Staging Of Bladder Cancer Research Articles

A novel T-cell proliferation-associated regulator signature pre-operatively predicted the prognostic of bladder cancer.

BackgroundBladder cancer (BCa) is a remarkably malignant and heterogeneous neoplastic disease, and its prognosis prediction is still challenging. Even with the mounting researches on the mechanisms of tumor immunotherapy, the prognostic value of T-cell proliferation regulators in bladder cancer remains elusive.MethodsHerein, we collected mRNA expression profiles and relevant clinical information of bladder cancer sufferers from a publicly available data base. Then, the LASSO Cox regression model was utilized to establish a multi-gene signature for the TCGA cohort to predict the prognosis and staging of bladder cancer. Eventually, the predictive power of the model was validated by randomized grouping.ResultsThe outcomes revealed that most genes related to T-cell proliferation in the TCGA cohort exhibited different expressions between BCa cells and neighboring healthy tissues. Univariable Cox regressive analyses showed that four DEGs were related to OS in bladder cancer patients (p<0.05). We constructed a histogram containing four clinical characteristics and separated sufferers into high- and low-risk groups. High-risk sufferers had remarkably lower OS compared with low-risk sufferers (P<0.001). Eventually, the predictive power of the signature was verified by ROC curve analyses, and similar results were obtained in the validation cohort. Functional analyses were also completed, which showed the enrichment of immune-related pathways and different immune status in the two groups. Moreover, by single-cell sequencing, our team verified that CXCL12, a T-lymphocyte proliferation regulator, influenced bladder oncogenesis and progression by depleting T-lymphocyte proliferation in the tumor microenvironment, thus promoting tumor immune evasion.ConclusionThis study establishes a novel T cell proliferation-associated regulator signature which can be used for the prognostic prediction of bladder cancer. The outcomes herein facilitate the studies on T-cell proliferation and its immune micro-environment to ameliorate prognoses and immunotherapeutic responses.

Untargeted ultra-high-resolution mass spectrometry metabolomic profiling of blood serum in bladder cancer

Bladder cancer (BC) is a common urological cancer of high mortality and recurrence rates. Currently, cystoscopy is performed as standard examination for the diagnosis and subsequent monitoring for recurrence of the patients. Frequent expensive and invasive procedures may deterrent patients from regular follow-up screening, therefore it is important to look for new non-invasive methods to aid in the detection of recurrent and/or primary BC. In this study, ultra-high-performance liquid chromatography coupled with ultra-high-resolution mass spectrometry was employed for non-targeted metabolomic profiling of 200 human serum samples to identify biochemical signatures that differentiate BC from non-cancer controls (NCs). Univariate and multivariate statistical analyses with external validation revealed twenty-seven metabolites that differentiate between BC patients from NCs. Abundances of these metabolites displayed statistically significant differences in two independent training and validation sets. Twenty-three serum metabolites were also found to be distinguishing between low- and high-grade of BC patients and controls. Thirty-seven serum metabolites were found to differentiate between different stages of BC. The results suggest that measurement of serum metabolites may provide more facile and less invasive diagnostic methodology for detection of bladder cancer and recurrent disease management.

LC-MS metabolomics of urine reveals distinct profiles for non-muscle-invasive and muscle-invasive bladder cancer.

