Advanced bladder cancer is cancer that has spread beyond your bladder. It may be in your lymph nodes, or even in other organs. As a result, you have a poorer prognosis than someone whose cancer is only in their bladder. But there is some good news: There are now ways to target advanced bladder cancer using your immune system.
Immunotherapy has been a real game changer when it comes to treatment for advanced bladder cancer. It has improved survival rates, notes Ashish Kamat, MD, MBBS, director of bladder cancer research at the MD Anderson Cancer Center in Houston. It also provides a targeted immune response, meaning it can kill off cancerous cells while sparing healthy ones. Immunotherapy generally has fewer severe side effects versus other treatments like chemotherapy, he says.
Here's a closer look at immunotherapy for advanced bladder cancer: what it is, how it works, who's a candidate, as well as other targeted treatments and advances for bladder cancer.
What Is Immunotherapy for Advanced Bladder Cancer?
Immunotherapy uses medications to help your immune system recognize and attack cancer cells. There are some drugs that are used to treat early-stage bladder cancer, and other medicines that treat advanced bladder cancer. If you have advanced bladder cancer, your cancer team may recommend that you use a class of immunotherapy drugs known as immune checkpoint inhibitors.
Normally, your body relies on "checkpoint" proteins to help run your immune system. They act like light switches: When they turn on, they stimulate your immune system to fight cancerous cells, and they also turn off to prevent your immune system from attacking normal cells. Cancer cells hijack these "checkpoint" proteins so that they don't work properly.
Immune checkpoint inhibitors block checkpoint proteins so that they can't turn off. This allows your immune system to ramp up and kill cancer cells. Some drugs your doctor may recommend include:
- Avelumab (Bavencio). This drug is often used if your advanced bladder cancer is stable or has shrunk with regular chemotherapy drugs.
- Durvalumab (Imfinzi). It's often used to treat a type of bladder cancer called muscle invasive bladder cancer (MIBC). In this type, cancer has spread into the muscle layer of the bladder, but not to other parts of the body. It can be used along with chemotherapy before you have surgery to remove your bladder or alone after surgery.
- Nivolumab (Opdivo). Your doctor may want to use this if your advanced bladder cancer has not responded to chemotherapy.
- Pembrolizumab (Keytruda). This is also used if your cancer hasn't responded to chemotherapy, or you're not able to tolerate chemo.
- Another drug, atezolizumab (Tecentriq) was FDA approved to treat advanced bladder cancer in the United States, but its maker pulled it off the market for this use in 2022 after research showed it didn't work any better than chemotherapy alone. It's still used to treat lung and liver cancer.
Avelumab and durvalumab target the protein PD-L1, while nivolumab and pembrolizumab target PD-1. In both cases, these proteins are blocked so that your immune system ramps up its response against cancer cells.
Your doctor will decide which drug to use based on the type of tumor you have. They may want to test your cancer cells for proteins like PD-L1 and PD-1. They'll also take into account your overall health, prior treatments, and how easy it is to get the drug, says Kamat.
How Does Immunotherapy for Advanced Bladder Cancer Work?
The immunotherapy medicine is injected into your blood through a vein, or intravenously. This way, the medicine spreads throughout your entire body to reach cancer cells outside of your bladder.
Generally, you get these treatments anywhere from once a week to once every few weeks. You usually go to your doctor's office or an outpatient clinic. You don't need to stay in the hospital.
Immunotherapy can also be used with other treatments. Durvalumab and nivolumab, for example, are often used alongside chemotherapy.
Other Targeted Treatments for Advanced Bladder Cancer
Targeted therapy is a type of precision or personalized medicine to treat advanced bladder cancer. It targets specific features, changes, or mutations in cancer cells. The goal is to stop their growth and spread.
There are two main types of targeted therapy to treat advanced bladder cancer:
Antibody-drug conjugates (ADCs). These medicines consist of a chemo drug linked to a monoclonal antibody, which is a lab-made version of an immune system protein that attaches to a specific target on cancer cells. There's one ADC available to treat advanced bladder cancer, a drug called enfortumab vedotin (Padcev). It contains an antibody that attaches to a protein called the nectin-4 protein that's on the surface of bladder cancer cells. Once the antibody is connected with the protein, it releases a specific type of chemotherapy called monomethyl auristatin E (MMAE) inside the cancer cell.
Enfortumab vedotin is often used along with the immunotherapy drug pembrolizumab in people with advanced bladder cancer. The FDA approved the use of both medications together in December 2023. The combination has been shown to double survival rates of people with advanced bladder cancer, compared to those who were just being treated with chemotherapy.
