Newly Diagnosed
Medical Disclaimer
The information provided on the Gallbladder Cancer Foundation Website is for general information purposes only. It is not intended as medical advice and should not be relied upon as a substitute for professional consultation with a qualified healthcare provider familiar with your individual medical needs. The Gallbladder Cancer Foundation is not responsible or liable, directly or indirectly, for any form of damages resulting from the use (or misuse) of information contained in or implied by the information on this site.
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What is ?
Anatomy of the Pancreas, Liver and Gallbladder image provided by macrovector on Freepik
Gallbladder cancer is a rare and aggressive type of cancer of the gallbladder that is usually not diagnosed until advanced stages. The gallbladder is a pear-shaped organ located beneath the liver that stores bile, a digestive fluid produced by the liver. Bile helps in digesting fats in the small intestine. You may also see gallbladder cancer referred to as a biliary tract cancer. Biliary tract cancers consist of ampulla of vater, cholangiocarcinoma (bile duct cancer), and gallbladder cancer.
Gallbladder cancer affects ~5,000 people in the United States annually and ~122,000 people worldwide annually.
Signs & Symptoms
Gallbladder cancer can be challenging to detect because its symptoms often don’t manifest in the early stages. Moreover, the symptoms that do appear may resemble those of more prevalent conditions like gallstones.
Some Symptoms of Gallbladder Cancer can include:
- Lumps in the abdomen
- Pain or discomfort in your upper abdomen
- Jaundice (yellowing of the skin and whites of the eyes)
- Fever
- Weight loss (unexplained)
- Nausea and vomiting
- Bloating
Risk Factors
Although the exact cause of gallbladder cancer remains unknown, certain risk factors can increase the likelihood of developing this condition.
Some risk factors include:
- Age
- Over age 65
- Average Age at Diagnosis is 72
- Gallstones
- Gallstones are commonly linked to gallbladder cancer. Patients diagnosed with gallbladder cancer frequently have multiple or large gallstones. Despite gallstones being very common, gallbladder cancer remains rare, and the majority of individuals with gallstones will not develop gallbladder cancer.
- Female sex
- Gallbladder cancer is more prevalent in women than in men.
- Ethnicity & Geography
- US
- Mexican-Americans and Native Americans are more likely to develop gallbladder cancer.
- Globally
- Gallbladder cancer is more common in South Asians, Latin Americans, & East Asians.
- US
- Other gallbladder conditions
- Cholecystitis
- Chronic inflammation of the gallbladder
- Gallbladder polyps
- Small, typically benign growths that protrude from the lining of the gallbladder.
- Porcelain gallbladder
- Calcification of the gallbladder wall
- Obesity
- Similar to other cancers obesity (High Body Mass Index) can increase the risk of developing gallbladder cancer.
- Typhoid
- Chronic infection of the bacteria that causes typhoid called Salmonella enterica serovariant Typhi
- Cholecystitis
Diagnosis/Evaluation
Gallbladder cancer is often diagnosed late because signs and symptoms don’t appear typically in early stages. Gallbladder cancer is usually discovered because patients have gallstones or have had their gallbladder removed for other reasons. Some of the following tests may be performed to help diagnose gallbladder cancer:
- Lab Tests
- Liver Function Test
- Tumor markers
- CEA
- CA19-9
- Imaging
- Abdominal Ultrasound
- A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram.
- Abdominal Ultrasound
- Computed Tomography (CT) scan
- A procedure that makes a series of detailed pictures of areas inside the body, such as the chest, abdomen, andpelvis, taken from different angles. The pictures are made by a computer linked to an x-ray. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly.
- Computed Tomography (CT) scan
- MRI
- A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. A substance called gadolinium is injected into a vein. The gadolinium collects around the cancer cells so they show up brighter in the picture. This procedure is also called nuclear magnetic resonance imaging (NMRI).
- MRI
- Surgical procedures
- Biopsy
- The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. The biopsy may be done after surgery to remove the tumor. If the tumor clearly cannot be removed by surgery, the biopsy may be done using a fine needle to remove cells from the tumor. This is the only way to confirm a gallbladder cancer diagnosis.
- Biopsy
- Laparoscopy
- A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples for biopsy. Laparoscopy helps to find out if the cancer is within the gallbladder only or has spread to nearby tissues and if it can be removed by surgery.
