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The Management of Bacillus Calmette-Guerin (BCG) Failure in High-Risk Non-muscle Invasive Bladder Cancer: A Review Article.

ABSTRACT: Non-muscle invasive bladder cancer (NMIBC) is a common urological malignancy, and bacillus Calmette-Guérin (BCG) therapy is the gold standard treatment in intermediate and high-risk groups. However, BCG failure occurs in a significant proportion of patients, emphasizing the need for effective alternative treatment modalities to address this burden. These treatments include immunotherapy, enhanced drug delivery, targeted therapy, device-assisted chemotherapy, vaccine therapy, and gene therapy, which show varying degrees of safety and efficacy. The objective of this review is to summarize the current evidence and ongoing research on these emerging therapies, offering insight into their potential for improving patient outcomes and quality of life. Although radical cystectomy remains the standard of care for high-risk NMIBC patients unresponsive to BCG, novel treatment modalities hold promise for the future management of this challenging patient population.

SUBMITTER: Kodera A

PROVIDER: S-EPMC10369196 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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The Management of Bacillus Calmette-Guérin (BCG) Failure in High-Risk Non-muscle Invasive Bladder Cancer: A Review Article.

Kodera Ahmed A Mohammed Mahmoud M Lim Paul P Abdalla Omer O Elhadi Mohammed M

Cureus 20230626 6

Non-muscle invasive bladder cancer (NMIBC) is a common urological malignancy, and bacillus Calmette-Guérin (BCG) therapy is the gold standard treatment in intermediate and high-risk groups. However, BCG failure occurs in a significant proportion of patients, emphasizing the need for effective alternative treatment modalities to address this burden. These treatments include immunotherapy, enhanced drug delivery, targeted therapy, device-assisted chemotherapy, vaccine therapy, and gene therapy, wh ...[more]

PMID: 37503461

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Project description:ObjectivesThe treatments for high-grade non-muscle invasive bladder cancer (NMIBC) vary between bladder preserving intravesical approaches and radical cystectomy. The impact of these treatments on health-related quality of life may vary widely. The purpose of this study was to elicit the general public's perspective on quality of life, measured as utility scores associated with treatment for Bacillus Calmette-Guerin (BCG)-unresponsive NMIBC and disease progression, for supporting economic evaluation of newly developed treatments for NMIBC.Materials and methodsPart I involved the development and testing of health states describing NMIBC, which was informed by a rapid review, expert input and a patient advisor. Part II involved elicitation of societal utility values for the different health states. Time trade-off (TTO) interviews were conducted with members of the UK general public. Five health states described different NMIBC scenarios including disease recurrence and progression. Participants ranked each health state, followed by the TTO valuation exercise. Descriptors included NMIBC symptom severity, impact and treatment characteristics.ResultsIn total, 202 members of the general public participated. The mean age was 46 (standard deviation [SD] 14.6) years. Sample mean (SD) EQ-5D-5L visual analogue scale (VAS) and index scores were 83.2 (12.3) and 0.89 (0.18), respectively. Mean utilities were 0.781 for No High-Grade Recurrence, 0.586 for High-Grade Recurrence, 0.572 for > 1-Year Post-cystectomy and 0.283 for metastatic disease. The First Year Post-cystectomy path health state had a mean utility of 0.288. Pairwise comparisons found statistically significant differences between utilities (p < 0.001), except between High-Grade Recurrence and > 1-Year Post-cystectomy (p = 0.524). There were significant differences in utility scores by age and employment status.ConclusionThis study provides utility scores for health states describing living with NMIBC, which is associated with a significant health-related quality-of-life burden. These values address an existing gap in available data and have the potential to be used in models evaluating the cost-effectiveness of both current and newly developed treatments for bladder cancer.

Project description:BackgroundIntravesical Bacillus Calmette-Guerin (BCG) is an effective treatment for bladder superficial carcinoma and it is being tested in interstitial cystitis patients, but its precise mechanism of action remains poorly understood. It is not clear whether BCG induces the release of a unique set of cytokines apart from its pro-inflammatory effects. Therefore, we quantified bladder inflammatory responses and alterations in urinary cytokine protein induced by intravesical BCG and compared the results to non-specific pro-inflammatory stimuli (LPS and TNF-alpha). We went further to determine whether BCG treatment alters cytokine gene expression in the urinary bladder.MethodsC57BL/6 female mice received four weekly instillations of BCG, LPS, or TNF-alpha. Morphometric analyses were conducted in bladders isolated from all groups and urine was collected for multiplex analysis of 18 cytokines. In addition, chromatin immune precipitation combined with real-time polymerase chain reaction assay (CHIP/Q-PCR) was used to test whether intravesical BCG would alter bladder cytokine gene expression.ResultsAcute BCG instillation induced edema which was progressively replaced by an inflammatory infiltrate, composed primarily of neutrophils, in response to weekly administrations. Our morphological analysis suggests that these polymorphonuclear neutrophils are of prime importance for the bladder responses to BCG. Overall, the inflammation induced by BCG was higher than LPS or TNF-alpha treatment but the major difference observed was the unique granuloma formation in response to BCG. Among the cytokines measured, this study highlighted the importance of IL-1beta, IL-2, IL-3, IL-4, IL-6, IL-10, IL-17, GM-CSF, KC, and Rantes as discriminators between generalized inflammation and BCG-specific inflammatory responses. CHIP/Q-PCR indicates that acute BCG instillation induced an up-regulation of IL-17A, IL-17B, and IL-17RA, whereas chronic BCG induced IL-17B, IL-17RA, and IL-17RB.ConclusionTo the best of our knowledge, the present work is the first to report that BCG induces an increase in the IL-17 family genes. In addition, BCG induces a unique type of persisting bladder inflammation different from TNF-alpha, LPS, and, most likely, other classical pro-inflammatory stimuli.

Dataset Information

The Management of Bacillus Calmette-Guerin (BCG) Failure in High-Risk Non-muscle Invasive Bladder Cancer: A Review Article.

Publications

The Management of Bacillus Calmette-Guérin (BCG) Failure in High-Risk Non-muscle Invasive Bladder Cancer: A Review Article.

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