Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease

Anne-Marleen van Keulen¹, Stefan Buettner¹, Pim B Olthof², Heinz-Josef Klümpen³, Joris I Erdmann⁴, Laura Izquierdo-Sanchez^{5

6}, Jesus M Banales^{5

6

7

8}, Benjamin Goeppert^{9

10

11}, Stephanie Roessler¹¹, Krzysztof Zieniewicz¹², Angela Lamarca^{13

14

15}, Juan W Valle^{14

15}, Adelaida La Casta¹⁶, Frederik J H Hoogwater¹⁷, Matteo Donadon¹⁸, Alexander Scheiter¹⁹, Marco Marzioni²⁰, Jorge Adeva²¹, Edita Kiudeliene²², Jesús María Urman Fernández²³, Gianpaolo Vidili^{24

25}, Tudor Mocan²⁶, Luca Fabris^{27

28}, Marcin Krawczyk^{29

30}, Trine Folseraas³¹, Cristina Dopazo³², Olivier Detry³³, Theodor Voiosu³⁴, Viorel Scripcariu³⁵, Francesca Biancaniello³⁶, Chiara Braconi^{37

38

39}, Rocio I R Macias⁴⁰, Bas Groot Koerkamp¹

Affiliations

¹ Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
² Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. p.olthof@erasmusmc.nl.
³ Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁴ Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
⁶ National Institute for the Study of Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III" (ISCIII), CIBERehd, Madrid, Spain.
⁷ Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
⁸ Basque Foundation for Science, Bilbao, Spain.
⁹ Institute of Pathology and Neuropathology, RKH Klinikum Ludwigsburg, Ludwigsburg, Germany.
¹⁰ Institute of Pathology, Kantonsspital Baselland, Liestal, Switzerland.
¹¹ Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
¹² Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
¹³ Department of Oncology - OncoHealth Institute, Fundación Jiménez Díaz University Hospital, Madrid, Spain.
¹⁴ Department of Medical Oncology, The Christie NHS Foundation, Manchester, England.
¹⁵ Division of Cancer Sciences, University of Manchester, Manchester, UK.
¹⁶ Medical Oncology Department, OSI Donostialdea/Biodonostia, San Sebastián, Spain.
¹⁷ University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁸ Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
¹⁹ Institute of Pathology, University of Regensburg, Regensburg, Germany.
²⁰ Clinic of Gastroenterology and Hepatology, Universita Politecnica delle Marche, Ancona, Italy.
²¹ Department of Medical Oncology, Hospital Universitario, 12 de Octubre, Madrid, Spain.
²² Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²³ Servicio de Aparato Digestivo, Complejo Hospitalario de Navarra, Pamplona, Navarra, España.
²⁴ Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy.
²⁵ Department of Internal Medicine, Day Hospital of the Medical Area, Azienda Ospedaliero Universitaria, AOU, Sassari, Italy.
²⁶ Babeș-Bolyai University - UBB Med Department, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania.
²⁷ Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy.
²⁸ Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA.
²⁹ Laboratory of Metabolic Liver Diseases, Medical University of Warsaw, Warsaw, Poland.
³⁰ Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
³¹ Section of Gastroenterology and the Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
³² Department of HPB Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain.
³³ Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, Liege, Belgium.
³⁴ Gastroenterology Department, Faculty of Medicine, Colentina Clinical Hospital, UMF Carol Davila, Bucharest, Romania.
³⁵ University of Medicine and Pharmacy "Gr T Popa", Regional Institute of Oncology, Iasi, Romania.
³⁶ Department of Translational and Precision Medicine, Sapienza" University of Rome, Rome, Italy.
³⁷ Royal Marsden NHS Trust, London, Surrey, UK.
³⁸ Beatson West of Scotland Cancer Centre, Glasgow, UK.
³⁹ School of Cancer Sciences, University of Glasgow, Glasgow, UK.
⁴⁰ Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, CIBERehd, Salamanca, Spain.

PMID: 38896226
PMCID: PMC11413094
DOI: 10.1245/s10434-024-15582-5

Comparative Study

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease

Anne-Marleen van Keulen et al. Ann Surg Oncol. 2024 Oct.

. 2024 Oct;31(10):6495-6503.

doi: 10.1245/s10434-024-15582-5. Epub 2024 Jun 19.

