Gallbladder cancer is a rare disease, often with a poor prognosis. Fewer than 5,000 Americans are diagnosed with this form of cancer each year. People commonly don’t experience any symptoms of gallbladder cancer during the early stages of disease. But even if they do, their symptoms may mimic the signs for gallstones, so the cancer may evade detection. In fact, doctors often discover gallbladder cancer when they remove the gallbladder to treat a seemingly benign condition.

Women are twice as likely as men to get gallbladder cancer, and age is a factor; it’s commonly diagnosed when people are in their 60s or older.

“We have a multidisciplinary hepatobiliary team at Yale, including surgeons, medical oncologists, radiation oncologists, gastroenterologists, and interventional radiologists that discuss the best treatment plan for each patient,” says Stacey Stein, MD, Assistant Professor of Medicine and Medical Oncology at Yale School of Medicine. “Depending on the stage of this tumor, this may include surgery, radiation, and chemotherapy.” 

Gallbladder cancer is the most common cancer of the biliary tract, which includes the gallbladder and the bile ducts. This form of cancer develops in the tissue lining of the gallbladder.

The gallbladder is a small organ that holds bile, a liquid the liver produces that helps the body digest fatty foods. Sometimes, bile contains too much cholesterol or not enough bile salts, which may lead to the formation of hard, small gallstones. When a gallstone is very large, or when it blocks a bile duct, it may lead to pain and inflammation within the gallbladder. People who have chronic gallstones and chronic inflammation of the gallbladder are at increased risk of gallbladder cancer. Over time, inflammation may lead to mutations in cells within the gallbladder, and the mutations may develop into cancerous cells.

Most people with gallbladder cancer are diagnosed at a late stage. This happens because the early stages of gallbladder cancer typically don’t have noticeable symptoms, and also because the gallbladder is located deep within the abdomen, beneath the liver, in an area that isn’t easily monitored. There are no routine tests that check on gallbladder health.

Doctors don’t know the exact cause of gallbladder cancer, but it often occurs when the person has chronic inflammation of the gallbladder. It’s believed that extended periods of inflammation within the gallbladder may lead to cellular changes, which eventually mutate into cancerous cells. The changes don’t happen quickly; they may take place over the course of about 15 years.

One of the most common reasons for inflammation of the gallbladder is a history of gallstones. At least 75% of people with gallbladder cancer have previously had gallstones. Gallstones may increase the risk of cancer four- or five-fold.

Many people with gallbladder cancer don’t experience symptoms. Those who do may have:

• Chronic abdominal pain, sometimes in the upper right region
• Bloating
• Nausea and/or vomiting
• Fever
• Unexplained weight loss
• Fatigue
• Abdominal lumps
• Jaundice, including a yellowing of the whites of the eyes
• Itchy skin

Women and older adults are at greater risk of gallbladder cancer.

Additionally, people are more likely to develop gallbladder cancer if they have, or have had:

• Gallstones
• Gallbladder polyps
• Chronic gallbladder inflammation
• Gallbladder calcification
• Bile duct cysts
• A family history of gallstones or gallbladder cancer
• Been exposed to pesticides, heavy metals (including lead), water pollution and radiation
• Occupational exposure to chemicals in the textile, shoemaking, paper mill, or petroleum industries
• Anatomical abnormalities in the biliary system, which includes the gallbladder and bile ducts
• Inflammatory bowel disease
• Obesity
• Smoking
• A high-carbohydrate diet
• Chronic liver disease
• Hereditary nonpolyposis colon cancer
• Gardner syndrome
• Neurofibromatosis type I
• Lynch syndrome

Gallbladder cancer is a difficult condition to diagnose, because people generally don’t experience pain or other symptoms in its early stages. It’s often diagnosed when a person has their gallbladder removed.

When a doctor suspects gallbladder cancer, they’ll ask about that person’s personal and family medical history, to find out if anyone has had gallstones or other problems related to the gallbladder or digestive system. The doctor may also ask about the patient’s smoking history, whether they’ve been exposed to chemicals or pesticides at work and what medications they’ve taken.

During a physical exam, the doctor will look for signs of abdominal pain, an enlarged gallbladder, bloating or other symptoms that may indicate a problem.

When doctors suspect gallbladder cancer, they may order tests to help diagnose the problem, including:

• Imaging tests, including ultrasound, CT scan, MRI or PET scan
• Blood tests, which look for the presence of specific proteins that could indicate cancer
• Liver function tests
• Urine tests

To confirm a gallbladder cancer diagnosis, a biopsy must be performed. Sometimes the biopsy is done using ultrasound for guidance.

When gallbladder cancer is diagnosed early, surgery may cure the condition, if the cancer hasn’t spread. During surgery, doctors remove the gallbladder, along with some adjacent lymph nodes and liver tissue. Sometimes, it’s also necessary to remove a portion of bile duct during surgery. After surgery, many people receive chemotherapy, with or without radiation.

Some people don’t find out that they have gallbladder cancer until they’ve had their gallbladder surgically removed for another reason. If a post-operative examination of the gallbladder reveals the presence of cancer, it’s common to have a second surgery to remove some of the lymph nodes and adjacent liver tissue.

It’s important to note that only 25% of people who are diagnosed with gallbladder cancer are eligible for surgery that may cure the condition. In many cases, a tumor is too large for surgery when it’s discovered, or the cancer has spread beyond the gallbladder. When a tumor is too large to be surgically removed, doctors may offer chemotherapy to try to shrink the tumor, with hopes of removing it surgically once its size has been reduced.

If gallbladder cancer has spread to other body parts before diagnosis, the condition is inoperable, and surgery isn’t appropriate. Instead, a person may receive chemotherapy, with or without radiation. The treatments won’t be curative, but they may help a patient live longer. Sometimes, immunotherapy treatments are offered to certain patients when gallbladder cancer has spread to other body parts. In addition, molecular testing can be performed on gallbladder cancers to look for targetable mutations. Targeted therapy may be available for certain mutations.   

When gallbladder cancer is detected and treated early, it’s possible to cure the condition. However, the majority of people aren’t diagnosed until they have advanced disease, when treatment is difficult.

About 15 to 20% of people who are diagnosed with gallbladder cancer survive for five years or longer.

“We have a dedicated multidisciplinary team to provide the best care to our GI cancer patients,” says Dr. Stein. “The hepatobiliary program meets to discuss the treatment plans for each patient, and we perform molecular testing to look for any options for targeted therapy.  We have clinical trials for patients with advanced disease both in our GI team and in the phase 1 team at Yale.”