OnCo

Gallbladder cancer compared with its neighbours

The four cancers share the bile-carrying tract and most of their drug trials, and differ in almost everything else. Each cell is read from the record it names or from a paper linked beside it; a cell with nothing behind it says so. 42 of 44 cells are filled from 4 records and the papers linked in them; checked 2026-09-24.

FieldGallbladder cancerthis page’s cancerIntrahepatic cholangiocarcinomaExtrahepatic cholangiocarcinomaAmpullary cancer
Where it starts

The gallbladder is a pear-shaped pouch about 8 cm long under the right lobe of the liver that concentrates and stores bile

Intrahepatic cholangiocarcinoma arises from the bile ducts beyond the second-order branches within the liver and presents as a mass

Extrahepatic cholangiocarcinoma is divided at the cystic duct into perihilar tumours, described by Klatskin in 1965 and classified by Bismuth and Corlette according to how far they extend into the right and left hepatic ducts, and distal tumours of the common bile duct.

Ampullary adenocarcinoma arises from the ampulla of Vater, the papilla where the common bile duct and main pancreatic duct open into the duodenum.

How commonThe record's burden field, as written.

Around 1,300 people a year in the UK, seven in ten of them women and more than half aged 75 or over; rare here, but common where gallstones are common, above all Bolivia, Chile, northern India and Pakistan (Cancer Research UK; GLOBOCAN).

Bile duct cancer arising within the liver, the second commonest primary liver cancer after hepatocellular carcinoma and rising in incidence worldwide; it carries most of the targetable mutations in biliary cancer, with FGFR2 fusions in about one in eight and IDH1 mutations in about one in seven.

Cancers of the bile ducts outside the liver, from the hilum where the ducts join to the lower duct near the pancreas; perihilar tumours are the commonest cholangiocarcinoma overall, and they present with jaundice, which brings both early symptoms and the risks of biliary obstruction.

Rare: well under one case per 100,000 per year, but it makes up a disproportionate share of resectable pancreatoduodenectomies because it obstructs the bile duct early and presents with jaundice.

Main risk factors

gallstones are the strongest (pooled relative risk 4.9 for a history of benign gallbladder disease, Randi 2006; odds ratio 7.26 for gallbladder cancer in a 2021 meta-analysis of 30 studies, Huang

Risk factors include cirrhosis, hepatitis B and C, primary sclerosing cholangitis, liver flukes in Thailand and neighbouring countries, and hepatolithiasis, but most cases in the West have none.

Primary sclerosing cholangitis, choledochal cysts and liver flukes are risk factors.

Familial adenomatous polyposis carries a large relative risk of ampullary adenoma and carcinoma, and endoscopic surveillance of the duodenum is part of FAP care.

Typical presentation

A large share is found by the pathologist after a cholecystectomy for presumed gallstone disease: 0.25 to 0.89 percent of all cholecystectomy specimens in the series reviewed by Soreide (2019)

presents as a mass, often found incidentally or with vague pain and weight loss, in contrast to the jaundice of extrahepatic tumours

Both present with painless jaundice, pale stools, dark urine and itching, often with cholangitis, and CA 19-9 is raised but unreliable in the presence of obstruction.

it obstructs the bile duct early and presents with jaundice

HER2 (ERBB2)Prevalence rows on the HER2 target record; where a record has none, the Hiraoka 2020 series scored by the gastro-oesophageal guideline.

8-10% Amplification

4-8% Activating mutation (S310F/Y hotspot)

9-31% Protein overexpression (IHC)

HER2-positive in 3.7% of 110 intrahepatic cholangiocarcinomas (Hiraoka 2020)

10-20% IHC 3+ or amplification (recorded on Biliary tract cancer (cholangiocarcinoma))

HER2-positive in 16.4% of 79 ampullary carcinomas (Hiraoka 2020)

FGFR2

1% Fusion, mutation or amplification

10-15% Fusion (intrahepatic) (recorded on Biliary tract cancer (cholangiocarcinoma))

Not recorded
IDH1

10-20% IDH1 mutation (intrahepatic) (recorded on Biliary tract cancer (cholangiocarcinoma))

Not recorded
KRAS

11% Mutation (amplification rarer)

KRAS altered in 22% of 412 intrahepatic cholangiocarcinomas (Javle 2016)

KRAS altered in 42% of 57 extrahepatic cholangiocarcinomas (Javle 2016)

intestinal-type tumours resemble colorectal cancer (CDX2, MUC2; APC and KRAS mutations) and pancreatobiliary-type tumours resemble pancreatic cancer (MUC1, CK7; KRAS, TP53, SMAD4)

Surgery with curative intentThe standard-of-care row on each record for resectable disease.

