• Genomic profiling: Reading the DNA (and sometimes RNA) of a tumour, usually with a panel of a few hundred genes, to list its mutations, fusions and amplifications and match them to approved drugs or trials.
• Prophylactic (preventive) cholecystectomy: Removing a gallbladder that contains stones before it causes trouble, in the hope of preventing a cancer that almost always arises in a gallbladder with stones.
• Metaplasia, dysplasia, carcinoma in situ: the flat route to gallbladder cancer: Most gallbladder cancers grow out of flat, invisible changes in the lining: years of irritation from stones turn the mucosa metaplastic, then dysplastic, then into carcinoma in situ, and finally into invasive cancer, a process estimated at 10 to 15 years.
• HER2 and genomic testing for biliary cancer on the NHS: Asking for HER2 testing and a tumour gene panel at diagnosis of advanced gallbladder cancer is reasonable, because about one in ten tumours is HER2-positive on staining (more carry a HER2 gene change) and a HER2 antibody is now funded on the NHS; the test is arranged by your hospital team on a sample already taken.
• Intracholecystic papillary-tubular neoplasm (ICPN): An ICPN is a raised, polyp-like growth of the gallbladder lining 1 cm or larger that can turn into cancer.
• Salmonella Typhi carriage and gallbladder cancer: People who carry typhoid bacteria in their gallbladder for years have roughly four to five times the risk of gallbladder cancer.
• Weight loss, fat digestion and enzymes with gallbladder cancer: Many people with gallbladder cancer lose appetite and weight; small frequent meals, prescribed nutritional drinks, a dietitian, and enzyme capsules if fat is not being digested are the standard NHS-side answers.
• A clinical trial or standard treatment for gallbladder cancer: Joining a trial is a decision like any other: the NHS explains that most trials compare a new treatment with the standard one, that a placebo is used only where no proven treatment exists, and that you can leave at any time without it affecting your care.
• When to seek urgent help with gallbladder cancer (NHS 111 and 999): Call 999 for signs of sepsis or heavy bleeding; ring the hospital's 24-hour line or NHS 111 the same day for a temperature or shivering with a stent, for new or returning jaundice, for pain the painkillers do not control, or for being sick for more than two days.
• Pain with gallbladder and bile duct cancer: Pain in the upper tummy is common with gallbladder cancer and can be controlled for most people with the right painkillers; tell the team early, keep a note of the pattern, and ask for the palliative care or pain team if it is not settling.

Diagnosis and staging: Ultrasound, contrast CT, MRI with MRCP, FDG PET-CT before radical surgery, staging laparoscopy; frozen section rather than needle biopsy when the mass is resectable.

Newly diagnosed advanced disease: HER2 and genomic testing: HER2 testing (immunohistochemistry and in situ hybridisation) and a tumour gene panel at diagnosis of advanced disease: about one in ten gallbladder cancers is HER2-positive on staining and about one in seven carries a HER2 gene change, and zanidatamab is licensed (MHRA, February 2026) and NICE-recommended (TA1153, May 2026) for HER2-positive biliary cancer after chemotherapy; mismatch repair, BRAF V600E and NTRK results open tumour-agnostic options. On the NHS the hospital team requests the test through the Genomic Medicine Service on tissue already taken.

