Invasive Bladder Carcinoma Research Articles

P285 Does the presence of detrusor muscle in the initial transurethral resection affect the efficacy of immediate second transurethral resection in improving recurrence and progression in T1 high-grade non-muscle invasive bladder carcinoma?

P285 Does the presence of detrusor muscle in the initial transurethral resection affect the efficacy of immediate second transurethral resection in improving recurrence and progression in T1 high-grade non-muscle invasive bladder carcinoma?

P286 Is there a role for Bacillus Calmette-Güerin in very high-risk non-muscle invasive bladder carcinoma? A real-world multicenter analysis

P286 Is there a role for Bacillus Calmette-Güerin in very high-risk non-muscle invasive bladder carcinoma? A real-world multicenter analysis

Repair of Vaginal Cuff Dehiscence after Laparoscopic Radical Cystectomy with Gracilis Myocutaneous Flap

Vaginal cuff dehiscence after total hysterectomy or total cystectomy had been increasing since laparoscopic or robotic surgery became a common surgery among gynecologists and urologists. A 52-yearold woman underwent laparoscopic radical total cystectomy for muscle invasive bladder carcinoma at Rakuwakai Otowa Hospital. She was emergently admitted with a fist-sized lump protruding from her vagina four months after surgery. Physical examination and her past history on admission disclosed vaginal cuff dehiscence after cystectomy. Computed tomographic scan and magnetic resonance imaging showed no bowel evisceration in the lump. We confirmed that the content of lump was peritoneal tissue and removed it by laparoscopic surgery. Simultaneously, we repaired the vaginal cuff dehiscence with a gracilis myocutaneous flap. There was no subsequent recurrence of vaginal dehiscence or bladder carcinoma in one-year follow-up.

Long term outcomes and impact on renal function following radical cystectomy.

To assess clinical, oncological outcomes and impact on renal function in patients who underwent the radical cystectomy with pelvic lymphadenectomy for muscle invasive and high risk non-muscle invasive transitional cell carcinoma of urinary bladder without evidence of non-regional lymph nodes and distant metastasis. With curative intent total 156 patients underwent radical cystectomy with pelvic lymphadenectomy from January 2015 to December 2022. Total 132/156 patients had primary transitional cell carcinoma of bladder. Thirty patients, presented with obstructive nephropathy, operated after stabilization of renal function. Pre-operatively and post-operatively eGFR calculated using modified diet in renal disease formula. In present study 114 (86.36%) patients had high grade TCC, 70 (53.02%) patients had organ confined disease. Nodal extension seen in 74 (56.06%) patients. Perioperative mortality noted in 36 (27.2%) patients. The overall survival and recurrence free survival (RFS) over 5 years was 66.67 and 45.45%. RFS was significantly related to pathological stage, nodal status, histological-grade, positivity of surgical margin and time of surgery from diagnosis. Total 92/132 (69.7%) patients had recurrence. Pelvic recurrence in 10/92 (10.87%) whereas 82/92 (89.13%) patients had distant recurrence. Pre-operatively mean creatinine was 2.6 mg/dl and mean eGFR was 38.9 ml/h in patients who presented with obstructive nephropathy after stabilization of renal function. Post-operatively in 46/132 (34.8%) patients had improvement in eGFR while 86/132 (65.2%) patients had deterioration of eGFR over 62 months of median follow up. Radical cystectomy provides good overall survival outcomes. Pre-operative eGFR has significant impact on post-operative renal function in long term.

Clinico-pathological Outcomes of Muscle Invasive Carcinoma Bladder in Post Neoadjuvant Chemotherapy Radical Cystectomy

