the evolving treatment landscape for patients with advanced urothelial carcinoma.

Platinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) for decades, based on the proven efficacy and established safety profiles of cisplatin- and carboplatin-based regimens. With the emergence of novel regimens, it is important to reevaluate and contextualize the role of 1L platinum-based chemotherapy. Platinum-based chemotherapy followed by avelumab 1L maintenance in patients without disease progression following platinum-based chemotherapy was established as a standard 1L regimen based on the JAVELIN Bladder 100 phase III trial. More recently, the EV-302 phase III trial showed the superiority of 1L enfortumab vedotin (EV) + pembrolizumab versus platinum-based chemotherapy, and the Checkmate 901 phase III trial showed the superiority of 1L nivolumab + cisplatin/gemcitabine versus cisplatin/gemcitabine alone. These 2 regimens have now been included as standard 1L options in treatment guidelines for advanced UC. EV + pembrolizumab is now the preferred 1L treatment, and in locations where EV + pembrolizumab is not available or individual patients are not considered suitable, recommended options are platinum-based chemotherapy followed by avelumab maintenance or nivolumab + cisplatin-based chemotherapy. In this review, we discuss current treatment options for advanced UC recommended in guidelines, practical considerations with platinum-based chemotherapy, the role of avelumab 1L maintenance, recent phase III trials of EV + pembrolizumab and nivolumab + cisplatin/gemcitabine, safety profiles of recommended 1L treatments, and second-line treatment options.

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

OBJECTIVES: To evaluate the safety and effectiveness of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC), and open radical cystectomy (ORC) in bladder cancer. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The Impact of Fibroblast Growth Factor Receptor Alterations in Clinical Outcomes of Patients With Advanced Urothelial Carcinoma: Real-World Data From a Latin American Population.

INTRODUCTION: Fibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes. PATIENTS AND METHODS: A multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics. RESULTS: In total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049). CONCLUSIONS: This is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort.

Assessment of pathological grade and variants of bladder cancer with a continuous-time random-walk diffusion model.

Purpose: To evaluate the efficacy of high b-value diffusion-weighted imaging (DWI) with a continuous-time random-walk (CTRW) diffusion model in determining the pathological grade and variant histology (VH) of bladder cancer (BCa). Methods: A total of 81 patients (median age, 70 years; range, 35-92 years; 18 females; 66 high grades; 30 with VH) with pathologically confirmed bladder urothelial carcinoma were retrospectively enrolled and underwent bladder MRI on a 3.0T MRI scanner. Multi-b-value DWI was performed using 11 b-values. Three CTRW model parameters were obtained: an anomalous diffusion coefficient (D) and two parameters reflecting temporal (α) and spatial (ß) diffusion heterogeneity. The apparent diffusion coefficient (ADC) was calculated using b0 and b800. D, α, ß, and ADC were statistically compared between high- and low-grade BCa, and between pure urothelial cancer (pUC) and VH. Comparisons were made using the Mann-Whitney U test between different pathological states. Receiver operating characteristic curve analysis was used to assess performance in differentiating the pathological states of BCa. Results: ADC, D, and α were significantly lower in high-grade BCa compared to low-grade, and in VH compared to pUC (p < 0.001), while ß showed no significant differences (p > 0.05). The combination of D and α yielded the best performance for determining BCa grade and VH (area under the curves = 0.913, 0.811), significantly outperforming ADC (area under the curves = 0.823, 0.761). Conclusion: The CTRW model effectively discriminated pathological grades and variants in BCa, highlighting its potential as a noninvasive diagnostic tool.

Glutathione-S-Transferase Theta 2 (GSTT2) Modulates the Response to Bacillus Calmette-Guérin Immunotherapy in Bladder Cancer Patients.

Glutathione-S-transferases (GST) enzymes detoxify xenobiotics and are implicated in response to anticancer therapy. This study evaluated the association of GST theta 1 (GSTT1), GSTT2, and GSTT2B with Mycobacterium bovis Bacillus Calmette-Guérin (BCG) response in non-muscle-invasive bladder cancer treatment. In vitro assessments of GSTT2 knockout (KO) effects were performed using cell lines and dendritic cells (DCs) from GSTT2KO mice. Deletion of GSTT2B, GSTT1, and single-nucleotide polymorphisms in the promoter region of GSTT2 was analysed in patients (n = 205) and healthy controls (n = 150). Silencing GSTT2 expression in MGH cells (GSTT2BFL/FL) resulted in increased BCG survival (p < 0.05) and decreased cellular reactive oxygen species. In our population, there are 24.2% with GSTT2BDel/Del and 24.5% with GSTT2BFL/FL. With ≤ 8 instillations of BCG therapy (n = 51), 12.5% of GSTT2BDel/Del and 53.8% of GSTT2BFL/FL patients had a recurrence (p = 0.041). With ≥9 instillations (n = 153), the disease recurred in 45.5% of GSTT2BDel/Del and 50% of GSTT2BFL/FL. GSTT2FL/FL patients had an increased likelihood of recurrence post-BCG therapy (HR 5.5 [1.87-16.69] p < 0.002). DCs from GSTT2KO mice produced three-fold more IL6 than wild-type DCs, indicating a robust inflammatory response. To summarise, GSTT2BDel/Del patients respond better to less BCG therapy and could be candidates for a reduced surveillance regimen.

