Non-muscle Invasive Bladder Carcinoma Research Articles

Immunoexpression of p53 and Ki-67 in Urinary Bladder Carcinoma and Their Association with Tumor Grade and Muscle-invasiveness

Background: Urinary bladder carcinoma is one of the threatening causes of human morbidity and mortality. Various molecular studies and prognostic biomarkers are helpful to assess the outcome of urinary bladder carcinoma. High expression of p53 and Ki-67 represents the aggressiveness of the disease and indicates poor prognosis. Methods: This cross-sectional study was conducted at the Department of Pathology, Sylhet MAG Osmani Medical College from September 2018 to July 2020 to observe the immunoexpression of p53 and Ki-67 in urinary bladder carcinoma and their association with tumor grade and muscle-invasiveness. Total 57 transurethral resection (TURBT) samples of radiologically and clinically suspected bladder tumor cases were diagnosed histopathologically included in the study. Results: Age of the study patients ranged from 35 to 80 years with a mean of 60.60 ± 11.14 and male to female ratio was 4.7:1. There were 31 (54.4%) high grade and 26 (45.6%) low grade urinary bladder carcinomas on histopathological examination. Thirty (52.6%) cases were histopathologically muscle invasive bladder carcinoma (MIBC) and 27 (47.4%) cases were non-muscle invasive bladder carcinoma (NMIBC). Positive p53 expression was observed in 24 (77.4%) cases of high grade carcinoma while only in 6 (23.1%) cases of low grade urinary bladder carcinoma. Positive p53 expression was seen in 22 (73.3%) cases of MIBC and 8 (29.6%) cases of NMIBC. Ki-67 expression was found positive in 27 (87.1%) cases of high grade carcinoma while only in 7 (26.9%) cases of low grade urinary bladder carcinoma. Positive Ki-67 expression was seen in 25 (83.3%) cases of MIBC and 9 (33.3%) cases of NMIBC. Statistically significant association (P<0.05) was observed in histopathological grades and muscle invasiveness of UBC with p53 and Ki-67 expression. Conclusion: p53 and Ki-67 immunomarker may be helpful to provide additional prognostic information in urinary bladder carcinoma.

Co-delivery of oxaliplatin prodrug liposomes with Bacillus Calmette-Guérin for chemo-immunotherapy of orthotopic bladder cancer

To reduce recurrence rate after transurethral resection of bladder tumor, long-term intravesical instillations of Bacillus Calmette-Guérin (BCG) and/or chemotherapeutic drugs is the standard treatment for non-muscle invasive bladder carcinoma. However, the main challenges of intravesical therapy, such as short retention time and poor permeability of drugs in the bladder, often require frequent and high-dose administrations, leading to significant adverse effects and financial burden for patients. Aiming at addressing these challenges, we developed a novel approach, in which the cell-penetrating peptide modified oxaliplatin prodrug liposomes and a low-dose BCG were co-delivered via a viscous chitosan solution (LRO-BCG/CS). LRO-BCG/CS addressed these challenges by significantly improving the retention capability and permeability of chemotherapy agents across the bladder wall. Then, oxaliplatin triggered the immunogenic cell death, and the combination of BCG simultaneously further activated the systemic anti-tumor immune response in the MB49 orthotopic bladder tumor model. As a result, LRO-BCG/CS demonstrated superior anti-tumor efficacy and prolonged the survival time of tumor-bearing mice significantly, even at relatively low doses of oxaliplatin and BCG. Importantly, this combinational chemo-immunotherapy showed negligible side effects, offering a promising and well-tolerated therapeutic strategy for bladder cancer patients.

Recurrence of non-muscle invasive bladder carcinoma after transurethral resection with hexaminolevulinate photodynamic diagnosis or regular cystoscopy.

To compare the recurrence of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection employing cystoscopy with hexaminolevulinate-based photodynamic diagnosis (PDD) or with standard white light. We included patients with newly suspected NMIBC in this retrospective cohort study and compared those undergoing transurethral resection by white light cystoscopy (WLC) (2008-2010) and PDD (2010-2012). All patients were treated following established criteria for good quality resection. The primary outcome was the difference in the recurrence rate after 60 months' follow-up, but we also stratified recurrence by risk groups, as set by the European Organization for Research and Treatment of Cancer. The mean recurrence-free survival was compared between the cohorts. Odds ratios or hazard ratios are reported with their 95% confidence intervals. The WLC and PDD cohorts comprised 124 and 91 subjects, respectively. There were no significant differences in recurrence rates between the cohorts at 6 months (recurrence rate 9/123; 7.3%), 12 months (17/118; 14.4%) or 60 months (39/102; 38.2%), with odds ratios of 1.23 (CI 0.48-3.25), 1.32 (CI 0.67-2.62) and 1.12 (CI 0.70-1.79), in favour of WLC, respectively. Further analysis showed no significant effect of PDD on either recurrence by risk group or on mean recurrence-free survival (hazard ratio, 1.12 [CI 0.70-1.79]). We found no relevant differences in the recurrence of NMIBC after the introduction of PDD with hexaminolevulinate compared to standard WLC when used for transurethral resection in our single institution.

