# Ampullary cancer (ampulla of Vater)

Source: https://onco.cc/cancers/ampullary/  
OnCo record `ampullary` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Ampullary cancer, a biliary tract cancer, starts where the bile and pancreatic ducts empty into the small bowel. Because it blocks bile flow early it is often caught while still removable, and the Whipple operation cures a good share of patients. Tumours come in two flavours, intestinal-like and pancreas-like, and chemotherapy is increasingly chosen by which one the pathologist sees.

## Summary

Ampullary adenocarcinoma arises from the ampulla of Vater, the papilla where the common bile duct and main pancreatic duct open into the duodenum. It is grouped with periampullary cancers (distal cholangiocarcinoma, duodenal adenocarcinoma, pancreatic head cancer) at surgery but behaves better than pancreatic cancer because it obstructs the bile duct and is diagnosed early. Two histomolecular subtypes matter: intestinal-type tumours resemble colorectal cancer (CDX2, MUC2; APC and KRAS mutations) and pancreatobiliary-type tumours resemble pancreatic cancer (MUC1, CK7; KRAS, TP53, SMAD4), with the latter behaving more aggressively. Familial adenomatous polyposis carries a large relative risk of ampullary adenoma and carcinoma, and endoscopic surveillance of the duodenum is part of FAP care.

Curative treatment is pancreatoduodenectomy (Whipple); small adenomas and some early T1 lesions can be removed endoscopically by papillectomy. Adjuvant chemotherapy is extrapolated: ESPAC-3 periampullary (JAMA 2012) showed a survival advantage for adjuvant gemcitabine or fluorouracil in multivariable analysis, and practice now leans on subtype, with oxaliplatin-fluoropyrimidine (FOLFOX or CAPOX) for intestinal-type and gemcitabine-based or modified FOLFIRINOX regimens for pancreatobiliary-type tumours. For metastatic disease the same logic applies, and tumour-agnostic biomarkers (MSI-high, HER2, NTRK, BRAF) should be tested because they are found more often than in pancreatic cancer.

The active questions are prospective subtype-directed adjuvant trials, ctDNA to guide adjuvant decisions, and neoadjuvant therapy for node-positive disease.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: Ampulla of Vater carcinoma; Periampullary cancer; Ampullary adenocarcinoma
- Tags: nci-coverage; rare; gastrointestinal
- Group: gastrointestinal
- Burden: 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.
- Subtypes: Intestinal-type adenocarcinoma; Pancreatobiliary-type adenocarcinoma; Mixed type; Ampullary adenoma (precursor; sporadic or FAP-associated); Ampullary neuroendocrine tumour (rare; see neuroendocrine)
- Biomarkers: Histomolecular subtype by IHC (CDX2, MUC2 vs MUC1, CK7); Lymph node status and margin status after Whipple; MSI / mismatch repair; HER2, BRAF V600E, NTRK fusions; KRAS, TP53, SMAD4 (pancreatobiliary), APC (intestinal); CA 19-9 and CEA for monitoring; Germline APC (FAP) where duodenal polyposis is present

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/ampullary/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/ampullary/#overview [4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/ampullary/#what-it-is [5 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/ampullary/#finding-it [7 biomarkers]
- Treating it (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/ampullary/#treating-it [4 settings, 2 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/ampullary/#evidence [21 trials, 3 key papers, 5 milestones]
- The science (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/ampullary/#science [5 targets, 3 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/ampullary/where-you-are/
- Living with it (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/ampullary/#living-with-it [16 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/ampullary/coming/ [9 medicines, 21 trials, 4 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/ampullary/data/ [65 connected records]

