What You Need To Know About Gallbladder Cancer

Unless you’ve had gallstones, you’ve probably never given a second thought to your gallbladder. However, gallbladder cancer, when found at an advanced stage, is quite deadly. Fortunately, it’s relatively uncommon in the U.S., affecting fewer than 5,000 people annually.

Located under the liver in the upper right side of the abdomen, the gallbladder is a small, pear-shaped organ that stores bile, which is produced in the liver. Bile is a fluid that helps us digest fatty foods.

Who Gets It
While rare in the U.S., the incidence of gallbladder cancer is high in some parts of the world and, in some areas, has even reached epidemic proportions. “Gallbladder cancer is more common in South America,” says Dr. Zoe Goldberg, a medical oncologist at Memorial Sloan Kettering Cancer Center. “Chile has a high incidence. Southeast Asia, Japan, India, Pakistan and Korea also have a much higher incidence,” she adds. Gallbladder cancer in these areas is correlated with a high rate of gallbladder stones and chronic salmonella infection.

In the U.S., individuals with Native American heritage have high rates of gallbladder cancer as well, says Dr. Debashish Bose, a surgical oncologist at Orlando Health UF Health Cancer Center. “There are probably some environmental factors that predispose them,” he says.

Risk Factors
The primary risk factor for gallbladder cancer is gallstones, which are hardened bits of digestive fluids that can block the bile ducts and cause pain and swelling. Bose says everyone will eventually get gallstones if they live long enough, although for many people the stones will never cause symptoms. In fact, 80 percent of people with gallstones can go years without experiencing symptoms, according to the American College of Surgeons.

As many as 85 percent of people with gallbladder cancer have gallstones. Larger stones, those greater than three centimeters, pose a greater risk for cancer than smaller stones. That said, most people with gallstones do not develop cancer, Goldberg says. In fact, fewer than 3 percent of people with gallstones do.

Obesity is the other big risk factor. According to a review published in the journal Clinical Epidemiology, for each five-point increase in body mass index (a measure of body fat), the relative risk of developing gallbladder cancer increases by nearly 60 percent for women (who already have a higher incidence of gallbladder cancer) and 9 percent for men. Obesity also raises the risk for diabetes, which is a risk factor for developing gallstones and a risk factor for gallbladder cancer even absent gallstones.

Part of the reason cancer rates are low in the U.S. is because so many people have their gallbladders removed due to gallstones. Bose says that among general surgeons, gallbladder removal, or cholecystectomy, is the most often performed operation in the country, typically due to pain from gallstones. So, most cases of gallbladder cancer are found incidentally, when the gallbladder is removed or imaged for some other reason.

Gallbladder cancer has few symptoms, so it’s rarely diagnosed early, and the symptoms that do present are vague and similar to gallstones. These include pain in the right side or under the ribs, nausea, vomiting, weight loss, trouble with certain foods and possibly jaundice (yellowing of the skin), Bose says.

If the cancer is contained and has not penetrated into the wall or gone through the wall of the gallbladder, removing the organ is usually enough, Bose says. However, fewer than 10 percent of patients have tumors that can be removed surgically, and about 50 percent of tumors have already spread to the lymph nodes by diagnosis. If the cancer has gone through the wall of the gallbladder and invaded the liver or other nearby structures, it has a very poor prognosis, Bose says. “Despite our best efforts, most of these people will not be alive two years out,” he explains.

Goldberg says patients with advanced stages of gallbladder cancer need to see a surgeon who specializes in biliary cancers, as they may need more surgery. Because gallbladder cancer is not common, most general surgeons do not see many cases.

Following surgery, Goldberg says patients may need additional cancer therapy, such as chemotherapy or radiation, to help reduce the likelihood of recurrence. These therapies are controversial, she says, since there is no data from randomized clinical trials (the gold standard for medical research) to show they are effective. However, in the absence of clinical trial data, Goldberg says the consensus among oncologists is to use chemotherapy or chemotherapy plus radiation therapy in patients who have advanced disease. Unfortunately, even with treatment, she says, the risk of recurrence is very high.

Goldberg says it’s important for gallbladder cancer patients with resectable cancer (cancer than can be removed surgically) to enroll in a randomized clinical trial if one is available. She says oncologists are also doing more molecular testing on tumors, which may eventually provide opportunities for additional therapies. At Sloan Kettering Memorial Cancer Center, where she practices, Goldberg says they are looking at more than 400 genes that could be mutated in tumors. At this point, most of the results are not applicable to gallbladder cancer patients because active therapies don’t exist to address specific mutations. However, Goldberg says, for a small percent of patients who do have mutations, clinical trials might give them better outcomes than standard palliative chemotherapy.