Immunotherapy is one of the newest types of bladder cancer treatments. This type of treatment has become an important option for people with advanced bladder cancer or bladder cancer that’s spread to other parts of the body (called metastatic bladder cancer). These advanced stages of bladder cancer often have a poor prognosis (outlook), as surgery is not typically an option, leaving fewer treatment alternatives.

For early-stage bladder cancer, five-year relative survival rates range from 71 percent to 96 percent, meaning most people are still alive five years after their diagnosis. However, the survival rates drop significantly as the cancer spreads. When bladder cancer reaches nearby tissues, the five-year survival rate is 39 percent, and it falls to 8 percent when the cancer spreads to distant areas. Several immunotherapies have shown they can improve the prognosis for advanced and metastatic bladder cancer.

This article will explain how immunotherapy works for bladder cancer and how effective it is for treating advanced and metastatic stages of the disease.

What Is Immunotherapy?

Immunotherapy is a cancer treatment that uses your immune system to fight cancer. Some types boost your immune system to help it find and destroy cancer cells. Others use laboratory-made immune proteins, such as antibodies, to make your immune system work better.

Immunotherapy is a cancer treatment that uses your immune system to fight cancer.

Intravesical Immunotherapy

Intravesical immunotherapy is a bladder cancer treatment that’s often used to treat some early-stage bladder cancers, such as non-muscle-invasive bladder cancer (NMIBC).

In this therapy, a liquid drug is placed directly into the bladder using a catheter (thin tube) inserted through the urethra, the opening that carries urine out of the body. Because intravesical immunotherapy only targets the bladder’s inner lining, it cannot treat cancer that has spread deeper into the bladder wall or to other parts of the body.

Following are three immunotherapies approved by the U.S. Food and Drug Administration (FDA) for use in intravesical therapy.

Bacillus Calmette-Guérin

Bacillus Calmette-Guérin (Tice BCG) was the first immunotherapy for bladder cancer and has been used for almost 60 years. It’s the most common intravesical immunotherapy used to treat early-stage bladder cancer. BCG is made from bacteria related to tuberculosis but that is not harmful. The treatment helps to activate your immune system to recognize and attack cancer cells.

A systematic review, which is a detailed analysis of multiple studies on the same topic, found that between 54 percent and 89 percent of people with NIMBC lived at least two years without cancer recurrence (returning) after treatment. However, research from 2024 found that about half of people treated with BCG may experience recurrence.

Nadofaragene Firadenovec

Nadofaragene firadenovec (Adstiladrin) uses a virus to deliver a gene with instructions for producing interferon alfa-2b. Interferon alfa-2b is an immune system protein that encourages the body’s immune system to attack cancer cells. It’s with BCG for people who don’t improve enough with BCG treatment alone.

In clinical trials, about half of people treated with nadofaragene firadenovec after BCG therapy survived at least five years without needing a cystectomy (bladder removal surgery).

Several immunotherapies have shown they can improve the prognosis for advanced and metastatic bladder cancer.

Nogapendekin Alfa Inbakicept

Nogapendekin alfa inbakicept (Anktiva) is an interleukin (IL)-15 receptor agonist. It works by activating the immune system to attack cancer cells. It’s used with BCG for people who don’t improve enough with BCG treatment alone.

In clinical trials, 58 percent of people had no signs of bladder cancer for one year after treatment. After two years, 40 percent of people still had no signs of bladder cancer.

Immune Checkpoint Inhibitors

Immune checkpoint inhibitors (ICIs) are a type of immunotherapy that helps your immune system find and attack cancer cells.

Normally, checkpoint proteins prevent immune cells from harming healthy cells. Some cancer cells use these proteins to hide from the immune system. ICIs work by inhibiting (blocking) these checkpoint proteins, making it easier for immune cells to recognize and destroy cancer cells.

As of December 2024, there are three FDA-approved ICIs for bladder cancer.

Avelumab

Avelumab (Bavencio) targets a checkpoint protein called PD-L1, which is found on cancer cells. It can be used as maintenance therapy for people with advanced or metastatic cancer that hasn’t progressed after first-line chemotherapy and cannot be treated with surgery.

