Bladder Tumor Research Articles

Cystoscopy and Transurethral Resection of Bladder Tumors with Stent and Foley Catheter Placement

Cystoscopy and Transurethral Resection of Bladder Tumors with Stent and Foley Catheter Placement

Comprehensive analysis of single-cell and bulk RNA sequencing reveals postoperative progression markers for non-muscle invasive bladder cancer and predicts responses to immunotherapy.

Non-muscle-invasive bladder cancer (NMIBC) is renowned for its high recurrence, invasiveness, and poor prognosis. Consequently, developing new biomarkers for risk assessment and investigating innovative therapeutic targets postoperative in NMIBC patients are crucial to aid in treatment planning. Differential gene expression analysis was performed using multiple Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between NMIBC and normal tissue, as well as between NMIBC and muscle-invasive bladder cancer (MIBC). Functional enrichment analysis was conducted based on the DEGs identified. Subsequently, prognosis-related genes were selected using Kaplan-Meier (KM) analysis and Cox regression analysis. The Boruta algorithm was utilized to further screen for core DEGs related to postoperative progression in NMIBC based on the aforementioned prognosis-related genes. Single-cell and clinical correlation studies were performed to verify their expression across various stages of bladder cancer. To investigate the link between core genes and the immune microenvironment, single-sample gene set enrichment analysis (ssGSEA) was utilized, and Receiver Operating Characteristic (ROC) and KM analyses were performed to confirm predictive power for immune therapy outcomes. Machine learning (ML) models were constructed using the DepMap dataset to predict the efficacy of core gene inhibitors in treating bladder cancers. The prognostic performance of the core genes was evaluated using ROC curve analysis. An online prediction tool was developed based on the core genes to provide prognostic predictions. Finally, RT-qPCR, CCK-8, and Transwell assays were used to verify the pro-tumor effects of the GINS2 in bladder cancer. A total of 70 DEGs were identified, among which 11 prognostic genes were obtained through KM analysis, and an additional 8 prognostic genes were obtained through COX analysis. The Boruta algorithm selected AURKB, GINS2, and UHRF1 as the three core DEGs. Single-cell and clinical variable correlation analyses indicated that the core genes promoted the progression of bladder cancer. The analysis of immune infiltration revealed a strong positive association between the core genes and both activated CD4 T cells and Type 2 helper T cells. Two random forest (RF) models were constructed to effectively predict the treatment effect of bladder cancer after targeted inhibition of AURKB and GINS2. In addition, an online nomogram tool was developed to effectively predict the risk of postoperative progression in NMIBC patients undergoing TURBT. Finally, RT-qPCR, CCK8, and Transwell assays showed that GINS2 promoted the growth and progression of bladder cancer. AURKB, GINS2, and UHRF1 have the potential to enhance postoperative management of NMIBC patients undergoing transurethral resection of bladder tumor (TURBT) and can predict immunotherapy response, establishing them as promising therapeutic targets.

Abstract A071: Performance of the Oncuria®-Detect test for the evaluation of patients presenting with hematuria: Results from a real world clinical setting

