OnCo

Gallbladder cancer: the decisions you may face

15 treatment settings, 7 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.

Interactive aids for this cancer

Answer a few questions from a report and read the guideline statement that applies, quoted word for word with its source. Educational aids, not advice.

Other settings

Suspected cancer in primary care

One path named

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.

The path, in plain words
UltrasoundStandard of care

Ultrasound uses sound waves to make live pictures; it is cheap, safe, and used to guide needles into lumps.

  • Real-time, portable, no radiation
  • Ideal biopsy guidance
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Operator dependent
  • Cannot see through bone or air
Questions to ask about this decision
  1. Is Ultrasound the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
    Why: A single standard does not mean a single choice; timing and trials are decisions too.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NICE NG12 (2015, updated)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

4 options

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.

The options, in plain words
UltrasoundStandard of care

Ultrasound uses sound waves to make live pictures; it is cheap, safe, and used to guide needles into lumps.

  • Real-time, portable, no radiation
  • Ideal biopsy guidance
CT (computed tomography)Standard of care

A CT scan is a fast 3D X-ray that shows the size and shape of tumours and whether they have spread.

  • Fast, ubiquitous
  • Sub-millimetre resolution
  • Standard for RECIST response
MRIStandard of care

MRI uses a strong magnet and radio waves, with no ionising radiation, to picture soft tissue in finer contrast than CT, so it is the standard scan for brain tumours, prostate, rectal cancer staging, liver lesions and breast screening in high-risk women. It is slow, expensive and blurred by movement.

  • No ionising radiation
  • Best soft-tissue and brain imaging
  • Functional sequences (diffusion, perfusion)
PET/CTStandard of care

PET and CT in one machine, so hot spots on the PET are pinned to exact locations on the CT.

  • Anatomy plus biology
  • Standard for lymphoma, lung, melanoma, head and neck staging
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Operator dependent
  • Cannot see through bone or air
  • Anatomic only; cannot distinguish scar from live tumour
  • Radiation dose
  • Poor for brain, marrow, and small peritoneal disease
  • Slow and expensive
  • Motion artefacts
  • Gadolinium concerns in renal impairment
  • CT radiation added to PET dose
Questions to ask about this decision
  1. Between Ultrasound, CT (computed tomography), MRI and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Tis or T1a found in the cholecystectomy specimen

Described in words

No further surgery when the cystic duct margin is clear; the simple cholecystectomy is curative in almost all cases.

The path, in plain words

This setting names no product or technology record yet; the approach above is the standard as written. Ask your team which specific treatments they mean.

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision
  1. Which specific treatments are you proposing for this setting, and what are the alternatives?
    Why: The standard of care here is described in words rather than named products; ask for the names.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

T1b, T2 or T3 (incidental or suspected before surgery)

Described in words

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.

The path, in plain words

This setting names no product or technology record yet; the approach above is the standard as written. Ask your team which specific treatments they mean.

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision
  1. Which specific treatments are you proposing for this setting, and what are the alternatives?
    Why: The standard of care here is described in words rather than named products; ask for the names.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (AHPBA consensus statement (HPB 2015)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

After resection

One path named

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.

The path, in plain words

Capecitabine (Xeloda) is a tablet form of the chemotherapy fluorouracil. It is a backbone of treatment for bowel cancer and a standard option in advanced breast cancer.

The evidence behind it
  • Adjuvant capecitabine for 6 months vs observation after resection of biliary tract cancer

    OS 51.1 vs 36.4 months; ITT HR 0.81 (p=0.097), per-protocol HR 0.75.

    Overall survival (ITT) (months): Capecitabine 51.1 (n=223) vs Observation 36.4 (n=224) · HR 0.81 · source
  • Adjuvant gemcitabine and cisplatin for 24 weeks versus standard of care (observation, later capecitabine) after curative-intent resection of cholangiocarcinoma or muscle-invasive gallbladder carcinoma, in two separate cohorts

    No headline result recorded yet.

