Critical shortage in BCG immunotherapy: How did we get here and where will it take us?

Harvey, Michael; Chislett, Bodie; Perera, Marlon; Lawrentschuk, Nathan; Bolton, Damien; Jack, Gregory S.

doi:10.1016/j.urolonc.2021.09.022

Cited by 19 publications

(9 citation statements)

References 15 publications

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“…The past decade has seen international shortages of BCG, mainly related to difficulty in scaling up production in the face of fewer approved manufacturers and growing demand [130]. Given these shortages, instillation of a reduced dose of BCG has been proposed.…”

Section: Current Treatment Schedule Guidelinesmentioning

confidence: 99%

BCG in Bladder Cancer Immunotherapy

Jiang

Redelman-Sidi

2022

Cancers

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BCG is a live attenuated strain of Mycobacterium bovis that is primarily used as a vaccine against tuberculosis. In the past four decades, BCG has also been used for the treatment of non-muscle invasive bladder cancer (NMIBC). In patients with NMIBC, BCG reduces the risk of tumor recurrence and decreases the likelihood of progression to more invasive disease. Despite the long-term clinical experience with BCG, its mechanism of action is still being elucidated. Data from animal models and from human studies suggests that BCG activates both the innate and adaptive arms of the immune system eventually leading to tumor destruction. Herein, we review the current data regarding the mechanism of BCG and summarize the evidence for its clinical efficacy and recommended indications and clinical practice.

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Section: Current Treatment Schedule Guidelinesmentioning

confidence: 99%

BCG in Bladder Cancer Immunotherapy

Jiang

Redelman-Sidi

2022

Cancers

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“…Decreasing resistance and improving responsiveness to BCG therapy is particularly critical to decreasing morbidity and mortality from bladder cancer due to the current shortage of BCG, which has led many clinicians to strategize on how to conserve doses. 48 Nevertheless, the limited reserve of BCG has generated an opportunity to accelerate research and clinical trials exploring the relationship between the urinary tract microbiome and urothelial carcinoma. For example, the SILENTEMPIRE trial plans to investigate signatures in urinary and gut microbial profiles of NMIBC patients as predictors for BCG therapy response.…”

Section: Applications To Urothelial Carcinomamentioning

confidence: 99%

Examining the Role of Microbiota-Centered Interventions in Cancer Therapeutics: Applications for Urothelial Carcinoma

Drobner

Lichtbroun

Singer

et al. 2023

Technol Cancer Res Treat

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Modern advances in genomic and molecular technologies have sparked substantial research on the human intestinal microbiome over the past decade. A deeper understanding of the microbiome has illuminated that dysbiosis, or a disruption in the microbiome, is associated with inflammatory disease states and carcinogenesis. Novel therapies that target the microbiome and restore healthy flora may have value in dampening the immunopathologic state induced by dysbiosis. A narrative review of the literature on the use of microbiota-centered interventions (MCIs) was conducted. Several randomized clinical trials show that MCIs can augment response to immune checkpoint inhibitor (ICI) therapy in patients with metastatic cancer. Clinical trials have also demonstrated that modulation of the intestinal microbiome can enhance recovery and reduce infectious complications in the surgical management of colorectal adenocarcinoma. Overall, these major discoveries suggest future clinical applications of MCIs for a wide range of immune-mediated conditions. These results may also translate to improved patient outcomes in systemic immunotherapy for urothelial carcinoma as well as in patients recovering from radical cystectomy (RC), which is complicated by high infection rates. Further research is needed to evaluate the optimal bacterial composition of microbiota-centered therapies and the specific cellular changes that lead to improved tumor antigen recognition after microbiota-centered therapies.

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“…This may also have an impact on the methods of instillation of upper urinary tract carcinoma topical therapy agents 38 with differing volumes needed to overcome the instrument dead space, particularly in periods of worldwide shortage. 41,42 Prior studies have evaluated ureteroscope parameters such as irrigation flow, 29,30 direct in scope suction, 17 intrarenal pressure, 43,44 and dust particle size aspirated. 16,31 How IDS impacts these parameters is of high interest and certainly TherapeuTic advances in urology deserves future evaluation in separate studies.…”

Section: Therapeutic Advances In Urologymentioning

confidence: 99%

Instrumental dead space and proximal working channel connector design in flexible ureteroscopy: a new concept

Kwok

Coninck

Pietropaolo

et al. 2023

Therapeutic Advances in Urology

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Objective: The objective of this study was to evaluate a new concept in flexible ureteroscopy: instrumental dead space (IDS). For this purpose, various proximal working channel connector designs, as well as the impact of ancillary devices occupying the working channel were evaluated in currently available flexible ureteroscopes. Design and methods: IDS was defined as the volume of saline irrigation needed to inject at the proximal connector for delivery at the distal working channel tip. Because IDS is related to working channel diameter and length, proximal connector design, as well as occupation of working channel by ancillary devices, these parameters were also reviewed. Results: IDS significantly varied between flexible ureteroscope models, ranging from 1.1 ml for the Pusen bare scopes, to 2.3 ml for Olympus scopes with their 4-way connector ( p < 0.001). Proximal connector designs showed a high degree of variability in the number of available Luer locks, valves, seals, angles, and rotative characteristics. The measured length of the working channel of bare scopes ranged between 739 and 854 mm and significantly correlated with measured IDS ( R2 = 0.82, p < 0.001). The coupling of scopes with an alternative ancillary proximal connector and the insertion of ancillary devices into the working channel significantly reduced IDS (mean IDS reduction of 0.1 to 0.5 ml; p < 0.001). Conclusions: IDS appears as a new parameter that should be considered for future applications of flexible ureteroscopes. A low IDS seems desirable for several clinical applications. The main factors impacting IDS are working channel and proximal connector design, as well as ancillary devices inserted into the working channel. Future studies should clarify how reducing IDS may affect irrigation flow, intrarenal pressure, and direct in-scope suction, as well as evaluate the most desirable proximal connector design properties.

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Critical shortage in BCG immunotherapy: How did we get here and where will it take us?

Cited by 19 publications

References 15 publications

BCG in Bladder Cancer Immunotherapy

BCG in Bladder Cancer Immunotherapy

Examining the Role of Microbiota-Centered Interventions in Cancer Therapeutics: Applications for Urothelial Carcinoma

Instrumental dead space and proximal working channel connector design in flexible ureteroscopy: a new concept

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