In clinical trials, researchers evaluated the efficacy of avelumab by looking at overall survival. Overall survival is the length of time people live after the start of treatment. The median overall survival for people treated with avelumab was 21.4 months. This means half of the people treated with avelumab were alive at least 21.4 months after starting treatment. This was significantly longer than people treated with the best available supportive care, which had a median overall survival of 14.3 months.

Pembrolizumab

Pembrolizumab (Keytruda) targets a checkpoint protein found on immune cells called PD-1. Pembrolizumab by itself can be used to treat some people with bladder cancer, including those with:

• Advanced or metastatic bladder cancer who can’t take platinum-containing chemotherapy
• Advanced or metastatic bladder cancer who don’t respond to platinum-containing chemotherapy
• NMIBC with a high risk of recurrence who don’t respond to intravesical therapy with BCG and can’t have a cystectomy

Several clinical trials with pembrolizumab have shown the drug’s potential benefit. ​​In people with advanced or metastatic bladder cancer who didn’t respond to chemotherapy, pembrolizumab extended overall survival by about three months, increasing median survival from 7.4 months with chemotherapy to 10.3 months. In a follow-up study five years later, 14.9 percent of people treated with pembrolizumab were still alive compared to the 8.7 percent treated with chemotherapy.

In people with NMIBC, 46 percent treated with pembrolizumab had no signs of bladder cancer for at least 12 months.

Researchers are also looking into using this drug earlier in treatment. A 2024 clinical trial found that people with muscle-invasive bladder cancer (MIBC) who took pembrolizumab for a year after a cystectomy had a median disease-free survival of 29.6 months, compared to 14.2 months for those who didn’t receive the drug. This means that for at least 29.6 months after treatment, cancer did not worsen in half of the people who received pembrolizumab.

Nivolumab

Nivolumab (Opdivo) targets PD-1. This drug can be used to treat bladder cancer in a few different ways:

• Adjuvant therapy ( after surgery) for people with a high risk of recurrence
• In combination with chemotherapy drugs cisplatin and gemcitabine, followed by maintenance therapy, for people with metastatic or inoperable bladder cancer
• In people with advanced or metastatic bladder cancer whose disease has progressed after taking a platinum-containing chemotherapy

When used after surgery, nivolumab nearly doubled the time people lived without their cancer worsening or returning: The median disease-free survival was 20.8 months versus 10.8 months among those who received a placebo (inactive treatment). When nivolumab was combined with cisplatin and gemcitabine, people lived nearly three months longer (21.7 months vs. 18.9 months) than those treated with chemo alone.

Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) are drugs that combine a monoclonal antibody (laboratory-made immune protein) with a chemo drug. The monoclonal antibody is designed to target cancer cells and brings the attached chemo drug right where it’s needed.

Enfortumab Vedotin

Enfortumab vedotin is an ADC approved for treating advanced bladder cancer. It can be used alone to treat people with advanced bladder cancer who have already tried an ICI. People who can’t take cisplatin but have tried at least one other type of drug treatment can also take enfortumab vedotin. In clinical trials, 44 percent of participants treated with enfortumab vedotin saw their tumors shrink or their disease stop progressing.

Combination Therapies

Pembrolizumab can be combined with the ADC enfortumab vedotin as an initial treatment for people with advanced bladder cancer. This combination offers a promising option for those who may not tolerate traditional chemotherapy. In clinical trials, 68 percent of people saw their tumors shrink during treatment. Additionally, about 12 percent of people saw all signs of their cancer disappear.

Take the Next Step

Immunotherapy is transforming how bladder cancer is treated, especially for advanced and metastatic cases that are difficult to manage with traditional therapies. These treatments offer new hope by harnessing the body’s immune system to target cancer cells. Clinical trials continue to show the major benefits of these treatments, like longer survival and long-lasting results.

If you or a loved one is facing bladder cancer, speak with your doctor about whether immunotherapy might be right for you. With the growing number of FDA-approved options and combination therapies available, a personalized treatment plan can make a meaningful difference in outcomes.

Talk With Others Who Understand

MyBladderCancerTeam is the social network for people with bladder cancer and their loved ones. On MyBladderCancerTeam, members come together to ask questions, give advice, and share their stories with others who understand life with bladder cancer.

Have you taken immunotherapy for bladder cancer? How did it work for you? Share your experience in the comments below, or start a conversation by posting on your Activities page.