Extrahepatic cholangiocarcinoma (perihilar and distal)
Extrahepatic cholangiocarcinoma blocks the main bile ducts outside the liver and shows itself as jaundice. Perihilar tumours need part of the liver removed with the duct and distal tumours a Whipple operation; where surgery is impossible, stenting relieves the jaundice and chemotherapy with immunotherapy follows, with HER2-directed antibodies for the one in six tumours that carry that target.
Overview
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. 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. Primary sclerosing cholangitis, choledochal cysts and liver flukes are risk factors. The genome differs from intrahepatic disease: KRAS and TP53 mutations dominate, HER2 amplification occurs in about one in six, and FGFR2 fusions and IDH1 mutations are rare.
Surgery is the only cure and is among the most demanding in abdominal oncology: perihilar tumours require resection of the bile duct with the ipsilateral hemiliver and caudate lobe, often after portal vein embolisation to grow the remnant and biliary drainage to reverse jaundice, while distal tumours are removed by pancreaticoduodenectomy. Clear margins are achieved in perhaps half of cases. Adjuvant capecitabine for six months follows BILCAP. For unresectable perihilar tumours in primary sclerosing cholangitis or under 3 cm, the Mayo protocol of chemoradiation followed by liver transplantation achieves long-term survival in selected patients and is offered in a few centres.
Unresectable disease is treated with gemcitabine and cisplatin plus durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966), the biliary standards since 2022; FOLFOX is the second line after ABC-06, and liposomal irinotecan failed in NALIRICC. HER2-positive tumours respond to zanidatamab, which had a response rate of 41 percent in HERIZON-BTC-01 and gained accelerated FDA approval in 2024, and to trastuzumab deruxtecan; the phase 3 HERIZON-BTC-302 tests zanidatamab in the first line. Biliary stenting, endoscopic or percutaneous, and treatment of cholangitis are as important to survival as the anticancer drugs, since obstruction and infection are what usually end treatment.
State of the art
- Surgery for perihilar tumours has become safer with portal vein embolisation and staged drainage, but remains the domain of a few high-volume centres.
- Immunotherapy with gemcitabine-cisplatin is the first-line standard, and HER2 has become the actionable target of extrahepatic disease as FGFR2 and IDH1 are of intrahepatic.
- Liver transplantation after chemoradiation offers cure to a small, carefully selected group with unresectable perihilar tumours.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowHypophysitis or adrenal crisis
Persistent headache with extreme tiredness, nausea, dizziness on standing or low blood pressure. Vomiting, severe weakness or collapse is adrenal crisis.
- Emergency services nowBlood clot (lenalidomide, pomalidomide, thalidomide)
A swollen painful calf, or sudden breathlessness with chest pain; venous and arterial thromboembolism is a boxed warning and blood-thinning prophylaxis is recommended.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Emergency services nowSkin reaction
Blisters, peeling, or sores in the mouth or eyes with a rash. Enfortumab vedotin carries a boxed warning for Stevens-Johnson syndrome and toxic epidermal necrolysis, mostly in the first cycle.
- Call the 24-hour line nowInterstitial lung disease or pneumonitis
Any new or worsening cough, breathlessness or fever. The label says to interrupt treatment for any suspected ILD and to permanently discontinue for grade 2 or higher.
See all on the product pages:CapecitabineDabrafenib + trametinibDurvalumabFOLFOX (5-FU, leucovorin, oxaliplatin)Gemcitabine + cisplatinPembrolizumabTrastuzumab deruxtecan·Printable cards in the navigator
Anatomy and lymph node drainage
- Pancreatic head (most PDAC)
- Body and tail
- Ampulla
- Islets (pancreatic NET)
- Intrahepatic ducts
- Perihilar (Klatskin)
- Distal bile duct
- Gallbladder
- Nodes: peripancreatic
- Nodes: hepatic hilar
- Nodes: coeliac and superior mesenteric
Most pancreatic cancers arise in the head next to the bile duct, which is why jaundice is the presenting sign; bile duct cancers are named by where along the tree they sit.
- Pancreatic head (most PDAC)Periductal-infiltrating versus papillary growth
- Body and tail
- Ampulla
- Islets (pancreatic NET)
- Intrahepatic ducts
- Perihilar (Klatskin)Perihilar (Klatskin) cholangiocarcinoma, Bismuth-Corlette types I to IV
- Distal bile ductDistal (common bile duct) cholangiocarcinoma · HER2-positive extrahepatic cholangiocarcinoma (zanidatamab) · Extrahepatic cholangiocarcinoma in primary sclerosing cholangitis (transplant protocols)
- Gallbladder
- peripancreatic
- hepatic hilar
- coeliac and superior mesenteric
Same organ: Pancreatic ductal adenocarcinoma, Biliary tract cancer (cholangiocarcinoma), Intrahepatic cholangiocarcinoma, Biliary tract cancer (all types), Neuroendocrine tumours, Gallbladder cancer, Ampullary cancer (ampulla of Vater)
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.
