Mapping the landscape of biliary tract cancer in Europe: challenges and controversies

Lorenza Rimassa^{1

2}, Shahid Khan³, Bas Groot Koerkamp⁴, Stephanie Roessler⁵, Jesper B Andersen⁶, Chiara Raggi⁷, Ana Lleo^{1

8}, Jean-Charles Nault^{9

10}, Julien Calderaro^{11

12

13}, Chiara Gabbi¹⁴, Jakob N Kather^{15

16

17}, Jesus M Banales^{18

19

20

21}, Irene Bargellini^{22

23}, Helen Morement²⁴, Marcin Krawczyk^{25

26}, Paraskevi A Farazi²⁷, Guido Carpino²⁸, Matias A Avila²⁹, Anna Saborowski³⁰, Vincenzo Cardinale³¹, Chiara Braconi^{32

33

34}, Rocio I R Macias³⁵

Affiliations

¹ Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy.
² Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via A. Manzoni 56, 20089, Rozzano, Milan, Italy.
³ Department of Metabolism, Digestion and Reproduction, Imperial College London, Liver Unit, St Mary's Hospital Campus, South Wharf Road, W2 1NY, London, UK.
⁴ Department of Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
⁵ Heidelberg University, Medical Faculty, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
⁶ Biotech Research & Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen N, DK-2200, Denmark.
⁷ Department of Experimental and Clinical Medicine, University of Florence, Cubo Centro Polivalente 2, Viale Pieraccini 6, 50139, Florence, Italy.
⁸ Internal Medicine and Hepatology Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
⁹ Cordeliers Research Center, Sorbonne University, Inserm, Paris Cité University, "Functional Genomics of Solid Tumors" Team, Ligue Nationale Contre le Cancer Accredited Team, Labex OncoImmunology, 16 rue de l'École de Médecine, 75006, Paris, France.
¹⁰ Liver Unit, Avicenne Hospital, APHP, University Sorbonne Paris Nord, 125 Avenue de Stalingrad, 93000, Bobigny, France.
¹¹ Université Paris Est Créteil, INSERM, IMRB, 61 Av. du Général de Gaulle, 94000, Créteil, France.
¹² Department of Pathology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, 1 Rue Gustave Eiffel, 94010, Créteil, France.
¹³ MINT-Hep, Mondor Integrative Hepatology, 1 Rue Gustave Eiffel, 94010, Créteil, France.
¹⁴ Humanitas Medical Care, Via Domodossola 9/a, 20145, Milan, Italy.
¹⁵ Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307, Dresden, Germany.
¹⁶ Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307, Dresden, Germany.
¹⁷ Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
¹⁸ Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute - Donostia University Hospital, CIBERehd, Paseo Dr. Begiristain, s/n, 20014, San Sebastian, Spain.
¹⁹ IKERBASQUE, Basque Foundation for Science, Euskadi Pl., 5, Abando, 48009, Bilbao, Spain.
²⁰ Department of Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Barrio Sarriena, s/n, 48940, Leioa, Spain.
²¹ Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Calle Irunlarrea 1, 31008, Pamplona, Spain.
²² Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy.
²³ Division of Diagnostic and Interventional Radiology, Candiolo Cancer Institute FPO-IRCCS, Strada Provinciale 142, 10060, Candiolo (TO), Italy.
²⁴ AMMF - The Cholangiocarcinoma Charity, Enterprise House, Bassingbourn Road, Stansted, CM24 1QW, Essex, UK.
²⁵ Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
²⁶ Laboratory of Metabolic Liver Diseases, Medical University of Warsaw, Banacha Street 1B, 02-097, Warsaw, Poland.
²⁷ School of Medicine, European University Cyprus, 6 Diogenes Street, 2404, Engomi, Nicosia, Cyprus.
²⁸ Department of Anatomical, Histological, Legal Medicine and Orthopedic Sciences, Sapienza University of Rome, Via Alfonso Borelli 50, 00161, Rome, Italy.
²⁹ Hepatology Laboratory, Solid Tumors Program, CIMA, IdiSNA, CIBERehd, University of Navarra, Calle Irunlarrea 1, 31008, Pamplona, Spain.
³⁰ Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany.
³¹ Department of Translational and Precision Medicine, Sapienza University of Rome, Via Alfonso Borelli 50, 00161, Rome, Italy.
³² School of Cancer Sciences, University of Glasgow, Switchback rd, G61 1QH, Glasgow, UK.
³³ Beatson West of Scotland Cancer Centre, 1053 Great Western rd, G12 0YN, Glasgow, UK.
³⁴ CRUK Scotland Cancer Centre, G61 1BD, Glasgow, UK.
³⁵ Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, CIBERehd, Campus M. Unamuno s/n, 37007, Salamanca, Spain.