- Laparoscopy
Classification
- Incidental
- Approximately 66% of gallbladder cancer cases in the US are discovered incidentally. An incidental finding means that cancer was discovered during a test (imaging) or procedure (surgery) that was being performed for an unrelated reason or without suspicion of cancer.
- Per primam
- Per primam is a Latin term that essentially means “through the first” or “by the first means”.
- The remaining ~34% of cases are discovered in advanced stages with intention and not due to unrelated reasons as in incidental cases.
Types of Treatment
Surgery
A medical procedure that removes cancer from the body. It’s often the most effective treatment for solid tumors that are contained in one area. During surgery, a surgeon removes the cancer and some surrounding tissue, called the surgical margin, to ensure that all cancer is eliminated. The surgeon may also remove lymph nodes near the tumor to check for cancer cells.
In the following video Dr. Christopher Stahl talks about the surgical management of gallbladder cancer.
Direct Link: https://www.youtube.com/watch?v=YmfXqcNgUQc
Chemotherapy
Treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemotherapy may be given by mouth, injection, or infusion, or on the skin, depending on the type and stage of the cancer being treated. It may be given alone or with other treatments, such as surgery, radiation therapy, or biologic therapy.
The following video from City of Hope discusses how cancer chemotherapy works.
Direct Link: https://www.youtube.com/watch?v=Q3W-93gNErA
Immunotherapy
Immunotherapy is a cancer treatment that uses the body’s immune system to fight cancer. This animation from the National Cancer Institute (NCI) explains one type of immunotherapy that uses immune checkpoint inhibitors to treat cancer. Checkpoint proteins, such as PD-L1 (programmed cell death ligand 1) on tumor cells and PD-1 (programmed cell death protein 1) on T cells, help keep immune responses in check. The binding of PD-L1 to PD-1 keeps T cells from killing tumor cells in the body. Blocking the binding of PD-L1 to PD-1 with an immune checkpoint inhibitor (anti-PD-L1 or anti-PD-1) allows the T cells to kill tumor cells. Think of it as taking the “brakes” off the immune system.
Direct Link: https://www.youtube.com/watch?v=GIUu239FWMg
Radiation Therapy
A cancer treatment that uses high-energy radiation to kill cancer cells or slow their growth. Radiation therapy damages the DNA of cancer cells, preventing them from growing and dividing. This causes the tumor to shrink and sometimes die.
The following video from Winship Cancer Center discusses what radiation therapy is and how it is used to treat cancer.
Direct Link: https://www.youtube.com/watch?v=3hISw_b9BdQ&t=5s
Targeted Therapy
Targeted therapy is a type of cancer treatment that targets proteins that control how cancer cells grow, divide, and spread. It is the foundation of precision medicine. As researchers learn more about the DNA changes and proteins that drive cancer, they are better able to design treatments that target these proteins.
The following animation from the Cholangiocarcinoma Foundation discusses targeted therapy.
Direct Link: https://www.youtube.com/watch?v=JFUJLVjPy-4
Palliative Care
Palliative care is care given to improve the quality of life and help reduce pain in people who have a serious or life-threatening disease, such as cancer. The goal of palliative care is to prevent or treat, as early as possible, the symptoms of the disease and the side effects caused by treatment of the disease. It also attends to the psychological, social, and spiritual problems caused by the disease or its treatment. For cancer, palliative care may include therapies, such as surgery, radiation therapy, or chemotherapy, to remove, shrink, or slow the growth of a tumor that is causing pain. It may also include family and caregiver support. Palliative care may be given with other treatments from the time of diagnosis until the end of life.
Direct link: https://www.youtube.com/watch?v=eUaU6S-DtIw
For a list of examples of chemotherapy, immunotherapy, and targeted therapy drugs used to treat gallbladder cancer please visit our Resources page and download the Gallbladder and Bile Duct Cancer Guidelines for Patients from the NCCN website. The table of treatment examples is listed in the Systemic Therapy section of the document.
DPD/DPYD Deficiency Testing
Important Note: Patients starting Capecitabine (Xeloda) or 5-FU (Fluorouracil) chemotherapy need to be aware of DPD (Dihydropyrimidine dehydrogenase) deficiency testing.