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Background: CA 19-9. Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
MRI with cholangiography and CT for staging, endoscopic brushing or biopsy, and biliary drainage by stent or percutaneous route with antibiotics for cholangitis.
Bile duct resection with hemihepatectomy and caudate lobectomy after portal vein embolisation and drainage where needed, then six months of capecitabine (BILCAP).
Pancreaticoduodenectomy (Whipple) with lymphadenectomy, then adjuvant capecitabine.
Neoadjuvant chemoradiation followed by liver transplantation under the Mayo protocol in specialist centres.
Gemcitabine and cisplatin with durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966).
Zanidatamab (HERIZON-BTC-01) or trastuzumab deruxtecan; zanidatamab first line in HERIZON-BTC-302.
FOLFOX (ABC-06); pembrolizumab for microsatellite-unstable tumours, dabrafenib-trametinib for BRAF V600E.
Subtypes & biomarkers
top- Perihilar (Klatskin) cholangiocarcinoma, Bismuth-Corlette types I to IV
- Distal (common bile duct) cholangiocarcinoma
- HER2-positive extrahepatic cholangiocarcinoma (zanidatamab)
- Extrahepatic cholangiocarcinoma in primary sclerosing cholangitis (transplant protocols)
- Periductal-infiltrating versus papillary growth
- Bismuth-Corlette type and vascular involvement on MRI and CT (resectability)
- CA 19-9 after biliary decompression
- HER2 amplification and overexpression (about one in six)
- KRAS and TP53 (prognostic)
- Microsatellite instability and BRAF V600E (rare, actionable)
- Bilirubin and future liver remnant volume before surgery
How often this target appears
- 1965Klatskin describes adenocarcinoma at the hepatic duct bifurcation
- 1975Bismuth and Corlette classify perihilar tumours by ductal extension
- 2010ABC-02: gemcitabine plus cisplatin standard for advanced biliary cancer
- 2019BILCAP: adjuvant capecitabine after resection
- 2021ABC-06: FOLFOX as second line
- 2022TOPAZ-1: durvalumab added to gemcitabine-cisplatin
- 2024Zanidatamab receives accelerated approval for HER2-positive biliary tract cancer
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 12 changes by month →- 2026-09-17This recordExtrahepatic cholangiocarcinoma (perihilar and distal)Facts on this page last checked
When this page itself was last checked or edited.
- 2024MilestoneZanidatamabZanidatamab receives accelerated approval for HER2-positive biliary tract cancer
A milestone in how this cancer is treated.
- 2023Trial resultKEYNOTE-966KEYNOTE-966 reported
OS 12.
- 2022Trial resultTOPAZ-1TOPAZ-1 reported
OS HR 0.
- 2022MilestoneTOPAZ-1TOPAZ-1: durvalumab added to gemcitabine-cisplatin
A milestone in how this cancer is treated.
- 2021MilestoneFOLFOX (5-FU, leucovorin, oxaliplatin)ABC-06: FOLFOX as second line
A milestone in how this cancer is treated.
What is in development for Extrahepatic cholangiocarcinoma (perihilar and distal), drawn from the whole corpus: 5 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Trials under way · 1
- HERIZON-BTC-302 · phase 3 · Jazz / Zymeworks
Trials reported · 3
- BILCAP · phase 3 · 2017 · mixed
- KEYNOTE-966 · phase 3 · 2023 · positive
- TOPAZ-1 · phase 3 · 2022 · positive
Combinations being explored · 1
Open problems and what is being done
Most perihilar tumours are unresectable at presentation, and half of resections leave microscopic disease.
Biliary obstruction and cholangitis, not the cancer's growth, often end treatment.
