Primary sclerosing cholangitis-associated cholangiocarcinoma: special considerations and best practices

ABSTRACT

Introduction: Primary sclerosing cholangitis (PSC) is a rare, heterogenous, chronic cholestatic liver disease that causes fibro-inflammatory destruction of the intra- and/or extrahepatic bile ducts. The disease course may be variable, though in many cases it ultimately leads to biliary cirrhosis and its associated complications. PSC is also associated with malignancies, in particular cholangiocarcinoma (CCA), a dreaded neoplasm of the biliary tract with a poor prognosis. Risk stratification and surveillance for this malignancy are important components of the care of patients with PSC.

Areas covered: In this review, we discuss important considerations in the clinical epidemiology, risk factors, diagnosis, and surveillance of PSC-associated CCA.

Expert opinion: Despite growing awareness of PSC, high-quality evidence regarding the management of PSC and its associated risk of CCA remains limited. Early diagnosis of PSC-associated CCA remains difficult, and treatment options are limited, especially when diagnosed at later stages. The recent introduction of recommendations for CCA surveillance will likely improve outcomes, though an optimal surveillance approach has yet to be validated prospectively. Further research is needed in the development of high-accuracy (and noninvasive) surveillance and diagnostic tools that may facilitate earlier diagnosis of CCA and potential disease cure.

KEYWORDS:

• Biliary tract cancer
• biomarkers
• cholangiocarcinoma
• primary sclerosing cholangitis
• surveillance

Article highlights

• PSC is a chronic, progressive, cholestatic liver disease associated with a significantly increased risk of CCA as well as other major complications compared to the general population.

• The pathogenesis of PSC-associated CCA remains unclear, though chronic inflammation, cellular senescence, and deleterious alterations of the ECM are believed to play a role.

• Improvements in non-invasive imaging and endoscopic modalities have improved the detection of CCA, though early diagnosis of CCA in patients with PSC remains challenging.

• Novel biomarkers show promise in providing ancillary methods for differentiating between benign and malignant disease in PSC.

• New guidelines for the surveillance of CCA in PSC suggest periodic screening with cross-sectional imaging (e.g. MRI/MRCP with contrast) and serum CA 19-9.

• Further research is needed to refine surveillance protocols and improve patient outcomes.

Author contributions

BMF reviewed the literature for relevant original studies and other content, designed the figures, and drafted the manuscript. JHT critically reviewed the manuscript. All authors provided critical input and approved the final version of the manuscript.

Declaration of interest

No potential conflict of interest was reported by the author(s).