Abstract Bladder cancer is the 9th most diagnosed cancer worldwide with higher incidences reported in Europe and the United States. Here, we evaluate the performance of a novel, commercially available multiplex immunoassay querying for 10 proteins associated with a bladder cancer diagnostic signature (Oncuria®-Detect, Nonagen Bioscience Corp, Los Angeles, CA, US) for the detection of de novo bladder cancer, in a large prospectively collected real world cohort comprised of 995 patients, across seven centers, presenting with hematuria. The results were compared with the patients’ clinical data and final diagnosis as defined by the results of cystoscopy, with a prevalence of bladder cancer of 15.9%. In the test cohort, Oncuria®-Detect detected bladder tumors in 94/109 cancers, giving overall sensitivity of 86.2% and an overall negative predictive value (NPV) of 96.7% with corresponding specificity of 80.2% with favorable performance characteristics in high grade bladder cancer and muscle-invasive bladder cancer. Patient summary: We conducted a large cross-sectional clinical study for detecting de novo bladder cancer with a novel, simple urine test (Oncuria®-Detect), which measures 10 bladder cancer associated proteins in a single voided urine sample. We analyzed urines from 995 patients and demonstrated that the new urine test can detect bladder cancer with a high degree of accuracy, specifically in patients with high grade or high stage disease. In conclusion, the novel Oncuria®-Detect urine test can be used to help detect new bladder cancers. Citation Format: Ian Pagano, Sergei Tikhonenkov, Florence Le Calvez-Kelm, Steve Goodison, Zhen Zhang, Toru Sakatani, Kaoru Murakami, Howard Kim, Riko Lee, Sunao Tanaka, Charles J Rosser, Hideki Furuya. Performance of the Oncuria®-Detect test for the evaluation of patients presenting with hematuria: Results from a real world clinical setting [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A071.

Assessing expression patterns of PTGR1, a potential biomarker for acylfulven sensitivity in urothelial carcinoma

BackgroundMetastatic urothelial carcinoma (mUC) has a poor prognosis, despite recent therapeutic advancements. Prostaglandin Reductase 1 (PTGR1) is essential for activating acylfulvens, a promising class of drugs for treating a subset of urothelial carcinoma (UC) patients. The efficacy of acylfulvens depends on PTGR1 activity and defects in the nucleotide excision repair (NER) pathway, notably ERCC2 mutations present in 10–15% of bladder tumors. This study identifies patients eligible to be included in acylfulven clinical trials based on the presence of PTGR-1 by immunohistochemistry (IHC) staining, RNA expression level and mutations in the NER pathway. Additionally, it evaluates PTGR-1 expression as a prognostic biomarker.MethodsThree PTGR-1 antibodies were tested in a kidney cancer cell line A498 and in tissues with known PTGR1 expression (liver, tonsils, pancreas, small intestine, etc.). Patients with untreated mUC receiving 1st line platinum from Dec. 2019 to Dec. 2021 in the Capital Region, Denmark, were included retrospectively. FFPE tumor samples were collected, and tissue microarrays (TMAs) were constructed. TMAs were stained with the best-performing PTGR1 antibody, RNA expression was analyzed using Nanostring nCounter PanCancer panel and gene mutations were assessed using a targeted genomic panel (TSO-500). Kaplan-Meier and multivariate Cox regression assessed overall survival and covariate impacts.ResultsThe AB181131 PTGR1 antibody was the most reliable in validation tissues. Tumors from 71 mUC patients were used to construct the TMA, and 40% of tumors scored positive for PTGR1 by IHC staining. A normalized PTGR1 RNA cutoff at 2,550 normalized counts achieved an AUC of 0.9, defining 35 samples as positive with a sensitivity of 96% and specificity of 85% in relation to IHC-positivity. Differential expression showed a significant upregulation of PTGR1 RNA in PTGR1 IHC-positive cases. NER-deficiency and PTGR1 positivity (mutations in ERCC1, ERCC2, ERCC3, ERCC4) was seen in 9 patients (13%). Median overall survival was 16 months in the cohort. Overall survival (OS) analysis indicates that overexpression of PTGR1 RNA was associated with a reduced median OS (12 months vs. 25 months, p = 0.039, log-rank).ConclusionPTGR1 IHC staining pattern using the Abcam AB181131 antibody is highly correlated with PTGR1 RNA expression. 13% in our cohort were identified as NER deficient and PTGR1 positive. Lower levels of PTGR1 indicates better outcome in this cohort.

