Immunotherapy for bladder cancer is a treatment approach that uses your immune system to find and destroy cancer cells. It’s one of the most established immunotherapy success stories in oncology, with a form of it (BCG) used in bladder cancer treatment since the 1970s. Today, immunotherapy spans everything from a liquid solution placed directly into the bladder for early-stage disease to intravenous drugs that treat advanced cancer that has spread beyond the bladder wall.
How BCG Works for Early-Stage Bladder Cancer
The oldest and most common form of bladder cancer immunotherapy is BCG, short for Bacillus Calmette-Guérin. It’s a weakened form of the bacteria used in tuberculosis vaccines, and it remains the standard treatment for non-muscle-invasive bladder cancer, which is cancer that hasn’t grown into the deeper muscle layers of the bladder wall. This includes high-grade tumors, carcinoma in situ (a flat, aggressive type confined to the bladder lining), and stage T1 tumors that have reached the connective tissue beneath the lining but not the muscle.
BCG works through several mechanisms at once. When the solution contacts the bladder lining, it triggers a strong local immune response, drawing immune cells to the area to attack cancer cells. The bacteria can also be absorbed directly into cancer cells, causing those cells to essentially flag themselves for immune destruction. On top of that, BCG has a direct toxic effect on cancer cells, triggering a process of programmed cell death. Studies show BCG reduces bladder cancer recurrence by roughly 60% when used according to guidelines.
Not every patient with non-muscle-invasive bladder cancer needs BCG. People with low-risk disease, meaning a single, first-time, low-grade tumor, generally do not receive it. Those with intermediate-risk tumors (multiple or recurring low-grade tumors) are typically treated with BCG induction followed by at least one year of maintenance therapy. For high-risk patients, BCG with both induction and maintenance is considered standard of care.
What a BCG Treatment Session Looks Like
BCG is delivered directly into the bladder through a procedure called intravesical instillation. You’ll empty your bladder first, then a healthcare provider inserts a thin catheter through the urethra and injects the liquid BCG solution. The catheter is removed, and you hold the solution in your bladder for two hours before urinating it out.
A standard induction course is typically six weekly sessions. If your cancer responds, you’ll move to maintenance therapy: periodic treatments spread over one to three years. The most common side effects are bladder irritation, a frequent or urgent need to urinate, and mild flu-like symptoms that usually resolve within a day or two. Serious complications are uncommon but can include persistent fever or a systemic infection if the bacteria enter the bloodstream.
Checkpoint Inhibitors for Advanced Bladder Cancer
When bladder cancer invades the muscle wall or spreads to other parts of the body, treatment shifts to systemic immunotherapy, meaning drugs delivered through an IV that work throughout the entire body. The main class used is checkpoint inhibitors, which block proteins that cancer cells use to hide from the immune system.
Your immune cells have built-in “brakes” that prevent them from attacking healthy tissue. Cancer cells exploit these brakes by displaying proteins (particularly PD-L1) that tell immune cells to stand down. Checkpoint inhibitors release those brakes, allowing immune cells to recognize and kill the cancer. Pembrolizumab (Keytruda) is the most widely used checkpoint inhibitor in bladder cancer today. Atezolizumab (Tecentriq) was one of the first approved for this cancer type, though its indication for previously treated metastatic disease was later withdrawn.
In March 2025, the FDA approved durvalumab (Imfinzi) for muscle-invasive bladder cancer. This approval covers its use alongside chemotherapy before surgery, followed by continued durvalumab treatment after surgery. This before-and-after approach, called neoadjuvant and adjuvant therapy, aims to shrink tumors before they’re removed and then mop up any remaining cancer cells.
Antibody-Drug Conjugates: A Targeted Approach
One of the most significant advances in bladder cancer treatment is enfortumab vedotin (Padcev), an antibody-drug conjugate. This isn’t immunotherapy in the traditional sense, but it uses an antibody (an immune system protein) to deliver a potent cancer-killing drug directly to tumor cells. The antibody locks onto a protein called Nectin-4 that sits on the surface of most bladder cancer cells. Once attached, the entire package is pulled inside the cell, where it releases a compound that disrupts the cell’s internal scaffolding and triggers cell death. Because the drug is delivered so precisely, it causes less collateral damage to healthy tissue than traditional chemotherapy.
Combination Therapy as First-Line Treatment
The most promising recent development is combining checkpoint inhibitors with antibody-drug conjugates. The FDA has approved pembrolizumab plus enfortumab vedotin for muscle-invasive bladder cancer, based on trial results showing a dramatic improvement over surgery alone. In the pivotal trial, patients who received the combination before and after surgery had significantly longer event-free survival. The median time before cancer returned was not even reached in the combination group, compared to 15.7 months for patients who had surgery alone. Overall survival was also significantly better, with the combination cutting the risk of death in half.
This combination is reshaping how muscle-invasive bladder cancer is treated, offering some patients a realistic chance at long-term remission that was previously difficult to achieve with chemotherapy and surgery alone.
Side Effects of Systemic Immunotherapy
Checkpoint inhibitors work by unleashing the immune system, which means they can sometimes cause the immune system to attack healthy organs. These are called immune-related adverse events and can affect the skin, gut, liver, lungs, thyroid, or other organs. In a study of 200 patients treated with checkpoint inhibitors for metastatic bladder cancer, about 8% experienced side effects serious enough to require a treatment pause of at least two weeks or permanent discontinuation. Among those patients, roughly two-thirds needed steroid treatment to calm the overactive immune response.
Most immune-related side effects are manageable when caught early. Common symptoms to watch for include new skin rashes, persistent diarrhea, unusual fatigue, shortness of breath, or joint pain. The side effect profile is generally different from chemotherapy: hair loss and severe nausea are less common, but autoimmune-type reactions are more of a concern. Your treatment team will monitor bloodwork and symptoms regularly throughout your infusion schedule.
Which Type of Immunotherapy Applies to You
The type of immunotherapy you receive depends almost entirely on how far your cancer has progressed. For non-muscle-invasive bladder cancer (stages Ta, T1, and carcinoma in situ), BCG delivered directly into the bladder is the primary immunotherapy. For muscle-invasive cancer that hasn’t spread, checkpoint inhibitors like durvalumab or the pembrolizumab/enfortumab vedotin combination may be used before and after surgery. For metastatic bladder cancer that has spread beyond the bladder, checkpoint inhibitors and antibody-drug conjugates become the main options, often after or instead of platinum-based chemotherapy.
Response to immunotherapy varies significantly between patients. Some people achieve complete remission, while others see little benefit. Researchers are still working to understand why BCG works well for some patients but fails in others. One factor involves the cancer cells themselves: BCG can increase expression of PD-L1, the same “don’t attack me” signal that checkpoint inhibitors are designed to block. This may partly explain why some patients eventually stop responding to BCG, and it has opened the door to using checkpoint inhibitors as a follow-up option for BCG-unresponsive disease.