Insights into the Interplay between the Urinary Microbiome and Bladder Cancer: A Comprehensive Review.

New insights in the urinary microbiome have led to a better understanding being built of the shifts in bacterial representations from health to disease; these hold promise as markers for diagnosis and therapeutic responses. Although several efforts have been made to identify a "core urinary microbiome", different fingerprints have been identified in men and women that shift with age. The main bacterial groups overall include Firmicutes, Actinobacteria, Fusobacteria, and Bacteroidetes. Although patients with bladder cancer have a microbiome that is similar to that of healthy individuals, differences have been observed at the species level with Fusobacterium nucleatum and Ralstonia, and at the genus level with Cutibacterium. Different bacterial representations may influence extracellular matrix composition, affecting tumor metastatic spreading and tumorigenic metalloproteinase expression. Furthermore, gene expression affecting targets of immune therapy, such as PD-L1, has been associated with changes in bacterial representations and therapeutic response to BCG. This comprehensive review aims to examine the influence of the urinary microbiome in bladder cancer.

The accuracy and quality of image-based artificial intelligence for muscle-invasive bladder cancer prediction.

PURPOSE: To evaluate the diagnostic performance of image-based artificial intelligence (AI) studies in predicting muscle-invasive bladder cancer (MIBC). (2) To assess the reporting quality and methodological quality of these studies by Checklist for Artificial Intelligence in Medical Imaging (CLAIM), Radiomics Quality Score (RQS), and Prediction model Risk of Bias Assessment Tool (PROBAST). MATERIALS AND METHODS: We searched Medline, Embase, Web of Science, and The Cochrane Library databases up to October 30, 2023. The eligible studies were evaluated using CLAIM, RQS, and PROBAST. Pooled sensitivity, specificity, and the diagnostic performances of these models for MIBC were also calculated. RESULTS: Twenty-one studies containing 4256 patients were included, of which 17 studies were employed for the quantitative statistical analysis. The CLAIM study adherence rate ranged from 52.5% to 75%, with a median of 64.1%. The RQS points of each study ranged from 2.78% to 50% points, with a median of 30.56% points. All models were rated as high overall ROB. The pooled area under the curve was 0.85 (95% confidence interval (CI) 0.81-0.88) for computed tomography, 0.92 (95% CI 0.89-0.94) for MRI, 0.89 (95% CI 0.86-0.92) for radiomics and 0.91 (95% CI 0.88-0.93) for deep learning, respectively. CONCLUSION: Although AI-powered muscle-invasive bladder cancer-predictive models showed promising performance in the meta-analysis, the reporting quality and the methodological quality were generally low, with a high risk of bias. CRITICAL RELEVANCE STATEMENT: Artificial intelligence might improve the management of patients with bladder cancer. Multiple models for muscle-invasive bladder cancer prediction were developed. Quality assessment is needed to promote clinical application. KEY POINTS: Image-based artificial intelligence models could aid in the identification of muscle-invasive bladder cancer. Current studies had low reporting quality, low methodological quality, and a high risk of bias. Future studies could focus on larger sample sizes and more transparent reporting of pathological evaluation, model explanation, and failure and sensitivity analyses.

Excluding confusable diseases in patients with presumptive diagnosis of interstitial cystitis: A large patient cohort study.

OBJECTIVE: To analyze the results of excluding confusable diseases in patients with a presumptive diagnosis of interstitial cystitis (IC). METHODS: We retrospectively reviewed the electronic medical records of consecutive patients with IC between October 2005 and December 2019. RESULTS: Patients with pelvic pain underwent an initial workup. Of these, 646 patients (164 men, 25.4%; 482 women, 74.6%) underwent observational cystoscopy under the suspicion of IC. Fourteen patients had genitourinary tract malignancies (2.2%) (bladder cancer, n = 13; prostate cancer, n = 1). Of the 13 patients with bladder cancer, three were diagnosed during initial observation cystoscopy. The remaining 10 patients were diagnosed during subsequent follow-up cystoscopic surgery. Urinary tuberculosis was identified in seven (1.1%) of 646 patients during the examination. Five (0.8%) of the six patients with suspected urinary tuberculosis at baseline imaging were positive for tuberculosis in the acid-fast bacillus test. One patient developed tuberculous granulomas in the bladder tissue after a cystectomy for intractable pelvic pain. CONCLUSION: Our results show that continuous efforts to rule out bladder tumors or tuberculosis are still essential in the follow up of patients with suspected IC, even if these diseases are not excluded at the initial examination. Imaging studies are necessary to rule out tuberculosis.

