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Review
. 2024 Feb 16;31(2):1063-1078.
doi: 10.3390/curroncol31020079.

BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer

Sarah Lidagoster  1   2 , Reuben Ben-David  1 , Benjamin De Leon  1   3 , John P Sfakianos  1
Affiliations
Review

BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer

Sarah Lidagoster et al. Curr Oncol. .

Abstract

Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to resect the tumor endoscopically will usually be followed by different intravesical instillations. The goal of intravesical therapy is to decrease the recurrence and/or progression of the tumor. In the current landscape of bladder cancer treatment, BCG is given intravesically to induce an inflammatory response and recruit immune cells to attack the malignant cells and induce immune memory. While the response to BCG treatment has changed the course of bladder cancer management and spared many "bladders", some patients may develop BCG-unresponsive disease, leaving radical surgery as the best choice of curative treatment. As a result, a lot of effort has been put into identifying novel therapies like systemic pembrolizumab and Nadofaragene-Firadenovac to continue sparing bladders if BCG is ineffective. Moreover, recent logistic issues with BCG production caused a worldwide BCG shortage, re-sparking interest in alternative BCG treatments including mitomycin C, sequential gemcitabine with docetaxel, and others. This review encompasses both the historic and current role of BCG in the treatment of non-muscle-invasive bladder cancer, revisiting BCG alternative therapies and reviewing the novel therapeutics that were approved for the BCG-unresponsive stage or are under active investigation.

Keywords: BCG; BCG failure; bladder cancer; intravesical therapy.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
BCG mechanism of action to induce immune response [17].
Figure 2
Figure 2
Current and future landscape of available treatments for non-muscle-invasive bladder cancer. Some therapies like BCG and MMC are not seen. All those shown are given through intravesical instillation (except pembrolizumab, which is given systemically). Drugs that are found in bold text are already approved for treatment; non-bolded drugs are under active investigation and have shown promising results (ALT-803, CG0070). Note: Created with BioRender.
See this image and copyright information in PMC

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