Bladder Adenocarcinoma in a Constellation of Multiple Site Malignancies: An Unusual Case and Systematic Review

Background and Objectives: Multiple primary malignant tumors represent a small percentage of the total number of oncological cases and can involve either metachronous or synchronous development and represent challenges in diagnosis, staging, and treatment planning. Our purpose is to present a rare case of bladder adenocarcinoma in a female patient with multiple primary malignant tumors and to provide systematic review of the available literature. Materials and Methods: A 67-year-old female patient was admitted with altered general condition and anuria. The past medical history of the patient included malignant melanoma (2014), cervical cancer (2017), colon cancer (2021), obstructive anuria (2023), and liver metastasectomy (2023). Transurethral resection of bladder tumor was performed for bladder tumors. Results: Contrast CT highlighted multiple pulmonary metastases, a poly nodular liver conglomerate, retroperitoneal lymph node, II/III grade left ureterohydronephrosis, and no digestive tract tumor masses. The pathological result of the bladder resection showed an infiltrative adenocarcinoma. Conclusions: The difference between primary bladder adenocarcinoma tumor and metastatic colorectal adenocarcinoma is the key for the future therapeutic strategy. Identification and assessment of risk factors such as viral infection, radiotherapy, chemotherapy, smoking, and genetics are pivotal in understanding and managing multiple primary malignant tumors. Personalized prevention strategies and screening programs may facilitate the early detection of these tumors, whether synchronous or metachronous. The use of multicancer early detection (MCED) blood tests for early diagnosis appears promising. However, additional research is needed to standardize these techniques for cancer detection.

A pilot intervention trial to reduce the use of post-procedural antimicrobials after common endourologic surgeries.

Post-procedural antimicrobial prophylaxis is not recommended by professional guidelines but is commonly prescribed. We sought to reduce use of post-procedural antimicrobials after common endoscopic urologic procedures. A before-after, quasi-experimental trial with a baseline (July 2020-June 2022), an implementation (July 2022), and an intervention period (August 2022-July 2023). Three participating medical centers. We assessed the effect of a bundled intervention on excess post-procedural antimicrobial use (ie, antimicrobial use on post-procedural day 1) after three types of endoscopic urologic procedures: ureteroscopy and transurethral resection of bladder tumor or prostate. The intervention consisted of education, local champion(s), and audit-and-feedback of data on the frequency of post-procedural antimicrobial-prescribing. 1,272 procedures were performed across all 3 sites at baseline compared to 525 during the intervention period; 644 (50.6%) patients received excess post-procedural antimicrobials during the baseline period compared to 216 (41.1%) during the intervention period. There was no change in the use of post-procedural antimicrobials at sites 1 and 2 between the baseline and intervention periods. At site 3, the odds of prescribing a post-procedural antimicrobial significantly decreased during the intervention period relative to the baseline time trend (0.09; 95% CI 0.02-0.45). There was no significant increase in post-procedural unplanned visits at any of the sites. Implementation of a bundled intervention was associated with reduced post-procedural antimicrobial use at one of three sites, with no increase in complications. These findings demonstrate both the safety and challenge of guideline implementation for optimal perioperative antimicrobial prophylaxis.This trial was registered on clinicaltrials.gov, NCT04196777.

A novel approach to engineering three-dimensional bladder tumor models for drug testing.