The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision
  1. Is Capecitabine the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
    Why: A single standard does not mean a single choice; timing and trials are decisions too.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in BILCAP and ACTICCA-1, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (BILCAP (Lancet Oncol 2019)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. Is six months of capecitabine tablets recommended for me, what does the evidence say it adds, and what are the side effects to watch for?
    Why: The BILCAP trial made adjuvant capecitabine the standard after biliary cancer surgery; Cancer Research UK notes capecitabine is a tablet and lists the side effects to report.
  7. How soon after surgery should chemotherapy start, and what if I have not recovered enough by then?
    Why: Chemotherapy after major surgery waits for eating and weight to be stable; ask what the window is and what happens if it is missed.
  8. Would chemoradiotherapy be considered if my margins were positive or lymph nodes were involved?
    Why: The site's record notes chemoradiation is considered for positive margins or node-positive disease; ask whether this applies to your pathology.

Add these to your appointment list, or take the full question set for this cancer.

Advanced, 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.

The options, in plain words

Gemcitabine plus cisplatin has been the chemotherapy backbone for bile duct cancer since 2010 and is now given with immunotherapy.

A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.

Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.

Also referenced:HER2
The evidence behind it
  • First-line advanced biliary tract cancer: gemcitabine-cisplatin + durvalumab vs + placebo
    Show survival figures (1)

    Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

    • OS HR 0.76; 2-year OS 23.6% vs 11.5%.
    Overall survival (updated) (months): Durvalumab + GemCis 12.9 (n=341) vs Placebo + GemCis 11.3 (n=344) · HR 0.76 · source
  • First-line advanced biliary tract cancer: gemcitabine-cisplatin + pembrolizumab vs + placebo

    OS 12.7 vs 10.9 months, HR 0.83.

    Overall survival (months): Pembrolizumab + GemCis 12.7 (n=533) vs Placebo + GemCis 10.9 (n=536) · HR 0.83 · source
The main trade-offs on record
Side effectAny gradeGrade 3+
Pneumonitis (any cause, PACIFIC) · vs 12.8% placebo; 1.1% fatal18.3%-

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients8%-
Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients3.4%-
Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients1.7%-
Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients0.7%-
  • No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision
  1. Between Gemcitabine + cisplatin, Durvalumab and Pembrolizumab, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in TOPAZ-1 and KEYNOTE-966, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. Which side effects of Durvalumab or Pembrolizumab are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  6. Does your recommendation follow the current guideline (NICE TA944 (2024)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

Screening, prevention and diagnosis

Polyps and precursors (prevention)

Described in words

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).

The path, in plain words

This setting names no product or technology record yet; the approach above is the standard as written. Ask your team which specific treatments they mean.

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision
  1. Which specific treatments are you proposing for this setting, and what are the alternatives?
    Why: The standard of care here is described in words rather than named products; ask for the names.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (Joint European polyp guideline (Eur Radiol 2022)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Jaundice from a blocked bile duct: stent or bypass

One path named

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.

The path, in plain words

A small tube placed by endoscope or through the skin reopens a blocked bile duct, relieving jaundice so chemotherapy can be given.

  • Rapid symptom relief
  • Enables chemotherapy dosing
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Cholangitis and stent occlusion
  • Pre-operative drainage is debated for resectable disease
Questions to ask about this decision
  1. Is Biliary stenting and drainage the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
    Why: A single standard does not mean a single choice; timing and trials are decisions too.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (Almadi 2017 meta-analyses (metal versus plastic stents); Cancer Research UK advanced gallbladder cancer), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. Would a stent or a surgical bypass suit me better, and if a stent, plastic or metal?
    Why: Cancer Research UK says metal stents are usual for advanced disease because they stay open longer; plastic is used when surgery is planned; bypass joins the duct above the blockage to the bowel.
  6. How will the stent be placed (through the mouth by ERCP or through the skin), and what are the risks of each?
    Why: Both routes are described on the Cancer Research UK advanced gallbladder cancer page; ask which is planned and why.
  7. What are the signs the stent has blocked or become infected, and who do I call at any hour?
    Why: Stents can block after a few months; a high temperature or shivering means contacting the team straight away (Cancer Research UK).

Add these to your appointment list, or take the full question set for this cancer.

Advanced, first line

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.

