An international multicentre evaluation of treatment strategies for combined hepatocellular-cholangiocarcinoma✰

Marco P A W Claasen; Tommy Ivanics; Berend R Beumer; Roeland F de Wilde; Wojciech G Polak; Gonzalo Sapisochin; Jan N M IJzermans

doi:10.1016/j.jhepr.2023.100745

An international multicentre evaluation of treatment strategies for combined hepatocellular-cholangiocarcinoma^✰

JHEP Rep. 2023 Mar 28;5(6):100745. doi: 10.1016/j.jhepr.2023.100745. eCollection 2023 Jun.

Authors

Marco P A W Claasen^{1

2}, Tommy Ivanics^{1

3

4}, Berend R Beumer², Roeland F de Wilde², Wojciech G Polak², Gonzalo Sapisochin^{1

5}, Jan N M IJzermans²

Affiliations

¹ Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada.
² Department of Surgery, Division of HPB & Transplant Surgery, Erasmus MC Transplant Institute, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
³ Department of Surgery, Henry Ford Hospital, Detroit, MI, USA.
⁴ Department of Surgical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden.
⁵ Division of General Surgery, University Health Network, Toronto, Ontario, Canada.

Abstract

Background & aims: Management of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is not well-defined. Therefore, we evaluated the management of cHCC-CCA using an online hospital-wide multicentre survey sent to expert centres.

Methods: A survey was sent to members of the European Network for the Study of Cholangiocarcinoma (ENS-CCA) and the International Cholangiocarcinoma Research Network (ICRN), in July 2021. To capture the respondents' contemporary decision-making process, a hypothetical case study with different tumour size and number combinations was embedded.

Results: Of 155 surveys obtained, 87 (56%) were completed in full and included for analysis. Respondents represented Europe (68%), North America (20%), Asia (11%), and South America (1%) and included surgeons (46%), oncologists (29%), and hepatologists/gastroenterologists (25%). Two-thirds of the respondents included at least one new patient with cHCC-CCA per year. Liver resection was reported as the most likely treatment for a single cHCC-CCA lesion of 2.0-6.0 cm (range: 73-93%) and for two lesions, one up to 6 cm and a second well-defined lesion of 2.0 cm (range: 60-66%). Nonetheless, marked interdisciplinary differences were noted. Surgeons mainly adhered to resection if technically feasible, whereas up to half of the hepatologists/gastroenterologists and oncologists switched to alternative treatment options with increasing tumour burden. Fifty-one (59%) clinicians considered liver transplantation as an option for patients with cHCC-CCA, with the Milan criteria defining the upper limit of inclusion. Overall, well-defined cHCC-CCA treatment policies were lacking and management was most often dependent on local expertise.

Conclusions: Liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Marked interdisciplinary differences were reported, depending on local expertise. These findings stress the need for a well-defined multicentre prospective trial comparing treatments, including liver transplantation, to optimise the therapeutic management of cHCC-CCA.

Impact and implications: Because the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), a rare form of liver cancer, is currently not well-defined, we evaluated the contemporary treatment of this rare tumour type through an online survey sent to expert centres around the world. Based on the responses from 87 clinicians (46% surgeons, 29% oncologists, 25% hepatologists/gastroenterologists), representing four continents and 25 different countries, we found that liver resection is considered the first-line treatment of cHCC-CCA, with many clinicians supporting liver transplantation within limits. Nonetheless, marked differences in treatment decisions were reported among the different specialties (surgeon vs. oncologist vs. hepatologist/gastroenterologist), highlighting the urgent need for a standardisation of therapeutic strategies for patients with cHCC-CCA.

Keywords: Biliary tract cancer; Biphenotypic; CCA; Cholangiolocarcinoma; HCC; Hepatocellular carcinoma; Hepatocholangiocarcinoma; Intermediate cell; Liver cancer; Mixed hepatocellular cholangiocarcinoma; Therapeutic management; Treatment policies.