Immunotherapy for Bladder Cancer

Bladder cancer is a common malignancy, and treatment options have advanced significantly over the years. 


Immunotherapy for Bladder Cancer: Treatment & What to Expect

Bladder cancer is a common malignancy, and treatment options have advanced significantly over the years. Among these advancements, immunotherapy has emerged as a powerful approach, harnessing the body's own immune system to fight cancer cells. This article will provide a comprehensive overview of immunotherapy for bladder cancer, explaining how it works, the types available, who might be a candidate, and what to expect during treatment.

What is Immunotherapy?

Immunotherapy is a type of cancer treatment that helps your immune system recognize and destroy cancer cells. Unlike chemotherapy, which directly attacks cancer cells, or radiation therapy, which uses high-energy beams to kill them, immunotherapy empowers the body's natural defenses. The immune system is constantly surveying the body for foreign invaders like bacteria and viruses, but cancer cells often develop ways to evade this detection.

How Does Immunotherapy Work for Bladder Cancer?

Cancer cells can develop mechanisms to hide from the immune system or turn off immune responses. Immunotherapy for bladder cancer primarily works by disrupting these evasive tactics. It aims to 'unmask' the cancer cells, making them visible targets for immune cells, or to boost the immune system's ability to attack them effectively.

A key mechanism involves targeting specific proteins on cancer cells or immune cells, known as immune checkpoints. These checkpoints act like "brakes" on the immune system. By blocking these brakes, immunotherapy allows the immune system to accelerate its attack on cancer.

Types of Immunotherapy for Bladder Cancer

Several types of immunotherapy are used for bladder cancer, depending on the stage and characteristics of the disease:

Intravesical BCG (Bacillus Calmette-Guérin)

BCG is the oldest and most established form of immunotherapy for bladder cancer. It is primarily used for non-muscle invasive bladder cancer (NMIBC), particularly for intermediate and high-risk cases. BCG is a weakened form of bacteria related to tuberculosis. It is instilled directly into the bladder through a catheter. Once inside, BCG triggers a strong immune response within the bladder lining, which helps to destroy cancer cells and prevent recurrence.

Immune Checkpoint Inhibitors

These are newer immunotherapy drugs that target immune checkpoints. For bladder cancer, the most common targets are the PD-1 (Programmed Death-1) protein on immune cells and its ligand, PD-L1 (Programmed Death-Ligand 1), found on cancer cells and other immune cells. By blocking the interaction between PD-1 and PD-L1, these drugs release the "brakes" on T-cells (a type of immune cell), allowing them to recognize and attack cancer more effectively.


  • PD-1 Inhibitors: Drugs like pembrolizumab and nivolumab block the PD-1 protein on immune cells.

  • PD-L1 Inhibitors: Drugs like atezolizumab, durvalumab, and avelumab block the PD-L1 protein, typically found on cancer cells.

Immune checkpoint inhibitors are often used for advanced or metastatic bladder cancer, especially after chemotherapy has been tried. They are also being explored and approved for use in earlier stages or in specific situations where patients cannot tolerate chemotherapy.

Who is a Candidate for Immunotherapy?

The decision to use immunotherapy depends on several factors, including:


  • Cancer Stage: BCG is standard for NMIBC. Immune checkpoint inhibitors are typically used for locally advanced or metastatic bladder cancer, or in certain situations for muscle-invasive bladder cancer (MIBC) that cannot be treated with surgery or chemotherapy.

  • Previous Treatments: Often, immune checkpoint inhibitors are considered if chemotherapy has not been effective or if a patient cannot receive chemotherapy.

  • Overall Health: A patient's general health and ability to tolerate potential side effects are crucial considerations.

  • Biomarkers: Sometimes, testing for PD-L1 levels on cancer cells can help predict how well a patient might respond to certain checkpoint inhibitors, though these tests are not always definitive.

A detailed discussion with an oncology team is essential to determine the most appropriate treatment plan.

Potential Side Effects of Immunotherapy

While immunotherapy can be highly effective, it can also cause side effects, which occur when the boosted immune system mistakenly attacks healthy cells and tissues. These are known as immune-related adverse events (irAEs).

Common side effects can include:


  • Fatigue

  • Skin rash or itching

  • Diarrhea

  • Nausea

  • Joint pain

  • Fever or flu-like symptoms

More serious, but less common, side effects can affect various organs and may require immediate medical attention. These can include inflammation of the lungs (pneumonitis), colon (colitis), liver (hepatitis), hormone-producing glands (endocrinopathies), kidneys, or heart. It is crucial for patients to report any new or worsening symptoms to their healthcare team promptly.

Outlook and Future Directions

Immunotherapy has revolutionized the treatment landscape for bladder cancer, offering new hope for many patients, especially those with advanced disease. Research continues to evolve rapidly, exploring:


  • Combination therapies (e.g., immunotherapy with chemotherapy, radiation, or other targeted therapies).

  • New immune checkpoint targets.

  • Biomarkers to better predict who will respond to treatment.

  • Use of immunotherapy in earlier stages of bladder cancer.

As our understanding of the immune system and cancer grows, immunotherapy is expected to play an even more significant role in the future of bladder cancer management.