Undiagnosed DPD deficiency is present in 3-5% of people. People with DPD deficiency have a greatly increased risk for severe or fatal toxicity from 5-FU or capecitabine. Fatal toxicity occurs in up to 10% of patients with undiagnosed DPD deficiency who are treated with 5-FU or capecitabine.
The European Medicines Agency (EMA) updated guidance in 2020 to recommend that DPD testing be performed before starting treatment with fluoropyrimidine-based chemotherapy drugs like 5-fluorouracil (5-FU) and capecitabine. In 2020 the Medicines Healthcare products Regulatory Agency (MHRA), the UK regulator also recommended that clinicians carry out DPD testing before prescribing fluoropyrimidine drugs. The EMA and MHRA are the equivalent of the FDA in Europe. Performing DPD deficiency testing has become standard practice in Europe prior to starting capecitabine or 5-FU.
Note: This is not currently standard practice in the United States. The FDA has made a safety announcement that highlights the importance of DPD deficiency discussions with patients prior to capecitabine or 5-FU treatment; however, it is not currently recommended in any clinical practice guidelines in the US which is why DPD deficiency testing is not widely adopted yet. You can view the FDA safety announcement at the following link: https://www.fda.gov/drugs/resources-information-approved-drugs/safety-announcement-fda-highlights-importance-dpd-deficiency-discussions-patients-prior-capecitabine
Patients with undiagnosed DPD deficiency who develop early onset of severe chemotherapy toxicity after starting 5-FU or capecitabine can be treated with uridine triacetate (Vistogard). Uridine triacetate is an antidote to 5-FU or capecitabine overdose, and 98% effective in preventing fatal toxicity when administered up until 96 hours after
the last dose of 5-FU/capecitabine.
For more information regarding DPD deficiency testing or if you need help advocating for testing please visit the Advocates for Universal DPD/DPYD Testing at www.test4dpd.org.
Cancer Imaging
The following video from the International Atomic Energy Agency provides an overview of the evolution of medical imaging techniques. Spanning initially from X-rays to Computed Tomography (CT) scans and Positron Emission Tomography (PET)/CT scans, which are instrumental in cancer diagnosis and treatment.
Direct Link: https://www.youtube.com/watch?v=EeZNhX0IqsY
The Evolution of Medical Imaging for Cancer Care (International Atomic Energy Agency -IAEA)
Biomarkers
For Cancer Patients, Biomarkers Matter Video (Cholangiocarcinoma Foundation)
Direct Link: https://www.youtube.com/watch?v=Hwo-kxBOoww
Biomarker Testing
Biomarkers are very important and can help identify potential targeted therapies or clinical trials for patients. It’s important to advocate for comprehensive testing with your medical team and make sure testing is performed early on when you are first diagnosed. That way you and your medical team can be aware of all possible treatment options.
Over time, if a therapy ceases to be effective or your cancer comes back, it could indicate that your tumor cells have evolved and acquired new mutations. In such cases, it’s advisable to consult your doctor about undergoing a second biomarker test. This may unveil new biomarkers that could be targeted for treatment.
There are two ways to perform biomarker testing:
- Tissue based testing
- Discuss with your healthcare team early on to ensure enough tissue is collected from your biopsy in order to perform biomarker testing.
- Requires a sample of the tumor tissue from either a biopsy or surgery. Pathology will need to send the tissue out for genomic testing.
- Blood based testing (Liquid biopsy)
- If a tissue biopsy isn’t feasible a less invasive method is to perform a liquid biopsy blood draw to test circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs) for mutations.
Biomarkers worth noting for gallbladder cancer
- Diagnostic Biomarkers
- A reliable validated diagnostic biomarker does not currently exist for gallbladder cancer. Markers such as CEA and CA19-9 are sometimes used. These markers are not reliable for diagnosis, but could be useful for certain patients. You can further discuss CEA and/or CA19-9 with your specialist.
- Diagnostic Biomarkers
- Predictive Biomarkers
- Targeted Therapy
- Having one of the following biomarkers may make you eligible for treatment with an FDA-approved targeted therapy:
- HER2 (ERBB2)
- HER2 has been shown to be an important biomarker in some cases of gallbladder cancer, with multiple approved targeted therapies now available.
