Bladder Cancer

Treatment Planning

Recent advances in understanding and treating bladder cancer are bringing hope to many people affected by this disease. More treatments are now available and even more are expected in the future. Research in clinical trials is advancing quickly to find more effective therapies and better ways to provide the best care for managing side effects of the disease and its treatment.

Once you receive a diagnosis, you will work closely with your doctor to develop a treatment plan. It is an important time to discuss any concerns you have and your expectations for maintaining independence with certain physical activities of daily living, as treatment may change the way you urinate. Always ask questions and request explanations for anything you do not understand.

Your doctor will continually monitor your condition and make adjustments for a number of reasons. Keep in mind that cancer is an ever-changing condition that presents many challenges, so flexibility and patience are important.

Treatment Options

To develop a treatment plan tailored to you and the type of cancer you have, your doctor considers many factors, including the tumor’s stage, grade and biomarker status; whether the cancer is non-muscle invasive or muscle-invasive; potential side effects; your general health; and your preferences concerning urine control. The following treatment options may be used alone or in combination.

Surgery is the primary method for treating a solid tumor. Removing it may offer the best chance of controlling the disease and keeping it from spreading, especially for people with early-stage disease.

Your doctor may also perform a surgical procedure to stage the cancer or to relieve or prevent symptoms that occur later. Different procedures include the following:

  • Transurethral bladder tumor resection (TURBT). A surgeon inserts a cystoscope through the urethra into the bladder and removes the tumor using an instrument with a small wire loop, a laser or high-energy electricity. TURBT may be used to diagnose, stage and treat bladder cancer.
  • Cystectomy. A radical cystectomy removes the entire bladder and may also include nearby tissues or organs. Lymph nodes in the pelvis are also removed. In addition, men may have their prostate and urethra removed, and women may have their uterus, fallopian tubes, ovaries and part of the vagina removed. A partial (segmental) cystectomy may be performed to remove only a portion of the bladder, preserving the ability to urinate normally. In some cases, a cystectomy may be done laparoscopically or robotically.
  • Urinary diversion. If your bladder is removed, a way to store and pass urine must be created. You and your treatment team will determine which of the three types of diversion will work best for you.
    • An ileal conduit involves creating a new tube from a piece of intestine (ileum) to allow your kidneys to drain and exit through a small opening called a stoma.
    • A continent cutaneous pouch is a pouch inside your body made from a segment of your intestine that is attached to your ureters, allowing urine to be stored internally and then removed through a hole in your abdomen.
    • A neobladder, also referred to as a substitute bladder, uses a portion of your intestine to connect the ureters and the other end to the urethra (tube through which urine exits the body).

Drug therapy may include chemotherapy, immunotherapy or targeted therapy. These therapies may be used alone or in combination with other therapies.

Chemotherapy uses drugs to kill rapidly multiplying cells throughout the body. It is typically delivered in cycles, with treatment periods followed by rest periods to give your body time to recover. A specific strategy may consist of a single chemotherapy drug, a combination given at the same time or drugs given one after another. Chemotherapy may be used alone or with other forms of treatment. It may be used before surgery (neoadjuvant) or after surgery (adjuvant).

In bladder cancer, chemotherapy may be given intravesically or systemically.

  • Intravesical (local) chemotherapy delivers drugs into the bladder through a catheter inserted through the urethra. Local treatment only destroys superficial tumor cells that come in contact with the chemotherapy solution. It cannot reach tumor cells that have invaded the muscular layer of the bladder wall or tumor cells that have spread to other organs.
  • Systemic chemotherapy is given intravenously (IV) through a small tube inserted into a vein or port (see Figure 1). It travels through the bloodstream.

Immunotherapy harnesses the potential of the body’s own immune system to recognize and destroy cancer cells. Several types of immunotherapy are approved for bladder cancer, including cytokines, immune checkpoint inhibitors, modified bacteria and monoclonal antibodies.

Cytokines aid in immune cell communication and play a big role in the full activation of an immune response. They are given intravesically.

Immune checkpoint inhibitors are drugs that prevent the immune system from slowing down, allowing it to keep up its fight against the cancer. They are given intravenously through a vein in your arm or a port.

Modified bacteria, such as bacillus Calmette-Guérin (BCG), have been changed to reduce the likelihood that they will not cause a harmful infection while stimulating an immune response. It is given intravesically over multiple weeks followed by a rest period of several weeks (see Figure 2).

Monoclonal antibodies (mAbs) are laboratory-made antibodies designed to target specific tumor antigens, which are specific proteins or other molecules on the surface of tumor cells that may trigger an immune response. In bladder cancer, mAbs target PD-1 or PD-L1 on the surface of the cancer cells.