No targeted therapy exists for the KRAS-mutant majority.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Landmark trials
Expert centres
topExpert centres
Seoul · hospital | South Korea | none recorded | 0 | 1,177 | 18,820 | none recorded | #4 |
Rochester, MN · hospital | United States | 0 | 4,511 | 44,748 | #5 | ||
Villejuif · cancer center | France | none recorded | 0 | 1,855 | 31,182 | #6 | |
Baltimore · cancer center | United States | 0 | 2,955 | 41,449 | #10 | ||
Tokyo · government | Japan | none recorded | 0 | 1,599 | 21,937 | none recorded | #13 |
London · consortium | United Kingdom | none recorded | 2 | not matched | - | none recorded | - |
Los Angeles · cancer center | United States | 0 | 2,019 | 32,934 | - | ||
Beijing · cancer center | China | none recorded | 0 | 1,344 | 18,195 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Rotterdam · cancer center | Netherlands | none recorded | 0 | 852 | 12,180 | - | |
Madrid · hospital | Spain | none recorded | 0 | 764 | 13,767 | - | |
Goyang · cancer center | South Korea | none recorded | 0 | 573 | 9,401 | - | |
Lausanne · hospital | Switzerland | none recorded | 0 | 509 | 9,176 | - | |
Brussels · cancer center | Belgium | none recorded | 0 | 489 | 8,689 | - | |
Shanghai · hospital | China | none recorded | 0 | 464 | 6,795 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Extrahepatic cholangiocarcinoma but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Extrahepatic cholangiocarcinoma
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example Bismuth-Corlette type and vascular involvement on MRI and CT, CA 19-9 after biliary decompression, HER2 amplification and overexpression, KRAS and TP53, Microsatellite instability and BRAF V600E), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Perihilarcholangiocarcinoma, Bismuth-Corlette types I to IV, Distalcholangiocarcinoma, HER2-positive extrahepatic cholangiocarcinoma.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis and jaundice
- For my situation (diagnosis and jaundice), which of the standard options do you recommend and why?Why: Guideline options include: MRI with cholangiography and CT for staging, endoscopic brushing or biopsy, and biliary drainage by stent or percutaneous route with antibiotics for cholangitis.
Resectable perihilar
- For my situation (resectable perihilar), which of the standard options do you recommend and why?Why: Guideline options include: Bile duct resection with hemihepatectomy and caudate lobectomy after portal vein embolisation and drainage where needed, then six months of capecitabine (BILCAP).
- Am I a candidate for Capecitabine, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of BILCAP apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Resectable distal
- For my situation (resectable distal), which of the standard options do you recommend and why?Why: Guideline options include: Pancreaticoduodenectomy (Whipple) with lymphadenectomy, then adjuvant capecitabine.
- Am I a candidate for Capecitabine, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of BILCAP apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Unresectable perihilar, selected
- For my situation (unresectable perihilar, selected), which of the standard options do you recommend and why?Why: Guideline options include: Neoadjuvant chemoradiation followed by liver transplantation under the Mayo protocol in specialist centres.
Advanced, first line
- For my situation (advanced, first line), which of the standard options do you recommend and why?Why: Guideline options include: Gemcitabine and cisplatin with durvalumab (TOPAZ-1) or pembrolizumab (KEYNOTE-966).
- Am I a candidate for Gemcitabine + cisplatin, Durvalumab, Pembrolizumab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of TOPAZ-1 and KEYNOTE-966 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Advanced, HER2-positive after chemotherapy
- For my situation (advanced, her2-positive after chemotherapy), which of the standard options do you recommend and why?Why: Guideline options include: Zanidatamab (HERIZON-BTC-01) or trastuzumab deruxtecan; zanidatamab first line in HERIZON-BTC-302.
- Am I a candidate for Zanidatamab, Trastuzumab deruxtecan, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of HERIZON-BTC-302 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Second line without a target
- For my situation (second line without a target), which of the standard options do you recommend and why?Why: Guideline options include: FOLFOX (ABC-06); pembrolizumab for microsatellite-unstable tumours, dabrafenib-trametinib for BRAF V600E.
- Am I a candidate for FOLFOX (5-FU, leucovorin, oxaliplatin), Pembrolizumab, Dabrafenib + trametinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Zanidatamab, HERIZON-BTC-302, Trastuzumab deruxtecan, Biliary stenting and drainage?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Most perihilar tumours are unresectable at presentation, and half of resections leave microscopic disease”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Biliary obstruction and cholangitis, not the cancer's growth, often end treatment”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Extrahepatic cholangiocarcinoma, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
11targets
4drugs
8companies
8terms
6trials
5pairings
1Latest papers
topQuery for this cancer: (TITLE:"Extrahepatic cholangiocarcinoma" OR ABSTRACT:"Extrahepatic cholangiocarcinoma" OR TITLE:"perihilar and distal" OR ABSTRACT:"perihilar and distal" OR TITLE:"Perihilar cholangiocarcinoma" OR ABSTRACT:"Perihilar cholangiocarcinoma" OR TITLE:"Klatskin tumour" OR ABSTRACT:"Klatskin tumour" OR TITLE:"Hilar cholangiocarcinoma" OR ABSTRACT:"Hilar cholangiocarcinoma" OR TITLE:"Distal cholangiocarcinoma" OR ABSTRACT:"Distal cholangiocarcinoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Extrahepatic cholangiocarcinoma (perihilar and distal), not a curated reading list.
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