Advances in Bladder Cancer Research

New Bladder Cancer Treatments

Bladder cancer treatments are based on the type of bladder cancer and the stage of the disease. The most common type of bladder cancer is transitional cell carcinoma, also called urothelial carcinoma, which begins in cells in the innermost tissue layer of the bladder. There are other types of bladder cancers such as squamous cell carcinoma, small cell carcinoma, and adenocarcinoma, among others.

The mainstays of bladder cancer treatment are surgery, radiation therapy, chemotherapy, and immunotherapy, depending on the stage. Recently, targeted therapies have been approved by the FDA for bladder cancer. Scientists continue to study novel treatments and drugs, along with new combinations of existing treatments. 

Non-muscle-invasive bladder cancer is cancer that has grown through the lining of the bladder but hasn’t yet invaded the muscle layer of the bladder. The common treatment approach for this cancer involves removing the tumor by scraping it from the bladder wall.

Some patients may receive additional treatment after surgery with an immune-based therapy called bacillus Calmette-Guérin (BCG), or with chemotherapy drugs such as mitomycin C (Jelmyto) or gemcitabine put directly into the bladder to reduce the risk that of cancer recurrence. 

Immunotherapy

Immunotherapy is treatment that helps the body’s immune system to fight cancer more effectively. Certain immunotherapy drugs, known as immune checkpoint inhibitors, are approved to treat some patients with locally advanced or metastatic bladder cancer. 

Patients whose bladder cancers respond to immune checkpoint inhibitors tend to maintain those responses for long periods. Ongoing clinical trials aim to determine whether these prolonged responses help people live longer. 

However, only a small number of patients respond to immune checkpoint inhibitors. Scientists are trying to develop biomarkers that could help doctors identify which patients with bladder cancer are likely to respond to these drugs. For example, the checkpoint protein called PD-L1 has been studied as a biomarker for predicting response to immune checkpoint inhibitor therapy.

Scientists have now begun to test immune checkpoint inhibitors in earlier stages of bladder cancer and in combination with other treatments, such as chemotherapy:

• In a large NCI-supported clinical trial (referred as AMBASSADOR trial) the immunotherapy drug pembrolizumab (Keytruda) doubled the length of time people high-risk muscle-invasive bladder cancer were cancer-free following surgical removal of the bladder. After a median follow-up of almost four years, people in the pembrolizumab group remained cancer-free for a median of 29.6 months, compared with 14. months for the observation group, researchers reported in 2024.
• In 2021, the Food and Drug Administration (FDA) approved the immune checkpoint inhibitor nivolumab (Opdivo) as an additional (adjuvant) treatment of patients with urothelial carcinoma who are at high risk of recurrence after undergoing surgery for the disease. This was the first FDA approval for the adjuvant treatment of patients with this type of cancer. In 2023, updated trial results showed that people who received nivolumab had a median disease-free survival of 22 months, compared with about 11 months for those who received a placebo. 
• In 2020, the FDA approved the immune checkpoint inhibitor avelumab (Bavencio) for people with advanced bladder cancer that has shrunk or stopped growing after receiving platinum-based chemotherapy. The approval is for the use of avelumab as maintenance therapy for advanced disease that has not spread (locally advanced) or disease that has spread beyond the bladder (metastatic).

Targeted Therapy 

Targeted therapy treats cancer by targeting proteins that control how cancer cells grow, divide, and spread. In 2019, erdafitinib (Balversa) became the first targeted therapy to be approved by FDA to treat patients with locally advanced or metastatic urothelial carcinoma. This drug can be used to treat some patients whose cancers have certain alterations in the FGFR2 gene or FGFR3 gene. Only about 20% of bladder cancers harbor an FGFR gene alteration.

An ongoing phase 3 study is comparing erdafitinib with standard chemotherapy and with pembrolizumab in patients with advanced bladder cancer whose tumors have an FGFR gene alteration. This study could help researchers learn whether patients with FGFR-altered bladder cancer benefit more from erdafitinib or an immune checkpoint inhibitor versus chemotherapy. 

Antibody Drug Conjugates

A monoclonal antibody is a type of protein made in the lab that can bind to certain targets in the body, such as those on cancer cells. An antibody drug conjugate is a substance made up of a monoclonal antibody that is chemically linked to a drug. It has the ability to kill cancer cells without harming other cells. 

