Advances in Bladder Cancer Research
NCI-funded researchers are working to improve our understanding of how to treat bladder cancer. With recent advances in immunotherapy and targeted therapy, treatment has the potential to become more effective and less toxic.
This page highlights some of the latest research in bladder cancer, including clinical advances that may soon translate into improved care and research findings from recent studies.
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. 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. Treatment for this cancer is usually to remove 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 the cancer will recur.
Immunotherapy is treatment that helps the body’s immune system fight cancer more effectively. Certain immunotherapy drugs, called 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 will help researchers learn whether these extended responses help patients 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, a checkpoint protein called PD-L1 has been studied as a biomarker for response to treatment with immune checkpoint inhibitors.
Scientists have now begun to test immune checkpoint inhibitors in earlier stages of bladder cancer and in combination with other treatments, such as chemotherapy:
- The NCI-sponsored AMBASSADOR trial is comparing the immune checkpoint inhibitor pembrolizumab (Keytruda) with observation. This is being done in patients with bladder cancer that invades the muscle layer of the bladder wall (localized muscle-invasive disease) or that has spread to nearby lymph nodes (locally advanced disease) and has been surgically removed. The trial will see if pembrolizumab improves overall survival or disease-free survival.
- 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 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.
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.
- 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 spread to the muscle in the bladder. Non-muscle-invasive bladder cancer is early-stage cancer, but it usually comes back after treatment. The two drugs may act 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 will focus on patients with locally-advanced and metastatic urothelial cancer, whereas other parts will focus on patients with muscle-invasive bladder cancer.
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.
The combination of enfortumab vedotin-ejfv and pembrolizumab is also being evaluated as a treatment for patients with previously untreated advanced bladder cancer.
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. By helping the immune system recognize and kill cancer cells, this treatment can benefit patients whose tumors don’t respond to the commonly used BCG therapy.
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.
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.
- 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
- Study Clarifies Timing of Immunotherapy for Advanced Bladder Cancer
- Enfortumab Vedotin Approved for Recurrent Bladder Cancer
View the full list of Bladder Cancer Research Results and Study Updates.