Bladder cancer (BC) is among the most frequent malignancies worldwide. Novel non-invasive markers are needed to diagnose and stage BC with more accuracy than invasive procedures like cystoscopy. To date, no study has identified urine metabolites characteristic of all BC stages. To discover novel urine metabolomic profiles to diagnose and stage non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) patients using mass spectrometry-based metabolomics. We prospectively recruited 198 BC patients and 98 age- and sex-matched healthy volunteers without evidence of renal or bladder condition confirmed by ultrasound, from whom we collected a first morning urine sample (before surgery in patients). In a discovery stage, an untargeted metabolomic analysis was conducted in urine samples of a selection of 64 BC patients (19 TaG1, 11 TaG3, 20 T1G3, 12 T2G3, 1 T2G2, 1 T3G3) and 20 controls to identify dysregulated metabolites. Next, after exhaustive multivariate analysis, confirmed dysregulated metabolites were validated in an independent cohort of 134 BC patients (19 TaG1, 62 TaG2, 9 TaG3, 15 T1G2, 16 T1G3, 4 T2G2, 9 T2G3) and 78 controls. We validated p-cresol glucuronide as potential diagnostic biomarker for BC patients compared to controls (AUC = 0.79). For NMIBC, p-cresol glucuronide was valuable as staging biomarker (AUC = 0.803). And among NMIBCs, p-coumaric acid may be a potential specific staging biomarker for the TaG1 NMIBC; however, future validation experiments should be conducted once the precise version of the standard is commercially available. Remarkably, for MIBC we validated spermine as potential specific staging biomarker (AUC = 0.882). Ours is the first metabolomics study conducted in urine of a thoroughly characterized cohort comprising all stages of NMIBC, MIBC and healthy controls in which we identified non-invasive diagnostic and staging biomarkers. These may improve BC management, thus reducing the use of current harmful diagnostic techniques.

Metabolomic and elemental profiling of blood serum in bladder cancer

Bladder cancer (BC) is one of the most frequently diagnosed types of urinary cancer. Despite advances in treatment methods, no specific biomarkers are currently in use. Targeted and untargeted profiling of metabolites and elements of human blood serum from 100 BC patients and the same number of normal controls (NCs), with external validation, was attempted using three analytical methods, i.e., nuclear magnetic resonance, gold and silver-109 nanoparticle-based laser desorption/ionization mass spectrometry (LDI-MS), and inductively coupled plasma optical emission spectrometry (ICP-OES). All results were subjected to multivariate statistical analysis. Four potential serum biomarkers of BC, namely, isobutyrate, pyroglutamate, choline, and acetate, were quantified with proton nuclear magnetic resonance, which had excellent predictive ability as judged by the area under the curve (AUC) value of 0.999. Two elements, Li and Fe, were also found to distinguish between cancer and control samples, as judged from ICP-OES data and AUC of 0.807 (in validation set). Twenty-five putatively identified compounds, mostly related to glycans and lipids, differentiated BC from NCs, as detected using LDI-MS. Five serum metabolites were found to discriminate between tumor grades and nine metabolites between tumor stages. The results from three different analytical platforms demonstrate that the identified distinct serum metabolites and metal elements have potential to be used for noninvasive detection, staging, and grading of BC.

Analysis of the Relationship between Bladder Cancer Gene Mutation and Clinical Prognosis by High-Throughput Sequencing.

Bladder cancer is one of the most common malignant tumors in urology in China. The analysis of gene mutation in bladder cancer and its relationship with clinical characteristics and prognosis will provide a basis for accurate treatment of bladder cancer. The aim of this study was to analyze the mutations and functional regions of bladder cancer-related genes based on high-throughput sequencing, and to explore the relationship between mutations and clinicopathological features, as well as its prognosis and clinical implication. From April 2020 to October 2020, a total of 47 patients with bladder cancer in the Department of Urology, Affiliated Hospital of Chengde Medical College were studied. Gene sequencing was performed using Nextseq CN500 System, a high-throughput sequencing platform. The results of gene detection were described, and the relationship and clinical value of high frequency mutated genes with clinicopathological features and prognosis were systematically analyzed. A total of 29 mutation genes, 61 exons, and 95 mutation sites were identified in this study. The frequencies of TP53, FGFR3, PIK3CA, ERBB2, MUC4, and KRAS mutation are relatively high, accounting for 59.92 % of the total mutation frequency. The TP53 was significantly associated with muscle invasive bladder cancer, T2 stage, and progression-free survival, while FGFR3 was significantly associated with non-muscle invasive bladder cancer and T1 stage. High-throughput sequencing technology provides a successful approach for detecting bladder cancer gene mutations. The TP53, FGFR3, PIK3CA, ERBB2, MUC4, and KRAS genes have high mutation frequencies in bladder cancer patients. The TP53, FGFR3 and PIK3CA genes may play a predictive role in the prognosis of bladder cancer, which may hold certain guiding significance for in-depth study of the pathogenesis of bladder cancer and the development of targeted therapies.