Background: Neoadjuvant chemotherapy (NAC) before radical cystectomy is advocated in patients with muscle invasive urothelial carcinoma of the bladder with the goal to improve survival by downstaging the primary tumour and eradicating micro-metastasis. The use of perioperative chemotherapy for bladder cancer, particularly in the neoadjuvant setting, remains limited. This study was designed to evaluate NAC plus RC regarding pathological response, perioperative morbidity and mortality outcomes. Methods: This is a prospective and retro prospective study that was carried out from Jan 2018 to Jan 2020 for patients with muscle invasive bladder carcinoma. All patients having operable muscle invasive bladder carcinoma, Eastern Cooperative Oncology Group (ECOG) performance status 0–1 were included. Patients found to have metastatic disease, recurrent disease, patient not able to tolerate NAC were excluded from the study. Results: Early complications occurred within 30 days after surgery & pathological response rates, perioperative morbidity, and mortality were compared. Conclusions: A short course of neoadjuvant chemotherapy was associated to a low incidence of serious adverse events and did not increase the post-operative morbidity. Results suggest that non-urothelial tumour showed no response to Platinum based combination chemotherapeutic regimens. After NAC, residual local disease, persistent nodal disease and status of surgical margins are the most powerful prognostic factors for patients who underwent RC.

Interleukin-1β/Interleukin (IL)-1-Receptor-Antagonist (IL1-RA) Axis in Invasive Bladder Cancer-An Exploratory Analysis of Clinical and Tumor Biological Significance.

Previous data indicate a role of IL-1 and IL-1RA imbalance in bladder carcinoma (BC); the inhibition of IL-1 signaling might be considered a treatment option. Objective: To assess expression patterns and the prognostic role of IL-1β and IL-1RA in invasive BC and to evaluate their interaction with AKT signaling and proliferation. The study included two independent cohorts of n = 92 and n = 102 patients who underwent a radical cystectomy for BC. Specimen from BC and benign urothelium (n = 22 and n = 39) were processed to a tissue microarray and immunohistochemically stained for IL-1β, IL-1RA, AKT, and Ki-67. Expression scores were correlated to clinical variables and Ki-67 and AKT expression. An association with outcome was assessed using Wilcoxon Kruskal-Wallis tests, Chi-square tests or linear regression, dependent on the variable's category. Kaplan-Meier and Cox proportional hazard analyses were used to estimate recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Both IL-1β and IL-1RA were significantly overexpressed in invasive BC compared to benign urothelium in both cohorts (p < 0.005). IL-1β was associated with vascular invasion (210 vs. 183, p < 0.02), lymphatic invasion (210 vs. 180, <0.05) and G3 cancer (192 vs. 188, <0.04). The survival analysis revealed favorable RFS, CSS, and OS in the case of high IL-1β expression (p < 0.02, <0.03, and <0.006, respectively). Multivariate analyses revealed an independent impact of (low) IL1β expression on RFS, CSS, and OS. The IL-1β and IL-1β/IL-1RA ratios were positively correlated to the AKT expression (p < 0.05 and <0.01, respectively). Additionally, the high expression of Ki-67 (>15%) correlated with higher levels of IL-1β (p = 0.01). The overexpression of IL-1β and IL-1RA is frequently found in BC, with a prognostic significance observed for the IL-1β protein expression. The observed link between the IL-1β/IL-1RA axis and AKT signaling may indicate possible autophagy activation processes besides the known tumor-promoting effects of AKT.

Do Fibroblast Growth Factor Receptor (FGFR) 2 and 3 Proteins Play a Role in Prognosis of Invasive Urothelial Bladder Carcinoma?

Bladder carcinoma ranks second in prevalence among males in Egypt. As a family of tyrosine kinases, fibroblast growth factor receptor (FGFR) dysregulation has been linked to some malignancies in humans. The aim of this study is to analyze the clinicopathological data of patients while investigating FGFR2 and FGFR3 immunohistochemical expression in invasive urothelial bladder carcinoma. This retrospective cross-sectional study included 60 invasive urothelial carcinoma (UC) cases in the Pathology department, Faculty of Medicine, Menoufia University, from 2009 to 2020. All biopsies were stained for FGFR2 and FGFR3 antibodies. Complete clinical data were available for 44 patients treated and followed in clinical oncology and nuclear medicine departments. Advanced stage and high grade are significantly correlated with FGFR2 positivity (P=0.048 and 0.044, respectively). Cases presented with Perineural invasion showed a higher percentage of FGFR2 (P=0.023). There is a significant indirect linear correlation between FGFR3 expression and lymph node positivity (r= -0.265, P=0.041). A high FGFR2 expression could be associated with poor prognostic parameters, while high FGFR3 expression would be associated with good prognostic parameters. These findings might highlight the importance of FGFR-targeted therapy as a FGFR2 antagonist and FGFR3 agonist for the treatment of urothelial carcinoma patients.

