Bacillus Calmette-Guérin (BCG) is the standard immunotherapy used to treat non-muscle-invasive bladder cancer (NMIBC), which represents approximately 75% of new bladder cancer diagnoses. This treatment is often administered after the initial surgical removal of the tumor, a procedure known as transurethral resection of bladder tumor (TURBT). BCG is considered the most effective agent for reducing the risk of cancer recurrence and preventing the disease from advancing to a more dangerous stage.
Understanding BCG Therapy
BCG is a live, attenuated strain of Mycobacterium bovis, the same bacteria used in the tuberculosis vaccine. This preparation is not a traditional chemotherapy drug that directly kills cancer cells; instead, it functions as an immunotherapy. The goal of BCG is to stimulate a powerful immune response within the bladder lining to specifically target and destroy cancer cells.
The treatment is administered intravesically. Once inside the bladder, the bacteria adhere to the bladder wall and are internalized by cancer cells. This process recruits various immune cells, such as T-cells and natural killer cells, to the site to launch a localized attack against the malignant cells.
BCG is typically reserved for patients with intermediate- or high-risk NMIBC. The therapy begins with an “induction” phase, which involves six weekly instillations of the drug. This is followed by a “maintenance” regimen consisting of three weekly treatments given at specific intervals over one to three years. Maintenance therapy is important for high-risk patients, providing a prolonged immune stimulus to suppress tumor growth.
Measuring Treatment Success
The success of BCG therapy is measured by two primary outcomes: preventing the cancer from returning (recurrence prevention) and preventing the cancer from invading the deeper muscle layer of the bladder wall (progression prevention). BCG is significantly more effective than surgery alone or intravesical chemotherapy at reducing both recurrence and progression risk.
For high-risk patients, the chance of remaining recurrence-free after five years with BCG treatment generally falls in the range of 40% to 70%, depending on the specific tumor characteristics. For instance, studies focusing on Carcinoma in Situ (CIS), a high-grade surface cancer, have shown that BCG can effectively clear the cancer in up to 70% of patients. However, recurrence remains a possibility, with up to 40% of patients experiencing the return of cancer at some point after treatment.
Progression prevention rates often exceed 85% at three to five years. The effectiveness of the treatment is strongly influenced by the patient’s adherence to the full maintenance schedule, as incomplete treatment significantly reduces long-term protection against recurrence. Tumor factors such as size, grade, and the presence of multifocal disease also influence the likelihood of a successful outcome.
Managing Side Effects
Since BCG is a live bacterium designed to provoke a strong immune response, side effects are common. The most frequently reported adverse effects are localized to the bladder and mimic the symptoms of a urinary tract infection. Patients often experience frequent urination, urgency, a burning sensation during urination (dysuria), and sometimes a small amount of blood in the urine (hematuria).
These symptoms typically begin shortly after the instillation and usually resolve within 48 hours. Patients also experience systemic, flu-like symptoms, such as a low-grade fever, chills, fatigue, and muscle or joint aches. Management often involves over-the-counter pain relievers, such as acetaminophen or non-steroidal anti-inflammatory drugs, and increased fluid intake.
More serious complications are rare, occurring in less than one percent of patients. These include a systemic BCG infection, known as BCG sepsis, which happens if the bacteria enters the bloodstream. BCG sepsis requires immediate treatment with multiple anti-tuberculosis medications, called tuberculostatics, often combined with corticosteroids. To minimize the risk of severe complications, the instillation is postponed if the patient has a urinary tract infection or any trauma to the bladder lining from recent procedures.
Alternative Treatments After BCG
If bladder cancer returns or persists despite adequate BCG therapy, the disease is classified as BCG-unresponsive NMIBC. Historically, the standard course of action for these patients has been a radical cystectomy. While curative, this procedure is highly invasive and significantly impacts a patient’s quality of life, leading to a strong desire for bladder-sparing alternatives.
Systemic immunotherapy is now available, such as the checkpoint inhibitor pembrolizumab, which has been approved for patients who have failed BCG and are not candidates for surgery. Other emerging approaches involve novel intravesical drug delivery systems. One example is nadofaragene firadenovec, a viral vector that delivers a gene into the bladder cells to stimulate an anti-tumor immune response.
Sequential intravesical chemotherapy regimens, such as a combination of gemcitabine and docetaxel, are also used. Ongoing clinical trials continue to explore these and other innovative therapies to provide effective alternatives to cystectomy for patients who do not respond to the primary BCG treatment.