BCG Therapy for Bladder Cancer

About Bladder Cancer

Bladder cancer arises from the urothelium (the thin layer of cells lining the inside of the bladder) and is one of the most common cancers of the urinary system, now ranking ninth worldwide.¹

70% of cases are initially diagnosed as non-muscle invasive bladder cancer (NMIBC), in which the tumor is confined to the bladder lining and has not invaded the bladder muscle. Although this stage is less immediately life-threatening, it is known for high recurrence rates, meaning tumors often return after removal. Because of this tendency to recur, treatment strategies often focus not only on removing visible tumors but also on preventing regrowth and progression to more dangerous disease.²

With a long medical history, one of the most common early-stage therapies is BCG (Bacillus Calmette-Guérin). It was first developed in the early 20th century by French scientists Albert Calmette and Camille Guérin. Decades later, researchers discovered that its immune-stimulating properties could be used to fight cancer. In the 1970s, urologist Alvaro Morales conducted the first successful clinical trial using BCG inside the bladder to treat bladder tumors, demonstrating that the therapy could significantly reduce recurrence rates.³

Traditional chemotherapy drugs directly destroy rapidly dividing cells, cancerous or not. BCG works by stimulating the body’s immune defenses. The presence of the weakened bacteria causes an inflammatory response in the bladder lining, which signals immune cells to move into the area and attack abnormal cells. This immune activity can eliminate remaining cancer cells that were too small to be removed during surgery.

Additional mechanisms include BCG attachment to bladder cells via fibronectin (a protein that helps cells stick to each other and their surroundings) and integrin (a receptor on cell surfaces that binds to fibronectin), internalization by tumor cells, and the release of immune-activating cytokines (signaling molecules that help immune cells communicate). Both innate and adaptive immune cells are recruited to the tumor site, creating a cascade that enhances anti-tumor activity. In other words, both general and specialized immune defenses work together to detect, attack, and remove residual cancer cells in the bladder.⁷

BCG can also exert direct cytotoxic (cell killing) effects on bladder cancer cells in some cases, causing apoptosis (programmed cell death), necrosis (cell death due to injury), and oxidative stress (damage from reactive molecules), which further helps eliminate residual tumor cells. This process helps by weakening or removing cancer cells, making them easier for immune cells to recognize and clear from the bladder.⁸

BCG is considered one of the earliest and most successful forms of cancer immunotherapy. It has been used for decades and remains a key strategy for reducing tumor recurrence and slowing disease progression in patients with early-stage bladder cancer.

After the tumor is removed through TURBT and the area has healed, BCG is then introduced directly into the bladder. The treatment schedule begins with an induction course, usually once weekly for six weeks, during which patients hold the BCG solution in the bladder for about two hours to maximize contact with the bladder lining.

Four hours before the treatment, fluids, especially caffeine, need to be stopped or limited. In the office, the bladder is emptied as a urine sample. Treatment providers must be informed about all currently prescribed and over-the-counter medications.

Because BCG contains live bacteria, certain precautions have to be taken throughout the treatment process: avoiding public restrooms, sitting to urinate, adding 2 cups of undiluted household bleach to the toilet after each urination, closing the lid for 15-20 minutes before flushing, washing hands and the genital area thoroughly, and drinking plenty of fluids. Sexual activity must be avoided for 48 hours after treatment, and condoms must be used as instructed throughout therapy. It is also dangerous to become pregnant during the course of treatment.

If the therapy is effective, a maintenance course may follow, consisting of weekly instillations for three weeks at specific intervals, sometimes continuing for up to three years to further reduce recurrence risk.⁹

Its effectiveness is enhanced when maintenance therapy is given after the initial induction period, as repeated BCG exposure strengthens the local immune response and further decreases the risk of recurrence.¹⁰ The goal is to preserve the bladder while reducing recurrence and progression, offering an effective, localized immunotherapy option.

Patients who are not candidates for BCG include those with active urinary infections, significant bleeding, or immune system deficiencies, as these conditions increase the risk of complications from the live bacteria. BCG is also avoided immediately after bladder surgery if the tissue has not sufficiently healed.

Treatment may also be delayed due to fever, infection, or blood in the urine.

Are there any Side Effects?

BCG therapy, while highly effective, is associated with a range of side effects, most of which are mild and temporary. Because the treatment involves live bacteria, it triggers an immune and inflammatory response in the bladder, which can affect how patients feel during and shortly after therapy.

The most common side effects include:

• Irritative urinary symptoms such as burning during urination (dysuria), frequent urination, or sudden urges to urinate. These symptoms typically appear a few hours after treatment and can last for one to three days.
• Mild hematuria (small amounts of blood in the urine), which often resolves without intervention.
• Flu-like symptoms such as low-grade fever, fatigue, chills, or mild muscle and joint aches. These symptoms usually resolve within a few days.

Mild urinary or flu-like symptoms are typically managed with rest, hydration, and temporary treatment delays if needed.