The options, in plain words

The tests that grade a breast or stomach cancer's HER2 level, from the original trastuzumab test in 1998 to the new 'HER2-low' and 'ultralow' cut-offs.

Sequencing hundreds of cancer genes at once from a biopsy to find the mutations a drug can target.

  • One test, all actionable alterations
  • Trial matching

Zanidatamab (Ziihera) is an antibody that grabs HER2 at two different spots, approved for HER2+ bile duct cancer.

The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Tissue quantity
  • VUS interpretation
  • 2-3 week turnaround
Questions to ask about this decision
  1. Between HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), Comprehensive genomic profiling and Zanidatamab, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Guidelines: Biliary Tract Cancers), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  5. Has my tumour been tested for HER2, and has a gene panel been sent? If not, can it be requested now?
    Why: About one in ten gallbladder cancers is HER2-positive on staining and about one in seven carries a HER2 gene change; the NHS says your hospital specialist requests genomic testing on tissue already taken.
  6. How long will the results take, is there enough tissue, and would a fresh biopsy be needed?
    Why: Tissue from a gallbladder removed elsewhere may need to be retrieved; ask early so results arrive before a treatment change is needed.
  7. Which results would change my treatment, and would any open a trial?
    Why: HER2, mismatch repair, BRAF V600E and NTRK results each map to a licensed drug or a trial; AMMF's molecular profiling booklet explains the idea.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

A clinical trial or standard treatment

Described in words

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.

The path, in plain words

This setting names no product or technology record yet; the approach above is the standard as written. Ask your team which specific treatments they mean.

The evidence behind it
  • First-line advanced biliary tract cancer: gemcitabine-cisplatin + pembrolizumab vs + placebo

    OS 12.7 vs 10.9 months, HR 0.83.

    Overall survival (months): Pembrolizumab + GemCis 12.7 (n=533) vs Placebo + GemCis 10.9 (n=536) · HR 0.83 · source
  • First-line HER2-positive advanced biliary tract cancer: zanidatamab + standard of care (GemCis ± PD-1) vs standard of care

    No headline result recorded yet.

The main trade-offs on record

No side-effect rates or interaction flags are recorded for these options yet. The side-effect lookup and interaction checker cover the products that have them.

Questions to ask about this decision
  1. Which specific treatments are you proposing for this setting, and what are the alternatives?
    Why: The standard of care here is described in words rather than named products; ask for the names.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in KEYNOTE-966 and HERIZON-BTC-302, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NHS: clinical trials; ESMO patient guide to biliary tract cancer), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.
  6. Is there a trial I could join now, what is the comparison arm, and is a placebo involved?
    Why: The NHS says a placebo is used only where no proven standard treatment exists; in biliary cancer the control arm is normally the standard chemotherapy.
  7. What extra visits, tests and travel would the trial involve, and are travel costs paid?
    Why: These are among the questions the NHS clinical trials page suggests asking before joining.
  8. If I join and then want to stop, or the trial treatment stops working, what happens to my standard treatment?
    Why: The NHS says you can leave at any point without giving a reason and without it affecting your care.

Add these to your appointment list, or take the full question set for this cancer.

Advanced, first line

Locally advanced, unresectable, non-metastatic

One path named

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.

The path, in plain words

Stereotactic body radiotherapy converges multiple beams with sub-millimetre accuracy to deliver tumour-destroying doses in one to five outpatient sessions, doing the job of surgery for inoperable early lung cancer and for metastases in liver, spine and brain. Tumour size and location limit its use, and late toxicity is a concern near the central airways.

  • Ablative doses with minimal recovery
  • Outpatient
The evidence behind it
  • First-line advanced biliary tract cancer: gemcitabine-cisplatin + durvalumab vs + placebo
    Show survival figures (1)

    Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

    • OS HR 0.76; 2-year OS 23.6% vs 11.5%.
    Overall survival (updated) (months): Durvalumab + GemCis 12.9 (n=341) vs Placebo + GemCis 11.3 (n=344) · HR 0.76 · source
  • Locally advanced, non-metastatic biliary tract cancer: six cycles of cisplatin and gemcitabine followed by stereotactic body radiotherapy versus eight cycles of cisplatin and gemcitabine, UK randomised phase 2, primary endpoint progression-free survival

    No headline result recorded yet.