P260 - Absence of Tumor (T0) on Second Transurethral Resection (ReTURB) Positively Impact Recurrence and Progression Risk Dynamics in a Contemporary Series of High-grade T1 Non-muscle Invasive Bladder Carcinoma Treated With Adequate Bacillus Calmette-Guérin

P260 - Absence of Tumor (T0) on Second Transurethral Resection (ReTURB) Positively Impact Recurrence and Progression Risk Dynamics in a Contemporary Series of High-grade T1 Non-muscle Invasive Bladder Carcinoma Treated With Adequate Bacillus Calmette-Guérin

P259 - Enhancing Predictions of the EAU21 Scoring Model in High-Grade Non-Muscle Invasive Bladder Carcinoma Treated with BCG using Explainable Machine Learning Survival Ensemble

P259 - Enhancing Predictions of the EAU21 Scoring Model in High-Grade Non-Muscle Invasive Bladder Carcinoma Treated with BCG using Explainable Machine Learning Survival Ensemble

Bladder Epicheck Test: A Novel Tool to Support Urothelial Carcinoma Diagnosis in Urine Samples.

Bladder cancer and upper urothelial tract carcinoma are common diseases with a high risk of recurrence, thus necessitating follow-up after initial treatment. The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection involves surveillance, intravesical therapy, and cytology with cystoscopy. Urinary cytology, cystoscopy, and radiological evaluation of the upper urinary tract are recommended during follow-up in the international urological guidelines. Cystoscopy is the standard examination for the first assessment and follow-up of NMIBC, and urine cytology is a widely used urinary test with high sensitivity for high-grade urothelial carcinoma (HGUC) and carcinoma in situ (CIS). In recent years, various urinary assays, including DNA methylation markers, have been used to detect bladder tumors. Among these, the Bladder EpiCheck test is one of the most widely used and is based on analysis of the methylation profile of urothelial cells to detect bladder neoplasms. This review assesses the importance of methylation analysis and the Bladder EpiCheck test as urinary biomarkers for diagnosing urothelial carcinomas in patients in follow-up for NMIBC, helping cytology and cystoscopy in doubtful cases. A combined approach of cytology and methylation analysis is suggested not only to diagnose HGUC, but also to predict clinical and histological recurrences.

Molecular classification of urothelial bladder carcinoma.

Urothelial bladder carcinoma (UC) ranks among the top ten most commonly diagnosed cancers worldwide on an annual basis. The standardized classification system for urothelial bladder tumors is the Tumor, Node, Metastasis classification, which reflects differences between non-muscle-invasive bladder carcinoma (NMIBC) and muscle-invasive bladder carcinoma (MIBC) and it depends on the extent to which tumor has infiltrated the bladder wall and other tissues and organs. NMIBC and MIBC exhibit great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. In recent years, studies based on mRNA expression profiling revealed the existence of biologically relevant molecular subtypes of UC, which show variant molecular features that can provide more precise stratification of UC patients. Here, we present a complex classification of UC based on mRNA expression studies and molecular subtypes of NMIBC and MIBC in detail with regard to different mRNA expression profiles, mutational signatures, and infiltration by non-tumor cells. The possible impact of molecular subtyping on treatment decisions and patients' outcomes is outlined, too.

Is it possible a surveillance deintensification in high-grade non-muscle invasive bladder carcinoma treated with bacillus Calmette-Guérin? A multiple survival approach for recurrence and progression risk dynamics

Is it possible a surveillance deintensification in high-grade non-muscle invasive bladder carcinoma treated with bacillus Calmette-Guérin? A multiple survival approach for recurrence and progression risk dynamics

Gene Screening for Prognosis of Non-Muscle-Invasive Bladder Carcinoma under Competing Risks Endpoints.