Biomarker results to ask for: T category on the cholecystectomy specimen (T1a versus T1b or deeper decides whether a second operation is offered), T2a versus T2b (peritoneal versus hepatic side), the strongest pathological predictor within T2, Cystic duct margin status (positive margin adds a bile duct resection), Lymph node count and number involved (N1 one to three, N2 four or more; six or more nodes examined for a reliable N stage), Grade 1 to 3 and histological type (adenosquamous and neuroendocrine carcinomas behave worse), Lymphovascular and perineural invasion; Rokitansky-Aschoff sinus involvement in early cancers, HER2 amplification or over-expression (more frequent than in cholangiocarcinoma; the molecular rows below carry the figures by cohort), Mismatch repair deficiency, BRAF V600E, NTRK fusions (tumour-agnostic treatments), CA 19-9 and CEA (often raised, neither diagnostic nor reliably prognostic), TP53 mutation: 63% (63% of 244 MSK-IMPACT samples (Giraldo 2022), KRAS mutation (amplification rarer): 11% (11% of 244 samples (Giraldo 2022), ERBB2 (HER2) amplification: 8-10% (8% amplification alone plus 1.5% amplification with a mutation among 260 patients (Mondaca 2024)), ERBB2 (HER2) activating mutation (s310f/y hotspot): 4-8% (4% mutation alone, 1.5% with amplification and 0.4% fusion among 260 patients (Mondaca 2024)), ERBB2 (HER2) protein overexpression (ihc): 9-31% (31.3% HER2-positive among 80 resected Japanese gallbladder carcinomas scored by the gastro-oesophageal guideline (Hiraoka 2020)), ERBB3 (HER3) mutation (amplification rarer): 7-12% (11.8% of 57 (Li 2014, a significantly mutated gene)), PIK3CA mutation: 11% (Mutation in 26 of 244 samples, 10.7%, in cBioPortal gbc_mskcc_2022 and 11 of 103, 10.7%, in gbc_msk_2018), CDKN2A / CDKN2B deletion or mutation: 21% (CDKN2A 21% (Giraldo 2022)), CDKN2B deep deletion (with cdkn2a): 14% (Deep deletion in 34 of 244 samples, 13.9%, in cBioPortal gbc_mskcc_2022 and 12 of 103, 11.7%, in gbc_msk_2018), ARID1A mutation (loss of function): 13-25% (13% of 85 (Javle 2016)), SMAD4 mutation or deletion: 21-38% (38% in Chile, 36% in Japan and 27% in the United States among 81 patients, with worse survival (10 versus 25 months), CTNNB1 mutation (wnt activation): 6% (Mutation in 15 of 244 samples, 6.1%, in cBioPortal gbc_mskcc_2022 and 6 of 103, 5.8%, in gbc_msk_2018), EGFR amplification or mutation: 1-3% (Amplification in 8 of 244 samples, 3.3%, and mutation in 3 of 244, 1.2%, in cBioPortal gbc_mskcc_2022), MDM2 amplification: 12% (Amplification in 29 of 244 samples, 11.9%, in cBioPortal gbc_mskcc_2022 and 12 of 103, 11.7%, in gbc_msk_2018), BRAF mutation: 3% (Mutation in 7 of 244 samples, 2.9%, in cBioPortal gbc_mskcc_2022 and 5 of 103, 4.9%, in gbc_msk_2018), IDH1 / IDH2 mutation: 0.4% (IDH1 mutation in 1 of 244 samples, 0.4%, and no IDH2 mutation in cBioPortal gbc_mskcc_2022), FGFR2 fusion, mutation or amplification: 1% (No FGFR2 fusion among the structural variants deposited for cBioPortal gbc_mskcc_2022), NTRK1 / NTRK2 / NTRK3 gene fusion: 0.4% (One LMNA::NTRK1 fusion patient (four samples) among 233 patients in cBioPortal gbc_mskcc_2022, about 0.4%), MLH1 / MSH2 / MSH6 / PMS2 microsatellite instability (msi-high): 0.6-2.5% (6 of 244 samples, 2.5%, called unstable by MSIsensor in cBioPortal gbc_mskcc_2022), Tumour mutational burden tmb (mutations per megabase): 1-12% (Median 4.1 non-synonymous mutations per megabase, with 28 of 244 samples, 11.5%, at 10 or more on the MSK-IMPACT panel (cBioPortal gbc_mskcc_2022)), BRCA1 / BRCA2 mutation (somatic or germline): 1-5% (BRCA2 mutation in 13 of 244 samples, 5.3%, and BRCA1 in 3 of 244, 1.2%, in cBioPortal gbc_mskcc_2022), ATM mutation: 7-16% (Mutation in 16 of 244 samples, 6.6%, in cBioPortal gbc_mskcc_2022 and 16 of 103, 15.5%, in gbc_msk_2018), PALB2 mutation: 1.6% (Mutation in 4 of 244 samples, 1.6%, in cBioPortal gbc_mskcc_2022), ELF3 frameshift and truncating mutation: 9% (Mutation in 21 of 244 samples, 8.6%, in cBioPortal gbc_mskcc_2022), STK11 mutation: 9% (Mutation in 22 of 244 samples, 9.0%, in cBioPortal gbc_mskcc_2022), CCNE1 amplification: 9% (Amplification in 22 of 244 samples, 9.0%, in cBioPortal gbc_mskcc_2022), CD274 (PD-L1) protein expression (ihc): 15-23% (Tumour cells positive at 1% or more in 23.0% of 174 Indian cases (SP263).