The antibody drug conjugate enfortumab vedotin-ejfv (Padcev) has been approved to treat advanced/metastatic bladder cancer. It showed positive results in patients who had previously been treated with chemotherapy and an immune checkpoint inhibitor. Researchers continue to study this drug to see whether it can be used to treat bladder cancer earlier in the disease process and to evaluate it in combination with immunotherapy and/or chemotherapy.

Recently, a study found that combination treatment of enfortumab vedotin-ejfv and pembrolizumab increased survival compared to chemotherapy in patients with untreated locally advanced or metastatic bladder cancer.  

Gene Therapy

In 2022, the FDA approved a type of gene therapy called nadofaragene firadenovec-vncg (Adstiladrin) for some adults with a certain type of high-risk, non-muscle-invasive bladder cancer. This treatment helps the immune system recognize and destroy cancer cells, offering a potential benefit for people whose tumors do not respond to the commonly used BCG therapy.

Combination Therapy

Researchers are testing many combinations of therapies for bladder cancer, either by combining several immunotherapy drugs or by combining an immunotherapy drug with another type of treatment.

• In 2024, the FDA approved a type of gene therapy called nogapendekin alfa inbakicept-pmln (Anktiva) for use in combination with BCG therapy in patients with non–muscle-invasive bladder cancer that did not respond effectively to BCG therapy alone. The drug belongs to a class of medications called interleukin-15 (IL-15) receptor agonists.
• An early-phase clinical trial for patients with muscle-invasive bladder cancer is studying the combination of durvalumab (Imfinzi) with tremelimumab before surgery. Giving these drugs together before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.
• A phase 3 trial is testing chemotherapy and radiation therapy with or without the immune checkpoint inhibitor atezolizumab in patients with localized muscle-invasive bladder cancer. Combining chemotherapy with radiation therapy may kill more tumor cells than chemotherapy alone. Adding atezolizumab (Tecentriq) to radiation therapy and chemotherapy may further improve outcomes in patients with localized muscle-invasive bladder cancer.
• A study is testing the safety and efficacy of the combination of the immune checkpoint inhibitor durvalumab and the drug oportuzumab monatox (Vicinium) for treating bladder cancer that has not invaded the bladder muscle. Non-muscle-invasive bladder cancer is an early-stage cancer, but it often recurs after treatment. The two drugs may work together to help the immune system find and destroy cancer cells.
• One study is testing the experimental drug enfortumab vedotin alone and with different combinations of treatments, including pembrolizumab, for treating bladder cancer. Some parts of the study focus on patients with locally-advanced and metastatic urothelial cancer, whereas other parts will focus on patients with muscle-invasive bladder cancer. 

For a complete list of all drugs, see Drugs Approved for Bladder Cancer.

Clinical Trials for Bladder Cancer

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for bladder cancer treatment.

NCI-Supported Research Programs

Many NCI-funded researchers working at the NIH campus and across the United States and the world are seeking ways to address bladder cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer. And some is more clinical, seeking to translate this basic information into improving patient outcomes.

The Bladder Specialized Program of Research Excellence, or SPORE, is a cornerstone of the NCI’s efforts to promote collaborative, interdisciplinary translational research on bladder cancer. It is currently located at Memorial Sloan Kettering Cancer Center. 

NCI’s Division of Cancer Epidemiology and Genetics (DCEG) conducts studies on bladder cancer to learn about risk factors for the disease.

Investigators in the Genitourinary Malignancies Branch of NCI’s Center for Cancer Research conduct basic, translational, and clinical studies on bladder cancer.

In addition, NCI has funding opportunities for researchers aimed at encouraging investigations of the biology and underlying mechanisms of bladder cancer. 

Bladder Cancer Research Results

The following are some of our latest news articles on bladder cancer research.

• Bladder Cancer Trial Finds Extended Lymph Node Surgery Doesn’t Improve Survival
• Immunotherapy after Surgery Helps People with High-Risk Bladder Cancer Live Cancer-Free Longer
• Groundbreaking Trial Results Expand Treatment Options for Some People with Bladder Cancer
• Loss of Y Chromosome in Men Makes Bladder Cancer More Aggressive
• Immunotherapy after Surgery Shows Long-Term Benefits for High-Risk Bladder Cancer
• For Common Form of Bladder Cancer, Chemo Combo Effective Alternative to BCG

View the full list of Bladder Cancer Research Results and Study Updates.