Surveillance Program Ineffective at Detecting Cholangiocarcinoma Early Enough for Benefit in Patients With PSC

Yearly surveillance with MRI and tumor marker carbohydrate antigen (CA) 19-9 of patients with primary sclerosing cholangitis (PSC) was an ineffective way to detect cholangiocarcinoma (CCA) early, according to a study published in Journal of Hepatology.

In patients with PSC, CCA is the most frequently occurring malignancy, with the incidence of the cancer at its highest level in the first year after PSC diagnosis, the authors explained. Imaging by ultrasound or MRI with magnetic resonance cholangiopancreatography (MRI/MRCP) with or without contrast and regular measurements of the tumor biomarker CA 19-9 are all potential surveillance strategies.

“The potential survival benefit of early cancer detection has warranted CCA surveillance in patients with PSC, but there is at present limited evidence of its efficacy,” they wrote.

The researchers conducted a prospective cohort study on 512 patients with PSC receiving treatment at 11 Swedish hospitals. Patients were enrolled in a 5-year surveillance program between November 1, 2011, and April 1, 2016. In addition to yearly MRI/MRCP and analysis of CA 19-9, patients underwent liver function tests and clinical examinations.

The majority (68%) of patients were male, the median age was 38 years, 82% had inflammatory bowel disease (IBD), 76% had colitis, and 17% had Crohn disease. At the time of inclusion, the median duration of PSC was 7 years and of IBD was 15 years.

At baseline:

• 6% of patients had small duct PSC
• 11% had PSC with features of autoimmune hepatitis (AIH)
• 12% of patients had cirrhosis
• 8% of patients had severe/progressive bile duct changes
  • None of these patients had small duct PSC or PSC with features of AIH

Ultimately, 37 patients did not complete the 5-year surveillance program, for a variety of reasons. During the 5-year follow-up, 1997 MRI/MRCPs were performed, although some centers deviated from the protocol.

Thirty-five patients were considered to have a new diagnosis (< 1 year) of PSC. Of these, 5 patients had severe/progressive bile duct changes and 2 of these patients were given a diagnosis of perihilar (pCCA).

During the study period, 11 patients (2%) received a CCA diagnosis: 4 had intrahepatic CCA (iCCA) and 7 had pCCA. Additionally, 2 patients received a diagnosis of perihilar high-grade dysplasia; 4, gallbladder carcinoma; 1, high-grade dysplasia with gallbladder carcinoma; and 1, hepatocellular carcinoma.

The 7 patients with pCCA received their diagnosis a mean 20 months after inclusion in the study. Only 1 patient was asymptomatic at diagnosis, but 3 patients had metastatic disease and in 4 patients, the diagnosis was “an unexpected finding.” Six of the patients experienced a recurrence and died within 5 years of their diagnosis.

For the 4 patients with iCCA, the mean time from inclusion to diagnosis was 33 months. All of the patients were symptomatic, and 3 of them had locally advanced/metastasized disease.

Gallbladder carcinoma was diagnosed a mean 31 months after inclusion in the study for 4 patients. Three of them were asymptomatic.

Of the patients with small duct PSC, none received a CCA diagnosis, while only 1 patient with PSC with features of AIH was told they had iCCA and 1 patient, gallbladder carcinoma.

For patients with CCA, levels of CA 19-9 fluctuated prior to their cancer diagnosis compared with patients with benign PSC, who had stable levels of CA 19-9 over the 5-year follow-up.

Of the patients with severe/progressive bile duct changes at baseline, 6 later received a diagnosis of CCA and/or gallbladder carcinoma. An additional 122 patients developed severe/progressive bile duct changes. Of these patients, 75% underwent endoscopic retrograde cholangiopancreatography (ERCP).

The prospective nature of the study and the unselected group of patients included, which represented the heterogeneity of the disease, were strengths of the study. Among the limitations of the study were the limited sample size; the low incidence of hepatobiliary malignancy and relatively short follow-up, both of which limited the analyses; inter-reader variability as MRI/MRCP was reviewed by local radiologists; and a delay in appointments later in the study during the COVID-19 pandemic.

Ultimately, the researchers determined a surveillance program of yearly CA 19-9 and MRI/MRCP followed by diagnostic ERCP in an unselected cohort of patients with PSC fails to detect CCA early enough for there to be a survival benefit. However, the program did detect gallbladder carcinoma early enough for a benefit.

“The low incidence of CCA and the limited capacity to discriminate between severe/progressive stricturing with or without underlying CCA questions the value of yearly MRI/MRCP for detection of early CCA in all PSC patients,” the authors concluded.

Reference

Villard C, Friis-Liby I, Rorsman F, et al. Prospective surveillance for cholangiocarcinoma in unselected individuals with primary sclerosing cholangitis. J Hepatol. Published online November 18, 2022. doi:10.1016/j.jhep.2022.11.011