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 will 
typically prevent escalation of toxicity. Simple dose reduction, appropriate 
antibiotics, and understanding treatment contraindications have greatly 
increased the safety of BCG. The 3-week maintenance schedule for 3 years has 
been evaluated in randomised clinical trials and appears to be the current 
optimal treatment. With the success achieved in bladder cancer and the relative 
safety and economy of BCG, consideration should be given to further research for 
its effectiveness in other genitourinary malignancies.