| Domain | Item | Key findings / numeric values | Citations |
|---|---|---|---|
| Epidemiology / burden | Global 2019 burden | 199,211 incident cases (95% UI 166,769–219,615); 256,340 prevalent cases (215,699–282,004); 172,441 deaths (144,899–188,615); 3,621,473 DALYs (3,102,423–3,969,071) worldwide in 2019 | (pqac-00000010) |
| Epidemiology / burden | 1990–2019 trends | Incident cases increased 84.8% from 107,787 to 199,211; age-standardized incidence declined by 0.48%/year; age-standardized prevalence declined by 0.27%/year; absolute counts rose 1.85-fold (incidence), 1.92-fold (prevalence), 1.82-fold (deaths), 1.68-fold (DALYs) | (pqac-00000009, pqac-00000010) |
| Epidemiology / burden | Sex and age patterns | Females had nearly double age-standardized incidence vs males in 2019: 14.0 vs 7.5 per 100,000; older adults and females are more susceptible overall; early-onset burden rose 52.4% from 1990–2019, especially in low-SDI regions | (pqac-00000011, pqac-00000012, pqac-00000014) |
| Epidemiology / burden | High-BMI attributable burden | High BMI accounted for 15.2% of deaths and 15.7% of DALYs globally in 2019; high-BMI-attributable absolute deaths and DALYs more than doubled from 1990–2021 despite declining age-standardized rates | (pqac-00000009, pqac-00000015) |
| Risk factors | Gallstones | Gallstones are described as the primary risk factor; gallstones accompanied gallbladder mass in 60–90% of sonographic series | (pqac-00000012, pqac-00000035) |
| Risk factors | Obesity / high BMI | Obesity/high BMI is a major attributable risk; burden is higher in high-SDI regions due to obesity prevalence, while low-SDI regions show higher EAPCs | (pqac-00000009, pqac-00000014, pqac-00000015) |
| Risk factors | Diabetes / metabolic disease | Obesity and diabetes are highlighted among major attributable risks for gallbladder/biliary tract cancer | (pqac-00000012) |
| Risk factors | Infectious associations | Chronic infections noted as relevant risks include HBV, parasites, and Aspergillus flavus; HBV prevalence exceeds 8% in parts of Asia/Africa and accounts for nearly 70% of all HBV-infected persons worldwide | (pqac-00000012) |
| Genomics / pathways | Top recurrent genes (WES 2024) | Recurrently mutated genes in 66 tumors: TP53 21%, SMAD4 16%, ERBB3 11%, KRAS 8%, PIK3CA 7%, ARID1A 5%, RB1 5%, AXIN1 3% | (pqac-00000025, pqac-00000029) |
| Genomics / pathways | Most altered genes / drivers | Eight most altered genes highlighted: TP53, SMAD4, ERBB3, KRAS, ARID1A, PIK3CA, RB1, AXIN1; driver genes also included CTNNB1, ELF3, ERBB2 | (pqac-00000025, pqac-00000028) |
| Genomics / pathways | Pathway frequencies | Figure-based summary in 66 tumors: RTK-RAS 52/66 (78.8%), WNT 47/66 (71.2%), TP53 35/66 (53.0%); other pathways included Notch 54.5%, Hippo ~53%, TGF-β 28.8% | (pqac-00000026, pqac-00000038) |
| Genomics / pathways | ERBB family | RTK-RAS pathway included ERBB2 26.92%, ERBB3 23.07%, ERBB4 11.53%, KRAS 13.46%; ERBB2/ERBB3 alterations are repeatedly highlighted as actionable/immune-relevant | (pqac-00000026, pqac-00000032) |
| Genomics / pathways | PI3K / PTEN | PI3K pathway altered in 27% overall; among pathway-altered cases PIK3CA 33.3%, MTOR 27.8%, PTEN 22.2%; PIK3CA gain-of-function and PTEN loss emphasized as therapeutically relevant | (pqac-00000026, pqac-00000027, pqac-00000028) |
| Genomics / pathways | WNT / CTNNB1 / AXIN1 | WNT pathway altered in 71.2%; CTNNB1 38.29%, AXIN1 14.89%; APC mutations noted in adenomas in single-cell/WGS progression analysis | (pqac-00000026, pqac-00000030) |
| Genomics / pathways | TP53 / SMAD4 / LOF | TP53 pathway altered in 53% with TP53 mutated in 86.11% of TP53-pathway–altered cases; all observed TP53 variants were loss-of-function; SMAD4/TGF-β alterations are prominent after TP53 | (pqac-00000026, pqac-00000028) |