Background: Discovering clinically useful molecular markers for predicting the survival of patients diagnosed with non−muscle-invasive bladder cancer can provide insights into cancer dynamics and improve treatment outcomes. However, the presence of competing risks (CR) endpoints complicates the estimation and inferential framework. There is also a lack of statistical analysis tools and software for coping with the high-throughput nature of these data, in terms of marker screening and selection. Aims: To propose a gene screening procedure for proportional subdistribution hazards regression under a CR framework, and illustrate its application in using molecular profiling to predict survival for non-muscle invasive bladder carcinoma. Methods: Tumors from 300 patients diagnosed with bladder cancer were analyzed for genomic abnormalities while controlling for clinically important covariates. Genes with expression patterns that were associated with survival were identified through a screening procedure based on proportional subdistribution hazards regression. A molecular predictor of risk was constructed and examined for prediction accuracy. Results: A six-gene signature was found to be a significant predictor associated with survival of non−muscle-invasive bladder cancer, subject to competing risks after adjusting for age, gender, reevaluated WHO grade, stage and BCG/MMC treatment (p-value < 0.001). Conclusion: The proposed gene screening procedure can be used to discover molecular determinants of survival for non−muscle-invasive bladder cancer and in general facilitate high-throughput competing risks data analysis with easy implementation.

A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study.

Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.

DNA methylation analysis in urinary samples: A useful method to predict the risk of neoplastic recurrence in patients with urothelial carcinoma of the bladder in the high-risk group.

Recently, it was reported that the Bladder EpiCheck test is likely to represent a valid tool in the diagnostic process of patients who have suspected bladder carcinoma, with some controversial management decisions because of the technical limitations of cytology. Two hundred ninety patients with a diagnosis of nonmuscle-invasive bladder carcinoma who were admitted at the authors' department from March 2019 to December 2019 were treated and followed for 1year. During follow-up, all patients were evaluated by voided urine cytology, white-light cystoscopy (according to European Association of Urology guidelines), and the Bladder EpiCheck test. The cytologic diagnoses of high-grade urothelial carcinoma (HGUC) and suspicious for HGUC were histologically confirmed in 5 of 20 patients (25%) who had quantitative Bladder EpiCheck scores (EpiScores) from 60 to 69, in 23 of 36 patients (64%) who had EpiScores from 70 to 79, and in 42 of 56 patients (75%) and 57 of 63 patients (90%) who had EpiScores between 80 and 89 and EpiScores >90, respectively. Of 48 patients who had a cytologic diagnosis of HGUC or suspicious for HGUC with EpiScores ≥60 and negative histology, 20 (42%) had a recurrence of HGUC, which was cytologically and histologically confirmed, at 6-12months during follow-up. To the best of the authors' knowledge, this is the first study in which patients at high risk for HGUC were stratified using the Bladder EpiCheck EpiScore. The results validate this methylation analysis tool as a useful method for predicting recurrent HGUC during the follow-up of patients with nonmuscle-invasive bladder carcinoma.

Check Cystoscopy Follow-up Practice for Low-Risk (pTa) Non-muscle Invasive Bladder Cancer in the United Kingdom

Objectives: To identify the best practice policy and guideline for surveillance with check cystoscopies follow up for low-risk pTa urothelial bladder tumour and to identify the recurrence rate and the progression rate of low-risk urothelial bladder tumour and how safe is it to discharge them at 1- versus 5-years of follow up. Objectives: To identify the best practice policy and guideline for surveillance with check cystoscopies follow up for low-risk pTa urothelial bladder tumour and to identify the recurrence rate and the progression rate of low-risk urothelial bladder tumour and how safe is it to discharge them at 1- versus 5-years of follow up. Secondary outcome: To estimate the cost-effectiveness of a reduced follow-up scheme, if this is deemed a safe practice to follow. Methodology: It is a single centre, retrospective review of all low-risk NMIBC patients diagnosed with low-risk bladder tumors at our Trust between 2012 and 2014 from our local urological cancer multi-disciplinary team (MDT) registry and ensured a 5-year time-lapse from diagnosis. Histology grade and staging from the first TURBT, receiving of mitomycin within 24 hrs following the initial TURBT, the timing of cystoscopy follow-up, cystoscopy findings (evidence of recurrence), further procedures (bladder biopsy, fulguration or TURBT), histology of further procedures, recurrence rate and time from the first TURBT to discharge to primary care are reviewed and analysed. Result: Our initial review revealed a high likelihood of recurrence (33.9%) in the low-risk NMIBC patients after 12 months of being cancer free. It also demonstrated that there is further progression in (23.8%) of those who had a later recurrence despite being asymptomatic. Conclusion: We would recommend a 5-year follow-up surveillance and further national collaboration to audit this patient subgroup to define a safe period of cystoscopic follow-up for these patients and bring further evidence for NICE to build up their recommendations.