Bladder cancer (BCa) poses a significant health challenge, particularly affecting men with higher incidence and mortality rates. Addressing the need for improved predictive models in BCa treatment, this study introduces an innovative 3D in vitro patient-derived bladder cancer tumor model, utilizing decellularized pig bladders as scaffolds. Traditional 2D cell cultures, insufficient in replicating tumor microenvironments, have driven the development of sophisticated 3D models. The study successfully achieved pig bladder decellularization through multiple cycles of immersion in salt solutions, resulting in notable macroscopic and histological changes. This process confirmed the removal of cellular components while preserving the native extracellular matrix (ECM). Quantitative analysis demonstrated the efficacy of decellularization, with a remarkable reduction in DNA concentration, signifying the removal of over 95% of cellular material. In the development of the in vitro bladder cancer model, muscle invasive bladder cancer patients' cells were cultured within decellularized pig bladders, yielding a three-dimensional cancer model. Optimal results were attained using an air-liquid interface technique, with cells injected directly into the scaffold at three distinct time points. Histological evaluations showcased characteristics resembling in vivo tumors derived from bladder cancer patients' cells. To demonstrate the 3D cancer model's effectiveness as a drug screening platform, the study treated it with Cisplatin (Cis), Gemcitabine (Gem), and a combination of both drugs. Comprehensive cell viability assays and histological analyses illustrated changes in cell survival and proliferation. The model exhibited promising correlations with clinical outcomes, boasting an 83.3% reliability rate in predicting treatment responses. Comparison with traditional 2D cultures and spheroids underscored the 3D model's superiority in reliability, with an 83.3% predictive capacity compared to 50% for spheroids and 33.3% for 2D culture. Acknowledging limitations, such as the absence of immune and stromal components, the study suggests avenues for future improvements. In conclusion, this innovative 3D bladder cancer model, combining decellularization and patient-derived cells, marks a significant advancement in preclinical drug testing. Its potential for predicting treatment outcomes and capturing patient-specific responses opens new avenues for personalized medicine in bladder cancer therapeutics. Future refinements and validations with larger patient cohorts hold promise for revolutionizing BCa research and treatment strategies.

The role of re-transurethral resection of bladder tumor in patients with TaHG non muscle invasive bladder cancer.

There is lack of evidence regarding the indication for re-transurethral resection of bladder tumor (reTURBT) for Ta high grade (HG) non-muscle invasive bladder cancer (NMIBC). This study aims to evaluate the oncological outcomes of patients with TaHG NMIBC to determine the benefit from performing reTURBT. We relied on a multicenter cohort of 317 TaHG NMIBC from 12 centers who underwent TURBT and a subsequent complete Bacillus Calmette-Guérin induction from 2009 to 2021. Kaplan Meier analyses estimated recurrence free survival (RFS) and progression free survival (PFS) according to reTURBT. Sub-analyses evaluated PFS in patients with multiple risk factors indicating necessity for reTURBT according to international guidelines (multifocality, size > 3cm, recurrent cancer, carcinoma in situ, lymph vascular invasion, histological variant, incomplete and absence of muscle layer at index TURBT). Multivariable cox-regression analysis predicted recurrence and progression. Of the 317 patients, 123 (39%) underwent reTURBT, while 194 (61%) did not. Residual disease was detected in 46% of cases, with a 3.2% upstaging rate. Median follow-up was 30months. The 3-year RFS was higher in patients who underwent reTURBT (79% vs. 58%, p < 0.001), but no significant difference was observed in PFS. ReTURBT reduced the risk of recurrence [multivariable hazard ratio: 0.45, 95% Confidence interval (CI) 0.29-0.71]. Among patients who did not undergo reTURBT, those with ≥ 2 risk factors had lower 3-year PFS (73% vs. 92%, p < 0.001) than those with 0-1 risk factor, whereas no difference in 3-year PFS was observed in patients who underwent reTURBT regardless of the number of risk factors (85% vs. 87%, p = 0.8). ReTURBT demonstrated efficacy in reducing recurrence among patients with TaHG NMIBC, yet its impact on progression remained uncertain. Our study underscores the importance of adhering to current international guidelines, particularly for patients with multiple risk factors indicating necessity for reTURBT.

Prospective Assessment of VI-RADS with Muscle Invasion in Urinary Bladder Cancer and Its Implication on Re-Resection/Restaging TURBT Patients.