PMID: 40093398
PMCID: PMC11910794
DOI: 10.1016/j.lanepe.2024.101171

Review

Mapping the landscape of biliary tract cancer in Europe: challenges and controversies

Lorenza Rimassa et al. Lancet Reg Health Eur. 2025.

. 2025 Feb 19:50:101171.

doi: 10.1016/j.lanepe.2024.101171. eCollection 2025 Mar.

Authors

Affiliations

¹ Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072, Pieve Emanuele, Milan, Italy.
² Medical Oncology and Hematology Unit, Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Via A. Manzoni 56, 20089, Rozzano, Milan, Italy.
³ Department of Metabolism, Digestion and Reproduction, Imperial College London, Liver Unit, St Mary's Hospital Campus, South Wharf Road, W2 1NY, London, UK.
⁴ Department of Surgery, Erasmus MC Cancer Institute, Doctor Molewaterplein 40, 3015 GD, Rotterdam, the Netherlands.
⁵ Heidelberg University, Medical Faculty, Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
⁶ Biotech Research & Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Ole Maaløes Vej 5, Copenhagen N, DK-2200, Denmark.
⁷ Department of Experimental and Clinical Medicine, University of Florence, Cubo Centro Polivalente 2, Viale Pieraccini 6, 50139, Florence, Italy.
⁸ Internal Medicine and Hepatology Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Milan, Italy.
⁹ Cordeliers Research Center, Sorbonne University, Inserm, Paris Cité University, "Functional Genomics of Solid Tumors" Team, Ligue Nationale Contre le Cancer Accredited Team, Labex OncoImmunology, 16 rue de l'École de Médecine, 75006, Paris, France.
¹⁰ Liver Unit, Avicenne Hospital, APHP, University Sorbonne Paris Nord, 125 Avenue de Stalingrad, 93000, Bobigny, France.
¹¹ Université Paris Est Créteil, INSERM, IMRB, 61 Av. du Général de Gaulle, 94000, Créteil, France.
¹² Department of Pathology, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, 1 Rue Gustave Eiffel, 94010, Créteil, France.
¹³ MINT-Hep, Mondor Integrative Hepatology, 1 Rue Gustave Eiffel, 94010, Créteil, France.
¹⁴ Humanitas Medical Care, Via Domodossola 9/a, 20145, Milan, Italy.
¹⁵ Else Kroener Fresenius Center for Digital Health, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307, Dresden, Germany.
¹⁶ Department of Medicine I, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, 01307, Dresden, Germany.
¹⁷ Medical Oncology, National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
¹⁸ Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute - Donostia University Hospital, CIBERehd, Paseo Dr. Begiristain, s/n, 20014, San Sebastian, Spain.
¹⁹ IKERBASQUE, Basque Foundation for Science, Euskadi Pl., 5, Abando, 48009, Bilbao, Spain.
²⁰ Department of Medicine, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Barrio Sarriena, s/n, 48940, Leioa, Spain.
²¹ Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Calle Irunlarrea 1, 31008, Pamplona, Spain.
²² Department of Surgical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy.
²³ Division of Diagnostic and Interventional Radiology, Candiolo Cancer Institute FPO-IRCCS, Strada Provinciale 142, 10060, Candiolo (TO), Italy.
²⁴ AMMF - The Cholangiocarcinoma Charity, Enterprise House, Bassingbourn Road, Stansted, CM24 1QW, Essex, UK.
²⁵ Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstraße 55, 45147, Essen, Germany.
²⁶ Laboratory of Metabolic Liver Diseases, Medical University of Warsaw, Banacha Street 1B, 02-097, Warsaw, Poland.
²⁷ School of Medicine, European University Cyprus, 6 Diogenes Street, 2404, Engomi, Nicosia, Cyprus.
²⁸ Department of Anatomical, Histological, Legal Medicine and Orthopedic Sciences, Sapienza University of Rome, Via Alfonso Borelli 50, 00161, Rome, Italy.
²⁹ Hepatology Laboratory, Solid Tumors Program, CIMA, IdiSNA, CIBERehd, University of Navarra, Calle Irunlarrea 1, 31008, Pamplona, Spain.
³⁰ Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School, Carl Neuberg Str. 1, 30625, Hannover, Germany.
³¹ Department of Translational and Precision Medicine, Sapienza University of Rome, Via Alfonso Borelli 50, 00161, Rome, Italy.
³² School of Cancer Sciences, University of Glasgow, Switchback rd, G61 1QH, Glasgow, UK.
³³ Beatson West of Scotland Cancer Centre, 1053 Great Western rd, G12 0YN, Glasgow, UK.
³⁴ CRUK Scotland Cancer Centre, G61 1BD, Glasgow, UK.
³⁵ Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, CIBERehd, Campus M. Unamuno s/n, 37007, Salamanca, Spain.