  • Locally advanced (T3-4) gallbladder cancer: neoadjuvant gemcitabine-based chemotherapy versus neoadjuvant chemoradiotherapy before attempted resection, with staging laparoscopy and PET-CT

    No headline result recorded yet.

  • Unresectable non-metastatic gallbladder carcinoma: systemic therapy (gemcitabine-cisplatin, gemcitabine-oxaliplatin, gemcitabine-cisplatin-durvalumab or gemcitabine-cisplatin-nab-paclitaxel) with or without radiotherapy

    No headline result recorded yet.

The main trade-offs on record
  • Size and location limits
  • Late toxicity near central airways
Questions to ask about this decision
  1. Is SBRT / SABR (stereotactic radiotherapy) the only reasonable path for me, or is there a trial, a different sequence or a wait-and-see option?
    Why: A single standard does not mean a single choice; timing and trials are decisions too.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in TOPAZ-1 and ABC-07, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  5. Does your recommendation follow the current guideline (NCCN Biliary Tract Cancers), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

Third line and beyond

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.

The options, in plain words

Zanidatamab (Ziihera) is an antibody that grabs HER2 at two different spots, approved for HER2+ bile duct cancer.

Trastuzumab deruxtecan (Enhertu) is the most successful ADC ever. It redefined HER2 by working in tumours with only tiny amounts of the protein, and in 2026 moved into early-stage breast cancer.

Also referenced:HER2
The evidence behind it
  • HER2-amplified unresectable, locally advanced or metastatic biliary tract cancer after gemcitabine-based therapy: zanidatamab 20 mg/kg every 2 weeks, single arm; cohort 1 IHC 2+ or 3+ (n=80), cohort 2 IHC 0 or 1+ (n=7)

    Confirmed ORR by independent central review 41.3% (33/80, 95% CI 30.4 to 52.8) in HER2 IHC 2+/3+ cohort; grade 3 treatment-related adverse events 18%; 53% of patients had gallbladder cancer.

    Grade 3 treatment-related adverse events (%): Zanidatamab 18 (n=87) · source
  • HER2-expressing (IHC 2+/3+) solid tumours after ≥1 line, seven cohorts including endometrial and cervical: trastuzumab deruxtecan

    Endometrial ORR 57.5% (84.6% in IHC 3+); cervical ORR 50%.

    Objective response rate, endometrial cohort (%): T-DXd (all HER2 IHC 2+/3+) 57.5 (n=40) vs T-DXd (IHC 3+ only) 84.6 (n=13) · source
  • Adult, paediatric and young adult patients with rare cancers, or common cancers with rare alterations, carrying HER2 amplification or activating mutations, gallbladder neoplasms among the listed conditions: trastuzumab plus pertuzumab, non-randomised treatment arm of the national DETERMINE platform

    No headline result recorded yet.

  • First-line HER2-positive advanced biliary tract cancer: zanidatamab + standard of care (GemCis ± PD-1) vs standard of care

    No headline result recorded yet.

  • Advanced biliary cancer (intrahepatic, perihilar or distal cholangiocarcinoma, or gallbladder carcinoma) after induction gemcitabine and cisplatin: molecular targeted maintenance therapy matched to the tumour's alteration versus standard of care, international platform phase 3

    No headline result recorded yet.

The main trade-offs on record
Side effectAny gradeGrade 3+
Neutropenia · DESTINY-Breast03/04; all-grade rates ≥20% per label-18%
Nausea · DESTINY-Breast03/04; all-grade rates ≥20% per label-7%
Anaemia · DESTINY-Breast03/04; all-grade rates ≥20% per label-7%
Fatigue · DESTINY-Breast03/04; all-grade rates ≥20% per label-6%
  • Interstitial lung disease in 10-15%: hold for any respiratory symptom and image; permanently discontinue for grade 2 or above. Moderately emetogenic: three-drug prophylaxis.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision
  1. Between Zanidatamab and Trastuzumab deruxtecan, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in HERIZON-BTC-01 and DESTINY-PanTumor02, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. Which side effects of Trastuzumab deruxtecan are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  6. Does your recommendation follow the current guideline (NICE TA1153 (7 May 2026)), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

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.

