Estimated new cases and deaths from gallbladder (and other biliary) cancer in the United States in 2024:[1]
Cancer that arises in the gallbladder is uncommon.
The most common symptoms caused by gallbladder cancer are jaundice, pain, and fever.
In patients whose superficial cancer (T1 or confined to the mucosa) is discovered on pathological examination of tissue after gallbladder removal for other reasons, the disease is often cured without further therapy. In patients who present with symptoms, the tumor is rarely diagnosed preoperatively.[2] In such cases, the tumor often cannot be removed completely by surgery and the disease cannot be cured, although palliative measures may be beneficial. For patients with T2 or greater disease, extended resection with partial hepatectomy and portal lymph node dissection may be an option.[3,4]
Cholelithiasis is an associated finding in most cases, but less than 1% of patients with cholelithiasis develop this cancer.
Some histological types of gallbladder cancer have a better prognosis than others. Papillary carcinomas have the best prognosis. The histological types of gallbladder cancer include the following:[1]
The American Joint Committee on Cancer (AJCC) has designated staging by the TNM classification to define gallbladder cancer.[1]
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Gallbladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 303–9. | ||
| 0 | Tis, N0, M0 | Tis = Carcinoma in situ. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Gallbladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 303–9. | ||
| I | T1, N0, M0 | T1 = Tumor invades the lamina propria or muscular layer. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Gallbladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 303–9. | ||
| IIA | T2a, N0, M0 | T2a = Tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Gallbladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 303–9. | ||
| IIB | T2b, N0, M0 | T2b = Tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Gallbladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 303–9. | ||
| IIIA | T3, N0, M0 | T3 = Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. |
| N0 = No regional lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Gallbladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 303–9. | ||
| IIIB | T1–3, N1, M0 | T1 = Tumor invades the lamina propria or muscular layer. |
| –T1a = Tumor invades the lamina propria. | ||
| –T1b = Tumor invades the muscular layer. | ||
| T2 = Tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). Or, tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver. | ||
| –T2a = Tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). | ||
| –T2b = Tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver. | ||
| T3 = Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. | ||
| N1 = Metastases to one to three regional lymph nodes. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Gallbladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 303–9. | ||
| IVA | T4, N0–1, M0 | T4 = Tumor invades the main portal vein or hepatic artery or invades two or more extrahepatic organs or structures. |
| N0 = No regional lymph node metastasis. | ||
| N1 = Metastases to one to three regional lymph nodes. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis. | ||
| aReprinted with permission from AJCC: Gallbladder. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 303–9. | ||
| IVB | Any T, N2, M0 | TX = Primary tumor cannot be assessed. |
| T0 = No evidence of primary tumor. | ||
| Tis = Carcinoma in situ. | ||
| T1 = Tumor invades the lamina propria or muscular layer. | ||
| –T1a = Tumor invades the lamina propria. | ||
| –T1b = Tumor invades the muscular layer. | ||
| T2 = Tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). Or, tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver. | ||
| –T2a = Tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). | ||
| –T2b = Tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver. | ||
| T3 = Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. | ||
| T4 = Tumor invades the main portal vein or hepatic artery or invades two or more extrahepatic organs or structures. | ||
| N2 = Metastases to four or more regional lymph nodes. | ||
| M0 = No distant metastasis. | ||
| Any T, Any N, M1 | TX = Primary tumor cannot be assessed. | |
| T0 = No evidence of primary tumor. | ||
| Tis = Carcinoma in situ. | ||
| T1 = Tumor invades the lamina propria or muscular layer. | ||
| –T1a = Tumor invades the lamina propria. | ||
| –T1b = Tumor invades the muscular layer. | ||
| T2 = Tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). Or, tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver. | ||
| –T2a = Tumor invades the perimuscular connective tissue on the peritoneal side, without involvement of the serosa (visceral peritoneum). | ||
| –T2b = Tumor invades the perimuscular connective tissue on the hepatic side, with no extension into the liver. | ||
| T3 = Tumor perforates the serosa (visceral peritoneum) and/or directly invades the liver and/or one other adjacent organ or structure, such as the stomach, duodenum, colon, pancreas, omentum, or extrahepatic bile ducts. | ||
| T4 = Tumor invades the main portal vein or hepatic artery or invades two or more extrahepatic organs or structures. | ||
| NX = Regional lymph nodes cannot be assessed. | ||
| N0 = No regional lymph node metastasis. | ||
| N1 = Metastases to one to three regional lymph nodes. | ||
| N2 = Metastases to four or more regional lymph nodes. | ||
| M1 = Distant metastases. | ||
Localized and Locally Advanced
Patients with stage I disease have cancer confined to the gallbladder wall that can be completely resected. Patients with stage I tumors that are discovered incidentally and resected during routine cholecystectomy have 5-year survival rates of nearly 100%.[2]
Patients with stage II or III disease have tumors with direct extension into the muscular layer, serosa, or adjacent organs, with or without involvement of locoregional lymph nodes.
