BCG-unresponsive high-grade non-muscle invasive bladder cancer: what does the practicing urologist need to know?

Lebâcle, C.; Loriot, Yohann; Irani, Jacques

doi:10.1007/s00345-021-03666-w

Cited by 22 publications

(25 citation statements)

References 49 publications

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“…The current study ( 40 , 43 , 44 ) found that trained immunity was one of the key mechanisms of BCG immunotherapy and might provide protection against COVID-19, which may explain why “SARS-CoV-2” may be a potential research direction from Figure 7B . Furthermore, the possibility of combining BCG with other therapies, such as ICIs ( 45 , 46 ), is gaining increasing interest, and more researches are required to develop new strategies.…”

Section: Discussionmentioning

confidence: 99%

The global research of bladder cancer immunotherapy from 2012 to 2021: A bibliometric analysis

Qiu

Deng²,

Li³

et al. 2022

Front. Oncol.

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Intravesical instillation of Bacillus Calmette-Guérin has been used as an immunotherapy to treat superficial bladder cancer for almost half a century. In recent years, the approval of several monoclonal antibody treatments has transformed the treatment landscape for patients with muscle-invasive or metastatic uroepithelial carcinoma. The purpose of this study was to conduct a thorough review of immunotherapy in bladder cancer through a bibliometric approach. Publications related to bladder cancer immunotherapy were obtained from the Web of Science Core Collection on July 1st, 2022. We conducted a bibliometric analysis of literature information using CiteSpace IV, VOSviewer, and Scimago Graphica, including co-authorship or co-citation of authors, countries/regions, journals, references, and keyword co-occurrence. There was a total of 2,352 papers included, with the most contributions coming from the United States, China, and Italy. The United States had the highest H-index value and was the leading country in this field. Meanwhile, the number of publications in China was steadily growing. The top three productive researchers were Kamat AM, Necchi A, and Shariat SF, with Powles T as the top co-cited author. Most papers were published by the University of Texas System. The majority of papers in this field were published in Urologic Oncology Seminars and Original Investigations and European Urology was the most influential journal with the highest H-index. The tumor microenvironment and complete molecular characterization may still be the frontier in this research area, allowing us to obtain a better understanding of the pathogenesis and clinical prognosis of bladder cancer. More research are conducted to identify clinically meaningful biomarkers that may provide opportunities for the personalization of bladder cancer therapy. This study provides clinicians and researchers with an overview and helpful guidance on how to choose the research direction and management of bladder cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

The global research of bladder cancer immunotherapy from 2012 to 2021: A bibliometric analysis

Qiu

Deng²,

Li³

et al. 2022

Front. Oncol.

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“…Furthermore, many patients refuse to undergo radical cystectomy or are not suitable for the procedure due to presence of comorbidities or advanced age (9). Intravesical chemotherapy is another treatment option but is less effective at preventing recurrence and progression (10).…”

Section: Introductionmentioning

confidence: 99%

Treatment patterns and outcomes of BCG-treated non-muscle invasive bladder cancer patients in Germany

Doobaree¹,

Quignot²,

Jiang³

et al. 2023

Preprint

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Background: Non-muscle-invasive bladder cancer (NMIBC) has a high rate of recurrence and progression. Nearly half of patients become unresponsive to guideline-recommended intravesical Bacillus Calmette-Guérin (BCG) treatment. We aimed to describe contemporary treatment patterns and outcomes of BCG-treated patients in Germany. Methods: This observational, retrospective cohort study using German statutory health insurance data included NMIBC patients who received BCG instillation between 1st January 2012 and 31st December 2017. Patients were followed from BCG initiation for treatment patterns and from final BCG instillation for recurrence, progression to muscle-invasive bladder cancer (MIBC), death or end of follow-up (31st December 2019). Results: Most of the BCG-treated cohort (N=1,049) were male with a mean age of 70.4 years. Overall, patients received a median (interquartile range) of 12.0 (6.0 – 18.0) BCG instillations over a median duration of 9.8 (2.3 – 21.3) months. After receipt of their final BCG instillation (median follow-up from final BCG instillation: 2.5 years), 57% of patients did not receive any further treatment while 11% had at least one evidence record of NMIBC recurrence and 30% progressed to MIBC. Among the 353 patients who received treatment following their final BCG instillation, 33% received mitomycin and 37% underwent a radical cystectomy. Conclusions: A substantial proportion of patients with NMIBC who received further treatment after their final BCG instillation underwent a radical cystectomy, and one third were treated with mitomycin; treatment options after mitomycin varied. Findings from this study suggest an unmet need for optimal treatments for BCG-unresponsive patients who are at higher risk of recurrence but unable or unwilling to undergo radical cystectomy.

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“…The current first-line therapy for NMIBC (intermediate-and high-risk papillary tumors and carcinoma in situ) consists in intravesical instillations of Bacillus Calmette-Guerin (BCG) as it significantly reduces the risk of progression to muscle invasive disease as it significantly reduces the risk of progression to muscle invasive disease. However, the high recurrence rate necessitates radical cystectomy or enrollment in clinical trials (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint and Telomerase Crosstalk Is Mediated by miRNA-138 in Bladder Cancer

et al. 2022

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BackgroundTumor recurrence and progression in non-muscle invasive bladder cancer (NMIBC), therapy failure, and severe side effects in muscle invasive bladder cancer (MIBC) are the major challenges in the clinical management of bladder cancer (BC). Here, we identify new molecular targetable signatures to improve BC patients’ stratification and the outcome of current immunotherapies.Material and MethodsIn a prospective cohort of 70 BC patients, we assessed the genetic and molecular regulation of TERT in maintaining telomere length in parallel to immune checkpoint and microRNA expression.ResultsTERT was undetectable in healthy bladder tissues but upregulated in invasive BC stages and high tumor grade. Its expression was linked with the combined effect of the C250T mutation and THOR hypermethylation, associated with progressing tumors and maintaining of telomere length. In the same cohort, PD-L1 scored highest in NMIBC, while PD-L2 was upregulated in MIBC. We also show that miR-100-5p and 138-5p were highly expressed in healthy bladder specimens and cell line, while expression decreased in the BC tissues and BC cell lines. In line with the binding prediction for these miRNAs on target genes, miRs 100-5p and 138-5p expression strongly inverse correlated with TERT, PD-L1, and PD-L2 expression, but not PD1.ConclusionWe identify a loop involving TERT, PD1-ligands, and miR-138-5p in BC, that might represent not only a useful biomarker for improved diagnosis and patients’ stratification but also as a promising axis that might be therapeutically targeted in situ.

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BCG-unresponsive high-grade non-muscle invasive bladder cancer: what does the practicing urologist need to know?

Cited by 22 publications

References 49 publications

The global research of bladder cancer immunotherapy from 2012 to 2021: A bibliometric analysis

The global research of bladder cancer immunotherapy from 2012 to 2021: A bibliometric analysis

Treatment patterns and outcomes of BCG-treated non-muscle invasive bladder cancer patients in Germany

Immune Checkpoint and Telomerase Crosstalk Is Mediated by miRNA-138 in Bladder Cancer

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