1733MO First results from BladderPath: A randomised trial of MRI versus cystoscopic staging for newly diagnosed bladder cancer

Transurethral resection of bladder tumour (TURBT) has been the mainstay of bladder cancer staging for a century. The objective of the trial was to assess the feasibility and efficacy of the substitution of TURBT with MRI and biopsy in the staging of patients with suspected muscle invasive bladder cancer (MIBC). The hypothesis being tested was that image directed staging would shorten time to correct treatment for MIBC patients.

Role of multiparametric magnetic resonance imaging in the diagnosis and staging of urinary bladder cancer.

ObjectivesTo assess the role of multiparametric magnetic resonance imaging (mp-MRI) in the diagnosis and staging of urinary bladder cancer (BC).Materials and methodsFifty patients diagnosed with bladder masses underwent mp-MRI study. The results of 3 image sets were analyzed and compared with the histopathological results as a reference standard: T2-weighted image (T2WI) plus dynamic contrast-enhanced (DCE), T2WI plus diffusion-weighted images (DWI), and mp-MRI, including T2WI plus DWI and DCE. The diagnostic accuracy of mp-MRI was evaluated using receiver operating characteristic curve analysis.ResultsThe accuracy of T2WI plus DCE for detecting muscle invasion of BC was 79.5% with a fair agreement with histopathological examination (κ = 0.59); this percentage increased up to 88.6% using T2WI plus DWI, with good agreement with histopathological examination (κ = 0.74), whereas mp-MRI had the highest overall accuracy (95.4%) and excellent agreement with histopathological data (κ = 0.83). Multiparametric MRI can differentiate between low- and high-grade bladder tumors with a high sensitivity and specificity of 93.3% and 98.3%, respectively.ConclusionsMultiparametric MRI is an acceptable method for the preoperative detection and accurate staging of BC, with reasonable accuracy in differentiating between low- and high-grade BC.

A retrospective cohort study of bladder cancer following the COVID-19 pandemic: Are patients presenting with more aggressive disease?

BackgroundThe COVID-19 pandemic has resulted in delays in the treatment of patients with urological malignancies. The management of bladder cancer (BC) in particular poses a significant challenge given the recurrent nature of the disease and the intense follow-up regime required for many cases. The aim of this study was to evaluate potential changes in the presentation and operative management of BC in our hospital following the pandemic. Materials and methodsThis is a retrospective cohort study. Potential BC cases were identified through the histopathology database between March 2019 and February 2021. Details were obtained on patient demographics, procedure type such as biopsy, resection or excision, grade and stage of BC. Cases were divided into two groups: period one (pre-COVID between March 2019 and February 2020) and period two (post-COVID between March 2020 and February 2021). ResultsA total of 207 procedures for confirmed BC were performed during the study period, 126 in period one and 81 in period two. New cases accounted for 52.4% (n = 66) and 53.1% (n = 43) of cases during periods one and two respectively. There was a higher rate of invasive disease (43.2% vs 26.2%) as well as high grade disease (47.4% vs 35.8%) in period two than in period one. ConclusionFewer BC procedures were performed in the COVID period. The higher rate of more advanced stage and grade of disease seen in period two suggests patients are presenting later. This should be considered when allocating resources in the management of non-COVID related diseases. Further studies are needed to assess the long-term impact of COVID-19 on bladder cancer outcome.

A pan-cancer analysis of FAT atypical cadherin 4 (FAT4) in human tumors.