BCG may occasionally cause systemic effects beyond the bladder. While rare, some patients can develop more serious reactions such as high fever, severe chills, widespread rash, difficulty breathing, or inability to urinate. These are considered medical emergencies and require prompt evaluation.

In addition to general immune activation, BCG can rarely lead to infection of the bladder or even spread through the bloodstream (hematogenous BCG infection). This is more likely if the bladder lining is damaged, there is a concurrent urinary tract infection, or BCG is administered too soon after surgery, before the tissue has healed. More significant complications may require antimycobacterial antibiotics under the supervision of an infectious disease specialist.

Overall, serious side effects are uncommon, and most patients tolerate BCG well. Because of its localized action, the therapy primarily affects the bladder lining and nearby immune cells rather than the whole body, allowing patients to continue daily activities with relatively minimal disruption.

Why the bleach?

While you are not ‘contagious’ in the traditional sense, the live bacteria can be shed in your urine. The bleach protocol is a precaution to ensure no bacteria are passed to family members or into the water system.

Work with a Well-versed Provider

Despite four decades of use, BCG is still an active area of research. Scientists are currently investigating how immune signaling, bacterial interaction with bladder cells, and tumor genetics influence treatment success or resistance. Understanding the mechanisms involved will eventually lead to improved therapies or combination treatments for patients whose cancers do not respond to BCG.¹¹

At Georgia Urology, we have decades of experience in diagnosing and treating bladder cancer, including the use of Blue Light Cystoscopy with Cysview and BCG therapy. Our team is nationally recognized for its expertise in urologic oncology, and our clinics are equipped with advanced technologies to ensure accurate diagnosis, personalized treatment plans, and careful monitoring during and after therapy.

If you or a loved one is facing bladder cancer, our team is ready to help you understand your options, navigate treatment decisions, and receive the highest standard of care. Schedule a consultation with Georgia Urology today to learn more about BCG therapy and other advanced bladder cancer treatments.

Resources:

1. Han, J., Gu, X., Li, Y., & Wu, Q. (2020). Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect. Biomedicine & Pharmacotherapy, 129, 110393. https://doi.org/10.1016/j.biopha.2020.110393.
2. Lv, M., Shang, S., Liu, K., Wang, Y., Xu, P., Song, H., Zhang, J., Sun, Z., Yan, Y., Zhu, Z., Wu, H., & Li, H. (2024). Revitalizing Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer: Nanotechnology and Bioengineering Approaches. Pharmaceutics, 16(8), 1067. https://doi.org/10.3390/pharmaceutics16081067.
3. Jiang, S., & Redelman-Sidi, G. (2022). BCG in Bladder Cancer Immunotherapy. Cancers, 14(13), 3073. https://doi.org/10.3390/cancers14133073.
4. Lv, M., Shang, S., Liu, K., Wang, Y., Xu, P., Song, H., Zhang, J., Sun, Z., Yan, Y., Zhu, Z., Wu, H., & Li, H. (2024). Revitalizing Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer: Nanotechnology and Bioengineering Approaches. Pharmaceutics, 16(8), 1067. https://doi.org/10.3390/pharmaceutics16081067.
5. Jiang, S., & Redelman-Sidi, G. (2022). BCG in Bladder Cancer Immunotherapy. Cancers, 14(13), 3073. https://doi.org/10.3390/cancers14133073.
6. Lv, M., Shang, S., Liu, K., Wang, Y., Xu, P., Song, H., Zhang, J., Sun, Z., Yan, Y., Zhu, Z., Wu, H., & Li, H. (2024). Revitalizing Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer: Nanotechnology and Bioengineering Approaches. Pharmaceutics, 16(8), 1067. https://doi.org/10.3390/pharmaceutics16081067.
7. Jiang, S., & Redelman-Sidi, G. (2022). BCG in Bladder Cancer Immunotherapy. Cancers, 14(13), 3073. https://doi.org/10.3390/cancers14133073.
8. Han, J., Gu, X., Li, Y., & Wu, Q. (2020). Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect. Biomedicine & Pharmacotherapy, 129, 110393. https://doi.org/10.1016/j.biopha.2020.110393.
9. Bladder Cancer Advocacy Network. (2024). What to Know About BCG Treatment for Bladder Cancer. Bladder Cancer Advocacy Network. https://bcan.org/bcg-treatment-for-bladder-cancer/.
10. Jiang, S., & Redelman-Sidi, G. (2022). BCG in Bladder Cancer Immunotherapy. Cancers, 14(13), 3073. https://doi.org/10.3390/cancers14133073.
11. Lv, M., Shang, S., Liu, K., Wang, Y., Xu, P., Song, H., Zhang, J., Sun, Z., Yan, Y., Zhu, Z., Wu, H., & Li, H. (2024). Revitalizing Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer: Nanotechnology and Bioengineering Approaches. Pharmaceutics, 16(8), 1067. https://doi.org/10.3390/pharmaceutics16081067.