EvidenceBiliary tract cancer (cholangiocarcinoma)

The IHC 3+ subgroup result is why the tumour-agnostic label is written at 3+ and not 2+, and why a gallbladder cancer with a strong HER2 stain now has two on-label choices (zanidatamab, trastuzumab deruxtecan) after chemotherapy. Lung toxicity again ran higher than in breast cancer.

A direct check of the HERIZON-BTC-01 testing algorithm in routine pathology: IHC 3+ can stand alone, 2+ needs ISH, and the low-level amplification in weakly stained tumours is the group where HER2 drugs are least likely to help.

For gallbladder cancer the sobering points are that HER2 can disappear under HER2-directed pressure, that SMAD4 co-mutation predicts a worse response, and that sequencing at progression, not just at diagnosis, may be needed to guide the next line.

For someone offered the test, these are the numbers that describe what a result means in an NHS population: about 1 in 100 tests came back positive each year, between 46 and 58 in 100 positives were cancer, and a negative result left about 1 in 100 with an undetected cancer within the year. The test found between a quarter and a third of all cancers diagnosed in a screening round, and about half to two thirds of the 12 cancer types it was designed to find. Whether finding them this way reduces late-stage diagnoses is the primary question, and this paper says only that the answer was no; the primary-endpoint paper had not appeared on Europe PMC by 23 September 2026.

Together with the JCO Precision Oncology cohort this makes residual disease testing in biliary cancer prognostic to the same degree as in colon cancer. Nobody has yet shown that acting on it helps; that is the trial gap the ideas on this page name.

NCCN is the source of the category grades quoted on the gallbladder cancer page; the adjuvant section leans on BILCAP for capecitabine and on SWOG S0809 for chemoradiation after margin-positive or node-positive resection.

Very wide confidence intervals from a small cohort, but the direction matches the larger 2026 analysis. Gallbladder cancer recurs early and distantly after re-resection, which is exactly the setting where a residual disease test could pick who gets more than capecitabine.

The tail of long survivors is the case for chemo-immunotherapy in gallbladder cancer, where the median gain is under two months. Who lands in that tail is still unknown; no biomarker in the trial predicts it.

Together with the DESTINY-PanTumor02 biliary cohort this is the evidence behind trastuzumab deruxtecan's tumour-agnostic IHC 3+ label being used in gallbladder cancer; the lung toxicity rate, higher than in breast cancer, is the caution for a population with pre-existing lung and liver compromise.

This is the reference European standard against which UK and NHS practice for gallbladder cancer is compared; it treats gallbladder cancer within biliary tract cancer rather than as its own disease.

For a UK patient with gallbladder cancer the nearest national guideline is about a neighbouring disease; the UK and NHS page for gallbladder cancer names the gap.

Japanese surgeons operate on gallbladder cancer far more often than UK surgeons and their guideline addresses prevention (pancreaticobiliary maljunction, polyps) as a clinical topic, which Western guidelines do not.

A positive randomised phase 2 that the German NALIRICC trial failed to reproduce; guidelines list the regimen as an option, and the disagreement is a reminder that single-country phase 2 results in biliary cancer need replication.

The first prospective evidence that HER2 blockade works in biliary cancer, which led to HERIZON-BTC-01 and the HER2 antibody-drug conjugate studies; the definition of HER2-positive here (amplification or overexpression) is looser than the later IHC 3+ label.

FOLFOX became the guideline second-line option for gallbladder cancer on this trial. The gain is real but small, which is why later-line care now starts with a search for a HER2 or other targetable alteration.

The highest gallbladder HER2 rate in the literature comes from whole resected tumours scored generously; biopsy-based trial screening finds fewer. Heterogeneity is the practical warning for pathologists and for why HER2-directed drugs do not work in every positive tumour.

GAIN closed in October 2024 with 68 participants according to ClinicalTrials.gov, one fifth of its target: the clearest example of how hard it is to run a randomised surgical trial in incidental gallbladder cancer, and why OPT-IN's result matters.

Biliary tumours are often diagnosed on tiny biopsies or brushings, so a blood-based panel that detects HER2 amplification and other targets in half of patients is a practical route to testing, with tissue confirmation where the blood is uninformative.

The concordance figures are the reference for how well plasma stands in for tissue in biliary cancer, and the profile changes on chemotherapy are the argument for re-testing at progression rather than treating on the diagnostic panel alone.

A Western benchmark for how rare MSI-high is in bile duct cancer; gallbladder cancer was not included, and the MSK gallbladder cohort's 2.5% by MSIsensor and the Indian 0.6% by panel bracket it.

The largest single-platform comparison; the abstract gives directions rather than percentages, so the figures on OnCo come from the other cohorts, but it supports testing gallbladder cancer for HER2, repair defects and immunotherapy markers.

The germline finding is the practical lesson: a meaningful minority of biliary cancer patients carry inherited repair-gene mutations that matter for PARP inhibitor eligibility and for their relatives, which argues for germline testing alongside tumour sequencing.

The clearest early head-to-head of the three biliary sites on one platform: for gallbladder cancer it made HER2 the target to test for and showed that IDH and FGFR inhibitors would rarely apply.

The paper that separated the biliary tree into molecular subtypes: FGFR2 and IDH belong to the intrahepatic ducts, while gallbladder cancer carries HER2, ELF3 and an APOBEC signature. Its hypermutated, checkpoint-high poor-prognosis group foreshadowed immunotherapy.