ObjectiveWe performed a pan-cancer analysis to explore the potential mechanisms of FAT4 in 33 different tumors.MethodsIn this study, we selected 33 types of cancers based on the datasets of TCGA (the cancer genome atlas). We analyzed the expression of FAT4 in tumor and normal tissues. Meanwhile, we analyzed the expression levels of FAT4 in tissues from tumors of different stages. Kaplan-Meier survival analysis, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI), immune infiltration analysis, Gene set enrichment analysis (GSEA), and FAT4-related gene enrichment analysis were performed.ResultsFAT4 expression in most tumor tissues was lower than in corresponding control tissues. FAT4 expression was different in different stages of bladder cancer (BLCA), kidney clear cell carcinoma (KIRC), and breast cancer (BRCA). In addition, the expression level of FAT4 in different types of tumors has an important impact on the prognosis of patients. FAT4 might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. We observed a statistically positive correlation between cancer-associated fibroblasts and FAT4 expression in most tumors. GSEA of BLCA indicated that low FAT4 expression groups were mainly enriched in calcium signaling pathway and chemokine signaling pathway. GSEA analysis of KIRC suggested low FAT4 expression groups were mainly involved in olfactory transduction and oxidative phosphorylation. Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the role of FAT4 in the pathogenesis of cancer may be related to human papillomavirus infection, Hippo signaling pathway, PI3K–Akt signaling pathway, etc. Gene Ontology (GO) enrichment analysis further showed that most of these genes were related to the pathways or cell biology, such as peptidyl–tyrosine phosphorylation, cell junction assembly, protein tyrosine kinase activity, etc.ConclusionOur study summarized and analyzed the antitumor effect of FAT4 in different tumors comprehensively, which aided in understanding the role of FAT4 in tumorigenesis from the perspective of clinical tumor samples. Pan-cancer analysis showed that FAT4 to be novel biomarkers for various cancers prognosis.

Fluorescence-Based Microendoscopic Sensing System for Minimally Invasive In Vivo Bladder Cancer Diagnosis.

Bladder cancer is commonly diagnosed by evaluating the tissue morphology through cystoscopy, and tumor resection is used as the primary treatment approach. However, these methods are limited by lesion site specificity and resection margin, and can thereby fail to detect cancer lesions at early stages. Nevertheless, rapid diagnosis without biopsy may be possible through fluorescence sensing. Herein, we describe a minimally invasive imaging system capable of sensing even small tumors through a 1.2 mm diameter flexible fiber bundle microprobe. We demonstrate that this new device can be used for the early diagnosis of bladder cancer in rats. Bladder cancer was induced in rats using the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), and a togglable filter capable of PpIX fluorescence sensing was installed in the microendoscopic system. Following 5-aminolevulinic acid administration, tissue in the early stages of bladder cancer was successfully identified with fluorescence detection and confirmed with hematoxylin/eosin and ferrochelatase staining. Although the time required for BBN to induce bladder cancer varied between 3 and 4 weeks among the rats, the microendoscopic system allowed the minimally invasive follow-up on cancer development.

Antioxidant status in patients with bladder cancer regarding cancer stage and grade

ObjectiveThe imbalance of antioxidants and pro-oxidants plays a crucial role in the carcinogenesis of bladder cancer (BC). This study aimed to evaluate serum antioxidant status in patients with BC and determine its potential use in the diagnosis and progression potential considerations following histopathological assessment. MethodsA cross-sectional study included 90 patients with BC, divided into Ta, T1, and T2–T4 stage subgroups, and according to cancer progression potential, into low-grade (LG) and high-grade (HG) subgroups. The control group (CG) included 30 healthy volunteers. Antioxidant status was determined using the spectrophotometric method and standard laboratory tests. ResultsSerum superoxide dismutase activity was significantly higher in BC patients regarding cancer stage in comparison to the CG (p<0.001). Catalase activity was highest in T2–T4 subgroup and was significantly higher compared to the Ta (p<0.01) and T1 (p<0.05) subgroups. Serum albumin level was significantly lower in the BC group compared to the CG (p<0.001). In addition, it was significantly lower in T2–T4 subgroup compared to T1 and Ta subgroups (p<0.01). A significant negative correlation was found between tumor size and serum albumin level only (r=−0.386, p<0.01). Catalase activity was higher in HG subgroup (p=0.009), while bilirubin level was higher in LG subgroup (p=0.035). The optimal cut-off value of catalase activity in differentiating patients with LG and HG BC subgroups was ≥11.96 IU/L, and the specificity and sensitivity were 51.1% and 82.2%, respectively. Bilirubin level, for a calculated optimal cut-off value of ≥11.95 μmol/L, had a specificity of 44.1% and sensitivity of 80.0%. ConclusionMore invasive stages of BC with greater progression potential are associated with an increase in enzymatic antioxidant activity and a decrease in non-enzymatic antioxidant capacity. It may suggest a possible role of antioxidants in the prediction and monitoring of illness trajectory.