Scans and tests linked to this cancer: Companion diagnostics, Comprehensive genomic profiling, CT (computed tomography), Cytogenetics and FISH, Histopathology & immunohistochemistry, Liquid biopsy (ctDNA).

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

• Polyps and precursors (prevention): Cholecystectomy for polyps of 10 mm or more, or 6 to 9 mm with a risk factor; ultrasound surveillance at 6, 12 and 24 months otherwise; no follow-up for polyps of 5 mm or less without risk factors (ESGAR, EAES, EFISDS and ESGE 2022). (Gallbladder polyp (polypoid lesion), Porcelain gallbladder, Anomalous pancreaticobiliary junction (pancreaticobiliary maljunction), Simple cholecystectomy)
• 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. (Radical (extended) cholecystectomy, Segment IVb and V liver resection (versus wedge resection), Hepatectomy (liver resection), Lymphadenectomy (lymph node dissection), Cystic duct margin, Port-site metastasis, Incidental gallbladder cancer (found after cholecystectomy))
• 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. (Gemcitabine + cisplatin, Durvalumab, Pembrolizumab, TOPAZ-1, KEYNOTE-966, HER2)
• Locally advanced, unresectable, non-metastatic: Gemcitabine and cisplatin with durvalumab as for metastatic disease; consider chemoradiotherapy or stereotactic radiotherapy within a trial (UK ABC-07; India POLCAGB, RUGB) and reassess for conversion surgery. (TOPAZ-1, ABC-07, POLCAGB, RUGB, SBRT / SABR (stereotactic radiotherapy))
• Suspected cancer in primary care: Urgent direct-access ultrasound for an upper abdominal mass consistent with an enlarged gallbladder (NICE NG12 1.2.10); urgent referral for jaundice; the UK pathway page carries the detail. (Ultrasound, Obstructive jaundice and biliary obstruction)
• Tis or T1a found in the cholecystectomy specimen: No further surgery when the cystic duct margin is clear; the simple cholecystectomy is curative in almost all cases. (Simple cholecystectomy, Cystic duct margin, Carcinoma in situ and dysplasia of the gallbladder)
• After resection: Adjuvant capecitabine for six months (BILCAP, a UK trial in a mixed biliary population that required muscle-invasive gallbladder cancer for entry); the BILCAP record carries the figures, and the UK CAPBIL cohort saw no matched benefit, so ACTICCA-1 is awaited. (Capecitabine, BILCAP, ACTICCA-1)
• Jaundice from a blocked bile duct: stent or bypass: A stent placed by ERCP, or through the skin (PTC), is the usual way to relieve jaundice; metal stents stay open longer than plastic and are used when surgery to remove the cancer is not planned; a surgical bypass (joining the bile duct above the blockage to the small bowel) is reserved for people already having an operation or when a stent cannot be placed. Jaundice must be relieved before chemotherapy can be given safely. (Biliary stenting and drainage, Stent or bypass for jaundice: the choice, Stenting (biliary, oesophageal, airway), Obstructive jaundice and biliary obstruction)