Bladder cancer (BCa) diagnosis relies on distinguishing muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC) forms. Transurethral resection of the bladder tumor (TURBT) is a standard procedure for initial staging and treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) enhances diagnostic accuracy for muscle invasiveness through advanced imaging techniques, potentially reducing reliance on repeat TURBT and improving patient management. We aimed to evaluate the role of VI-RADS in predicting muscle invasiveness in BCa and its potential to predict adverse pathology in high-risk NMIBC to avoid unnecessary repeat TURBT procedures. In this prospective study, we included 62 patients over the age of 18years who underwent TURBT. In a secondary phase, patients selected for restaging TURBT (re-TURBT) were included, but those with T2 tumors or low-risk NMIBC were excluded. Multiparametric magnetic resonance imaging (MRI) examinations were scored by a radiologist using the VI-RADS 5 method, while a pathologist analyzed TURBT and re-TURBT samples for accurate staging. Statistical analysis evaluated the role of VI-RADS in BCa staging. The VI-RADS score was the only predictive factor for muscle invasion in multivariate analysis. Setting the VI-RADS score at >3 resulted in the highest sensitivity, specificity, and diagnostic accuracy, with values of 67.0%, 89.0%, and 78%, respectively. The receiver operating characteristic area under the curve score for VI-RADS for muscle invasion was 85% for stage Ta, 61% for stage T1, and 88% for stage T2, which shows the utility of VI-RADS in the predictiveness of MIBC/NMIBC. VI-RADS is effective in stratifying BCa patients by predicting muscle invasiveness and identifying NMIBC cases that may not need repeat TURBT.

P282 Development of new bladder tumor following radical nephroureterectomy for Upper Tract Urothelial Carcinoma (UTUC)- a new disease or an old story?

P282 Development of new bladder tumor following radical nephroureterectomy for Upper Tract Urothelial Carcinoma (UTUC)- a new disease or an old story?

Successful Management of Incompletely Resected Transitional Cell Carcinoma with Sorafenib Tosylate in a Dog.

Most urinary bladder (UB) tumors are malignant, and transitional cell carcinoma (TCC) is the most common neoplasm affecting the UB in dogs. Sorafenib may be a potential therapeutic agent for canine TCC. A 12 yr old spayed female Maltese dog weighing 3.6 kg and with a history of hematuria was referred for a suspected UB tumor. Abdominal ultrasonography revealed a UB mass attached to the cranioventral wall. The remaining abdominal examinations, including that of the lymph nodes, were unremarkable. Ultrasound-guided traumatic catheterization of the UB mass was performed, and the cytological evaluation of the UB mass indicated TCC. Excision was performed by partial cystectomy, and histopathology confirmed TCC, although the tumor had infiltrated the surgical margins. A chemosensitivity assay was conducted using tissue from the excised tumor. Sorafenib tosylate, a tyrosine kinase inhibitor, showed the greatest effect in the chemosensitivity assay. Therefore, adjuvant chemotherapy with sorafenib tosylate and piroxicam was administered postoperatively. The dog lived without any clinical signs, including hematuria or tumor relapse, for more than 2 yr after the surgery. This is the first report of successful long-term management of TCC with sorafenib tosylate in a dog.

A luminal non-coding RNA-based genomic classifier confirms favourable outcomes in patients with clinically organ-confined bladder cancer treated with radical cystectomy.

To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non-coding RNA (lncRNA)-based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer. Transcriptome-wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high-grade, clinically organ-confined (cTa-T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy (n = 226). The lncRNA-based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer-specific mortality and upstaging at RC. In the study, 134 patients were clinical non-muscle-invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12-0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20-0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25-1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15-0.74; P = 0.007). This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.

P231 Validation of multiparametric magnetic resonance imaging prior to transurethral resection of bladder tumor. Preliminary results of a protocol established in a tertiary hospital

P231 Validation of multiparametric magnetic resonance imaging prior to transurethral resection of bladder tumor. Preliminary results of a protocol established in a tertiary hospital

Engineered VNP20009 expressing IL-15&15Rα augments anti-tumor immunity for bladder cancer treatment