Polymorphism with Bladder Cancer Risk and Staging

Polymorphism with Bladder Cancer Risk and Staging

Perioperative Complications and Oncologic Outcomes after Radical Cystectomy in End-Stage Renal Disease Patients with Bladder Cancer Obtained Using a Standardized Reporting System.

Simple SummaryUrothelial carcinoma (UC) of the bladder is the most common malignancy in dialysis patients in Taiwan compared with renal cell carcinoma in Western countries. Radical cystectomy is the standard of care for localized muscle-invasive bladder cancer (MIBC), as well as for selected patients with high-risk non-MIBC. Despite improvements in anesthetic competency, surgical techniques, and postoperative care, dialysis patients undergoing radical cystectomy are at a higher risk of perioperative morbidity and mortality than non-dialysis patients. Due to the relative rarity of the condition, published data on predictors of outcome in ESRD patients undergoing radical cystectomy are scant. Our study revealed that accurate reporting of complications is necessary for preoperative counseling, identifying modifiable risk factors, and planning risk mitigation strategies. High comorbidity and low-volume surgeons were interrelated as notable risk factors for major complications. In addition to tumor-related factors, male sex, older age, and major complications significantly influence survival.Background: We investigated the use of a standardized reporting system to study perioperative complications and oncologic outcomes after radical cystectomy in end-stage renal disease (ESRD) patients with bladder cancer. Methods: We reviewed retrospective outcomes in 141 ESRD patients with bladder cancer who underwent radical cystectomy between 2004 and 2015. Complications were graded using the Clavien–Dindo classification system with 0–2 classified as “No Major Complications” and Clavien 3–5 as “Major Complications”. Low-volume surgeons were classified as those performing fewer than nine cases during the study. Fisher’s exact test along with the chi-squared test, two-tailed t tests, logistic regression, and the Cox proportional hazard model were used to evaluate all clinically meaningful covariates. Results: Ninety-nine (99, 70.2%) patients had no major complications, and forty-two (29.8%) patients had major complications. Patients in the major complications group were older, had a higher Charlson comorbidity index (CCI), and had a longer hospitalization duration than those in the no major complications group (all, p < 0.05). Major complications were also more common when the procedure was performed by low-volume surgeons (p = 0.003). In multivariate logistic regression models, CCI ≥ 5 (p = 0.006) and low-volume surgeon (p = 0.004) were independent predictors of major complications. According to multivariate analysis with the Cox hazards regression, male sex, age > 70 years, CCI ≥ 5, bladder cancer stage ≥ 3, lymphovascular invasion, and experiencing major complications were significant poor prognostic factors for overall survival (all, p < 0.05). Conclusions: Accurate reporting of complications is necessary for preoperative counseling, identifying modifiable risk factors, and planning risk mitigation strategies. High comorbidity and low-volume surgeons were interrelated as notable risk factors for major complications. In addition to tumor-related factors, male sex, older age, and major complications significantly influence overall survival.

Bladder cancer-derived exosomal KRT6B promotes invasion and metastasis by inducing EMT and regulating the immune microenvironment