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&lt;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.

Do Fibroblast Growth Factor Receptor (FGFR) 2 and 3 Proteins Play a Role in the Prognosis of Invasive Urothelial Bladder Carcinoma?

Do Fibroblast Growth Factor Receptor (FGFR) 2 and 3 Proteins Play a Role in the Prognosis of Invasive Urothelial 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

Outcome of radical cystectomy in remote area of Pakistan: Recep Tayyip Erdogan Hospital, Muzaffargarh (IHHN)

Background: Radical cystectomy with bilateral pelvic lymphadenectomy is the standard treatment for high grade/ muscle invasive urinary bladder tumor. Continent or incontinent urinary diversion is the part of this major operation. High volume centers perform routinely but low volume centers do less frequent. It might be because of availability of equipment and trained surgeon in remote area of Pakistan. Objectives: to assess the results of radical cystectomy at a low-volume center for high-grade muscle-invasive bladder tumours. For patients aged 50 to 75, this involves evaluating surgical complications, overall survival, and the absence of tumour recurrence throughout a one-year follow-up period. Study design: A Retrospective StudyDuration and place of study: Recep Tayyip Erdogan hospital, Muzaffargarh from October 2018 to August 2022 Methods: total Cases from both genders and 50 to 75 years old with High grade/ Muscle invasive urinary bladder carcinoma, incomplete resection during TURBT due to high volume of mass (irresistible) included. Performa designed for collection of information. All the patients underwent same procedure by same urologist. Patients were followed for one year after surgery. Results: All participants were followed for one year. 33.3% patients had paralytic ileus (CDC I), 13.3% had wound infection (CDC I) and 6.7% had urinary leakage (CDC IIIb). There was 86.6% overall survival rate. 6.7% lost to follow up. Mean operative time was 308 ±95 minutes. There was no recurrence noted throughout the study period. Conclusion: Good operative results can also achieve at low volume centers. High level of surveillance and expertise help to achieve better outcomes in remote. Keywords: cystectomy, radical cystectomy, bladder tumor, ileal conduit

Diffusion Weighted MRI as a Predictor of Muscle Invasive Bladder Carcinoma: Review Article

Diffusion Weighted MRI as a Predictor of Muscle Invasive Bladder Carcinoma: Review Article

Loss of ORP3 induces aneuploidy and promotes bladder cancer cell invasion through deregulated microtubule and actin dynamics

We have recently shown that loss of ORP3 leads to aneuploidy induction and promotes tumor formation. However, the specific mechanisms by which ORP3 contributes to ploidy-control and cancer initiation and progression is still unknown. Here, we report that ORP3 is highly expressed in ureter and bladder epithelium while its expression is downregulated in invasive bladder cancer cell lines and during tumor progression, both in human and in mouse bladder cancer. Moreover, we observed an increase in the incidence of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced invasive bladder carcinoma in the tissue-specific Orp3 knockout mice. Experimental data demonstrate that ORP3 protein interacts with γ-tubulin at the centrosomes and with components of actin cytoskeleton. Altering the expression of ORP3 induces aneuploidy and genomic instability in telomerase-immortalized urothelial cells with a stable karyotype and influences the migration and invasive capacity of bladder cancer cell lines. These findings demonstrate a crucial role of ORP3 in ploidy-control and indicate that ORP3 is a bona fide tumor suppressor protein. Of note, the presented data indicate that ORP3 affects both cell invasion and migration as well as genome stability through interactions with cytoskeletal components, providing a molecular link between aneuploidy and cell invasion and migration, two crucial characteristics of metastatic cells.

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.

A study to assess the quality of life among patients with high grade non-muscle invasive carcinoma urinary bladder receiving immunotherapy

