Gallbladder cancer is a rare but serious disease in which malignant (cancerous) cells form in the tissues of the gallbladder. A gallbladder tumour or neoplasm refers to an abnormal growth in the gallbladder, which may be benign or malignant. The gallbladder is a small, pear-shaped organ located beneath the liver that stores and releases bile, a fluid that helps digest fats.
The chance of cure is good when gallbladder cancer is diagnosed in its early stages. However, most gallbladder cancers are found when they have progressed to a late stage, in which the prognosis is often poor. Approximately four in five patients with gallbladder cancer are diagnosed in the advanced or metastatic stage. The five-year relative survival rate of patients with the condition is around 15-20% if diagnosed in the early stage, but less than 5% if diagnosed in the advanced stage
The condition is difficult to diagnose and tends to present late as it may cause no symptoms in the early stages. In addition, due to the deep location of the gallbladder in the human body, it is easier for gallbladder cancer to grow without being detected. It can spread to nearby tissues or other parts of the body, through the lymphatic system or the blood's circulatory system.
Gallbladder cancer is uncommon, but its incidence varies by region. It is more frequently observed in Central and South America, Eastern Europe and Southeast Asia. Gallbladder cancer is the 22nd most common cancer worldwide. It is the 23rd most common cancer in men and the 20th most common cancer in women. It accounts for about 1.7% of all cancer mortality and approximately 3.5 million disability-adjusted life years (the loss of the equivalent of one year of full health) globally.
In Singapore, gallbladder cancer is rare, affecting 1.7 out of every 100,000 people.
It is more commonly diagnosed in older adults and individuals with specific risk factors such as gallstones or chronic inflammation of the gallbladder.
The signs and symptoms of gallbladder cancer are not always apparent in its early stages. When symptoms do appear, they may include:
Since the symptoms above can also be caused by more common conditions such as gallstones, infections or liver disease, it is important to seek medical attention if they persist or worsen over time. Early detection remains challenging, but individuals with known risk factors should be particularly vigilant.
There is no known way to prevent most gallbladder cancers. Many of the known risk factors for gallbladder cancer (age, sex, ethnicity, bile duct defects) are beyond one's control.
The following measures may help to lower the risk of developing the condition:
Most of these mutations are thought to arise from prolonged inflammation rather than hereditary factors.
Several factors may increase the risk of gallbladder cancer, including:
Early-stage gallbladder cancer can be difficult to detect, and its diagnosis often occurs incidentally during imaging for unrelated conditions or after gallbladder removal for gallstones.
Diagnostic tests for gallbladder cancer include:
Treatment depends on the stage of cancer and the overall health of the patient. Treatment options include:
Surgery
Early-stage gallbladder cancer may be treated with cholecystectomy (gallbladder removal), often including nearby tissues and lymph nodes.
If the cancer is advanced and inoperable, palliative surgery or procedures may be performed to relieve symptoms. Such options include:
Radiation therapy
External beam radiation therapy uses high-energy rays to target cancer cells and shrink tumours, either as a primary treatment or after surgery to reduce recurrence risk if resection margins are involved.
Chemotherapy
Systemic chemotherapy, using drugs such as Gemcitabine and Cisplatin, or 5-Fluorouracil based chemotherapy, is administered orally or intravenously to slow cancer progression and shrink tumours, particularly when surgery is not an option.
Targeted therapy
This approach uses drugs that targets specific genetic mutations in cancer cells. For example, ivosidenib targets IDH1 mutations, while infigratinib and pemigatinib target FGFR2 fusions. These are typically used in patients with advanced or inoperable disease who test positive for these mutations on next generation sequencing.
Immunotherapy
Immune checkpoint inhibitors such as pembrolizumab (PD-1) and durvalumab (PD-L1) help the immune system recognise and attack cancer cells. These may be considered for advanced-stage or recurrent gallbladder cancer that no longer responds to standard treatments, or in patients with certain mutations or deficient mismatch repair proteins.
Although gallbladder stones can raise your risk of gallbladder cancer, they do not directly cause the disease.
Early-stage gallbladder cancer can be treated successfully with surgery, but most cases are diagnosed at a later stage, making treatment more challenging. This highlights the importance of early detection.
There is a test to measure the amount of bilirubin in your blood, but there are no tests that can identify gallbladder cancer specifically. Bilirubin levels can increase as a result of gallbladder issues, including malignancy. Tumour markers such as Ca19-9 are not diagnostic for gallbladder cancer, but they can be monitored for diagnosed cases as a surrogate marker that indicates disease response (however, radiological imaging would still be a more objective parameter).
Survival rates depend on the stage. In the early stages of gallbladder cancer, a five-year survival rate of up to more than 50% can be achieved if stage-adjusted therapy is performed. Once cancer has spread beyond the gallbladder, however, survival rates are lower.
There are no routine screening tests, and it is often detected incidentally. Awareness of risk factors and early symptoms is important for early detection.
Gallbladder removal significantly reduces the risk of gallbladder cancer, especially in individuals with chronic gallbladder disease, but it does not eliminate the possibility of cancer developing in surrounding tissues.
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