## Standard of care

- Ampullary adenoma or early T1 lesion: Endoscopic papillectomy with surveillance; surgery if invasive cancer or unfavourable features on pathology. ([Endoscopic resection (EMR / ESD)](https://onco.cc/technologies/endoscopic-resection/), [Endoscopy (EGD, EUS, ERCP)](https://onco.cc/terms/endoscopy/))
- Resectable carcinoma: Pancreatoduodenectomy with regional lymphadenectomy; biliary stenting first only if cholangitis or delayed surgery. ([Whipple procedure (pancreaticoduodenectomy)](https://onco.cc/terms/whipple/), [Biliary stenting and drainage](https://onco.cc/technologies/biliary-stenting-drainage/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/))
- Adjuvant: Six months of chemotherapy chosen by subtype: oxaliplatin-fluoropyrimidine (FOLFOX or CAPOX) for intestinal-type; gemcitabine-based or modified FOLFIRINOX for pancreatobiliary-type; evidence is from ESPAC-3 periampullary and retrospective series. ([FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [CAPOX (capecitabine, oxaliplatin)](https://onco.cc/drugs/capox/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [ESPAC-3](https://onco.cc/trials/espac-3/))
- Metastatic: Subtype-directed chemotherapy; pembrolizumab for MSI-high; HER2-, BRAF- or NTRK-directed therapy where present; clinical trials. ([FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Gemcitabine + nab-paclitaxel](https://onco.cc/drugs/gemcitabine-nab-paclitaxel/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Larotrectinib](https://onco.cc/drugs/larotrectinib/))

## State of the art

- Ampullary cancer got its own NCCN guideline in 2022, separating it from pancreatic cancer and formalising subtype-directed chemotherapy.
- Histomolecular subtyping is the key advance: it tells the oncologist whether to treat the tumour like a bowel cancer or like a pancreatic cancer.
- Endoscopic papillectomy spares many patients with adenomas or early lesions a Whipple operation.
- Because the disease is rare, most systemic-therapy evidence is retrospective; prospective subtype-stratified trials and ctDNA-guided adjuvant studies are the next step.

## Open problems

- No prospective randomised trial has compared subtype-directed adjuvant regimens; retrospective consortia and the NCCN guideline are the current basis.
- Which patients with node-positive disease benefit from neoadjuvant therapy; extrapolation from pancreatic trials is being tested.
- Surveillance intensity after Whipple and the role of ctDNA to select adjuvant therapy.
- FAP-associated duodenal disease: timing of prophylactic surgery versus endoscopic control.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Ampullary_cancer
- NCI PDQ: pancreatic cancer (ampullary cancers are covered with periampullary tumours): https://www.cancer.gov/types/pancreatic
- NCCN: Ampullary Adenocarcinoma: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1520
- ESPAC-3 periampullary (JAMA 2012): https://doi.org/10.1001/jama.2012.7352