- HER2 (ERBB2)
- Having one of the following biomarkers may make you eligible for treatment with an FDA-approved targeted therapy:
- Targeted Therapy
- Predictive Biomarkers
- Other biomarkers may make you eligible for a clinical trial for a targeted therapy that is either still in development, already approved to treat another cancer, or has a tumor agnostic FDA approval. This may include some of the following biomarkers.
- NTRK fusion
- RET
- BRAF V600E
- KRAS G12C
- Other biomarkers may make you eligible for a clinical trial for a targeted therapy that is either still in development, already approved to treat another cancer, or has a tumor agnostic FDA approval. This may include some of the following biomarkers.
- Immunotherapy
- The following biomarkers may make you eligible for treatment with either an FDA approved immunotherapy or another immunotherapy being studied in a clinical trial.
- Microsatellite Instability-High/Mismatch Repair Deficiency (MSI-H/dMMR)
- Microsatellite instability-high and mismatch repair deficiency refer to a condition where a tumor has a defective DNA mismatch repair system, leading to a high rate of mutations in microsatellite regions, which are short, repeated sequences of DNA.
- There are FDA approved immunotherapies available for patients that are MSI-H/dMMR.
- Microsatellite instability-high and mismatch repair deficiency refer to a condition where a tumor has a defective DNA mismatch repair system, leading to a high rate of mutations in microsatellite regions, which are short, repeated sequences of DNA.
- PD-L1
- A protein that acts as a kind of “brake” to keep the body’s immune responses under control. PD-L1 may be found on some normal cells and in higher-than-normal amounts on some types of cancer cells. When PD-L1 binds to another protein called PD-1 (a protein found on T cells), it keeps T cells from killing the PD-L1-containing cells, including the cancer cells. Anticancer drugs called immune checkpoint inhibitors bind to PD-L1 and block its binding to PD-1. This releases the “brakes” on the immune system and leaves T cells free to kill cancer cells.
- High Tumor Mutational Burden (TMB-High)
- High tumor mutational burden (TMB-H) means a cancer has a large number of mutations in its DNA. This can make the cancer more likely to be recognized and attacked by the body’s immune system.
- Microsatellite Instability-High/Mismatch Repair Deficiency (MSI-H/dMMR)
- The following biomarkers may make you eligible for treatment with either an FDA approved immunotherapy or another immunotherapy being studied in a clinical trial.
- Immunotherapy
Does insurance cover biomarker testing?
- Biomarker testing holds immense value in treatment decisions, and most insurance companies acknowledge this and cover the cost of testing.
Note: Genomic testing is not the same as genetic testing. Genomic testing examines your tumor for biomarkers, while genetic testing checks for inherited mutations from your parents that could elevate your risk for specific types of cancers.
Remember to request a copy of your biomarker report for your personal medical records. If you have a copy of your biomarker report please visit our partner Genomic Focus. Upload your report and get matched to personalized clinical trials based on your specific biomarkers. This is a free service for patients. Just click the Genomic Focus Logo below or visit our Genomic Focus page for more information.
Clinical Trials
A clinical trial is a type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease.
Benefits of clinical trial participation:
- Can help researchers learn more about gallbladder cancer and help other patients in the future.
- You may have access to treatments in the study that are not available to people outside of the trial.
- The clinical trial team will monitor you closely and add an extra layer of care to your health.
- If the treatment being studied is more effective than the current standard treatment, you could be among the first to benefit from it.
Questions to ask before joining a clinical trial
- The National Cancer Institute has a list of questions you may want to ask your oncologist and the study research team before joining a clinical trial. You can access the list of questions at the following link: https://www.cancer.gov/research/participate/clinical-trials/why-participate
Additionally, The KidneyFund has a great video explaining the 4 different phases of clinical trials. Please view the video below for more information.
The Four Phases of Clinical Trials (American Kidney Fund)
Direct Link: https://www.youtube.com/watch?v=kZCzN8FXt3I
ClinicalTrials.gov & NCI List of Gallbladder Cancer Clinical Trials
ClinicalTrials.gov is a website and online database of clinical research studies and information about their results. You can search the database by going to https://clinicaltrials.gov/ and entering “gallbladder cancer” or “biliary tract cancer” in the Condition/disease field. You are also able to enter your location to search for which trials are available near you. The results will show status for the trials, which can be listed as actively recruiting, completed, not yet recruiting, terminated, withdrawn, or unknown.
