Bladder Cancer: Staging and Treatment

What is staging for cancer?

Staging is the process of learning how much cancer is in your body and where it is. Tests like cystoscopies, X-rays, ultrasounds, CTs, and intravenous pyelograms are done to help stage your cancer. Your providers need to know about your cancer and your health so that they can plan the best treatment for you.

Staging looks at the size of the tumor and where it is, and if it has spread to other organs. The staging system for bladder cancer is called the “TNM system,” as described by the American Joint Committee on Cancer. It has three parts:

• T-describes the size/location/extent of the "primary" tumor. It describes how far the tumor has grown into the wall of the bladder.
• N-describes if the cancer has spread to the lymph nodes. The lymph nodes near the bladder and those along the common iliac artery are called regional lymph nodes. All other lymph nodes are called distant.
• M-describes if the cancer has spread to other organs (metastases).

When looking at the “T” part of your staging, it is important to know that the bladder is made of 4 main layers:

• The urothelium or transitional epithelium is the innermost lining.
• The lamina propria is the next layer, made up of connective tissue, blood vessels, and nerves.
• The next layer is a thick layer of muscle tissue, called the muscularis propria.
• The outside layer is made of fatty connective tissue and separates the bladder from other organs.

Your healthcare provider will use the results of the tests you had to determine your TNM result and combine these to get a stage from 0 to IV.

How is bladder cancer staged?

Staging is based on:

• Which layers of the bladder there is cancer.
• Any evidence of spread to other organs (metastasis).
• Tests to see if your lymph nodes have cancer cells.

The staging system is very complex. Below is a summary of the staging system. Talk to your provider about the stage of your cancer.

• Stage 0a (Ta, N0, M0): This stage is for non-invasive papillary carcinoma. The cancer has grown toward the center of the bladder but not into the connective tissue or muscle of the bladder wall. It also has not spread to lymph nodes or to other parts of the body.
• Stage 0is (Tis, N0, M0): This is carcinoma in situ, meaning it is flat and non-invasive. It is only in the inner lining layer, and it has not spread to lymph nodes or other parts of the body.
• Stage I (T1, N0, M0): The cancer has grown into the connective tissue of the bladder but not the muscle layer. It has not spread to the lymph nodes or other parts of the body.
• Stage II (T2a or T2b, N0, M0): The cancer has grown into the muscle layer of the bladder but not the muscle layer in the bladder wall, and it has not spread to the lymph nodes or other parts of the body.
• Stage IIIA:
  • T3a, T3b or T4a, N0, M0: The cancer has grown through the muscle layer of the bladder and into the fatty tissue. It may be found in the prostate, seminal vesicles, uterus, or vagina, but not into the pelvic or abdominal wall, the nearby lymph nodes, or distant parts of the body.
  • T1-4a, N1, M0: The cancer has grown into the connective tissue under the lining of the bladder wall, the muscle layer of the bladder wall, the layer of fatty tissue around the bladder, the prostate, the seminal vesicles, the uterus, or the vagina. It has not grown into the pelvic or abdominal wall, it has spread to 1 lymph nodes in the pelvis, but it has not spread to distant parts of the body.
• Stage IIIB (T1-T4a, N2 or N3, M0): The cancer has grown into the layer of connective tissue of the bladder wall, the muscle layer of the bladder wall, the fatty tissue that surrounds the bladder, the prostate, seminal vesicle, uterus, or vagina but not into the pelvic or abdominal wall. The cancer has spread to 2 or more lymph nodes in the pelvis or to nodes along the common iliac arteries. It has not spread to distant parts of the body.
• Stage IVA:
  • T4b, Any N, M0: The cancer has grown through the bladder wall into the pelvic or abdominal wall, may or may not be in the nearby lymph nodes, and it has not spread to distant sites.
  • Any T, Any N, M1a: The cancer may or may not have grown through the bladder wall and into nearby organs, may or may not have spread to nearly lymph nodes, and has spread to distant lymph nodes.
• Stage IVB (Any T, Any N, M1b): The cancer has or has not grown through the wall of the bladder into nearby organs, may or may not have spread to nearby lymph nodes, and has spread to 1 or more distant organs like the bones, liver, or lungs.

How is bladder cancer treated?

Treatment for bladder cancer depends on many factors, like your cancer stage, age, overall health, and testing results. Your treatment may include:

• Surgery.
• Intravesicular Therapy.
• Chemotherapy.
• Radiation Therapy.
• Immunotherapy.
• Targeted Therapy.
• Bladder Preservation.
• Clinical Trials.

In some cases, no treatment is done. Instead, cystoscopies are done every few months to monitor the cancer. During a cystoscopy, a tube with a light on the end of it (a cystoscope) is used to look at the bladder and urethra to check for any changes.

Surgery

There are a few different types of surgeries that can be used to treat bladder cancer, depending on your stage. For superficial bladder cancer:

• TURBT (transurethral resection of the tumor) removes the bladder through the urethra. TURBT is the main treatment for superficial disease since all of the tumor is often able to be removed. After a TURBT, you may have intravesicular chemotherapy to prevent the cancer from coming back.

