Bacillus Calmette-Guérin (BCG), a vaccine originally developed for tuberculosis, is also used to treat a specific type of bladder cancer. This attenuated strain of Mycobacterium bovis functions as immunotherapy, harnessing the body’s defenses. It aims to eliminate cancer cells within the bladder by stimulating a targeted immune response.
Mechanism of Action
When introduced into the bladder, the live, weakened bacteria in the BCG solution interact directly with bladder cancer cells and the bladder lining. This interaction prompts cancer cells to internalize BCG through a process called macropinocytosis. Once inside, BCG activates a localized immune response within the bladder.
The presence of BCG triggers the recruitment of immune cells, including macrophages and T lymphocytes, to the bladder wall. These cells release pro-inflammatory signaling molecules such as cytokines and chemokines, creating an inflammatory environment. This immune reaction attacks and destroys nearby bladder cancer cells, leading to direct cytotoxic effects and inducing programmed cell death (apoptosis).
The BCG Treatment Regimen
BCG treatment is administered directly into the bladder through a catheter. A liquid solution containing the BCG bacteria is slowly instilled after numbing the area with an anesthetic gel. Patients retain the solution in their bladder for one to two hours to allow interaction with the bladder lining.
The standard treatment often begins with an “induction course” of weekly instillations for six consecutive weeks. Following this initial phase, a “maintenance course” may be recommended to sustain the immune response and reduce cancer recurrence. Maintenance schedules vary but commonly involve three weekly treatments at specific intervals, such as months 3, 6, 12, 18, 24, 30, and 36 after induction. Before beginning BCG, all visible cancerous tissue is typically removed through transurethral resection of the bladder tumor (TURBT).
Potential Side Effects
Patients undergoing BCG treatment may experience a range of reactions, many of which are common and manageable. Flu-like symptoms, such as a low-grade fever, chills, fatigue, and body aches, are frequently reported and usually subside within two to three days after each treatment. These systemic symptoms often indicate the immune system is responding to the therapy.
Local bladder irritation is also common, manifesting as frequent or painful urination, urgency, and occasionally a small amount of blood in the urine. These bladder symptoms can feel similar to a urinary tract infection and may include bladder spasms. Simple pain relief medications, increased fluid intake, and sometimes muscle relaxants can help manage these discomforts.
While less common, more serious side effects can occur if the BCG bacteria enter the bloodstream, leading to a systemic infection known as BCGosis. Symptoms of a widespread infection include a persistent high fever, skin rash, cough, or joint pain, and require immediate medical attention. Due to the risk of infection, BCG is generally not recommended for individuals with compromised immune systems.
Efficacy and Patient Candidacy
BCG is an effective immunotherapy, primarily used for non-muscle invasive bladder cancer (NMIBC), especially high-risk forms such as carcinoma in situ (CIS). This treatment significantly reduces the risk of cancer recurrence and progression to more invasive stages. Studies indicate recurrence-free survival rates ranging from 61% to 75% at five years, with progression-free survival rates around 93%.
Patients with intermediate- or high-risk NMIBC are typically considered candidates for BCG therapy. However, certain conditions may make a person ineligible for treatment. Contraindications include an active urinary tract infection, visible blood in the urine, or a recent traumatic catheterization. Additionally, individuals with a compromised immune system, such as those with certain immunodeficiencies or undergoing immunosuppressive treatments, are generally advised against BCG due to the risk of systemic infection.