Gallbladder 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. For gall bladder cancer, blood tests like metabolic chemistry, liver function tests and tumor marker levels (CEA and CA 19-9), and other tests like ultrasound, cholangiography,  CT, MRI, and/or PET scans  may be used 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 gallbladder 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 in the gallbladder.
• N-describes if the cancer has spread to the lymph nodes.
• M-describes if the cancer has spread to other organs (metastases). 

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 gallbladder cancer staged?

Most gallbladder cancers start on the inside wall of the gallbladder. This is called the epithelium. The tumor can then grow toward other parts of the gallbladder and may take up all or some of the space within the gallbladder. 

Staging for gallbladder cancer is based on:

• The location, size of the tumor and if it has grown through the wall of the gallbladder to nearby organs.
  • Because the gallbladder is made of many layers, how deep the tumor grows from the inside layer (epithelium) to the outer layers (lamina propria, musclaris, perimuscular fibrous tissue and serosa) is important in the staging.
• If the tumor has spread to the lymph nodes. If so, how many lymph nodes are affected?
• If the tumor has spread to other organs. This is called metastasis.

Staging is important because it helps to guide your treatment options. The staging system is very complex. Below is a summary staging system. Talk to your provider about the stage of your cancer.

• Stage 0: The tumor is only in the inner layer of the gallbladder and has not grown into any other layers of the gallbladder. The tumor has not spread to lymph nodes or other organs.
• Stage I: The tumor has grown into more layers of the gallbladder like the lamina propria or the muscularis (muscle layer). The tumor has not spread to lymph nodes or other organs.
• 
  Stage II( A or B): The tumor has spread through the muscularis. It may have also spread in the tissue lining the abdominal cavity (the peritoneum) or the tissue on the side of the liver (but has not spread to the liver). The tumor has not spread to lymph nodes or other organs.
• Stage III (A or B): The tumor has grown through the outer layer of the gallbladder (serosa). The tumor may have grown into the liver or another part of the body like the stomach, small intestine, colon, bile ducts or pancreas. The tumor has not grown into the veins/arteries that go into the liver. The tumor may have also grown into the lymph nodes but no more than three lymph nodes are involved. It has not spread to other organs beyond the stomach, small intestine, colon, bile ducts or pancreas.
• Stage IV (A or B): The tumor has grown into the veins/arteries that go into the liver or 2 organs outside of the liver. There is tumor spread to the lymph nodes and other organs.

Your provider may also use the grade of your cancer when planning your treatment. The grade tells more about what the tumor cells look like under the microscope. The grade can be 1-3. Higher grade tumors may grow faster. If the cancer can be removed by surgery, it is called resectable. If not, it is unresectable. This can also impact your treatment plan.

How is gallbladder cancer treated?

Treatment for gall bladder cancer is based on the size and location of the tumor and if it has spread to the lymph nodes or other organs. There can be more than one type of treatment used to treat gallbladder cancer. Some of the treatments used for gallbladder cancer are:

• Surgery.
• Radiation.
• Chemotherapy.
• Palliative Therapy.

Surgery 

If the tumor is early stage and only in the inner layer of the gallbladder, the whole gallbladder can be removed. This is called a cholecystectomy. Once the tumor has grown into the muscle, parts of the liver may also need to be removed. If the tumor is larger, an entire lobe of the liver may need to be removed. This is called hepatectomy/lobectomy. Sometimes a procedure known as a Whipple (pancreaticduodenectomy) is used in later stage gallbladder tumors.

There are also palliative procedures where the goal is not to remove the cancer, but to relieve symptoms the cancer may be causing. This could include relieving a blockage of the bile duct (biliary stent). Stage IV tumors are usually not treated with surgery.

Radiation

Radiation is the use of high-energy x-rays to kill cancer cells. Radiation can be used after surgery or to relieve symptoms. If you can’t have surgery because the tumor is later stage or because of other health problems that might impact your recovery, radiation can be used with or without chemotherapy to improve symptoms that may develop as a result of tumor and/or metastases. Radiation usually targets the tumor (or tumor bed, if post-surgery) and the lymph nodes in that area. 

Chemotherapy

Chemotherapy is the use of anti-cancer medicines that go through your whole body. These medicines may be given through a vein (IV, intravenously) or by mouth. Researchers are also studying giving chemotherapy for gallbladder cancer directly into the main artery that supplies the liver called the hepatic artery. This artery also supplies the gallbladder. The goal is to deliver more chemotherapy directly to the tumor. However, to have hepatic artery infusion, you will need to be well enough to have surgery to put a catheter into the hepatic artery. If the cancer is advanced, you may not be well enough to have this procedure.

Chemotherapy is used to treat gallbladder cancer either after surgery (adjuvant therapy) or as the only type of treatment. Chemotherapy can also be used to relieve symptoms. This is called palliative therapy. The chemotherapy medications used to treat gall bladder cancer are 5-FU, cisplatin, capecitabine, oxaliplatin, gemcitabine and albumin-bound paclitaxel. These medications may be used alone or in combination.

Targeted therapies target specific genetic or molecular markers on tumors. Some gallbladder tumors have these markers. Your team may test a sample of your tumor for them. Targeted medications used in the treatment of some gall bladder cancers are entrectinib, larotrectinib, pembrolizumab and dostarlimab-gxly.

Palliative Therapy

Palliative therapy is used to relieve symptoms that are caused by the tumor. They do not cure the cancer. Symptoms that can be treated with palliative therapy include pain, nausea, or jaundice (yellowing of the skin/eyes). A biliary stent or catheter can be placed to treat jaundice. This will help the bile drain out of the bile ducts. A surgical biliary bypass is another palliative procedure that can be used in some patients to allow bile to flow more freely. 

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.