Gallbladder Cancer Treatments

What are the treatment options for gallbladder cancer?

Treatment depends on the stage of cancer, whether the tumor can be surgically removed, and the patient's overall health. The main treatment approaches include:

• Surgery

• Chemotherapy

• Immunotherapy

• Targeted therapy for selected molecular alterations

• Radiation therapy

• Clinical trials

• Supportive and palliative care

Surgery offers the best opportunity for a cure when the cancer can be completely removed. For advanced or metastatic disease, systemic therapy is usually the main treatment approach.

Surgery for gallbladder cancer

Surgery is the preferred treatment for many patients with early-stage gallbladder cancer. The type of surgery depends on how deeply the tumor has invaded and whether nearby structures are involved.

Simple cholecystectomy

A cholecystectomy removes the gallbladder. For certain very early gallbladder cancers, particularly T1a tumors confined to the lamina propria, gallbladder removal alone may be sufficient.

Extended or radical cholecystectomy

For cancers that invade more deeply, a more extensive operation may be necessary. This may involve removing:

• The gallbladder

• A portion of the liver adjacent to the gallbladder

• Nearby lymph nodes

• Additional involved tissues when necessary

This procedure is sometimes called an extended or radical cholecystectomy. The goal is to remove all visible cancer and achieve negative surgical margins.

Surgery for incidental gallbladder cancer

When gallbladder cancer is discovered after routine gallbladder removal, the pathology report helps determine whether additional surgery is necessary. Patients with T1a disease and negative margins may not require further surgery. Patients with T1b or more advanced disease may be evaluated for additional liver resection and regional lymph node removal. The recommendation depends on the pathology, imaging findings, and the patient's overall condition.

Chemotherapy for gallbladder cancer

Chemotherapy uses medications to kill cancer cells or interfere with their growth. It may be used:

• After surgery to reduce recurrence risk

• As part of treatment for locally advanced cancer

• For unresectable or metastatic disease

• When cancer returns after treatment

Capecitabine after surgery

Capecitabine (Xeloda) is an oral chemotherapy medication. For many patients who undergo curative-intent surgery for biliary tract cancer, including gallbladder cancer, approximately six months of adjuvant capecitabine is a commonly recommended approach. Adjuvant treatment means treatment given after surgery to lower the risk of cancer returning. The decision depends on surgical findings, recovery, overall health, and other factors.

Gemcitabine and cisplatin

Gemcitabine and cisplatin have long been a standard chemotherapy combination for advanced biliary tract cancers. These medications are given intravenously. Today, immunotherapy is often added to this combination for eligible patients.

Immunotherapy for gallbladder cancer

Immunotherapy helps the immune system recognize and attack cancer cells. Immune checkpoint inhibitors are now an important part of first-line treatment for many patients with unresectable or metastatic biliary tract cancer, including gallbladder cancer.

Durvalumab (Imfinzi)

Durvalumab is an immune checkpoint inhibitor that blocks the PD-L1 protein. For eligible patients with advanced biliary tract cancer, durvalumab may be combined with gemcitabine and cisplatin. The combination was studied in the TOPAZ-1 clinical trial, which demonstrated an overall survival benefit compared with chemotherapy alone. After the initial chemotherapy treatment, durvalumab may continue as maintenance treatment.

Pembrolizumab (Keytruda)

Pembrolizumab is an immune checkpoint inhibitor that targets PD-1. Pembrolizumab combined with gemcitabine and cisplatin is another first-line treatment option for eligible patients with locally advanced unresectable or metastatic biliary tract cancer. The KEYNOTE-966 trial demonstrated an overall survival benefit for this combination compared with chemotherapy alone. These regimens are supported by evidence from broader biliary tract cancer populations, which included patients with gallbladder cancer.

What are the side effects of chemotherapy and immunotherapy?

Potential chemotherapy side effects include:

• Nausea and vomiting

• Fatigue

• Low blood counts

• Increased infection risk

• Kidney problems

• Nerve damage

• Hearing changes

Immunotherapy can cause immune-related side effects because it activates the immune system. These may include inflammation affecting:

• Skin

• Intestines

• Liver

• Lungs

• Thyroid

• Other hormone-producing glands

Some immune-related reactions can be serious. Patients should report new or worsening symptoms to their oncology team promptly.

Targeted therapy for gallbladder cancer

Targeted therapies are medications designed to interfere with specific molecular features of cancer cells. Molecular testing is increasingly important for patients with advanced biliary tract cancers. However, not all molecular alterations found in bile duct cancer occur at the same frequency in gallbladder cancer. For example, FGFR2 fusions and IDH1 mutations are much more strongly associated with intrahepatic cholangiocarcinoma than gallbladder cancer.

HER2 alterations

HER2 is a protein involved in cell growth. Some gallbladder cancers have HER2 amplification or overexpression. HER2-directed treatments may be appropriate for selected patients with advanced disease. One example is zanidatamab (Ziihera), a HER2-directed bispecific antibody approved for certain previously treated, unresectable or metastatic HER2-positive biliary tract cancers. Eligibility depends on the specific HER2 test results, previous treatment, and current prescribing criteria.

Other actionable biomarkers

Some tumors may have molecular characteristics that support specific treatments. Examples include:

• MSI-H or dMMR: May support treatment with certain immune checkpoint inhibitors.

• NTRK gene fusions: May support treatment with NTRK-targeted therapies.

• BRAF V600E mutations: May support BRAF- and MEK-directed therapy in appropriate circumstances.

• RET fusions: May provide a targeted treatment option for certain advanced solid tumors.

• High tumor mutational burden: May be relevant to selected immunotherapy indications.

These alterations are uncommon, and not every patient will have an actionable biomarker.

Should patients have molecular testing?

Patients with unresectable, recurrent, or metastatic gallbladder cancer should discuss comprehensive molecular profiling with their oncology team. Testing may help identify:

• Targeted treatment opportunities

• Immunotherapy-related biomarkers

• Eligibility for clinical trials

Tumor tissue is commonly used for testing. In some circumstances, circulating tumor DNA testing from blood may provide additional information.

A negative blood-based test does not always exclude an actionable tumor alteration.

Radiation therapy for gallbladder cancer

Radiation therapy uses high-energy radiation to damage cancer cells. It may be considered:

• After surgery in selected higher-risk cases

• For certain locally advanced tumors

• To relieve pain

• To control bleeding

• To reduce symptoms caused by tumor growth

Radiation may be given alone or combined with chemotherapy. Not every patient with gallbladder cancer requires radiation.

What happens if the cancer blocks a bile duct?

Gallbladder cancer may obstruct the flow of bile. This can cause jaundice, itching, infection, and liver dysfunction. A doctor may recommend a procedure to relieve the obstruction.

Biliary stent

A stent is a small tube placed inside a blocked bile duct to allow bile to flow. Stents are often placed during ERCP.

Percutaneous biliary drainage

If endoscopic drainage is not possible, a radiologist may place a drainage catheter through the skin and into the biliary system. These procedures can improve symptoms and may make it possible to begin or continue cancer treatment.

Supportive and palliative care

Supportive care focuses on reducing symptoms and improving quality of life. It can be provided alongside cancer-directed treatment at any stage. Services may include:

• Pain management

• Nausea treatment

• Nutritional counseling

• Management of jaundice and itching

• Treatment of bile duct obstruction

• Psychological support

• Physical therapy

• Palliative care consultation