Surgical resection combined with intravesical instillation of chemotherapeutics or Bacillus Calmette-Guerin (BCG) to remove residual cancer cells is the gold standard for the clinical treatment of patients with bladder cancer. In a recent clinical trial, a new super-agonist complex of IL-15 - N803, has shown promising results when used in combination with BCG to treat patients with bladder cancer who do not respond to BCG. Herein, we used temperature-controlled pBV220 plasmid encoding Interleukin-15 and its receptor alpha subunit (IL-15&15Rα) to transform VNP20009, an attenuated salmonella typhimurium strain, obtaining engineered bacteria named 15&15Rα@VNP. After induction at 42 °C, 15&15Rα@VNP can secrete functional IL-15&15Rα stably. It was found that intravesical instillation of thermally activated 15&15Rα@VNP could inhibit the growth of bladder tumors if used alone. Moreover, the sequential intravesical instillation of epirubicin (EPI), a first-line bladder cancer drug, followed by thermally activated 15&15Rα@VNP, could achieve further improved therapeutic responses, without causing significant side effects. Therefore, this study shows that 15&15Rα@VNP can be effectively used in the treatment of bladder cancer and can be used as a complementary therapy to chemotherapy agents, promising for potential clinical translation in bladder cancer treatment.

A Novel Gene Expression Scoring System Predicts Recurrence in Non-Muscle-Invasive Bladder Cancer Patients.

Despite the high recurrence rate of non-muscle-invasive bladder cancer (NMIBC), there are limitations in accurately predicting recurrence after transurethral resection of bladder tumor (TURBT) based on clinicopathological factors alone. However, prediction of recurrence using biomolecular characteristics of bladder tumors has not been applied to clinical practice. The objective of this study was to establish a new gene expression scoring system for identifying patients at high risk of recurrence. NMIBC and normal bladder samples were subjected to microarray analysis to obtain gene expression profiles. We identified 6 genes that were specifically upregulated in bladder cancer and also in recurrent cases. All patients were randomly grouped into a discovery cohort (n = 59) and a validation cohort (n = 30). Gene expression score (GES) was defined as the mean Z-score of the 6 genes specific for recurrent bladder cancer. The intravesical recurrence rate of the high GES group (n = 38) was higher than the low GES group (n = 21). GES was significantly associated with recurrence-free survival in the validation cohort as well. In prognostic analysis, the European Organization for Research and Treatment of Cancer (EORTC) risk classification was not related to recurrence after TURBT in either univariate or multivariate analysis. On the other hand, the GES we developed was an independent factor for recurrence in NMIBC. A novel gene expression scoring system was shown to predict recurrence in NMIBC patients after TURBT and might be helpful in clinical decision-making for NMIBC patients.

Comparison of prognosis after transurethral resection of bladder tumor between solitary and multiple bladder cancers.

This study investigates the difference in overall survival rates after transurethral resection of bladder tumor between solitary and multiple bladder cancers, aiming to provide guidance for clinical practitioners. A retrospective analysis was conducted on 133 patients with bladder cancer who underwent transurethral resection of bladder tumor from April 2017 to October 2023, of which 112 patients had complete clinical and follow-up data. Clinical and follow-up data were collected, and the overall survival rates after surgery were compared between solitary and multiple bladder cancers. In this study, the recurrence rate after transurethral resection of bladder tumor was 23.21% (26/112), and the overall survival rate was 80.36% (90/112). The overall survival rate after transurethral resection of bladder tumor was 92.11% (35/38) in the solitary bladder cancer group and 74.32% (55/74) in the multiple bladder cancer group, with a statistically significant difference between the 2 groups (P = .025). The proportion of high-grade pathology was 7.89% (3/38) in the solitary bladder cancer group and 25.68% (19/74) in the multiple bladder cancer group after transurethral resection of bladder tumor, with a statistically significant difference between the 2 groups (P = .025). The mean tumor diameter after transurethral resection of bladder tumor was 2.76 ± 1.66 cm in the solitary bladder cancer group and 4.04 ± 3.17 cm in the multiple bladder cancer group, with a statistically significant difference between the 2 groups (P = .023). Univariate and multivariate regression analyses revealed that the number of bladder tumors is a risk factor for overall survival after bladder cancer surgery (P = .004). Multiple bladder cancers have a higher pathological grade, larger tumor diameter, and poorer prognosis after transurethral resection of bladder tumor compared to solitary bladder cancers. The number of bladder tumors is an independent risk factor for overall survival after bladder cancer surgery.