The options, in plain words

Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.

Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.

The first drug approved for a gene fusion regardless of where the cancer started; it works in about 75% of NTRK-fusion cancers, from infant fibrosarcoma to salivary and thyroid cancers.

Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.

Sotorasib (Lumakras) was the first drug to hit KRAS, approved in 2021 after four decades of failure.

Adagrasib was the second KRAS G12C inhibitor, with a long half-life and brain penetration, and is approved in lung and colorectal cancer.

Pemigatinib was the first targeted therapy for bile duct cancer, for tumours with an FGFR2 gene fusion.

Futibatinib is a covalent FGFR inhibitor for FGFR2-fusion bile duct cancer, with the highest response rate of the first-generation drugs.

The first drug to block a mutant metabolic enzyme in cancer. With azacitidine it tripled survival in IDH1-mutated AML that could not take intensive chemotherapy.

Sequencing hundreds of cancer genes at once from a biopsy to find the mutations a drug can target.

  • One test, all actionable alterations
  • Trial matching
The evidence behind it
  • BRAF V600E-mutated rare cancers in nine histology cohorts, including previously treated unresectable, metastatic or recurrent biliary tract cancer (n=43): dabrafenib 150 mg twice daily plus trametinib 2 mg daily, single arm

    Biliary cohort ORR 51% (22/43, investigator) and 47% (independent review); grade 3 or worse GGT rise 12%.

    Overall response rate, biliary tract cancer cohort (investigator-assessed) (%): Dabrafenib + trametinib 51 (n=43) · source
  • Advanced solid tumours in histology-defined and biomarker-defined cohorts, including previously treated advanced biliary adenocarcinoma of the gallbladder or biliary tree (n=104; ampullary excluded): pembrolizumab 200 mg every 3 weeks, single arm
    Show survival figures (1)

    Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

    • Biliary cohort ORR 5.8% (6/104); median OS 7.4 months; median PFS 2.0 months; median duration of response not reached.
    Objective response rate, biliary adenocarcinoma cohort (independent central review) (%): Pembrolizumab 5.8 (n=104) · source
The main trade-offs on record
  • Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
Side effectAny gradeGrade 3+
Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients8%-
Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients3.4%-
Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients1.7%-
Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients0.7%-
  • No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Avoid grapefruit.
  • Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
Side effectAny gradeGrade 3+
Hepatotoxicity · CodeBreaK 10025%12%
Interstitial lung disease · CodeBreaK 1002.2%1.1%
Diarrhoea · CodeBreaK 10042%-
Musculoskeletal pain · CodeBreaK 10035%-
  • No adjustment for mild impairment; hepatotoxicity is common and worse after recent immunotherapy.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Hepatotoxicity · KRYSTAL-1 NSCLC37%10%
Dyspnoea · KRYSTAL-1 NSCLC35%10%
Fatigue · KRYSTAL-1 NSCLC59%7%
Musculoskeletal pain · KRYSTAL-1 NSCLC41%7%
  • Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Side effectAny gradeGrade 3+
Differentiation syndrome · AGILE combination arm14%-
  • Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

  • Tissue quantity
  • VUS interpretation
  • 2-3 week turnaround
Questions to ask about this decision
  1. Between Dabrafenib + trametinib, Pembrolizumab, Larotrectinib and the other options, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in ROAR (Rare Oncology Agnostic Research) basket: BRAF V600E biliary tract cancer cohort and KEYNOTE-158, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. Which side effects of Pembrolizumab or Sotorasib are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  6. Does your recommendation follow the current guideline (NCCN Biliary Tract Cancers; NICE TA722, TA948, TA1005), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

Second line

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).

The options, in plain words

FOLFOX is the workhorse chemotherapy combination for bowel cancer, used after surgery to cure and in advanced disease as the backbone that targeted drugs are added to.

Irinotecan wrapped in a fat bubble so it circulates longer. It is approved for pancreatic cancer, and in bile duct and gallbladder cancer one Korean trial found it helped as second-line treatment while a German trial did not.