Intravesical Bacillus Calmette-Guerin and its complications: 12 years of learning experience in a single local institution.

Intravesical Bacillus Calmette-Guerin (BCG) therapy is the standard adjuvant treatment for non-muscle-invasive bladder carcinoma (NMIBC) with carcinoma in situ, in addition to tumour resection. We aimed to study BCG complications that preclude adequate treatment of NMIBC in an Asian population. This retrospective study was conducted using a large, prospectively maintained bladder cancer database. 336 patients received intravesical BCG therapy for bladder cancer in our institution between 2004 and 2016, with an average follow-up duration of 63 months. The study included 258 (76.8%) male and 78 (23.2%) female patients. The median age of the patients at diagnosis of bladder cancer was 69 (range 17-94) years, and the median number of BCG instillations was 6 (range 1-27). 52 (15.5%) patients received maintenance therapy. The most common complications included urinary tract infection with/without sepsis (n = 18, 5.4%), haematuria (n = 9, 2.7%) and acute urinary retention (n = 4, 1.2%). 93.3% of the patients with complications presented early, within one month of completion of therapy. 22 out of 30 complications were Clavien-Dindo grade ≤ 2. 10 (33.3%) patients were admitted to hospital because of BCG-related adverse effects. The most common reasons for termination were urosepsis (2/30, 6.7%) and acute urinary retention (2/30, 6.7%). Patients aged ≥ 80 years at diagnosis were at higher risk of developing BCG-related complications (19.0% vs. 7.5%, p = 0.01). This retrospective cohort and subgroup study showed that intravesical BCG therapy is well tolerated and has a low incidence of complications even in the elderly and patients with multiple comorbidities.

The bladder epicheck test and cytology in the follow-up of patients with non-muscle-invasive high grade bladder carcinoma.

The management of non-muscle invasive bladder carcinoma (NMIBC) after transurethral resection of a bladder tumor consists of adjuvant intravesical therapy and strict and long surveillance with urine cytology and cystoscopy. The Bladder EpiCheck test (Nucleix Ltd) (BE) is a newly developed urinary markers based on DNA methylation changes in a panel of 15 genomic biomarkers, with a promising performance in term of non-invasive NMIBC detection.In this study we prospectively enrolled 151 consecutive patients with high grade NMIBC, treated with intravesical BCG and mitomycin C therapy and evaluated during the follow-up by voided urine cytology and white-light cystoscopy, according to the European Association of Urology Guidelines. The Bladder EpiCheck test was performed at the same time of urine cytology in voided specimen. In all cases with positive cytology the diagnosis was confirmed by histology and a diagnosis was made according to the 2017 tumor, node, metastasis (TNM) classification and graded using both the 1973 and the 2004 World Health Organization (WHO) classifications.At three months of follow-up, we reported similar overall specificity rates for BE and urine cytology (85,1% vs 86,3%). In the group of patients with carcinoma in situ (CIS), we found the same specificity for BE and urine cytology (81,4%), while in the groups of patients with papillary high grade NMIBC, the specificity of BE was higher compared to cytology (96,3% vs 90,4%). The sensitivity of BE was always higher compared to cytology during all the follow-up both for papillary NMIBC and CIS.In the early follow-up of NMIBC the EpiCheck test might replace urinary cytology.

Upper Tract Urinary Cancer Recurrence after Radical Cystectomy: Risk Assessment of Intraoperative Frozen Section

Introduction: Upper tract urinary cancer recurrence (UTUCR) after radical cystectomy (RC) is outcome-limiting. Surgical recommendations on intraoperative performance of frozen section analysis (FSA) and management of positive ureteral margin (PUM) are lacking. Methods: 634 RC cases were identified (2010–2018). In patients with PUM, sequential ureteral resections up to a negative margin were performed. We investigated the accuracy of FSA, significance of PUM, and identified risk factors (RFs) to stratify patients for UTUCR. Results: FSA was performed in 355 patients, including a total of 693 ureters. FSA sensitivity was 0.93 and specificity 0.99. PUM conversion was possible in 52 (91.2%) cases. UTUCR occurred in 17 (4.8%) patients. Identified UTUCR RFs are non-muscle invasive bladder carcinoma (NMIBC) (OR 3.8, 95% confidence intervals [CI] 1.4–10.2, p = 0.008), multifocal bladder cancer in cystectomy specimen (OR 4.7, CI 1.1–20.8, p = 0.042), and recurrent NMIBC (OR 4.1, CI 1.5–10.9, p = 0.006). Risk-group stratification showed a six-fold increase in UTUCR risk (low-to high-risk). Conclusion: FSA is a sensitive and specific method to identify PUM. UTUCR occurs significantly more often in patients with recurrent, multifocal NMIBC at the time of RC. Patients can be risk stratified for UTUCR. In case of NMIBC-PUM, surgeons can safely opt for a kidney preserving strategy.