Unresectable
Patients with disease that has spread beyond the locoregional lymph nodes or to distant organs have unresectable tumors, and standard therapy is directed at palliation. Patients with earlier-stage disease with poor performance status and/or significant comorbidities may be deemed poor surgical candidates.
Previously unsuspected gallbladder cancer that is incidentally discovered in the mucosa of the gallbladder during pathological examination is curable in more than 80% of patients. However, symptomatic gallbladder cancer that is suspected prior to surgery often penetrates the muscularis and serosa. This type of gallbladder cancer is curable in less than 5% of patients.
One study reported the patterns of lymph node spread from gallbladder cancer and outcomes of patients with metastases to lymph nodes in 111 consecutive surgical patients in a single institution from 1981 to 1995.[1][Level of evidence C1] The standard surgical procedure was removal of the gallbladder, a wedge resection of the liver, resection of the extrahepatic bile duct, and resection of the regional (N1 and N2) lymph nodes. Kaplan-Meier estimates of the 5-year survival rates were 42.5% ± 6.5% for patients with node-negative tumors pathologically staged as T2 to T4 and 31% ± 6.2% for patients with similar node-positive tumors.
Treatment options for localized and locally advanced gallbladder cancer include the following:
In patients with previously unsuspected gallbladder cancer that is discovered in the surgical specimen after a routine gallbladder operation and confined to mucosa (T1), most disease is cured.[2,3] During laparoscopic removal of an unsuspected cancer, implantation of carcinoma at all port sites (including the camera site) is possible.[4] All port sites are typically excised completely, even for stage I cancers.
The need for reexploration for more extended resection in incidentally discovered T1b disease is controversial. A multicenter retrospective review identified lymph node metastases in 12% of patients who underwent re-resection after cholecystectomy, but there are no prospective data regarding relative outcome with a second surgery in these patients.[5][Level of evidence C2]
Patients with T2 or T3 disease have higher rates of unsuspected invasive disease at the time of diagnosis. A multicenter retrospective review was performed in patients who underwent re-resection after carcinoma was discovered incidentally. Residual disease was present in 57% of patients with T2 disease (including 31% with lymph node involvement and 10% with liver involvement) and in 77% of patients with T3 disease (including 46% with lymph node metastases and 36% with liver involvement).[5] On the basis of these observations, eligible patients may undergo reexploration to resect liver tissue near the gallbladder bed, portal lymph nodes, and lymphatic tissue in the hepatoduodenal ligament. Retrospective analyses suggest that extended re-resection can delay recurrences and potentially improve survival.[6-8][Level of evidence C2]
For patients with locoregional lymph node involvement (at the cystic duct, common bile duct, hepatic artery, and portal vein), long-term disease-free survival can occasionally be achieved with radical resection. In patients with jaundice (stage III or stage IV), preoperative percutaneous transhepatic biliary drainage for relief of biliary obstruction should be considered.
Surgery with curative intent is not considered possible in patients with metastatic spread beyond the locoregional lymph nodes or to distant organs.
The use of EBRT with or without chemotherapy as a primary treatment has been reported to produce short-term disease control in small groups of patients. Similar benefits have been reported for radiation therapy, with or without chemotherapy, administered after resection.[9,10]
There are no phase III studies to support the use of adjuvant radiation therapy, even for patients with high-risk localized disease.