A 3-arm randomized control trial to compare the efficacy of re-circulant hyperthermic intravesical chemotherapy versus conventional intravesical mitomycin C and BCG therapy for intermediate-risk non-muscle invasive bladder cancer.

To evaluate the efficacy and side effects of re-circulant hyperthermic intravesical chemotherapy versus conventional treatments for intermediate risk non-muscle invasive bladder cancer (NMIBC). A randomized 3-arm, parallel group trial was conducted at a single tertiary care centre. 135 patients with low-grade intermediate-risk cancer, having undergone complete resection of bladder tumor were included. Patients were assigned 1:1:1, to receive intra-vesical chemo-hyperthermia (C-HT), mitomycin-C (MMC) or BCG therapy. There was no treatment crossover. Patients were followed up with check cystoscopy every 3 months for histopathological recurrence. The three arms were comparable in terms of age, gender, tumor size, number of tumors and clinical stage or grade of tumors. Mean tumor size was 2.58 (± 0.88) cm and the mean number of tumors resected was 2.04 (± 1.02) (Range 1-5). There was no significant difference between the various groups for tumor recurrence (χ2 = 1.96, p = 0.375) or time to recurrence (13.6 vs. 10.8 vs. 9.8 months, p = 0.844)though incidence of non-healing necrotic area was higher with C-HT (22.2% vs. 11.1% and 4.8%, χ2 = 6.093, p = 0.048). Median (IQR) follow up period was 26 (12-52) months. Treatment discontinuation or drug intolerance was significantly higher in BCG arm (p = 0.03). Intravesical C-HT with MMC, conventional MMC and BCG are equally effective and comparable alternatives for intravesical therapy in low-grade intermediate-risk NMIBC. Higher incidence of non-healing resection site with C-HT and higher local symptoms with BCG are a concern.

Oncogenic role of lncRNA SBF2-AS1 in bladder cancer

IntroductionBladder cancer is a malignant neoplasm with increasing incidence rates. LncRNAs play an important role in cancer, including development, prognosis, and response to therapies. It is known that lncRNA SBF2-AS1 was associated with cell proliferation and worse prognosis in various tumor types, but its role remains incompletely understood in bladder cancer. In this context, our objective was to evaluate the effect of lncRNA SBF2-AS1 silencing on bladder cancer cells. MethodsJ82 and UM-UC-3 high-grade bladder tumor cells were treated with two siRNAs specific for SBF2-AS1 to evaluate cytotoxicity, clonogenic survival, morphology, cell migration, and cell cycle progression. ResultsExpression inhibition of SBF2-AS1 resulted in cytotoxicity, morphological changes, and decreased clone formation and cell migration. Cell cycle alterations were not observed. ConclusionOur study revealed that SBF2-AS1 plays an oncogenic role and holds promise as a potential target for the treatment of bladder cancer.

Cohort Profile: VZNKUL-NMIBC Quality Indicators Program: A Flemish Prospective Cohort to Evaluate the Quality Indicators in the Treatment of Non-Muscle-Invasive Bladder Cancer.