• A clinical trial or standard treatment: At every stage a trial can be a reasonable choice beside standard treatment: ask what the comparison arm is, whether a placebo is used (in KEYNOTE-966 the control arm had chemotherapy plus placebo, never placebo alone), what extra visits are involved, and that you can leave at any time. AMMF lists biliary trials open in the UK; HERIZON-BTC-302 is the first-line HER2 trial. (A clinical trial or standard treatment for gallbladder cancer, Clinical trial, Informed consent, Placebo, KEYNOTE-966, HERIZON-BTC-302)
• HER2-positive (IHC 3+ or amplified), after first-line therapy: Zanidatamab (HERIZON-BTC-01: 41 percent response, 53 percent gallbladder cancer; FDA 2024, EU 2025, MHRA February 2026, NICE TA1153 May 2026) or trastuzumab deruxtecan for IHC 3+ (DESTINY-PanTumor02 biliary cohort 45 percent response; FDA tumour-agnostic 2024, not NICE-appraised); trastuzumab with pertuzumab through the UK DETERMINE platform; first-line zanidatamab within HERIZON-BTC-302 and SAFIR-ABC10. (Zanidatamab, HERIZON-BTC-01, Trastuzumab deruxtecan, DESTINY-PanTumor02, DETERMINE arm 04: trastuzumab with pertuzumab in HER2-amplified or mutated rare cancers, HERIZON-BTC-302, SAFIR-ABC10, HER2)
• Other actionable alterations (rare in gallbladder cancer): BRAF V600E: dabrafenib with trametinib (ROAR biliary cohort 51 percent response; FDA tumour-agnostic 2022). Mismatch-repair deficiency or high tumour mutational burden: pembrolizumab (KEYNOTE-158). NTRK fusion: larotrectinib or entrectinib. KRAS G12C: sotorasib or adagrasib off-label or in trials. FGFR2 fusions (pemigatinib, futibatinib) and IDH1 mutations (ivosidenib) are intrahepatic features; the licences and NICE appraisals (TA722, TA1005, TA948) cover cholangiocarcinoma and the trials enrolled almost no gallbladder cancer. (Dabrafenib + trametinib, ROAR (Rare Oncology Agnostic Research) basket: BRAF V600E biliary tract cancer cohort, Pembrolizumab, KEYNOTE-158, Larotrectinib, Entrectinib, Sotorasib, Adagrasib, Pemigatinib, Futibatinib, Ivosidenib, Comprehensive genomic profiling)
• Palliation of obstruction and symptoms: Biliary drainage by ERCP metal stent, percutaneous transhepatic drainage for hilar block or failed ERCP, or EUS-guided drainage (non-inferior to ERCP with fewer complications in a 125-patient randomised trial); duodenal stent or gastrojejunostomy for gastric outlet obstruction by expected survival (SUSTENT); opioids with coeliac plexus block for visceral pain; paracentesis or tunnelled catheter for ascites; early integrated palliative care. (Biliary drainage routes: ERCP stent, percutaneous (PTC) and EUS-guided, Biliary stenting and drainage, Duodenal stenting and gastrojejunostomy for malignant gastric outlet obstruction, Symptom control in advanced gallbladder cancer: pain, ascites and nutrition, Early integrated palliative care)
• Second line, no actionable target: FOLFOX with active symptom control (ABC-06, UK: overall survival 6.2 versus 5.3 months; gallbladder cancer eligible); liposomal irinotecan with fluorouracil is an NCCN option on NIFTY but was negative in NALIRICC and is not commissioned in the UK; trials preferred (SEVILLA ivonescimab versus FOLFOX at UCL; ComboMATCH for MAPK-mutant disease). (FOLFOX (5-FU, leucovorin, oxaliplatin), ABC-06, Liposomal irinotecan, NIFTY, NALIRICC (AIO), SEVILLA)

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