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Gallbladder puzzle pieces

What causes gallbladder cancer?

Although progress is being made in detecting and understanding many types of cancer and what might cause them, gallbladder cancer remains something of a mystery. 

“There’s not a single factor I’m aware of that could be influenced by behavior or lifestyle modification that could increase or decrease your risk,” says Roderich Schwarz, MD, PhD, co-director of the Liver and Pancreas Tumor Center at Roswell Park Comprehensive Cancer Center. “That’s simply not known. It’s too uncommon a cancer.”

Only 5,000-7,000 patients are diagnosed each year in the United States, but that tally also includes other bile duct and biliary cancers, he notes. 

People who struggle with their gallbladder — with inflammation, recurring gallstones or inflammation of other parts of their bile duct system due to an autoimmune disease — might be at higher risk of developing gallbladder cancer, but that is not always the case. 

“Patients who have gallbladder cancer often have had problems with their gallbladder,” Dr. Schwarz says, adding that those patients might or might not have been aware of those problems. “Half the time we diagnose it, we find gallbladder cancer by chance, because it shows up on a scan that’s done for a different reason. Sometimes we diagnose a patient because we remove a gallbladder for chronic gallstones and we find there’s a small cancer inside, or it’s found because it’s truly causing symptoms and it’s already very advanced and becomes a challenging problem to treat.”

A mysterious cancer

Unlike prostate, lung, colon, breast or other cancers, there is currently no screening test for gallbladder cancer, and with a small number of cases diagnosed every year, it’s challenging to learn more about what causes it, Dr. Schwarz says. 

“A lot of future progress depends on understanding the cancer better. If you ever wanted to make a big impact on changing the outlook for individuals who have cancer, that comes through insight, learning what drives the disease, what causes it to grow.

“We know what drives the changes: It probably starts in a single cell in the lining of the gallbladder wall that then gets some kind of signal and gradually, over a longer period of time than we think, turns into an actively growing process, which is why it’s often linked with chronic inflammation and chronic irritation of that organ.”

The gallbladder is a storage organ, keeping a supply of bile for food digestion; it is not as vital as other organs, and therefore it’s harder to know when there’s a problem. It might not be apparent that something’s wrong until a secondary condition, such as jaundice or yellowing skin, appears.

Some gallbladder cancers aren’t diagnosed until the disease has progressed to a more advanced stage, possibly even spreading to other organs or tissue inside the abdomen. “If someone is losing weight and feels bloated but doesn’t know what is going on, we might learn that there’s a problem that originated in the gallbladder and that it may have spread,” he says.

“The goal is to identify the disease at a stage in which it’s treatable — or prevent it. With colon cancer, a colonoscopy removes the polyp, and the likelihood of getting colon cancer is significantly reduced. Unfortunately, we can’t do that for gallbladder cancer.” 

Chemotherapy, radiation treatments improving

When someone is diagnosed with gallbladder cancer, a few treatment options are available. Chemotherapy has “come of age” for gallbladder cancer in the past few decades. “Up to 20 years ago, little to nothing was effective, but now we have chemotherapy options that are useful for patients with biliary tract cancers, including gallbladder cancer,” Dr. Schwarz says.

“Patients should be considered for chemotherapy if they have a large cancer that cannot be completely removed. Chemotherapy can help shrink the tumor so we can consider getting to a removal step later on, or if removal shows an actively growing tumor and that lymph nodes are now involved, giving chemotherapy in addition to an operation is an option.” 

New treatments offer promising advances

New treatments in development hold promise for the future. 

The first is targeted therapy or biologic therapy, designed to block “driver” molecules that are believed to power the cancer. Some of these molecules can be found not only in the gallbladder but also in other areas of the bile duct system, including inside the liver. “These molecules drive the disease and we have specific medications that can block the activity related to these molecules. That’s better than any conventional chemotherapy and can lead to more lasting effects,” Dr. Schwarz says.

The other promising treatment is immunotherapy, a growing field that is making strides against other kinds of cancer. “We can’t make the statement now that immune treatment is the solution for many patients with gallbladder cancer, but we have some patients whose tumors did not respond to chemotherapy, or their side effects from conventional chemotherapy built up. There’s an opportunity to consider immune therapy. The objective is to find the cancers and patients who are good candidates for immune therapy — and if we know that ahead of time, perhaps we can recommend this treatment right away.”

Why Roswell Park for Gallbladder Cancer

Find out what makes Roswell Park unique in treating gallbladder cancer.

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Dr. Schwarz adds that high-quality diagnostic imaging can make a big difference in a patient’s life. “Occasionally lab tests are performed to pinpoint what’s wrong. If we suspect cancer, often that includes an ultrasound. If a mass is found on a CT scan, ultrasound or MRI, it can be helpful to assume that a patient has gallbladder cancer until it is proven otherwise.

“If there’s a concern over cancer, I’d invite the person to spend a day with us, to give us a call and be seen here,” Dr. Schwarz says. “Roswell Park has a lot to offer; in this case, a complete team of experts from different medical specialties that have a lot of experience in diagnosing and treating gallbladder cancer.”