Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Oct 15, 2021; 13(10): 1336-1366
Published online Oct 15, 2021. doi: 10.4251/wjgo.v13.i10.1336
Review of incidence and outcomes of treatment of cholangiocarcinoma in patients with primary sclerosing cholangitis
Francesca Saffioti, Vasileios K Mavroeidis
Francesca Saffioti, Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, Oxfordshire, United Kingdom
Francesca Saffioti, UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital, University College London, London NW3 2QG, United Kingdom
Vasileios K Mavroeidis, Department of Surgery, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, United Kingdom
Vasileios K Mavroeidis, Department of Transplant Surgery, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, United Kingdom
Author contributions: Mavroeidis VK conceptualised the study; Both authors designed the study, did the literature search, analysis and interpretation of data, drafted the manuscript, made critical revisions and approved the final version.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Vasileios K Mavroeidis, MD, MSc, FRCS, FICS, MFSTEd, Surgeon, Department of Surgery, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, United Kingdom.
Received: March 29, 2021
Peer-review started: March 29, 2021
First decision: June 23, 2021
Revised: July 5, 2021
Accepted: August 23, 2021
Article in press: August 23, 2021
Published online: October 15, 2021

Primary sclerosing cholangitis (PSC) is a premalignant condition and a well-documented risk factor for cholangiocarcinoma (CCA) which is the most common malignancy in this setting and the leading cause of deaths in the recent years, with an increasing incidence. PSC-associated CCA has a geographical distribution that follows the incidence of PSC, with an observed ascending gradient from the Eastern to the Western and from the Southern to the Northern countries. It may arise at any location along the biliary tree but is most common in the perihilar area. Patients with PSC and intrahepatic or perihilar CCA are typically not suitable for liver resection, which is otherwise the treatment of choice with curative intent in patients with resectable tumours, providing a radical resection with clear margins can be achieved. This largely relates to the commonly advanced stage of liver disease at presentation, which allows consideration for liver resection only for a very limited number of suitable patients with PSC. On the other hand, remarkable progress has been reached in the last decades with the implementation of a protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) for the treatment of perihilar CCA, within specific criteria. Excellent results have been achieved particularly for PSC patients with this cancer, who seem to benefit the most from this treatment, having converted this into an accepted indication for transplantation and the standard of care in several experienced centres. Intrahepatic CCA as an indication for OLT remains controversial and has not been accepted given disappointing previous results. However, as recent studies have shown favourable outcomes in early intrahepatic CCA, it may be that under defined criteria, OLT may play a more prominent role in the future. Distal CCA in the context of PSC requires aggressive surgical treatment with curative intent, when feasible. This review provides insight about particular features of CCA in the setting of PSC, with a main focus on its incidence, considerations relating to its anatomical location and implications to treatment and outcomes, through the viewpoint of historical evolution of management, and future perspectives.

Keywords: Cholangiocarcinoma, Primary sclerosing cholangitis, Liver resection, Liver transplantation, Neoadjuvant therapy, Adjuvant therapy

Core Tip: Cholangiocarcinoma (CCA) in primary sclerosing cholangitis (PSC) has become the leading cause of death. Major hepatic resection is commonly not possible in PSC patients to treat CCA, but overwhelming progress with excellent results in the last two decades has established an increasing role of protocolised combination of neoadjuvant chemoradiation and orthotopic liver transplantation. We review in detail, the incidence, as well as aspects of treatment and outcomes according to the different anatomical locations of CCA in PSC, through the viewpoint of historical evolution of treatment paradigms.