• FGFR2 fusions and rearrangements: A broken-and-rejoined FGFR2 gene that drives about one in eight intrahepatic bile duct cancers and can be switched off with pills.
• Anomalous pancreaticobiliary junction (pancreaticobiliary maljunction): A birth variation in which the bile duct and pancreatic duct join outside the wall of the bowel, so pancreatic juice flows back up into the bile ducts and gallbladder and irritates their lining for life.
• Gallbladder cancer in biliary tract cancer trials (eligibility and subgroups): Almost every drug trial for gallbladder cancer also enrols bile duct cancers, so the evidence comes from mixed groups in which gallbladder cancer is usually a fifth to a half of patients.
• HER2 testing in biliary tract cancer (IHC, ISH and NGS): Bile duct and gallbladder tumours are scored for HER2 with the stomach cancer rules, not the breast ones, and a strong stain (3+) is enough for zanidatamab.
• Biliary drainage routes: ERCP stent, percutaneous (PTC) and EUS-guided: When a gallbladder or bile duct tumour blocks the bile duct, the bile has to be let out.
• Symptom control in advanced gallbladder cancer: pain, ascites and nutrition: Advanced gallbladder cancer causes pain under the right ribs, fluid in the abdomen and weight loss.
• Lewis-negative (Lewis antigen-negative, CA 19-9 non-secretor) status: About one person in ten to twenty cannot make the sugar that the CA 19-9 blood test measures, because they lack a working copy of the Lewis blood-group gene.
• Intrahepatic, perihilar, distal and gallbladder cancer: Bile duct cancers are named by where they start: inside the liver, at the hilum where the ducts join, in the lower duct near the pancreas, or in the gallbladder.
• Stenting (biliary, oesophageal, airway): Placing a small mesh or plastic tube to hold open a duct or passage that a tumour is squeezing shut, relieving jaundice, swallowing difficulty or breathlessness.
• Obstructive jaundice and biliary obstruction: Yellowing of the skin and eyes because a tumour blocks the bile duct, most often pancreatic or bile duct cancer.

Diagnosis and staging: Contrast CT/MRI with MRCP; ERCP or EUS-guided biopsy; molecular profiling (DNA + RNA NGS) for all advanced disease; biliary drainage if jaundiced.

Biomarker results to ask for: FGFR2 fusions (~15% intrahepatic), IDH1 (~15%), HER2 (~15% extrahepatic/gallbladder), NRG1, MSI, BRAF, FGFR2 fusions/rearrangements (RNA or DNA NGS), IDH1 mutation, HER2 amplification / IHC 3+, NRG1 fusion, BRAF V600E, MSI/dMMR, KRAS, TP53 (prognostic), CA 19-9 (monitoring), PD-L1 (not predictive so far).

Scans and tests linked to this cancer: Companion diagnostics, Comprehensive genomic profiling, Endoscopic ultrasound and EBUS systems, Liquid biopsy (ctDNA), MRI, RNA sequencing & expression profiling.

Bring copies of scan reports, pathology and blood results, and a list of every medicine and supplement.

• Resectable: Surgery + adjuvant capecitabine.
• Resectable: Margin-negative resection (hepatectomy, Whipple, or radical cholecystectomy) with lymphadenectomy; adjuvant capecitabine 6 months (BILCAP). (BILCAP, Robotic & minimally invasive surgery)
• Unresectable perihilar in selected patients: Neoadjuvant chemoradiation then liver transplantation (Mayo protocol) at experienced centres. (Liver transplantation for cancer (Milan criteria and beyond))
• Advanced: Gem-cis + PD-(L)1; targeted therapy by genotype second line. (Durvalumab, Pembrolizumab, Zanidatamab, Zenocutuzumab, Trastuzumab deruxtecan)
• Advanced, first line: Gemcitabine-cisplatin + durvalumab (TOPAZ-1) or + pembrolizumab (KEYNOTE-966); zanidatamab added in HER2+ disease within HERIZON-BTC-302. (TOPAZ-1, KEYNOTE-966, Gemcitabine + cisplatin, Durvalumab, Pembrolizumab, HERIZON-BTC-302)
• Advanced, FGFR2 fusion after chemotherapy: Pemigatinib or futibatinib; tinengotinib in FIRST-308 after progression. (Pemigatinib, Futibatinib, Tinengotinib, FIGHT-202, FOENIX-CCA2, FIRST-308)
• Advanced, IDH1 mutation after chemotherapy: Ivosidenib (ClarIDHy). (Ivosidenib, ClarIDHy)
• Advanced, HER2-positive after chemotherapy: Zanidatamab (IHC 3+ or amplified); trastuzumab deruxtecan (IHC 3+, tumour-agnostic). (Zanidatamab, Trastuzumab deruxtecan)
• Advanced, other alterations: Zenocutuzumab (NRG1 fusion, approved 2026); dabrafenib-trametinib (BRAF V600E); pembrolizumab or dostarlimab (MSI-H/dMMR); larotrectinib/entrectinib (NTRK). (Zenocutuzumab, Dabrafenib + trametinib, Pembrolizumab, Dostarlimab)
• Locoregional (intrahepatic, liver-confined): Y-90 radioembolisation, hepatic arterial infusion pump chemotherapy, or SBRT at specialised centres; no phase 3 proof of survival benefit. (Radioembolisation (TARE / SIRT, yttrium-90), SBRT / SABR (stereotactic radiotherapy))
• Second-line, no target: FOLFOX (ABC-06, modest benefit); liposomal irinotecan/5-FU had conflicting results (NIFTY positive, NALIRICC negative); clinical trials preferred. (NALIRICC (AIO), Cytotoxic chemotherapy)

From the standard of care recorded for this cancer; which apply depends on your stage and biomarkers. Ask which the team recommends and why.