PMID: 40093398
PMCID: PMC11910794
DOI: 10.1016/j.lanepe.2024.101171

Abstract

Biliary tract cancer (BTC) is becoming more common worldwide, with geographic differences in incidence and risk factors. In Europe, BTC may be associated with primary sclerosing cholangitis, lithiasis, and liver cirrhosis, but is more frequently observed as a sporadic disease. BTC increasingly affects patients under 60 years, resulting in a significant social and economic burden. Early diagnosis remains challenging due to vague symptoms in 50% of patients with BTC, and lack of specific biomarkers, resulting in late presentation and poor prognosis. The identification of patients at increased risk and reliable biomarkers require collaborative efforts to make faster progress. This Series paper highlights the disparities in access to diagnostic tools and multidisciplinary care in Europe, particularly in economically disadvantaged regions, while identifying priority areas for improvement. Addressing these inequities requires harmonised guidelines, accelerated pathways to curative treatments, and improved awareness among healthcare professionals and the public. Multidisciplinary teams (MDTs) are crucial for the diagnosis of BTC and for improving patient outcomes, yet inconsistencies exist in their implementation not only between different countries, but also between different centres within a country. Collaboration and standardisation of diagnostic and treatment protocols across Europe are essential to effectively address the management of patients with BTC.

Keywords: Access to diagnosis; Biliary tract cancer; Biomarkers; Cholangiocarcinoma; Epidemiology; Europe; Gallbladder carcinoma.

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Conflict of interest statement