## Connected records

- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Localised small bowel adenocarcinoma (stage I to III, resected)](https://onco.cc/cancers/localised-small-bowel-adenocarcinoma/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/resectable-pdac/), [Small intestine cancer (small bowel adenocarcinoma)](https://onco.cc/cancers/small-bowel/)
- technologies: [Biliary stenting and drainage](https://onco.cc/technologies/biliary-stenting-drainage/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Endoscopic resection (EMR / ESD)](https://onco.cc/technologies/endoscopic-resection/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [BRAF](https://onco.cc/targets/braf/), [HER2](https://onco.cc/targets/her2/), [KRAS](https://onco.cc/targets/kras/), [NTRK](https://onco.cc/targets/ntrk/)
- drugs: [CAPOX (capecitabine, oxaliplatin)](https://onco.cc/drugs/capox/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [FOLFIRINOX / mFOLFIRINOX](https://onco.cc/drugs/folfirinox/), [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Gemcitabine](https://onco.cc/drugs/gemcitabine/), [Gemcitabine + nab-paclitaxel](https://onco.cc/drugs/gemcitabine-nab-paclitaxel/), [Larotrectinib](https://onco.cc/drugs/larotrectinib/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/), [Signatera](https://onco.cc/drugs/signatera/)
- pathways: [p53 / RB / cell-cycle checkpoint](https://onco.cc/pathways/p53-cell-cycle/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [CA 19-9](https://onco.cc/terms/ca19-9/), [Endoscopy (EGD, EUS, ERCP)](https://onco.cc/terms/endoscopy/), [Hereditary cancer syndromes](https://onco.cc/terms/hereditary-cancer-syndromes/), [Lymphadenectomy (lymph node dissection)](https://onco.cc/terms/lymphadenectomy/), [Obstructive jaundice and biliary obstruction](https://onco.cc/terms/obstructive-jaundice/), [Whipple procedure (pancreaticoduodenectomy)](https://onco.cc/terms/whipple/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/), [Trials enrol too few, too slowly](https://onco.cc/bottlenecks/b-trial-enrolment/)
- key papers: [Clinical practice guidelines for the management of biliary tract cancers 2019: The 3rd English edition](https://onco.cc/key-papers/paper-jshbps-biliary-tract-cancer-guidelines-2019-jhbps-2021/), [Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer](https://onco.cc/key-papers/paper-hiraoka-her2-status-biliary-hum-pathol-2020/), [Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial](https://onco.cc/key-papers/paper-neoptolemos-jama/)
- trials: [A Multicenter, Prospective, Randomized, Open-label Phase Ib/II Study of Celecoxib Plus Pembrolizumab and Gemcitabine/Cisplatin Versus Pembrolizumab and Gemcitabine/Cisplatin in Patients With CK5/6-High Unresectable Locally Advanced or Metastatic Intrahepatic Cholangiocarcinoma](https://onco.cc/trials/nct07632235/), [A Phase II Study of Adjuvant Durvalumab Combined With GEMOX/GC Chemotherapy Followed by Lenvatinib Versus Capecitabine in Biliary Tract Cancer.](https://onco.cc/trials/nct07679399/), [A Phase II Study of GV20-0251 in Combination With Anti-PD-1 Monoclonal Antibodies in Patients With Unresectable, Locally Advanced, or Metastatic Solid Tumors.](https://onco.cc/trials/nct07623642/), [A Phase II Study of Pemigatinib Plus Durvalumab in Previously Treated Advanced Intrahepatic Cholangiocarcinoma Patients With FGFR-2 Fusion or Rearrangement](https://onco.cc/trials/nct06728410/), [A Study to See the Effects That a New Combination of the Three Drugs, Nab-paclitaxel, Gemcitabine, and Cisplatin Has on Biliary Tract Cancer](https://onco.cc/trials/nct02632305/), [Adjuvant Chemotherapy for BTC Based on 3D-PTA](https://onco.cc/trials/nct07296666/), [Adoptive Transfer of Tumor Infiltrating Lymphocytes for Biliary Tract Cancers](https://onco.cc/trials/nct03801083/), [Alternating Chemo-immunotherapy and FGFR Inhibitor for FGFR-positive Biliary or Cholangiocarcinoma](https://onco.cc/trials/nct07780838/), [ASCOT (JCOG1202)](https://onco.cc/trials/ascot-jcog1202/), [CisPlatin plUs Gemcitabine and Nabpaclitaxel (GAP) as pReoperative Chemotherapy Versus Immediate Resection in patIents With resecTable BiliarY Tract Cancers (BTC) at High Risk for Recurrence](https://onco.cc/trials/nct06037980/), [ESPAC-3](https://onco.cc/trials/espac-3/), [Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer](https://onco.cc/trials/nct07745296/), [Lenvatinib Plus Paclitaxel for Patients With Advanced Biliary Tract Cancer Who Failed to Gemcitabine-based Treatment](https://onco.cc/trials/nct05170438/), [mFOLFOX/mFOLFIRI vs. mFOLFOX in Advanced or Recurrent Biliary Tract Cancer Second-line](https://onco.cc/trials/nct07062536/), [PD-L1 Antibody Combined With CTLA-4 Antibody for Patients With Advanced Intrahepatic Cholangiocarcinoma Who Progressed After Standard Treatment](https://onco.cc/trials/nct04634058/), [Phase 2 Study of Daraxonrasib in Recurrent KRAS-Mutant Biliary Tract Cancer](https://onco.cc/trials/nct07793253/), [Phase II Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Albumin-Bound Paclitaxel and Lenvatinib as Second-Line Therapy for Unresectable or Metastatic Biliary Tract Cancer](https://onco.cc/trials/nct07530445/), [Testing A New Combination of Anti-cancer Immune Therapies, Atezolizumab and CDX-1127 (Varlilumab) With or Without the Addition of a Third Anti-cancer Drug, Cobimetinib, for Advanced-Stage Biliary Tract Cancer](https://onco.cc/trials/nct04941287/), [Testing Mitazalimab in Combination With Standard Chemotherapy in Immunotherapy Resistant Advanced Biliary Tract Cancers](https://onco.cc/trials/nct07437287/), [Trial Comparing Standard of Care Therapy With and Without Sequential Cytoreductive Intervention for Patients With Metastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid (ctDNA) Levels](https://onco.cc/trials/nct07282912/), [Trifluridine/Tipiracil + Oxaliplatin in Participants With Advanced or Metastatic Biliary Tract Cancer](https://onco.cc/trials/nct07146646/)

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JSON: https://onco.cc/api/v1/entities/ampullary.json