The use of intravesical BCG in urothelial carcinoma of the bladder

Abstract

The high recurrence and progression rates of non-muscle invasive bladder cancer (NMIBC) have led investigators to study the use of intravesical therapy in order to prevent them. Bacillus Calmette–Guérin (BCG) has been successfully used for this indication to treat NMIBC for more than four decades.BCG is the only intravesical agent shown to reduce the risk of progression of NMIBC to muscle-invasive disease. Despite over 40 years of clinical use, the precise mechanism of action for what has often been considered the most successful cancer immunotherapy in humans remains largely unknown.Unfortunately, BCG therapy is not a universal panacea and it still fails in up to 40% of patients. Many of these patients, especially in the high-risk category (T1 high-grade disease, carcinoma in situ) will require aggressive therapy like cystectomy or in selected cases, bladder-sparing options like chemo-radiation. Indeed, there is no gold standard intravesical treatment after BCG failure.

BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?

“…Subsequently, BCG was shown to exhibit protective effects against leprosy, buruli ulcer, and several other diseases, including those not associated with mycobacteria 28,29 . BCG is a potent immunomodulator, especially of the cell-mediated immunity, and is employed for the treatment of cancers such as that of the bladder 30 . It is actually being tested for several other cancers 31 .…”

Bacille Calmette-Guérin (BCG) vaccine and the COVID-19 pandemic: responsible stewardship is needed

“…9 These non-specific immunological effects of BCG are used to treat bladder carcinoma in adults. 10 A recent ecological study (yet to be peer-reviewed), has been widely disseminated in the general and social media, and claims a possible association between BCG vaccination and protection against severe disease and fatal outcome from SARS-CoV-2 infection (i.e., ). 11 This paper provides interesting circumstantial evidence but does not confirm causality.…”

Systematic Review: Safety of Intravesical Therapy for Bladder Cancer in the Era of COVID-19

“…[9] BCG first attaches to the urothelium via fibronectin and integrins and is then internalized by urothelial cells and captured by the initial innate immune response. [17] It is then that antigen presentation and cytokine release results in the upregulation of major histocompatibility complex (MHC) II, IL-6, Il-8 and granulocytemacrophage colony-stimulating factor (GM-CSF). [17] This stimulates local recruitment of immune cells such as granulocytes, CD4 and CD8 T cells, natural killer (NK) cells and macrophages that produce TH-1 cytokines.…”

“…[17] It is then that antigen presentation and cytokine release results in the upregulation of major histocompatibility complex (MHC) II, IL-6, Il-8 and granulocytemacrophage colony-stimulating factor (GM-CSF). [17] This stimulates local recruitment of immune cells such as granulocytes, CD4 and CD8 T cells, natural killer (NK) cells and macrophages that produce TH-1 cytokines. [17] According to Prescott et al, [18] the antitumor activity of BCG in bladder cancer appears to be a local phenomenon confined to the site of administration.…”

“…[17] This stimulates local recruitment of immune cells such as granulocytes, CD4 and CD8 T cells, natural killer (NK) cells and macrophages that produce TH-1 cytokines. [17] According to Prescott et al, [18] the antitumor activity of BCG in bladder cancer appears to be a local phenomenon confined to the site of administration. In another study, peripheral blood mononuclear cells (PBMC), urine and serum were obtained from patients with superficial carcinoma at various times during the course of BCG instillation, and found an increase in systemic immune activity.…”