The Role of New Technologies in the Diagnosis and Surveillance of Non-Muscle Invasive Bladder Carcinoma: A Prospective, Double-Blinded, Monocentric Study of the XPERT© Bladder Cancer Monitor and Narrow Band Imaging© Cystoscopy

Simple SummaryPatients with bladder cancer (BC) require close follow-up with white-light cystoscopy (WLC) and cytology. In this study, we sought to assess (a) the performance of a novel cystoscopy technology based on Narrow Band Imaging© (NBI), and (b) a new urine test (XPERT© Bladder Cancer Monitor, XBCM) that detects cancer proteins. We compared these to the established standard follow-up diagnostics. Our study showed that NBI cystoscopy does not provide any additional benefit over standard WLC. However, the XBCM urine test performed particularly well in instances of aggressive high-grade tumor recurrence. Therefore, XBCM may have enhanced utility in the early detection of potentially harmful BC recurrence.Follow-up is essential for the early detection of recurrent non-muscle invasive bladder cancers (NMIBC). This study investigates the clinical relevance of new diagnostic tools such as an mRNA-based urine test (XPERT© Bladder Cancer Monitor, XBCM) and Narrow Band Imaging© (NBI) and compares them with the established follow-up diagnostics (white-light cystoscopy (WLC) and urine cytology). This was a prospective, double-blind, single-center study that involved patients undergoing NMIBC screening at a tertiary care center. Enrollment occurred between January 2018 and March 2020. In addition to standard care (WLC, cytology, and ultrasound), patients underwent XBCM urine testing and NBI cystoscopy. In total, 301 WLCs were performed; through this, 49 patients demonstrated NMIBC recurrence. NBI cystoscopy was congruent with WLC in all patients. Cytology showed a sensitivity (SE) and specificity (SP) of 27% and 97% (PPV: 65%; NPV 87%), respectively, whereas XBCM showed SE and SP of 58% and 89%, respectively (PPV: 51%; NPV: 92%; AUC: 0.79 (0.716–0.871)). Subgroup analysis showed improved SE and similar SP (PPV, NPV) for high grade (HG) recurrence, with a SE of 74% and SP of 89% (39%, 97%). NBI cystoscopy does not necessarily provide additional benefit over standard WLC. However, the XBCM may provide better SE and a diagnostic advantage in instances of HG disease recurrence.

Clinical efficacy of intravesical gemcitabine combined with ubenimex in patients with non-muscle-invasive bladder carcinoma after transurethral resection of bladder tumor.

Objectives:To evaluate the clinical value of intravesical gemcitabine combined with immunotherapy in patients with non-muscle-invasive bladder carcinoma (NMIBC) after transurethral resection of bladder tumor (TURBT).Methods:Eighty patients with non-muscle-invasive urothelial carcinoma treated in Baoding No.1 Hospital from November 2016 to November 2019 were randomly divided into two groups, with 40 patients in each group. Both groups underwent TURBT. After surgery, the research group was treated with intravesical chemotherapy using gemcitabine combined with ubenimex, while the control group was given 40 mg pirarubicin by intravesical instillation. Postoperative condition was evaluated by cystoscopy every three months in both groups. The recurrence six months, one year and two years after treatment, the incidence of lower urinary tract symptoms such as dysuria, hematuria and frequent urination, general adverse drug reactions such as rashes, liver function damage and gastrointestinal reaction, as well as the changes in CD3+, CD4+, CD8+ and CD4+/CD8+ T lymphocyte subsets before and after treatment were comparatively analyzed between the two groups.Results:The recurrence rate showed no statistical significance between the two groups 6 months after treatment (p=0.17), but significant differences one year (p=0.04) and two years (p=0.03) after treatment, which were significantly lower in the research group than the control group. The incidence of adverse drug reactions was 22.5% in the research group and 7.5% in the control group, without significant difference (p=0.36). The incidence of lower urinary tract symptoms was 32.5% and 55%, respectively, in the research group and the control group. The incidence of lower urinary tract symptoms in the research group was significantly lower compared with the control group, with a statistically significant difference (p=0.04). After treatment, CD3+, CD4+ and CD4+/CD8+ levels in the research group increased significantly than those in the control group, with statistically significant differences (CD3+, p=0.01; CD4+, p=0.00; CD4+/CD8+, p=0.00).Conclusions:For NMIBC patients receiving bladder-preserving surgery, intravesical gemcitabine combined with immunotherapy can reduce the recurrence rate, relieve lower urinary tract symptoms, increase the tolerance of patients to intravesical chemotherapy and significantly improve the function of T lymphocytes, without obvious increase in adverse drug reactions. Therefore, it is safe and effective, and has certain clinical value.

