Current advances in BCG-unresponsive non-muscle invasive bladder cancer

Tse, Jennifer; Singla, Nirmish; Ghandour, Rashed; Lotan, Yair; Margulis, Vitaly

doi:10.1080/13543784.2019.1655730

Cited by 27 publications

(26 citation statements)

References 103 publications

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“…60 Moreover, a Phase III trial is currently evaluating the antitumor activity of a recombinant adenovirus that is able to transduce IFN-α into cancer cells with a polyamide surfactant to facilitate adherence. 61 Due to the initial results in some studies demonstrating good response, we are waiting with high enthusiasm the coming results.…”

Section: Virus-based Treatmentsmentioning

confidence: 99%

<p>Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update</p>

Guallar-Garrido

Julián

2020

ITT

142

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Physicians treating patients affected by nonmuscle-invasive bladder cancer (NMIBC) have been in shock during the last six years since manufacturing restrictions on the production of the first-option medicine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), have resulted in worldwide shortages. This shortage of BCG has led to a rethinking of the established treatment guidelines for the rationing of the administration of BCG. Some possible schedule modifications consist of a decrease in the length of maintenance treatment, a reduction in the dose of BCG in intravesical instillations or the use of different BCG substrains. All these strategies have been considered valuable in times of BCG shortage. In addition, the lack of availability of BCG has also led to the general recognition of the need to find new treatment options for these patients so that they are not dependent on a single treatment. Few alternatives are committed to definitively replacing BCG intravesical instillations, but several options are being evaluated to improve its efficacy or to combine it with other chemotherapeutic or immunotherapeutic options that can also improve its effect. In this article, we review the current state of the treatment with BCG in terms of all of the aforementioned aspects.

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Section: Virus-based Treatmentsmentioning

confidence: 99%

<p>Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update</p>

Guallar-Garrido

Julián

2020

ITT

142

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“…Many BC trials are exploring immunotherapy, vaccines, chemotherapy, or gene therapy efficacy for BCG-unresponsive disease, advanced, recurrent, and metastatic BC. For a comprehensive list of drugs for several BC phenotypes, see Butt and Malik (2018), Rouanne et al (2018), and Soria et al (2019), while for specific NMIBCs, BCG-unresponsive, see Tse et al (2019). We included some clinical trials from no.…”

Section: Immunotherapy Of Bladder Cancer: New Frontiersmentioning

confidence: 99%

“…-Viruses can be delivered into the bladder through the current procedures and can have higher effectivity than BCG; by targeting specifically cancer cells, viruses could reduce adverse events compared with the use of the bacillus (Taguchi et al, 2017). Several ongoing clinical trials are testing this promising new strategy (Tse et al, 2019). -Bacteria utilization could be another possible strategy in the unresponsive NMIBC or in NMIBC patients who have developed side effects.…”

Section: Bacillus Calmette-guérin Unresponsive Patients: New Treatmentsmentioning

confidence: 99%

New Roadmaps for Non-muscle-invasive Bladder Cancer With Unfavorable Prognosis

et al. 2020

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About 70% of bladder cancers (BCs) are diagnosed as non-muscle-invasive BCs (NMIBCs), while the remaining are muscle-invasive BCs (MIBCs). The European Association of Urology (EAU) guidelines stratify NMIBCs into low, intermediate, and high risk for treatment options. Low-risk NMIBCs undergo only the transurethral resection of the bladder (TURB), whereas for intermediate-risk and high-risk NMIBCs, the transurethral resection of the bladder (TURB) with or without Bacillus Calmette-Guérin (BCG) immune or chemotherapy is the standard treatment. A minority of NMIBCs show unfavorable prognosis. High-risk NMIBCs have a high rate of disease recurrence and/or progression to muscle-invasive tumor and BCG treatment failure. The heterogeneous nature of NMIBCs poses challenges for clinical decision-making. In 2020, the EAU made some changes to NMIBCs BCG failure definitions and treatment options, highlighting the need for reliable molecular markers for improving the predictive accuracy of currently available risk tables. Nowadays, next-generation sequencing (NGS) has revolutionized the study of cancer biology, providing diagnostic, prognostic, and therapy response biomarkers in support of precision medicine. Integration of NGS with other cutting-edge technologies might help to decipher also bladder tumor surrounding aspects such as immune system, stromal component, microbiome, and urobiome; altogether, this might impact the clinical outcomes of NMBICs especially in the BCG responsiveness. This review focuses on NMIBCs with unfavorable prognoses, providing molecular prognostic factors from tumor immune and stromal cells, and the perspective of urobiome and microbiome profiling on therapy response. We provide information on the cornerstone of immunotherapy and new promising bladder-preserving treatments and ongoing clinical trials for BCG-unresponsive NMIBCs.

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“…Die klinische SAKK 06/14-Studie dazu ist abgeschlossen aber noch nicht publiziert. Weiterhin werden onkolytische Viren betrachtet; so untersucht eine Phase III-Studie einen adenoviralen Vektor von Interferon-alpha in BCG-resistentem Hochrisiko-NMIBC [15].…”

Section: Künftige Entwicklungen Und Fazitunclassified

“…Auch die Check-Point-Blockade-Inhibition wurde klinisch evaluiert, so der PD-1 Inhibitor Pembrolizumab; während die KEYNOTE-676-Studie BCG alleine vs. einer Kombination von BCG und Pembrolizumab untersucht, wurde in der einarmigen KEYNOTE-057-Studie bei etwa 100 Patienten mit BCG-resistentem CIS eine komplette Responserate von 41 % und ein mittleres Ansprechen über 16 Monate gezeigt, was zu einer FDA-Zulassung für das BCG-resistente Hochrisiko-NMIBC führte [15] und weitere immuntherapeutische Ansätze werden aktuell untersucht.…”

Section: Künftige Entwicklungen Und Fazitunclassified

Das Hochrisiko-nicht-muskelinvasive-Harnblasenkarzinom (HR-NMIBC) in Zeiten des BCG-Mangels: was für Optionen haben wir?

Burger

2020

Aktuelle Urol

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ZusammenfassungDas Hochrisiko-NMIBC ist eine Herausforderung, da es zwar noch nicht muskelinvasiv ist, aber eine hohe Progressionsneigung aufweist. Eine Erfassung der Prognosegruppe ist wichtig und über Nomogramme empfohlen. Neben einer gründlichen transurethralen Resektion empfiehlt sich eine adjuvante Therapie mit BCG, was momentan teils aber nur eingeschränkt verfügbar ist. Daneben ist eine hypertherme Chemotherapie untersucht, deren Datenbasis zum jetzigen Zeitpunkt aber keine breite Anwendung rechtfertigt. Neue Ansätze wie die Checkpoint-Blockade-Inhibition werden untersucht, bieten aber keine Möglichkeit zur breiten praktischen Anwendung bei uns. Eine radikale Zystektomie ist daher in Anbetracht der hohen Progressionsneigung bei ungünstiger Tumorkonstellation immer zu indizieren.

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Current advances in BCG-unresponsive non-muscle invasive bladder cancer

Cited by 27 publications

References 103 publications

<p>Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update</p>

<p>Bacillus Calmette-Guérin (BCG) Therapy for Bladder Cancer: An Update</p>

New Roadmaps for Non-muscle-invasive Bladder Cancer With Unfavorable Prognosis

Das Hochrisiko-nicht-muskelinvasive-Harnblasenkarzinom (HR-NMIBC) in Zeiten des BCG-Mangels: was für Optionen haben wir?

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