Background: Urinary bladder lesions are a great health concern as it lies among the top ten most common cancers in the world. These range from benign, harmless lesions that do not recur to life-threatening tumors. The present study was undertaken to assess the quality of life among patients with high-grade non-muscle invasive carcinoma of the urinary bladder receiving immunotherapy. Methods: A hospital-based experimental study was conducted in the Department of General Surgery of Sri Guru Ramdas Institute of Medical Sciences and Research, Amritsar from April 2021 to July 2022. To examine the Quality of Life of 60 patients before and after immunotherapy, the WHOQOL-BREF tool was employed. The participants were followed for a total of six months, with two follow-ups carried out at intervals of three months each. Results: The pre-test physical scores (20.70±8.66) were substantially lower than the other domains. At three and six months, the psychological scores were 21.93±8.51 and 49.37±12.27 respectively, while social scores were 23.93±12.16 and 49.15±24.09 correspondingly. Environment scores (p=0.45) showed no significant difference between groups after BCG treatment. Conclusions: It was vivid that the negative effects of NMIBC on QOL are most pronounced in the physical realm. Quality of life for those with high-grade NMIBC who had BCG treatment improved significantly across all dimensions except the environment. The quality of life of high-grade NMIBC patients was not affected by any of the socio-demographic characteristics except for education and occupational status.

Study of her2/neu and ki-67 expression in invasive urothelial carcinoma of bladder and their correlation with grade and stage

Urinary bladder cancer is one of the costliest diseases, which requires lifelong surveillance due to its rapid aggressive clinical course. Here, HER2/neu and Ki-67 expression, is studied, as important prognostic marker with therapeutic implications in invasive urothelial bladder carcinoma (IUBC). To study expression of HER2/neu and Ki-67 in histologically diagnosed cases of IUBC and their clinicopathological correlation.An observational, cross-sectional, study was performed in Pathology Department, NRS Medical College, Kolkata, from February 2020 to July 2021. Tissue sections, after proper processing, were stained in H&amp;E. A total of 75 IUBC cases were histopathologically diagnosed with grade and stage. HER2/neu and Ki-67 expression by immunohistochemistry was studied in them; which was compared with clinicopathological variables like age, sex, risk factors, histological type, grade, stage, etc. Statistical analysis software EPI INFO (TM) 7.2.2.2 was used, p&amp;#60;0.05 was taken to be statistically significant.Among 75 cases of IUBC, 60% were high grade and 72% were of lower (pT1) stage. HER2/neu was positive in 52% cases; significantly associated with males, haematuria, smoking, necrosis, high grade (p&amp;#60;0.00001) and higher stage (pT2/3/4) (p=0.0005). Ki-67 index was high in 56% cases; significantly associated with &amp;#62;50 years age group, haematuria, smoking, necrosis, LVI, high grade (p&amp;#60;0.00001) and higher stage (p&amp;#60;0.0001). Positive HER2/neu expression was also significantly associated with high Ki-67 index (p&amp;#60;0.00001).Positive HER2/neu expression and high Ki-67 index is significantly associated with high grade and stage of tumours. So, these patients may be considered for targeted therapy using Trastuzumab in addition to conventional therapy.

Development and Internal Validation of a Nomogram Predicting Overall Survival Based on Log ODDS of Positive Lymph-Nodes for Post Radical Cystectomy Patients in Muscle Invasive Carcinoma of Bladder.

To develop and validate a nomogram based on LODDS (Log ODDS of positive lymph-nodes) for prediction of overall survival (OS) in post radical cystectomy (RC) patients of muscle invasive bladder cancer (MIBC). Data was retrospectively collected from 282 cases of MIBC that underwent RC from 2011 to 2017 at our institute. Significant independent predictors were identified using Cox regression model and incorporated into a nomogram to predict 1, 2, and 4-year OS. Multivariate analysis showed that Neo-Adjuvant Chemo-Therapy (NACT) (P< .001), LODDS (P< .001), T-stage (Pi=.001), CCI (Charlson Comorbidity Index) (P=.034) and grade (P=.003) were independent predictors of OS. The C-index of nomogram (0.740) was higher than that of the American Joint Committee on Cancer (AJCC) staging system (0.614). The bias-corrected calibration plots showed that the predicted risks were in excellent accordance with the actual risks. The results of NRI, IDI, and DCA exhibited superior predictive capability and higher clinical use of the nomogram. A simple, easy to use nomogram to predict OS in cases of MIBC has been constructed. To best of our knowledge, LODDS has been incorporated for the first time. It has superior predictive ability and higher clinical use than AJCC system. It would help the clinicians for better patient counselling, planning follow-up strategies and designing a clinical trial for newer adjuvant therapy (eg immunotherapy) in post radical cystectomy patients of MIBC.