O6 - Treatment of EAU intermediate risk category non-muscle invasive bladder carcinoma by standard number and dose of BCG instillations versus reduced number and standard dose of BCG instillations. A subgroup analysis of the ‘NIMBUS’ phase III clinical trial

O6 - Treatment of EAU intermediate risk category non-muscle invasive bladder carcinoma by standard number and dose of BCG instillations versus reduced number and standard dose of BCG instillations. A subgroup analysis of the ‘NIMBUS’ phase III clinical trial

Significance of Vascular Endothelial Growth Factor Expression in the Bladder Urothelial Carcinoma and Its Association with Tumor Grade and Invasiveness

Background & Objective: Vascular Endothelial Growth Factor (VEGF) is one of the newer molecular markers that acts as a central mediator of tumor angiogenesis and is essential for tumor growth, progression, and metastasis. So anti-angiogenic drugs can be used as anticancer therapy. Treatments with anti-VEGF (Bevacizumab) therapy have been proved to improve relapse-free survival in many tumors. Urinary bladder tumor has become emerging cancer globally among elderly individuals. So, the identification and development of novel biomarkers for effective treatment of urinary bladder carcinoma is essential. The present study aimed to investigate the immunohistochemical expression of VEGF in urothelial carcinoma of urinary bladder and to assess its association with tumor grade and muscle invasiveness.Methods: This cross-sectional study was conducted in the Department of Pathology, Chittagong Medical College, Chattogram from September 2018 to August 2020. Fifty-six formalin-fixed paraffin-embedded tissue blocks of urinary bladder carcinoma were prepared for both histopathological and immunohistochemical examination. Each slide was evaluated by at least two pathologists.Results: Weak to strong positive expression of VEGF were observed in 52 cases (92.86%). The proportion of tumors positive for VEGF expression was higher among patients with high grade and non-muscle invasive bladder carcinoma. Conclusion: We found that VEGF expression has a significant association with tumor grade and an inverse association with muscle invasion. These findings may be useful for selecting the subset of patients likely to respond to anti-VEGF targeted therapy.

The prognostic significance of cyclin D1 expression in bladder urothelial carcinoma and correlation with clinicopathological parameters

Objective To determine the expression of cell cycle protein cyclin D1 in urothelial carcinoma and to correlate it with clinicopathological parameters and overall survival. Background Dysregulation of the cell cycle is a key mechanism for the occurrence of various types of tumors, including urinary bladder carcinoma (UBC). Cyclin D1 critically targets the proliferative signals and has been implicated in progression of UBC. Materials and methods This retrospective control study was conducted on 80 cases of urothelial carcinoma, which were classified according to muscularis propria invasion into 50 cases of muscle invasive bladder carcinoma and 30 cases of non-muscle-invasive bladder carcinoma (NMIBC). Immunohistochemistry staining for cyclin D1 antibody was done for all cases. Results Cyclin D1 was positive in 61 (76.2%) of 80 urothelial carcinoma cases. Cyclin D1 expression is significantly associated with early stage group (P = 0.031), early lymph node staging (P = 0.001), and absent perineural invasion (P = 0.037) in infiltrating urothelial carcinoma. NMIBC cases showed significant association with cyclin D1 expression (P = 0.025) and strong intensity (P = 0.018). Moreover, high immunoreactive score of cyclin D1 was significantly associated with NMIBC group (P = 0.001). Conclusion Cyclin D1 expression implies a good prognostic effect in UBC, as an inverse correlation between cyclin D1 expression and poor prognostic pathologic features (muscle invasive bladder carcinoma, advanced stage, perineural invasion and lymph node involvement) was displayed in the current study.