Bacillus Calmette-Guérin (BCG) immunotherapy is the established, first-line treatment for non-muscle-invasive bladder cancer (NMIBC). This powerful immunotherapy harnesses the body’s own defense systems to fight cancer, unlike chemotherapy. Derived from a weakened strain of the bacterium used in the tuberculosis vaccine, BCG is utilized to reduce the risk of cancer recurrence and progression in the bladder lining.
Understanding BCG’s Role in Bladder Cancer Treatment
Bacillus Calmette-Guérin is a live, attenuated form of Mycobacterium bovis, a close relative of the bacteria that causes tuberculosis. It is primarily used for high-risk NMIBC, including high-grade tumors and Carcinoma in Situ (CIS), an aggressive, flat form of the disease lining the bladder wall. BCG works as a localized immune stimulant, triggering a vigorous inflammatory response within the bladder.
The mechanism begins when BCG attaches to the urothelial cells lining the bladder and is internalized by both cancer and immune cells. This invasion acts as a pathogen-associated molecular pattern (PAMP), activating the body’s pattern recognition receptors (PRRs) on immune cells. This cascade involves the recruitment of immune cells, such as neutrophils, macrophages, and T-lymphocytes, to the bladder wall.
These activated immune cells release cytokines, including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-gamma (IFN-γ). These signaling molecules destroy the cancer cells lining the bladder. The goal is to create a sustained, localized immune memory that recognizes and eliminates future cancer cells, reducing the likelihood of recurrence or progression.
The Intravesical BCG Treatment Process
BCG is administered via intravesical instillation, meaning the liquid drug is delivered directly into the bladder using a thin, flexible tube called a catheter. The procedure typically begins after a transurethral resection of the bladder tumor (TURBT) has removed all visible disease and the bladder has sufficiently healed. Before the instillation, patients may be asked to limit fluid intake to ensure the BCG is not diluted in the bladder.
The initial course of treatment, known as the Induction phase, consists of one instillation per week for six consecutive weeks. After the BCG solution is placed into the bladder, the catheter is removed, and the patient is instructed to retain the liquid for as long as possible, typically for one to two hours, to maximize contact with the bladder lining. During this retention period, patients may be asked to change positions periodically to ensure the solution coats the entire bladder surface.
Following the Induction phase, patients who respond well proceed to a Maintenance phase, which is crucial for long-term success. This involves periodic, shorter courses, often consisting of three weekly instillations at scheduled intervals (e.g., at three, six, and twelve months). This maintenance schedule can continue for up to three years, as ongoing stimulation is required to sustain the anti-tumor immune response and prevent recurrence.
Expected Side Effects and Patient Monitoring
The local immune stimulation triggered by BCG often results in a range of expected side effects, which are generally temporary and manageable. The most common local effect is cystitis, or inflammation of the bladder, leading to symptoms that mimic a urinary tract infection. Patients frequently experience painful urination, increased urgency, and a need to urinate more often (dysuria and frequency).
Systemic side effects are also common and are indicative of the body’s immune system being activated. These often resemble flu-like symptoms, including low-grade fever, chills, fatigue, and muscle or joint pain, which usually begin within hours of the treatment. These temporary effects typically resolve within two to three days following the instillation.
Because BCG contains live, albeit weakened, bacteria, patients must take safety precautions following treatment to prevent transmission. Patients should urinate while sitting to minimize splashing and thoroughly wash their hands afterward. It is recommended to flush the toilet twice, and some centers suggest using bleach in the toilet after voiding for the first six hours. Although rare, a severe complication is systemic BCG sepsis, which requires immediate medical attention and is signaled by a high fever unresponsive to over-the-counter medication.
Treatment Response and Alternative Strategies
The efficacy of BCG is monitored closely after the induction phase is complete. The primary follow-up methods include cystoscopy, where a camera is used to visually inspect the bladder lining for new tumors, and urine cytology, which checks for the presence of cancer cells in the urine. Treatment is considered a success if the physician observes no sign of tumor recurrence.
Despite being the standard treatment, approximately one-third of patients with NMIBC will not respond to BCG, and about half of initial responders will eventually experience a recurrence. When the cancer persists or recurs after an adequate course of BCG, the disease is classified as BCG-unresponsive. This failure necessitates a change in strategy to prevent the cancer from progressing to a more dangerous, muscle-invasive stage.
The next step for patients with BCG-unresponsive disease involves alternative intravesical agents or systemic immunotherapies. Options include combination intravesical chemotherapy, such as sequential gemcitabine and docetaxel, or new agents like the PD-1 inhibitor pembrolizumab. For aggressive cases, or if alternative therapies fail, the definitive treatment remains radical cystectomy (surgical removal of the bladder).