LR reports grant/research funding (to institution) from AbbVie, Agios, AstraZeneca, BeiGene, Eisai, Exelixis, Fibrogen, Incyte, IPSEN, Jazz Pharmaceuticals, Lilly, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, TransThera Sciences, and Zymeworks; consulting fees from AbbVie, AstraZeneca, Basilea, Bayer, Bristol Myers Squibb, Eisai, Elevar Therapeutics, Exelixis, Genenta, Hengrui, Incyte, IPSEN, IQVIA, Jazz Pharmaceuticals, MSD, Nerviano Medical Sciences, Roche, Servier, Taiho Oncology, and Zymeworks; lecture fees from AstraZeneca, Bayer, Bristol Myers Squibb, Guerbet, Incyte, IPSEN, Roche, and Servier; and travel expenses from AstraZeneca. She is chair for the EORTC CITCG HBP/NET Task Force, treasurer for the International Liver Cancer Association, and Special Expert Clinical Trials Europe for NCI GISC Hepatobiliary (HB) Task Force (unpaid positions). BGK received equipments and materials from Tricumed and Intera Oncology. JBA received consulting fees from AstraZeneca, and grants (to institution) from Incyte and Adcendo. AL received consulting fees from Advanz Pharma, GSK, Ipsen, Gilead, Dr Falk, and AstraZeneca; speaker fees from Ipsen, Gore, AstraZeneca, Gilead, Abbvie, Advanz Pharma, AlfaSigma, GSK, and Incyte; support for attending meetings and/or travel from Ipsen; research funding (to institution) from Mirum, GSK, Ipsen, Dr. Falk, Intercept Pharma; and she is the Chair of the Scientific Committee of EASL. JCN received grants from Ipsen and Bayer, serves on Data Safety Monitoring Board for the Liver-NET1 study (NETRIS pharma), and has four patents [patent N°12306145.9 N° 61/714,383 “A new method for classification of liver samples and diagnosis of focal nodule dysplasia, hepatocellular adenoma, and hepatocellular carcinoma.”; patent N°12306146.7 and N° 61/704,360 “A new method for prognosis of global survival and survival without relapse in hepatocellular carcinoma”; patent B01811/WO-US; Réf. IT: BIO18522 US n° 17/605,524 “New adeno-associated virus (aav) variants and uses thereof for gene therapy”; patent PCT/FR2024/050073 “Methods of predicting the risk of recurrence and/or death of patients suffering from a hepatocellular carcinoma (HCC)”]. JNK reports grant (to institution) from GSK; consulting services for Bioptimus, Owkin, DoMore Diagnostics, Panakeia, AstraZeneca, Mindpeak, and MultiplexDx; lecture fees from AstraZeneca, Bayer, Daiichi Sankyo, Eisai, Janssen, Merck, MSD, BMS, Roche, Pfizer, and Fresenius; and stock options from StratifAI GmbH, Synagen GmbH. JMB declares consulting/advisory role from Albireo, Ipsen, Cymabay, Ikan Biotech, OWL-Rubió Metabolomic, Jazz Pharmaceuticals, AstraZeneca, and Servier; honoraria/lectures from Incyte, AstraZeneca, Intercept, Eisai, and Advanz), and research funding from Albireo, Incyte and Cymabay. IB reports consulting fees from Sirtex, Terumo, Boston Scientific, Roche, AstraZeneca, Eisai, Microbot Medical; lecture fees from AstraZeneca, Boston Scientific, Eisai, GE Healthcare, Guerbet, Roche, Sirtex, Terumo; travel expenses from Boston Scientific, Sirtex; and serves on Independent Data Safety Monitoring Board for AstraZeneca. AS received honoraria as speaker from BMS, Roche, Servier, Ipsen, Lilly, AstraZeneca, MSD, Eisai, travel support from Ipsen, Servier, Pierre-Fabre, MSD, Eisai, and declares advisory role for Heparegenix. VC reports grants from Ipsen, speaking fees from Ipsen, travel expenses from Advanz, and advisory role for Ipsen. CB received honoraria as speaker (Astrazeneca, Incyte, Servier) and consultant (Incyte, Servier, Boehringer Ingelheim, Astrazeneca, Tahio, Jazz Pharmaceuticals, Molecular Partners), received research funds (Avacta, Medannex, Servier) and her spouse is an employee of Astrazeneca. RIRM reports institutional funds from AstraZeneca, Incyte, Servier, Taiho and Jazz Pharmaceuticals. All other authors declare no competing interests.

Figures

**Fig. 1**
Worldwide mortality (age-standardised mortality rates [ASMR]/100,000) of intrahepatic CCA and average annual percentage change (AAPC) in 23 European countries compared with the USA, Canada, Australia and New Zealand (data extracted with permission from¹⁵). ASMR in European countries are ordered from highest to lowest considering the average between men and women. NA, not available.

**Fig. 2**
Worldwide mortality (age-standardised mortality rates [ASMR]/100,000) of extrahepatic CCA and average annual percentage change (AAPC) in 23 European countries compared with the USA, Canada, Australia and New Zealand (data extracted with permission from¹⁵). ASMR in European countries are ordered from highest to lowest considering the average between men and women. NA, not available.

**Fig. 3**
**Survey data from 47 clinicians from 36 European hospitals.** (a) Percentage of specialists involved in the survey. (b) Number of centres participating per country. (c) Management of patients with biliary tract cancer in a selection of European hospital in 19 countries. ERCP, endoscopic retrograde cholangiopancreatography; MDT, multidisciplinary team; PTC, percutaneous transhepatic cholangiography. , Yes; , No.

formula image — **Fig. 3**
**Survey data from 47 clinicians from 36 European hospitals.** (a) Percentage of specialists involved in the survey. (b) Number of centres participating per country. (c) Management of patients with biliary tract cancer in a selection of European hospital in 19 countries. ERCP, endoscopic retrograde cholangiopancreatography; MDT, multidisciplinary team; PTC, percutaneous transhepatic cholangiography. , Yes; , No.

See this image and copyright information in PMC

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Mapping the landscape of biliary tract cancer in Europe: challenges and controversies

Affiliations

Mapping the landscape of biliary tract cancer in Europe: challenges and controversies

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

LinkOut - more resources

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