Authors

Affiliations

¹ Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
² Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands. p.olthof@erasmusmc.nl.
³ Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁴ Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
⁵ Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain.
⁶ National Institute for the Study of Liver and Gastrointestinal Diseases, Instituto de Salud Carlos III" (ISCIII), CIBERehd, Madrid, Spain.
⁷ Department of Biochemistry and Genetics, School of Sciences, University of Navarra, Pamplona, Spain.
⁸ Basque Foundation for Science, Bilbao, Spain.
⁹ Institute of Pathology and Neuropathology, RKH Klinikum Ludwigsburg, Ludwigsburg, Germany.
¹⁰ Institute of Pathology, Kantonsspital Baselland, Liestal, Switzerland.
¹¹ Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
¹² Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.
¹³ Department of Oncology - OncoHealth Institute, Fundación Jiménez Díaz University Hospital, Madrid, Spain.
¹⁴ Department of Medical Oncology, The Christie NHS Foundation, Manchester, England.
¹⁵ Division of Cancer Sciences, University of Manchester, Manchester, UK.
¹⁶ Medical Oncology Department, OSI Donostialdea/Biodonostia, San Sebastián, Spain.
¹⁷ University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
¹⁸ Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
¹⁹ Institute of Pathology, University of Regensburg, Regensburg, Germany.
²⁰ Clinic of Gastroenterology and Hepatology, Universita Politecnica delle Marche, Ancona, Italy.
²¹ Department of Medical Oncology, Hospital Universitario, 12 de Octubre, Madrid, Spain.
²² Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
²³ Servicio de Aparato Digestivo, Complejo Hospitalario de Navarra, Pamplona, Navarra, España.
²⁴ Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy.
²⁵ Department of Internal Medicine, Day Hospital of the Medical Area, Azienda Ospedaliero Universitaria, AOU, Sassari, Italy.
²⁶ Babeș-Bolyai University - UBB Med Department, Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca, Romania.
²⁷ Department of Molecular Medicine, University of Padua School of Medicine, Padua, Italy.
²⁸ Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA.
²⁹ Laboratory of Metabolic Liver Diseases, Medical University of Warsaw, Warsaw, Poland.
³⁰ Department of Medicine II, Saarland University Medical Center, Homburg, Germany.
³¹ Section of Gastroenterology and the Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
³² Department of HPB Surgery and Transplants, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Barcelona Hospital Campus, Universitat Autónoma de Barcelona, Barcelona, Spain.
³³ Department of Abdominal Surgery and Transplantation, CHU Liege, University of Liege, Liege, Belgium.
³⁴ Gastroenterology Department, Faculty of Medicine, Colentina Clinical Hospital, UMF Carol Davila, Bucharest, Romania.
³⁵ University of Medicine and Pharmacy "Gr T Popa", Regional Institute of Oncology, Iasi, Romania.
³⁶ Department of Translational and Precision Medicine, Sapienza" University of Rome, Rome, Italy.
³⁷ Royal Marsden NHS Trust, London, Surrey, UK.
³⁸ Beatson West of Scotland Cancer Centre, Glasgow, UK.
³⁹ School of Cancer Sciences, University of Glasgow, Glasgow, UK.
⁴⁰ Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, University of Salamanca, IBSAL, CIBERehd, Salamanca, Spain.

PMID: 38896226
PMCID: PMC11413094
DOI: 10.1245/s10434-024-15582-5

Abstract

Background: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy.

Methods: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS.

Results: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07).

Conclusions: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

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Conflict of interest statement

Dr. Angela Lamarca declares travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan, Delcath Advanza Pharma, and Roche; speaker honoraria from Merck, Pfizer, Ipsen, Incyte, AAA, QED, Servier, Astra Zeneca, EISAI, Roche, and Advanz Pharma; advisory and consultancy honoraria from EISAI, Nutricia Ipsen, QED, Roche, Servier, Boston Scientific, Albireo Pharma, AstraZeneca, Boehringer Ingelheim, GENFIT, TransThera Biosciences, and Taiho; principal Investigator associated Institutional Funding form QED, Merck, Boehringer Ingelheim, Servier, AstraZeneca, GenFit, Albireo Pharma; she is a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. Chiara Braconi receives honoraria from AstraZeneca (consultant, speaker, spouse employee), Incyte (consultant, speaker), Servier (consultant), Boehringer-Ingelheim (consultant); she receives research funds from Avacta, Medannex, and Servier. Jesús María Bañales declares research grants (from Incyte and Albireo), personal fees for lecturer (from Intercept, AstraZeneca and Incyte), and consulting role (for Albireo, Rubió Metabolomics, Ikan Biotech, and CYMABay). Dr. Juan Valle reports personal fees from Agios, personal fees from AstraZeneca, personal fees from Baxter, personal fees from Genoscience Pharma, personal fees from Hutchison Medipharma, personal fees from Imaging Equipment Ltd (AAA), personal fees from Incyte, personal fees from Ipsen, personal fees from Mundipharma EDO, personal fees from Mylan, grants, personal fees and non-financial support from NuCana, personal fees from QED, personal fees from Servier, personal fees from Sirtex, personal fees from Zymeworks, outside the submitted work.

Figures

**Fig. 1**
*Patients who underwent an R0 resection or liver transplantation were excluded at preselection

**Fig. 2**
Overall survival of pCCA patients who underwent R1 resection and patients with localized pCCA who received palliative systemic chemotherapy

**Fig. 3**
Overall survival of patients who underwent a resection and had negative lymph nodes (N0) compared with positive lymph nodes (N+; N1 or N2)

See this image and copyright information in PMC

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Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease

Affiliations

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Medical