Targeted therapy uses drugs or other substances to identify and attack specific types of cancer cells. Unlike chemotherapy, which attacks healthy cells as well as cancer cells, targeted therapy is designed to affect only cancer cells. The types of targeted therapy approved for bladder cancer include a kinase inhibitor and monoclonal antibodies (mAbs).

A kinase inhibitor may treat some bladder cancers with the fibroblast growth factor receptor (FGFR2 or FGFR3) gene mutation. Data suggest that tumors with mutated FGFR3 are less likely to be recognized by the immune system, making targeted therapy an option for this gene mutation.

The approved mAbs are antibody-drug conjugates, which mean they consist of a monoclonal antibody that is linked to a chemotherapy drug. Each mAb is designed to target a specific protein on the surface of bladder cancer cells. Once the mAb finds the target on a cancer cell, it connects to it and delivers the chemotherapy drug directly into the cell to destroy it.

Chemoradiation therapy is a treatment approach that combines systemic chemotherapy and pelvic radiation therapy. It may be given after the bladder tumor is removed (using TURBT) or instead of surgery. This treatment approach is considered a “bladder-preservation” option because removal of the bladder may not be necessary if no cancer is detected after treatment. This may be an option for patients whose tumors appear to have been completely removed by TURBT, invaded no deeper than the muscle wall and have not obstructed the ureter.

Radiation therapy uses high-energy radiation to destroy cancer cells and shrink tumors. It may be given with chemotherapy to relieve symptoms or to treat advanced disease. External-beam radiation therapy (EBRT) uses a machine outside the body to send radiation toward the cancer (see Figure 3).

Clinical trials are medical research studies that may offer access to leading-edge treatments not yet widely available. Let your team know if you are open to considering a clinical trial. You can also search on your own. Once you find a potential trial, talk with your doctor. Keep in mind that some may be closed, and you may not qualify for every trial that interests you.

Every participant in a specific trial must meet the same eligibility criteria. Common criteria include cancer type, subtype, stage, biomarker status and treatment history. Your age, gender and other health conditions may also be factors. For example, if a trial requires that you have already had a specific treatment and you have not, you will not be eligible. Ask your doctor if this is an option to consider.

Researchers are evaluating improved ways of performing cystectomies and lymph node dissections, identifying changes to genes or proteins that may lead to bladder cancer, and finding new types of targeted therapy and immunotherapy, or new drug combinations.

Recurrent Bladder Cancer

It is possible for bladder cancer to return after treatment. This is known as a recurrence and it can happen weeks, months or even years after treatment stops. The potential for recurrence is why follow-up care is so important.

The cancer may return in the same area as the primary cancer or in a different area of the body. Treatment options for recurrent cancer depend on the location and extent of the tumor, treatment history and overall health.

If your bladder cancer returns, your doctor will begin a new cycle of testing to determine any changes in your type of cancer and physical symptoms. A new treatment plan may be developed, and you may add finding a clinical trial to your plan.

Terms to Know

You will hear many new words and phrases. These definitions will help.

First-line therapy: The first treatment used.

Second-line therapy: Given when the first-line therapy does not work or is no longer effective.

Standard of care: The best treatment known for the type and stage of cancer you have.

Local treatments: Directed to a specific organ or limited area of the body and includes surgery and radiation therapy.

Systemic treatments: Typically drug therapies such as chemotherapy, immunotherapy and targeted therapy that travel throughout the body.

Intravesical therapy: A type of drug therapy that is injected directly into the bladder.

Commonly Used Medications 

Chemotherapy
cisplatin
doxorubicin (Adriamycin)
methotrexate
mitomycin (Jelmyto, Mitozytrex, Mutamycin)
thiotepa (Tepadina)
valrubicin (Valstar)
Immunotherapy
   Cytokine
interferon (Roferon-A, Intron A, Alferon)
   Immune Checkpoint Inhibitors
atezolizumab (Tecentriq)
avelumab (Bavencio)
nivolumab (Opdivo)
pembrolizumab (Keytruda)
   Modified Bacteria
bacillus Calmette-Guérin (BCG)
Targeted Therapy
   Kinase Inhibitor
erdafitinib (Balversa)
   Monoclonal Antibody
enfortumab vedotin-ejfv (Padcev)
sacituzumab govitecan-hziy (Trodelvy)
Some Possible Combinations
carboplatin (Paraplatin) and gemcitabine (Gemzar)
cisplatin and gemcitabine (Gemzar)
Dose dense (DD)-MVAC (methotrexate, vinblastine [Velban, Velsar], doxorubicin [Adriamycin] and cisplatin)
MVAC - methotrexate, vinblastine (Velban, Velsar), doxorubicin (Adriamycin) and cisplatin
As of 5/12/22