Bacillus Calmette‐Guérin immunotherapy for genitourinary cancer

Abstract

What's known on the subject? and What does the study add? The administration of Bacillus Calmette‐Guérin (BCG) immunotherapy has become the standard of care for high‐grade non‐muscle invasive bladder cancer (NMIBC) and carcinoma in‐situ (CIS) in terms of prevention of recurrence and progression. While most agree on a 6 week induction cycle, various maintenance schedules (if any at all) have been implemented without a unifying consensus. This review assesses the historical emergence of BCG immunotherapy, beginning with its discovery as a vaccinatin for tuberculosis to its effect on the host immune system and potential therapeutic benefits for various oncologic conditions. The data establishing BCG immunotherapy as the standard of care for high‐grade NMIBC and CIS over other bladder instillation modalities is presented in addition to the effect maintenance BCG therapy has on sustaining the immuno‐protective effect. Bacillus Calmette‐Guérin (BCG) immunotherapy is currently the most effective treatment of non‐muscle invasive bladder cancer and one of the most successful applications of immunotherapy to the treatment of cancer. This review summarises the history and development of BCG as a modern cancer treatment, appraises current optimal application of BCG immunotherapy in bladder cancer, discusses promising new therapies closely related to BCG, and briefly explores the possibility that BCG or related treatments may have an application in other urological malignancies. BCG is a nonspecific stimulant to the reticuloendothelial system and induces a local inflammatory response with the infiltration of granulocytes followed by macrophages and lymphocytes, particularly helper T cells. The initial BCG controlled trial showed a statistically significant reduction in tumour recurrence and found the advantage increased with duration of follow‐up. Similar results were reported in much higher risk patients in an independent concurrent study. Follow‐up suggested that a single 6‐week course of intravesical BCG provided long‐term protection (up to 10 years) from tumour recurrence and even reduced disease progression. While induction BCG (six weekly instillations) reduced recurrence, progression and mortality at 10 years, this advantage was lost by 15 years, and patients remained at high risk for progression without the use of maintenance BCG. In a meta‐analysis by the Cochrane group, induction BCG was found to be markedly superior to mitomycin C in high‐risk patients but not in low‐risk patients. Additionally, the National Comprehensive Cancer Network guidelines lists the use of intravesical BCG as preferred therapy, citing Category 1 data for high‐grade Ta, all T1, and any Tis tumours. Maintenance BCG therapy may be the most important advance in BCG treatment of bladder cancer since the initial introduction. The risk of tumour recurrence and disease progression is life‐long in most patients, but the immune stimulation induced by BCG wanes with time. Logarithmic dose reduction of BCG in patients with increasing side‐effects wi...

Intravesical bacillus Calmette-Guérin versus chemohyperthermia for high-risk non-muscle-invasive bladder cancer

“…6 Even though new treatments have been reported, more results and larger studies are needed. 6,12,[14][15][16] Colombo and colleagues found that C-HT is more effective than MMC alone. 17 The 10-year disease-free survival rate for C-HT and MMC alone were 53% and 15%, respectively.…”

Consensus statement on best practice management regarding the use of intravesical immunotherapy with BCG for bladder cancer

“…The most commonly used treatment, repeated 6week instillations, has been found to be ineffective in one RCT. 13 Five RCTs com pared non3week maintenance schedules to BCG induction only (Table 1). [14][15][16][17][18] None of these alternative maintenance schedules showed a statistically significant reduction in recurrence (range -4% to 22%, average 7%).…”

BCG Immunotherapy for Bladder Carcinoma

“…However, other idea is that the profound effect of BCG on stimulation of the immune system is well recognized 6,7 . Evidence to date supports the idea that the antitumor effects of BCG are produced by an interplay between the direct effects on tumor cells by BCG infection and the host's immune response 8 .…”