T1b, T2 or T3 (incidental or suspected before surgery): Radical (extended) cholecystectomy: resection of the liver bed (wedge or segments IVb and V) with portal lymphadenectomy, bile duct resection only when the cystic duct margin is positive; re-resection 4 to 8 weeks after an incidental diagnosis; port sites not routinely excised.

Resectable: Hepatectomy with lymph node dissection followed by six months of adjuvant capecitabine (BILCAP).

Resectable perihilar: Bile duct resection with hemihepatectomy and caudate lobectomy after portal vein embolisation and drainage where needed, then six months of capecitabine (BILCAP).

Resectable distal: Pancreaticoduodenectomy (Whipple) with lymphadenectomy, then adjuvant capecitabine.

Resectable carcinoma: Pancreatoduodenectomy with regional lymphadenectomy; biliary stenting first only if cholangitis or delayed surgery.

First-line systemic treatmentThe standard-of-care row on each record for advanced disease, first line.

Unresectable or metastatic disease, first line: Gemcitabine and cisplatin with durvalumab (TOPAZ-1, in which 25 percent of patients had gallbladder cancer; NICE TA944) or with pembrolizumab (KEYNOTE-966; not appraised by NICE), with molecular profiling including HER2 at diagnosis and biliary drainage first if jaundiced. Second-line, HER2-directed and other targeted options follow in the rows below.

Advanced, first line: Gemcitabine and cisplatin with durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966).

Advanced, first line: Gemcitabine and cisplatin with durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966).

Metastatic: Subtype-directed chemotherapy; pembrolizumab for MSI-high; HER2-, BRAF- or NTRK-directed therapy where present; clinical trials.

Trial legacyHistory events on each record that name a trial.

2010: Gemcitabine and cisplatin become the biliary standard

2015: SWOG S0809: the only prospective adjuvant chemoradiation trial

2019: BILCAP: adjuvant capecitabine

2021: ABC-06 published: second-line FOLFOX

2022: TOPAZ-1: durvalumab added to chemotherapy

2023: KEYNOTE-966: pembrolizumab confirms the class effect

2023: HERIZON-BTC-01 published; ESMO biliary tract cancer guideline

2024: Zanidatamab for HER2-positive biliary cancer

2025: TOPAZ-1 three-year update; ctDNA residual disease shown prognostic after biliary resection

2010: ABC-02: gemcitabine plus cisplatin becomes the standard for advanced biliary cancer

2019: BILCAP: adjuvant capecitabine after resection

2020: FIGHT-202: pemigatinib approved for FGFR2 fusion-positive cholangiocarcinoma

2021: ClarIDHy: ivosidenib approved for IDH1-mutant cholangiocarcinoma

2022: FOENIX-CCA2: futibatinib approved; TOPAZ-1: durvalumab added to chemotherapy

2023: KEYNOTE-966: pembrolizumab added to chemotherapy

2010: ABC-02: gemcitabine plus cisplatin standard for advanced biliary cancer

2019: BILCAP: adjuvant capecitabine after resection

2021: ABC-06: FOLFOX as second line

2022: TOPAZ-1: durvalumab added to gemcitabine-cisplatin

2024: Zanidatamab receives accelerated approval for HER2-positive biliary tract cancer

Each cell names the record field it was read from or links the paper it quotes; an empty cell means the corpus records nothing for it yet. Rates are population-level and depend on the cohort and assay; open the target page for every cohort.

How to read this table

Computed rows read each record as it stands: the burden field, the standard-of-care row named under the label, the history events that name a trial, and the prevalence rows on the target record (a row recorded on a parent record, such as cholangiocarcinoma, says so). Hand-written rows quote a sentence of the record’s own text, or a paper linked in the cell. Nothing is estimated; a cell with nothing behind it is left empty. OnCo is orientation, not medical advice.