[Follow-up after urinary diversion]. / Nachsorge nach Harnableitung.

Radical cystectomy is currently the standard of care for muscle-invasive bladder cancer. Different parts of the small and large intestines can be utilized for continent and incontinent urinary diversion. The postoperative follow-up after urinary diversion should consider functional, metabolic and oncological aspects. The functional follow-up of (continent) urinary diversion includes stenosis, emptying disorders or incontinence. The oncological follow-up should focus on the detection of local, urethral and upper tract recurrences as well as distant metastases. As 90% of the tumor recurrences occur during the first 3 years, a close follow-up should be carried out during this period. Metabolic disturbances, such as vitamin B12 and bile acid deficits, acidosis and disorders of calcium metabolism can also occur during long-term follow-up. The metabolic follow-up should consider the metabolic consequences of the parts of the intestines utilized for the urinary diversion.

Tumor necrosis in magnetic resonance imaging predicts urothelial carcinoma with squamous differentiation in muscle-invasive bladder carcinoma.

PURPOSE: This study investigated radiologic features on preoperative MRI to differentiate urothelial carcinoma with squamous differentiation (UCSD) from conventional urothelial carcinoma (UC) in muscle-invasive bladder carcinoma. METHODS: Ninety-nine patients who underwent radical cystectomy and a preoperative bladder MRI scan within three months before surgery were retrospectively enrolled. Various MRI features, including tumor length, location, multiplicity, long-to-short axis ratio, morphology, radiologic stage, and degree of severe necrosis, were analyzed. Univariable and multivariable logistic regression analyses were performed to identify MRI features predictive of UCSD. The diagnostic performance of a significant MRI feature was assessed using 5-fold cross-validation. RESULTS: Among the MRI features, significant radiologic findings associated with UCSD in the univariable analysis included heterogeneous tumor signal intensity in T2-weighted images (odds ratio [OR], 3.365; 95% confidence interval [CI], 1.213-9.986; P = 0.022) and contrast-enhanced T1-weighted images (OR, 4.428; 95% CI, 1.519-12.730; P = 0.007), as well as marked (≥ 50%) severe necrosis (OR, 17.100; 95% CI, 4.699-73.563; P < 0.001). In the multivariable analysis, marked (≥ 50%) severe necrosis (odds ratio [OR], 13.755; 95% confidence interval [CI], 2.796-89.118; P = 0.004) was a significant predictor of UCSD. Marked (≥ 50%) severe necrosis showed a high specificity of 95.0% with a precision of 65.0% for diagnosing UCSD based on 5-fold cross-validation. CONCLUSION: Preoperative bladder MRI revealing marked severe necrosis may be indicative of UCSD and can assist in distinguishing it from conventional UC.

Long-term outcomes of bladder-sparing therapy vs radical cystectomy in BCG-unresponsive non-muscle-invasive bladder cancer.

OBJECTIVE: To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). PATIENTS AND METHODS: Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. RESULTS: Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). CONCLUSION: In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.

Mesentery-Sparing Technique: a New Intracorporeal Approach for Urinary Diversion in Robot-Assisted Radical Cystectomy

ABSTRACT Background Robotic-assisted radical cystectomy (RARC) with intracorporeal urinary diversion (ICUD) is associated with significant morbidity and mortality. We present an alternative technique that preserves the complete mesenteric vascularization during the isolation of the intestinal segment used in ICUD, including distal vessels. This approach aims to minimize the risk of ischemia in both the ileal anastomosis and the isolated loop at the diversion site. Methods This cohort study included 31 patients, both male and female, who underwent RARC with ICUD from February 2018 to November 2023, performed by a single surgeon. Intraoperative and postoperative complications data were retrieved for analysis, employing our proposed mesentery-sparing technique in all cases. The primary endpoint was the incidence of intraoperative and postoperative complications directly attributable to the mesentery-sparing approach in ICUD. Secondary endpoints included other postoperative variables not directly related to mesentery preservation, such as the incidence of postoperative ileus requiring parenteral nutrition and the duration of hospitalization. Results None of the patients experienced intraoperative or postoperative complications directly related to mesentery-sparing, such as intestinal fistulae or internal hernias. The median duration of hospitalization was 6 days, and postoperative ileus necessitating total parenteral nutrition occurred in 19% of the patients. Minor complications (Clavien-Dindo grades I-II) accounted for 27.6% of the cases and major complications (grades III-V) accounted for 20.6%. Conclusion The mesentery-sparing technique outlined herein offers an alternative method for preserving the vascularization of intestinal segments and reducing the risk of intestinal complications in ICUD during RARC.