BackgroundTumour-derived exosomes have recently been shown to participate in the formation and progression of different cancer processes, including tumour microenvironment remodelling, angiogenesis, invasion, metastasis, and drug resistance. However, the function and mechanism of exosome-encapsulated nucleic acids and proteins in bladder cancer remain unclear. This study aimed to investigate the effects of tumour-derived exosomes on the tumorigenesis and development of bladder cancer.MethodsIn this study, gene expression profiles and clinical information were collected from The Cancer Genome Atlas (TCGA) database and two independent Gene Expression Omnibus (GEO) datasets. The nucleic acids and proteins encapsulated in bladder cancer-derived exosomes were obtained from the ExoCarta database. Based on these databases, the expression patterns of exosomal mRNAs and proteins and the matched clinicopathological characteristics were analysed. Furthermore, we carried out a series of experiments to verify the relevant findings.ResultsA total of 7280 differentially expressed mRNAs were found in TCGA data, of which 52 mRNAs were shown to be encapsulated in bladder cancer-derived exosomes. Survival analysis based on the UALCAN database showed that among the top 10 upregulated and the top 10 downregulated exosomal genes, only the expression of KRT6B had a statistically significant effect on the survival of bladder cancer patients. Additionally, clinical correlation analysis showed that the elevated level of KRT6B was highly associated with bladder cancer stage, grade, and metastasis status. GSEA revealed that KRT6B was involved not only in epithelial–mesenchymal transition-related pathways but also in the immune response in bladder cancer. Ultimately, our experimental results were also consistent with the bioinformatic analysis.ConclusionKRT6B, which can be detected in bladder cancer-derived exosomes, plays an important role in the epithelial–mesenchymal transition and immune responses in bladder cancer. Further research will enable its potentially prognostic marker and therapeutic target for bladder cancer.

Multiorientation Simultaneous Computation of Back-Projection CT Image Reconstruction Algorithm in Staging Diagnosis of Bladder Cancer.

The objective of this research was to investigate the multidirectional synchronous calculation of the back-projection computed tomography (CT) image reconstruction algorithm (MSBP) in the staging diagnosis of bladder cancer. Sixty patients with bladder cancer admitted to the hospital were selected for enhanced CT scanning, all of which were randomly divided into control group (n = 30) and study group (n = 30). The filtered back-projection (FBP) algorithm was employed to reconstruct the scanned image, and the MSBP was additionally applied to the images of the study group. Fringe artifact (SA), overall mass (OQ), effective radiation dose (ED), CT dose-exponential volume (CTDI), and dose-length product (DLP) of the two groups of images were compared and analyzed. The results showed that the total time of the traditional algorithm was 5.473 s, and the total time of MSBP combined with FBP algorithm was 2.832 s, which was significantly higher than that of the traditional algorithm (P < 0.05). CT scan bladder cancer staging results of all patients were compared with surgical pathological staging results, and the results were evaluated according to the coincidence rate. SA in the study group was lower than that in the control group (P < 0.05), and OQ was not statistically significant. The ED of the study group was significantly lower than that of the control group by 33%. The coincidence rate of postoperative pathological staging results and CT staging results was 96%, and T1, T2a, and T4 coincidence rate was 100%, The coincidence rates of T2b, T3a, and T3b were 90%, 83.3%, and 66.67%, respectively. In summary, using MSBP method combined with FBP algorithm can improve OQ while reducing ED of patients. The introduction of MSBP into CT reconstruction image simplified the pixel location operation of projection calculation, showing an important application value in preoperative staging diagnosis of bladder cancer.

Radiologic Diagnosis and Staging of Bladder Cancer: An Update.

Although cystoscopic biopsy is the standard of care for initial diagnosis and local staging of bladder cancer, radiologic imaging plays a major role in identifying local invasion, nodal status, distant metastasis, and posttreatment surveillance. Recent development of the Vesical Imaging-Reporting and Data System for interpretation of multiparametric magnetic resonance imaging of the bladder has expanded the role diagnostic imaging in the management of bladder cancer. This article reviews multimodality imaging appearances, staging, and differential diagnosis of bladder cancer.

Abstract CT564: KEYNOTE-992: A randomized phase 3 trial of pembrolizumab versus placebo in patients with muscle-invasive bladder cancer receiving concurrent chemoradiotherapy