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Unresectable, metastatic, and recurrent gallbladder cancers are not curable. Symptoms can be significantly improved with relief of biliary obstruction. A few patients have very slow-growing tumors and may live several years. Patients with unresectable, metastatic, or recurrent gallbladder cancer should consider enrolling in clinical trials whenever possible. Information about ongoing clinical trials is available from the NCI website.
Treatment options for unresectable, metastatic, or recurrent gallbladder cancer include the following:
Relief of biliary obstruction is warranted when symptoms such as pruritus and hepatic dysfunction outweigh other symptoms of the cancer. The preferred approach is percutaneous transhepatic drainage or endoscopically placed stents.[1] Surgical bypass may be appropriate when these approaches are infeasible.
Palliative radiation therapy after biliary drainage may be beneficial. Patients may be candidates for inclusion in clinical trials that explore ways to improve the effects of radiation therapy with various radiosensitizers, such as hyperthermia, radiosensitizer drugs, or cytotoxic chemotherapeutic agents.
Systemic therapy is appropriate for selected patients with adequate performance status and intact organ function. Fluoropyrimidines, gemcitabine, platinum agents, and docetaxel have produced transient partial remissions in a few patients. The incidence of gallbladder cancer is low, and clinical trials often enroll patients with all subsites of biliary tract cancers. Therefore, data must be interpreted with caution when applied specifically to patients with gallbladder cancer. In clinical practice, treatment algorithms in advanced disease often follow those with biliary tract cancer, relying on extrapolation from other trials. In this section, only current landmark studies, or those that specifically enrolled patients with gallbladder cancer, have been explicitly summarized. For more information, see Bile Duct Cancer (Cholangiocarcinoma) Treatment.
The DPYD gene encodes an enzyme that catabolizes pyrimidines and fluoropyrimidines, like capecitabine and fluorouracil. An estimated 1% to 2% of the population has germline pathogenic variants in DPYD, which lead to reduced DPD protein function and an accumulation of pyrimidines and fluoropyrimidines in the body.[2,3] Patients with the DPYD*2A variant who receive fluoropyrimidines may experience severe, life-threatening toxicities that are sometimes fatal. Many other DPYD variants have been identified, with a range of clinical effects.[2-4] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient's DPYD genotype and number of functioning DPYD alleles.[5-7] DPYD genetic testing costs less than $200, but insurance coverage varies due to a lack of national guidelines.[8] In addition, testing may delay therapy by 2 weeks, which would not be advisable in urgent situations. This controversial issue requires further evaluation.[9]
Evidence (systemic therapy):
Pending additional clinical trials, cisplatin plus gemcitabine is considered the reference standard chemotherapy backbone for patients with unresectable, metastatic, or recurrent gallbladder cancer. Extrapolating from the results of the TOPAZ-1 and KEYNOTE-966 trials for biliary tract cancer, addition of a checkpoint inhibitor (durvalumab or pembrolizumab) to first-line therapy has become the standard of care. Potential alternative regimens include gemcitabine plus capecitabine, GEMOX, and XELOX. All patients should consider clinical trials.
All patients with unresectable, metastatic, or recurrent disease who have not already received checkpoint inhibitors should undergo molecular testing for deficient mismatch repair (dMMR) or microsatellite instability (MSI-H). Extrapolating from a subgroup of patients with gastrointestinal and hepatopancreatobiliary tumors in the I-PREDICT (NCT02534675) and KEYNOTE-158 (NCT02628067) studies, patients with either dMMR or MSI-H tumors can be considered for treatment with pembrolizumab.[15,16][Level of evidence C3]
Additional testing for IDH1 mutations, FGFR2 fusions, and HER2 expression may provide potential targets in clinical trials. In clinical practice, targeted treatments that have been approved by the U.S. Food and Drug Administration as second-line treatments for patients with cholangiocarcinoma could likely be used to treat appropriate patients with gallbladder cancer. Compelling treatment options for these patients are scarce. For more information, see the Targeted therapy section in Bile Duct Cancer (Cholangiocarcinoma) Treatment.
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Gallbladder Cancer
Updated statistics with estimated new cases and deaths for 2024 (cited American Cancer Society as reference 1).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of gallbladder cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Gallbladder Cancer Treatment are:
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The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Gallbladder Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/gallbladder/hp/gallbladder-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389371]
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