The National Cancer Institute also has a resource that lists clinical trials for gallbladder cancer that you can access with the following link: NCI Clinical Trial List. You can click on each available trial for more details on their website.
The ClinicalTrials.gov site can be confusing for patients and caregivers to navigate. Instead we recommend utilizing a free service provided by a partner of ours called Genomic Focus. Genomic Focus helps link patients to personalized clinical trials based on their biomarkers. There is also a non-targeted therapy map that makes it easy to see which non-targeted therapy trials are available near you. For more information please visit our Genomic Focus page or click on the Genomic Focus logo below to visit their website.
Finding a Gallbladder Cancer Specialist
Finding a specialist for gallbladder cancer can be difficult considering how rare this disease is. Having physicians with experience treating biliary tract cancers will be a critical component of your healthcare team. Biliary tract cancers consist of ampulla of vater, cholangiocarcinoma (bile duct cancer), and gallbladder cancer.
Physicians that are cholangiocarcinoma specialists will have the skillset and expertise required to treat gallbladder cancer as well since both are part of the biliary tract cancer family. Whether it’s to get a second opinion, find a surgeon, or a gastrointestinal medical oncologist to manage your treatment we recommend utilizing the map that the Cholangiocarcinoma Foundation has on their website to search for providers in your state in the USA by using this link: https://cholangiocarcinoma.org/specialist-map/#specialist-map-map
Even if a specialist is located far from you consider reaching out to them to see if they can manage your care virtually with a secondary oncologist managing treatment locally. For example, in the Patient Journey section of the site Balwinder had a medical oncologist in Sacramento, CA administering treatment while a gastrointestinal (GI) medical oncologist at UCSF in San Francisco guided her treatment plan as a subject matter expert. This allowed her to get specialist insight without traveling, which can be difficult for patients during treatment.
Note: If you are an international patient or caregiver and are looking for support and resources we may be able to connect you to a patient advocacy group in your country that can help connect you to specialists. For more information please visit our International resources page.
Second Opinion
If your medical oncologist does not have experience treating gallbladder or biliary tract cancers, ask to be referred to a gastrointestinal (GI) medical oncologist with expertise in these rare cancers. It’s crucial to make an informed health decision and seek insights from multiple experts. For a second opinion on your diagnosis and treatment plan, use the Cholangiocarinoma Foundation map to find a specialist with biliary tract cancer expertise in your area.
Some medical institutions may necessitate patients to travel for in-person visits to get a second opinion. However, if patients are too ill to travel, a virtual second opinion may be an option. The specific steps may vary from institution to institution, but generally, the process involves meeting with a healthcare professional (such as a nurse) for an intake session and discussing your medical situation. It’s important to note that insurance may not cover virtual second opinions and therefore you would need to pay a flat fee for the service, which can range from $590-$2500. Once the cost is covered, the institution will collect your medical records, and an expert will review them to provide a written second opinion report. Some institutions may offer the option of a virtual meeting with the expert who provided the written second opinion.
We recommend trying to find a biliary tract cancer specialist locally first by using the specialist map resource on the Cholangiocarcinoma Foundation’s website: https://cholangiocarcinoma.org/specialist-map/#specialist-map-map.
If you are unable to find a specialist locally you can look into the following institutions for a virtual second opinion. Note that these options are listed in alphabetical order and not based on ranking or specific recommendation. Just click on the name to be directed to the institution’s site for more information.
- Cedars-Sinai
- Cleveland Clinic
- Dana-Farber Cancer Institute
- Massachusetts General Hospital
- Memorial Sloan Kettering Cancer Center
- MSKCC has a good article on secondary opinions and discusses their options, which may also include a telemedicine option depending on where you live: https://www.mskcc.org/news/what-to-know-about-getting-second-opinion-after-cancer-diagnosis
- Stanford Medicine
- University of California San Francisco (UCSF)
Reminder: This may not be covered by insurance so make sure to check with each institution about costs associated with their respective virtual second opinion programs.
Patient Resources
Please visit out patient resources page to access additional resources such as patient guideline documents/patient guides documents from NCCN/ESMO, NCI dictionary of cancer terms, information about copay assistance funds, educational videos, diet & nutrition, the MyChart app, and more.