Abstract Background: Concurrent chemoradiotherapy (CRT) is recommended as a bladder-preserving treatment option for selected patients with muscle-invasive bladder cancer (MIBC). Pembrolizumab has shown clinical activity across many stages of bladder cancer, and ongoing phase 2 studies (ANZUP 1502, NCT02662062; NCT02621151) of pembrolizumab + CRT are promising. The global, randomized, double-blind, placebo-controlled, multicenter, phase 3 KEYNOTE-992 study (NCT04241185) will be conducted to evaluate the safety and efficacy of pembrolizumab + CRT in patients with previously untreated MIBC who opt for bladder preservation. Methods: Key patient eligibility criteria are age ≥18 years, histologically confirmed cT2-T4a, nonmetastatic MIBC, and decision to pursue bladder-preserving therapy. Approximately 636 patients will be randomly assigned 1:1 to receive CRT + either pembrolizumab 400 mg or placebo. Pembrolizumab or placebo will be administered intravenously (IV) every 6 weeks for up to 9 doses. Patients will be stratified by Eastern Cooperative Oncology Group performance status (ECOG PS) score (0 or 1 vs 2), PD-L1 combined positive score (&amp;lt;10 vs ≥10), T stage (T2 vs T3 or T4), and geographic region (US vs Europe vs rest of world). CRT regimen must be determined before randomization. The following radiotherapy (RT) regimens are permitted: conventional RT consisting of 64 Gy at 2 Gy/fraction over 6.5 weeks (whole bladder with or without pelvic nodes) or hypofractionated RT consisting of 55 Gy at 2.75 Gy/fraction over 4 weeks (whole bladder only). The following radiosensitizing chemotherapy regimens are permitted: cisplatin monotherapy (35 mg/m2 IV weekly), 5-fluorouracil (500 mg/m2 on days 1-5 and days 22-26) + mitomycin C (12 mg/m2 on day 1), and gemcitabine monotherapy (27 mg/m2 IV twice weekly). Efficacy will be assessed by cystoscopy (± biopsy), by CT or MRI with blinded independent central review, and by urine cytology at 10 weeks after CRT, then every 12 weeks until the end of year 2, and every 24 weeks thereafter. The primary end point is bladder-intact event-free survival, defined as time from randomization to residual/recurrent MIBC, nodal or distant metastases, radical cystectomy, or death from any cause. The key secondary end point is overall survival. Additional secondary end points are metastasis-free survival, time to any non-muscle-invasive bladder cancer, time to cystectomy, and safety. The study is enrolling at sites in Asia, Australia, Europe, North America, and South America. Citation Format: Neal D. Shore, Nicholas D. James, Michiel Simon Van der Heijden, Arjun Vasant Balar, Xiao Fang, Ekta Kapadia, Jeff M. Michalski, Shahrokh F. Shariat, Andrew James Weickhardt. KEYNOTE-992: A randomized phase 3 trial of pembrolizumab versus placebo in patients with muscle-invasive bladder cancer receiving concurrent chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT564.

Prevalence and outcomes of transurethral resection versus radical cystectomy for muscle-infiltrating bladder cancer in the United States: A population-based cohort study

IntroductionAlthough radical cystectomy is considered as the first choice for muscle-invasive bladder cancer (MIBC), there are also concerns regarding the cost of long-term morbidity, loss of body image, and compromised quality of life. Transurethral resection of bladder tumor (TURBT) is a candidate for bladder sparing treatments, but its viability as a substitute for radical cystectomy is questionable. Therefore, we conducted this population-based study to investigate the prevalence of TURBT in the treatments of T2-stage MIBC in the United States, and to compare its therapeutic efficiency with that of radical cystectomy. MethodsInformation on patients with T2-stage bladder cancer (BC) between 2000 and 2017 was extracted from the Surveillance, Epidemiology, and End Results program. The overall survival (OS) and disease-specific survival (DSS) of patients with different interventions were fitted. ResultsA total of 22,074 patients with T2-stage MIBC were enrolled, of whom 14,021 reached the main endpoint. Only 28% of the patients with T2-stage MIBC chose radical cystectomy as the initial surgical treatment, while TURBT was applied as the primary surgical treatment in 66.6% of the patients. The TURBT rate increased significantly with age at cancer diagnosis (40–44 years, 45.5% to > 85 years, 90.9%). The survival rate of patients undergoing TURBT was significantly lower than for those undergoing radical cystectomy (median OS: 1.5 versus 9.7 years; median DSS: 2.7 years versus not reached). Upon multivariable Cox analyses, the OS (HR: 2.34; p < 0.001) and DSS (HR: 2.68; p < 0.001) of TURBT were found to be significantly worse than those of radical cystectomy. ConclusionTwo-thirds of the patients with T2-stage MIBC were treated by TURBT in the United States. However, the long-term follow-up data indicate that the therapeutic efficiency of current TURBT techniques is far less effective than that of radical cystectomy. Further studies are urgently needed to devise the best management strategy for T2 stage bladder cancer.

