EvidenceGallbladder cancer

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.

Targeted therapy prevalence estimates from one country may not hold in another, so a UK cohort, with its own ancestry mix, would need its own molecular survey before assuming HER2 or other rates from Asian or Latin American series.

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.

A lower, more conservative prevalence than the 2017 meta-analysis, using the trial's own definition. Heterogeneity means a small biopsy can miss HER2, which argues for testing resection specimens and for reflex testing rather than testing on request.

This is the UK baseline for the incidental cancer pathway: a re-resection rate well above the Dutch registry's 24 percent, with the same selection caveat. The abstract leaves out the histology, referral and timing detail; the full paper holds it.

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.

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.

The adjuvant finding sits uneasily beside BILCAP, on which NHS adjuvant capecitabine rests; in a mostly gallbladder population the benefit is not visible. ACTICCA-1 and ARTEMIDE-Biliary01 are the trials that can settle it.

It softens the Ethun four-to-eight-week rule: timing within the range that services can deliver probably matters less than completing the operation at all and doing it with the liver bed and nodes cleared.

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.

HER2 is as frequent in India as in the West, so HER2 testing pays off in the highest-incidence population, while tumour-agnostic immunotherapy markers will rarely apply. The paper also shows plasma testing is feasible where tissue is scarce.

The clearest statement of where the burden falls and why late presentation, not drug choice, decides most outcomes in high-incidence regions; it is also the home of the POLCAGB trial.

The rationale for OPT-IN and GAIN in one place. Until OPT-IN reports in 2028 the neoadjuvant approach for incidental cancer remains a reasoned choice rather than a proven one.

Evidence that the immune environment of gallbladder cancer differs by population even when the mutations do not; a reason to report gallbladder cancer and its regions separately in immunotherapy trials rather than as one biliary subgroup.

Chile has the world's highest gallbladder cancer mortality and until this paper almost no tumour genomics; the lower TP53 rate and high TSC2 and NOTCH1 hint at a different mutational grammar, but the panel and sample size mean the figures need replication.

The cleanest split of HER2 alterations in gallbladder cancer into amplification and mutation, which matters because IHC and ISH only see the amplified tumours. It also shows the high-incidence Chilean population has not been sequenced at scale.

The most rigorous evaluation of the Chilean programme available; read alongside Mardones and Frenz (2019) and Samaniego and colleagues (2024).

The only national prophylactic cholecystectomy programme in the world has run for nearly twenty years without a design that can show whether it works. Targeting by region and risk, and building in an evaluation, is the obvious next step.

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.

One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.

The reference Western cohort for gallbladder cancer frequencies, deposited on cBioPortal as gbc_mskcc_2022, where the per-gene sample counts on OnCo were read. It supports panel testing at diagnosis: one patient in three has a targetable finding.

The best single starting point for a clinician or researcher new to the disease, written by the groups running the Chilean and Indian cohorts; its list of unmet needs is the skeleton of the ideas section on this page.

This is the polyp pathway UK radiologists and surgeons follow (a UK author, Foley, leads it). It is a surveillance-and-surgery guideline built on low to moderate quality evidence, and the Kaiser Permanente cohort published two years earlier questions whether following small polyps finds cancer at all.

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.

Molecular confirmation that the visible precursor is not always the parent of the cancer beside it, which tempers hopes that finding and removing dysplasia catches every tumour, and puts Wnt signalling through CTNNB1 at the start of the raised route.

The 98% figure shows how much antibody and scoring choices matter: it sits against 14.7% and 23% in the two large series. The tumour-size-dependent effect of T-cell density is a hypothesis about immune exhaustion in bulkier tumours.

The exome-level TMB here (0.82 per megabase) is an order of magnitude below panel estimates, a warning against comparing TMB across assays; and the survival signal sits in the microenvironment, which is where immunotherapy biomarkers for this disease may have to be found.

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.

The prognostic split is solid; the surgical consequence is not. Whether T2a tumours can safely skip liver resection, and whether T2b tumours gain from it, is a randomised or prospective-registry question that nobody has yet run.

The Western counterpart to the Indian series, with lower rates and a prognostic signal in the opposite direction from what immunotherapy enthusiasts might hope. The TIGIT and CD155 finding names a second checkpoint for future trials.

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.

Consistent with Kang and colleagues on prognosis, and more optimistic about liver resection for T2b. The adjuvant chemotherapy finding is retrospective and predates gallbladder-specific analysis of BILCAP, but it is a warning that the adjuvant benefit in this disease is not established.

Anatomy alone explains only about two thirds of the ranking of who lives longer; the 2026 staging review makes the same point and argues for molecular and nodal-burden modifiers alongside TNM.

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.

Six per thousand is the number behind the debate on routine versus selective histology of gallbladder specimens: applied to a national cholecystectomy volume it predicts a few hundred unsuspected cancers a year in a country the size of England.

A three-continent cohort from high-incidence countries, and the origin of the idea that a shared frameshift (ELF3) could be a vaccine target in a cancer with few targets. CTNNB1 and STK11 from this list recur in the MSK data.

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.

The largest natural history study of gallbladder polyps undermines the surveillance half of the 2022 European guideline: small polyps grow as a matter of course and almost never become cancer, while size at first scan carries most of the risk.

A whole-country picture of the gap between guideline and practice: three quarters of eligible patients never reached the second operation. The survival difference is confounded by selection but the residual disease rate is not.

India carries a large share of the world's gallbladder cancer and this is the only randomised test of radiotherapy's role before surgery; the registry's actual enrolment of 124 against a plan of 314 means the answer will be less certain than designed.

Together with the 2024 evaluation and the American Journal of Epidemiology analysis, this is the evidence base for whether a prophylactic cholecystectomy policy prevents gallbladder cancer deaths: suggestive in the target age band, not yet convincing nationally.

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 Indian epidemiology matters to the NHS: people of South Asian heritage make up a large part of several English cities, and Asian ethnicity is a named risk factor in the European polyp guideline.