For the treatment of invasive bladder cancer, a cystectomy may be done. This is the partial or complete removal of the bladder.

• A partial cystectomy removes only part of the bladder, which can be an option when the tumor is in one area of the bladder.
• A radical cystectomy removes the whole bladder, nearby lymph nodes, and part of the urethra (which carries urine from the bladder out of the body). In some cases of metastatic disease, the surgeon will also remove other nearby organs.

If your whole bladder is removed, you still need a way for urine to leave your body. This is called urinary diversion. The surgeon will perform this reconstructive surgery to create an ileal or colonic conduit, internal continent pouch or reservoir, or a neobladder.

Intravesicular Therapy

Intravesicular therapy is when chemotherapy or immune therapy is injected directly into the bladder. This treatment kills any remaining cancer cells. Both immunotherapy and chemotherapy medications can be used in intravesicular therapy.

Bacillus Calmette-Guerin (BCG) is an immunotherapy medication that is used. BCG is a type of virus that works to stimulate (rev up) the immune system to kill any cancer cells in the area. You will likely be given this medication many times. After treatment, you will have regular cystoscopies to watch if the cancer comes back (reoccurrence) or if there is new tumor growth.

Nadofaragene firadenovec is another immunotherapy that is made of a virus that contains the gene to make interferon alfa-2b. When the medication is put into the bladder, it delivers the gene into the bladder wall causing the cells to make extra interferon alfa-2b. This helps the body attack the cancer cells.

Mitomycin C and gemcitabine are chemotherapies that can be used in intravesicular therapy. Because the chemotherapy is given in the bladder and not into the bloodstream, there tends to be fewer side effects than with systemic (intravenous or oral) chemotherapy.

Chemotherapy

Chemotherapy can also be given directly into the bloodstream. It can be given before or after surgery, with or after radiation, or by itself. Some of the chemotherapies used are cisplatin, gemcitabine,fluorouracil, mitomycin, dose-dense methotrexate, vinblastine, doxorubicin, paclitaxel, ifosfamide, and pemetrexed. Your provider will talk to you about your regimen and potential side effects.

Radiation

Radiation is the use of high-energy x-rays to kill cancer cells. The type most used is external beam radiation therapy, which uses radiation from a source outside of the body and directs it at your bladder. Radiation may be used as the only treatment, with chemotherapy (called chemoradiation), or before or after surgery. It can also be used to treat side effects caused by advanced bladder cancer.

Immunotherapy

Immunotherapy is the use of medication to help your immune system fight cancer. Examples of immunotherapy are BCG and nadofaragene firadenovec intravesicular therapy. Other examples are:

• Immune checkpoint inhibitor medications that block proteins, in this case PD-1 and PD-L1, that stop the immune system from attacking cancer cells. Nivolumab and pembrolizumab are both PD-1 inhibitors. They target and block PD-1, which allows the immune system to attack cancer cells. Avelumab blocks PD-L1, which helps the immune system attack the cancer cells.
• Monoclonal antibodies are man-made versions of antibodies that target certain proteins on bladder cancer cells. Antibody-drug conjugates are monoclonal antibodies that are linked to chemotherapies. They help bring chemotherapy directly to cancer cells. Examples are enfortumab vedotin and sacituzumab govitecan.

Your provider will tell you if you could benefit from immunotherapy and which one is right for you.

Targeted Therapy

Targeted therapies are medications that target something specific to the cancer cells, stopping them from growing and dividing. Erdafitinib is an FGFR inhibitor. FGFR is a group of proteins found on some bladder cancer cells that helps them grow. This medication can be used to treat cases of bladder cancer that do not respond to chemotherapy. Enfortumab vedotin and sacituzumab govitecan can also be considered targeted therapies.

Bladder Preservation Therapy

Bladder preservation therapy may be an option for some people with cancer that is limited to one area of the bladder. This treatment begins with transurethral resection (TURBT), followed by a combination of radiation and chemotherapy. The goal is to shrink the tumor, preventing the need for cystectomy. A cystoscopy is done after radiation/chemotherapy. If the tumor is gone, you can be monitored and keep your bladder.

Clinical Trials

You may be offered a clinical trial as part of your treatment plan. To find out more about current clinical trials, visit the OncoLink Clinical Trials Matching Service.

Making Treatment Decisions

Your care team will make sure you are included in choosing your treatment plan. This can be overwhelming as you may be given a few options to choose from. It feels like an emergency, but you can take a few weeks to meet with different providers and think about your options and what is best for you. This is a personal decision. Friends and family can help you talk through the options and the pros and cons of each, but they cannot make the decision for you. You need to be comfortable with your decision – this will help you move on to the next steps. If you ever have any questions or concerns, be sure to call your team.

You can learn more about bladder cancer at OncoLink.org.