Multiparametric MRI Evaluation of VI-RADS for Bladder Tumors Located at the Ureteral Orifice.

Background The Vesical Imaging Reporting and Data System (VI-RADS) based on multiparametric MRI scans standardizes preoperative bladder cancer staging. However, limitations have been reported for VI-RADS, particularly for ureteral orifice tumors. Purpose To investigate the diagnostic performance and interobserver agreement of VI-RADS in evaluating muscle invasion for bladder tumors located at the ureteral orifice. Materials and Methods In this retrospective study, patients with histopathologically confirmed bladder cancer occurring at the ureteral orifice from January 2012 to November 2021 were analyzed. Two blinded radiologists independently scored multiparametric MRI scans according to VI-RADS. Interobserver agreement of the VI-RADS scores was evaluated with weighted κ analysis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of the VI-RADS scores in the prediction of muscle invasion. Results A total of 78 patients (mean age, 67 years ± 7 [SD]; age range, 46-90 years; 67 men) were included in the final analysis: 25 with non-muscle-invasive bladder cancer and 53 with muscle-invasive bladder cancer (MIBCa). At consensus reading, one (1%) case was scored as VI-RADS 1, 27 cases (35%) were scored as VI-RADS 2, six (8%) were scored as VI-RADS 3, 10 (13%) were scored as VI-RADS 4, and 34 (44%) were scored as VI-RADS 5. On comparison of the VI-RADS score with histopathologic findings, it was confirmed that the presence of muscle invasion was 0% (zero of one) for VI-RADS 1, 15% (four of 27) for VI-RADS 2, 83% (five of six) for VI-RADS 3, 100% (10 of 10) for VI-RADS 4, and 100% (34 of 34) for VI-RADS 5. The area under the receiver operating characteristic curve of VI-RADS in the detection of MIBCa was 0.96 (95% CI: 0.92, 1.00). Conclusion The Vesical Imaging Reporting and Data System could be used to accurately predict muscle invasion for bladder tumors occurring at the ureteral orifice. © RSNA, 2022 Online supplemental material is available for this article.

The Effect of Metformin on Bladder Cancer Incidence and Outcomes: A Systematic Review and Meta-Analysis.

Effective oral treatment options for urothelial bladder cancer (BC) are lacking. Metformin, the most frequently used oral drug in type II diabetes mellitus, has putative anticancer properties and could, therefore, influence BC incidence and treatment outcomes. We systematically reviewed the current literature regarding the effect of metformin on BC incidence and oncological outcomes in non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). This review was conducted according to the PRISMA guidelines. Literature was gathered through a systematic search in PubMed/Medline, EMBASE and the Cochrane library. Risk of bias was determined using the Cochrane risk-of-bias tool for randomized trials and the Newcastle-Ottawa Scale for non-randomized trials. Hazard ratios (HRs) were extracted and pooled in a random-effects meta-analysis. We reviewed 13 studies, including 3,315,320 patients, considering the risk of developing BC after metformin exposure and 9 studies, including 4,006 patients, on oncological outcomes of patients with BC. Metformin did not affect BC incidence (HR 0.97, 95% CI 0.87 -1.09) or oncological outcomes for NMIBC but did show a reduced risk of recurrence (HR 0.52, 95% CI 0.32 -0.84), cancer-specific mortality (HR 0.58, 95% CI 0.43 -0.78) and overall mortality (HR 0.66, 95% CI 0.47 -0.92) in MIBC. The role of metformin in the prevention and treatment of BC in patients remains unclear. Although a beneficial effect of metformin on treatment outcomes of certain stages of BC may exist, a definitive conclusion cannot be drawn. Prospective clinical trials are needed to assess the efficacy of metformin for BC treatment.