| Genomics / pathways | Mutational signatures / exposures | COSMIC 1, 6, 18, 29 linked to age and tobacco smoking/chewing; Signature 4 linked to tobacco mutagens; APOBEC enrichment score >2 in 24% of samples; median TMB 1.6 muts/Mb | (pqac-00000025, pqac-00000026, pqac-00000028, pqac-00000029) |
| Genomics / microenvironment | Single-cell / immune escape | scRNA-seq atlas of 230,737 cells from 15 GBCs and benign lesions identified OLFM4 as elevated; OLFM4 upregulated PD-L1 through MAPK-AP1 axis, linking epithelial programs to immune evasion | (pqac-00000001, pqac-00000030) |
| Treatment / standard of care | Historical chemotherapy backbone | Cisplatin + gemcitabine remained SOC for >10 years based on ABC-02: median OS 11.7 vs 8.1 months; HR 0.64 | (pqac-00000019, pqac-00000023) |
| Treatment / pivotal trial | TOPAZ-1 | Durvalumab + gemcitabine/cisplatin: median OS 12.8 vs 11.5 months; OS HR 0.80 (95% CI 0.66–0.97); median PFS 7.2 vs 5.7 months; PFS HR 0.75 (0.63–0.89) | (pqac-00000017, pqac-00000019) |
| Treatment / pivotal trial | KEYNOTE-966 | Pembrolizumab + gemcitabine/cisplatin: median OS 12.7 vs 10.9 months; OS HR 0.83 (95% CI 0.72–0.95); median PFS 6.5 vs 5.6 months; BICR PFS HR 0.86 (0.75–1.00) | (pqac-00000017, pqac-00000019, pqac-00000021) |
| Treatment / approvals | FDA approval dates | Durvalumab approved 2022-09-02; pembrolizumab approved 2023-10-31 for unresectable/metastatic biliary tract cancer with gemcitabine/cisplatin | (pqac-00000019) |
| Treatment / subgroup note | Gallbladder cancer subgroup | Exploratory subgroup analyses suggested smaller benefit in gallbladder cancer: OS HR 0.96 in GBC in FDA review; another review reported GBC subgroup median OS 10.7 vs 11.0 months, HR 0.94 (95% CI 0.65–1.37) | (pqac-00000017, pqac-00000018) |
| Treatment / real-world | Durvalumab + GemCis real-world cohort | German multicenter cohort (n=165): median OS 14.0 months (95% CI 10.3–17.7), PFS 8.0 months (6.8–9.2), ORR 28.5%, DCR 65.5%; gallbladder cancer subgroup median OS 9.0 months (5.5–12.4) and was an independent adverse prognostic factor | (pqac-00000024) |
| Treatment / safety | Durvalumab combination safety | In TOPAZ-1, any-grade AEs 99.4% vs 98.8%; grade 3–4 AEs 75.7% vs 77.8%; immune-related AEs 12.7% vs 4.7% with durvalumab vs placebo | (pqac-00000018, pqac-00000021) |
| Diagnostics | FNAC / cytology | FNAC sensitivity 90.63%, specificity 94.74%; USG-guided FNAC diagnostic accuracy ~95% for confirming diagnosis, especially in locally advanced/metastatic disease | (pqac-00000033) |
| Diagnostics | Ultrasound / sonography | Common sonographic patterns: mass lesion in 87%; intraluminal 59% vs infiltrative 41%; mass replacing gallbladder in 73%; gallstone with mass in 54% in one series | (pqac-00000035) |
| Diagnostics | CT / MRI resectability and staging | MDCT sensitivity 72.7%, specificity 100%, accuracy 85% for resectability; CT staging accuracy 93.3%; multiparametric MRI sensitivity 90% and specificity 88% for malignant thickened wall | (pqac-00000036) |
| Diagnostics | PET-CT / recurrence | PET-CT detected occult metastases in 46.6%; changed management in ~25% of resectable and 30–35% of locally advanced cases; PET/CT sensitivity/specificity for recurrence 97.6% / 90% | (pqac-00000036) |
| Differential diagnosis | Xanthogranulomatous cholecystitis mimic | XGC can mimic malignancy; characteristic cytology includes foam cells, histiocytes, bile, multinucleate giant cells, and mixed inflammatory infiltrate | (pqac-00000033) |


*Table: This table condenses high-yield, quantitatively anchored evidence on gallbladder cancer epidemiology, risk factors, molecular landscape, current systemic therapy, and diagnostic performance. It is designed as a reusable reference for a disease knowledge base entry and cites the specific available context IDs supporting each row.*