It can also be used alone in patients who have already been treated with one of the above immunotherapy drugs and chemotherapy or in patients who can't tolerate chemotherapy.
It's given via IV injection once a week for three weeks, followed by a week off. Each infusion takes about 30 minutes, and it's done at your doctor's office or at an infusion center. Your doctor will let you know how many treatment cycles you need.
FGFR inhibitors. FGFRs are a group of proteins on bladder cells. Sometimes, the genes that make them have mutations, which affects how these proteins are made and can ultimately lead to cancer. One drug, erdafitinib (Balversa), targets cells with FGFR gene changes and can help treat some people with advanced bladder cancer. It's usually used after you've already tried immunotherapy. It's taken every day as a pill.
How to Tell if Immunotherapy for Advanced Bladder Cancer Is Working
If you use immunotherapy to treat your advanced bladder cancer, your cancer care team will watch you closely. You'll have regular checkups with your doctor to examine you physically and see how you feel. Your doctor will watch your symptoms to make sure that they improve, says Kamat.
Who's a Candidate for Immunotherapy for Advanced Bladder Cancer?
Immunotherapy is a groundbreaking treatment for advanced bladder cancer. But not everyone's a candidate. In general, your doctor may recommend immunotherapy if:
- You have the right tumor type. Your doctor will test tumor tissue for certain proteins such as PD-1 or PD-L. This is known as biomarker testing. If you don't have these proteins in your tumor, you're less likely to respond to treatment.
- You can't safely use chemotherapy. The gold standard chemotherapy treatment for people with advanced bladder cancer is cisplatin. But people with certain conditions such as kidney disease or heart failure may not be able to take it.
- You haven't responded to other treatments. If you've tried other treatments, like chemotherapy, your doctor may recommend immunotherapy as a second or even third option.
Also, not everyone can safely use immunotherapy for advanced bladder cancer. If you have a severe autoimmune condition that's been hard to get under control, such as lupus, type 1 diabetes, or rheumatoid arthritis, you may not be a good candidate, says Kamat. Immunotherapy can increase inflammation throughout your body, which can make these diseases worse.
Bladder Cancer Advancements
When you meet with your doctor to discuss immunotherapy for advanced bladder cancer, Kamat recommends that you also ask about potential clinical trials. Some of the most exciting recent research includes:
Nivolumab and chemotherapy. A 2023 New England Journal of Medicine study found that combining the immunotherapy drug nivolumab with two types of chemotherapy, gemcitabine-cisplatin, among patients with advanced bladder cancer significantly boosted survival rates. About 22% of patients went into complete remission with the combined therapy, compared to 12% of those who just did the chemotherapy alone. The people on combined therapy also went into remission for just over three years, compared to about 13 months for those who only used chemotherapy.
The AMBASSADOR study. People with a type of advanced bladder cancer called muscle-invasive bladder cancer who received the immunotherapy drug pembrolizumab for a year after they had bladder surgery had a significantly longer period of disease-free survival than those who had surgery alone. They showed no signs or symptoms of bladder cancer for almost 2½ years, compared to about 14 months in the group that had only surgery.
Bispecific antibodies. These are artificial proteins designed to attack tumor cells, and boost immune cells like T cells or natural killer cells. Some early research studies suggest that they may help to fight against metastatic, or very advanced, bladder cancer.
Your doctor may be able to refer you to a research study in your area. You can also find a list of ongoing clinical trials here.
Show Sources
Photo Credit: iStock/Getty Images
SOURCES:
Ashish Kamat, MD, MBBS, director, bladder cancer research, MD Anderson Cancer Center, Houston.
American Cancer Society: "Targeted Therapy," "Immunotherapy for Bladder Cancer."
OncoLink: "Enfortumab Vedotin-ejfv (PADCEV)."
FDA: "FDA approves enfortumab vedotin-ejfv with pembrolizumab for locally advanced or metastatic urothelial cancer," "FDA approves erdafitinib for locally advanced or metastatic urothelial carcinoma."
UpToDate: "Patient education: Bladder cancer diagnosis and staging (Beyond the Basics)."
ASCO Daily News: "First-Line Treatment of Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: The Pursuit of Improved Outcomes."
MD Anderson Cancer Center: "Can immunotherapy treat cancer in patients with autoimmune diseases?"
The New England Journal of Medicine: "Nivolumab plus Gemcitabine-Cisplatin in Advanced Urothelial Carcinoma," "Adjuvant Pembrolizumab versus Observation in Muscle-Invasive Urothelial Carcinoma."
Journal of Clinical Oncology: "A novel CD28 x Nectin-4 costimulatory bispecific antibody for advanced bladder cancer."