The evidence behind it
  • Advanced biliary tract cancer after progression on gemcitabine and cisplatin: active symptom control with or without modified FOLFOX

    Modified FOLFOX plus active symptom control modestly improved overall survival over active symptom control alone.

    Overall survival (months): Active symptom control + FOLFOX 6.2 (n=81) vs Active symptom control alone 5.3 (n=81) · HR 0.69 · source
  • Metastatic biliary tract cancer after progression on gemcitabine and cisplatin: fluorouracil and leucovorin with or without liposomal irinotecan, open-label randomised phase 2b at five Korean centres

    BICR PFS 7.1 vs 1.4 months, HR 0.56 (0.39 to 0.81), p=0.0019; re-read PFS 4.2 vs 1.7 months, HR 0.61 (0.44 to 0.86).

    Progression-free survival by masked independent central review (updated, re-read) (months): Liposomal irinotecan + 5-FU/LV 4.2 (n=88) vs 5-FU/LV 1.7 (n=86) · HR 0.61 · source
  • Second-line biliary tract cancer after gemcitabine: liposomal irinotecan + 5-FU/LV vs 5-FU/LV

    OS 6.9 vs 8.2 months; not improved.

    Overall survival (months): nal-IRI + 5-FU/LV 6.9 vs 5-FU/LV 8.2
  • Second-line locally advanced or metastatic biliary cancer (intrahepatic, perihilar or distal cholangiocarcinoma, or gallbladder carcinoma; ampullary excluded): ivonescimab versus FOLFOX, randomised, primary endpoint progression-free survival

    No headline result recorded yet.

The main trade-offs on record
Side effectAny gradeGrade 3+
Neutropenia (grade 3-4) · NIFTY, liposomal irinotecan arm-24%
Fatigue or asthenia (grade 3-4) · NIFTY-13%

Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.

Questions to ask about this decision
  1. Between FOLFOX (5-FU, leucovorin, oxaliplatin) and Liposomal irinotecan, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. How closely do I match the people in ABC-06 and NIFTY, and does that change what the results mean for me?
    Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
  4. Which side effects of Liposomal irinotecan are most likely for me, which are reversible, and which would make us stop?
    Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
  5. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  6. Does your recommendation follow the current guideline (ABC-06 (Lancet Oncology 2021); NCCN Biliary Tract Cancers), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

Other settings

Palliation of obstruction and symptoms

2 options

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.

The options, in plain words

A small tube placed by endoscope or through the skin reopens a blocked bile duct, relieving jaundice so chemotherapy can be given.

  • Rapid symptom relief
  • Enables chemotherapy dosing

Specialist care for symptoms, decision-making and quality of life given alongside cancer treatment from diagnosis, not just at the end. Trials show it improves quality of life and mood and may lengthen survival.

  • Randomised evidence for better quality of life, mood and end-of-life care
  • Reduces futile treatment and hospital deaths
  • Telehealth delivery is equivalent to in-person
The evidence behind it

No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.

The main trade-offs on record
  • Cholangitis and stent occlusion
  • Pre-operative drainage is debated for resectable disease
  • Workforce shortage; referral often late or never
  • Perceived by patients and oncologists as 'giving up'
  • Opioid access absent in much of the world
Questions to ask about this decision
  1. Between Biliary stenting and drainage and Early integrated palliative care, which do you recommend for me, and what about my case would make you choose differently?
    Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
  2. What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?
    Why: The aim shapes how much side effect and disruption is worth accepting.
  3. What happens if I delay, or decline this step for now? Is the decision reversible?
    Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
  4. Does your recommendation follow the current guideline (NCCN Biliary Tract Cancers; ESMO 2023), and if it departs from it, why?
    Why: Departures from guidelines are sometimes right for an individual; they should be explained.

Add these to your appointment list, or take the full question set for this cancer.

How to read this page. Options and results come from OnCo records with their sources; the settings are the standard-of-care rows on the cancer page, and the lines of therapy are on the sequencing grid. Where a setting names one path, the choice is usually about timing, trials and where to be treated: see expert centres. OnCo is orientation, not medical advice.