Purpose: Bladder cancer (BC) is a heterogeneous disease with varying outcomes, influenced by disease heterogeneity and variability in treatment and follow-up. Risk groups have been established for non-muscle-invasive BC (NMIBC) to standardize therapy, and several quality control indicators (QCIs) monitor adherence to these risk group-based guidelines. However, controversial results had been obtained regarding the oncological benefits of these QCIs until recent high-quality studies from large registries showed their usefulness. To improve adherence to the European Association of Urology (EAU) Guidelines and benchmark current care in Flemish hospitals within Vlaams Ziekenhuisnetwerk-KU Leuven (VZNKUL), a QCI program for NMIBC was initiated in 2013. This study aims to describe the demographic, clinical, and treatment data of patients enrolled in this program. Participants: The VZNKUL-NMIBC Quality Indicators Program Registry is a prospective cohort including patients treated and followed up with at seven academic and non-academic Flemish hospitals since June 2013. Data collection includes patient characteristics, tumor data, treatment, and oncological outcomes. Findings to date: From June 2013 to December 2020, 4744 transurethral resections of bladder tumors (TURBTs) from 2237 unique patients were analyzed. Most patients (80%) were men with a median age of 73. The median time from diagnosis to TURBT was 19 days. A single tumor was detected in 37% of TURBTs. Tumors larger than 3 cm were found in 20.8% of cases. In 46% of TURBTs, a reTURBT was scheduled according to guidelines. The complication rates were 7.5% and 2.4% for bladder perforation and bleeding, respectively. Postoperative single intravesical instillation of chemotherapy (SIVIC) was administered to 56.9% of 1533 indicated patients with a median time to administration of 4.7 h. Among the cohort, 60.4% had NMIBC, and 9.3% had muscle-invasive BC. Of 972 high-risk patients, 60.7% received adequate BCG induction, while 39.4% received adequate maintenance. After BCG induction ± maintenance, 39.7% were tumor-free, with 17.7% recurrence and 4% progression to muscle-invasive BC. BCG treatment was terminated early for 17% of patients due to intolerance. Early cystectomy was performed for 2.4% of the BCG-naïve patients, and 27.7% of patients with BCG failure underwent a BCG rechallenge. For intermediate-risk patients, 2.1% received adequate BCG, and 23% received intravesical chemotherapy. The median follow-up was 57 months. Five-year recurrence-free, progression-free, cancer-free, overall, and cancer-specific survival rates were 53%, 91.6%, 89%, 70.6%, and 95.6%, respectively, for the NMIBC patients. Of 400 non-metastatic MIBC patients, 217 (54.3%) underwent radical cystectomy (RC), of whom 46% received neoadjuvant chemotherapy, while 18 (4.5%) refused RC, and 74 (18.5%) were considered unfit for the surgery. Future plans: The VZNKUL-NMIBC Quality Indicators Program Registry will continue collecting data to evaluate QCIs and monitor treatment quality, enabling hospitals to benchmark their performance and improve patient care. Additionally, the registry's real-world data can support research and international collaboration. Trial registration: The study was registered on ClinicalTrials.gov (NCT04167332).

A Systematic Review of the Use of Surgical Checklists in Transurethral Resection of Bladder Tumour.

Surgical checklists have previously been shown to improve surgical quality and patient outcomes. However, their use in transurethral resection of bladder tumour (TURBT), one of the most commonly performed urological procedures, has yet to be explored in depth. To evaluate the effect of surgical checklist implementation in TURBT on documentation quality, specimen quality, and oncological outcomes according to the existing literature. We then hope to develop an optimised TURBT checklist by identifying the most pertinent parameters for inclusion. A literature search using PubMed was performed to identify literature pertaining to the use of surgical checklists in the context of TURBT. A systematic review was then performed on the 41 identified studies, of which six were included in the final analysis. We explored three primary outcomes that arose from the literature, namely: (1) comprehensiveness of documentation; (2) resection quality; and (3) recurrence rates and recurrence-free survival (RFS). We found agreement in the literature that surgical checklist implementation does lead to an overall improvement in documentation. The effect of surgical checklists on resection quality and recurrence rates, however, was mixed in the literature, with some studies showing statistically significant improvements and others showing no significant change. There are multiple benefits to surgical checklist implementation in TURBT procedures. We propose an optimised 14-item surgical checklist that should be implemented in every TURBT report to ensure sufficient information documentation for risk stratification and post-operative management.