Only about one-fourth of patients with liver disease receive regular surveillance for hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), Amit Singal, MD, FAASLD, told the attendees at the American Association for the Study of Liver Diseases (AASLD) Virtual Annual Meeting on November 14, 2020.

The rates of regular screening for liver cancers are even lower when examining how many patients are assessed semi-annually, Dr Singal said, noting that while “one of the strongest correlates of surveillance that we see is subspecialty care by gastroenterology or hepatology,” only one quarter of these patients are routinely surveilled.

Dr Singal is a professor of medicine at the University of Texas Southwestern Medical Center in Dallas, Texas.

“One of the unique things about HCC is that we have an identifiable patient population, with over 80% to 90% of cases in the Western world occurring in patients with cirrhosis of any etiology,” he explained. “Once a patients develops cirrhosis, the annual risk of HCC is from 2% to 4%, with the higher risk in patients with viral hepatitis-related cirrhosis as opposed to patients with alcohol or [non-alcoholic steatohepatitis (NASH)]-related cirrhosis.”

Dr Singal pointed out that patients with fibrosis but without cirrhosis are at lower risk of HCC, and the rate of liver cancer is “exceedingly low in patients with NASH without cirrhosis. This suggests that surveillance for HCC should be performed in patients with cirrhosis, and not performed in patients without cirrhosis,” he noted.

The availability of treatment options for patients whose HCC is discovered at an early stage is an important premise in surveillance programs, Dr Singal said. “In HCC, patients whose disease is detected at an early stage are eligible for curative treatment, including surgical resection, liver transplantation, and local ablative therapies.” Median survival for patients who receive treatment when HCC is found at an early stage exceeds 5 years and often ranges from 7 to 10 years, whereas patients whose HCC is found at a later stage have a median survival of just 2 to 3 years.

“The highest level of evidence supporting HCC surveillance comes from a randomized controlled trial (RCT) of 18,000 patients with hepatitis B infection,” Dr Singal said. These patients were randomly assigned to receive surveillance or to not receive surveillance. Of those in the surveillance group, 60.5% had HCC found at stage 1 compared with 0% in nonsurveillance group. More than 46% of the patients whose HCC was found at stage 1 received curative treatment, while just 7.5% of the nonsurveillance group received curative therapies. In the group that had been surveilled, 32 of the 86 patients who developed HCC died, for a mortality rate of 83.2 per 100,000, while 54 out 67 patients in the nonsurveillance group who developed HCC died, for a mortality rate of 131.5 out of 100,000.

There are no similar RCTs supporting HCC surveillance among patients with cirrhosis, but cohort studies consistently show improved survival among patients who are surveilled for HCC, he added. Even adjusting for biases, “these studies consistently show improved outcomes” for patients with cirrhosis who undergo surveillance for HCC.

Dr Singal pointed out that guidelines from professional societies differ on the subject of the best modalities for surveillance. The most recent recommendation from AASLD calls for ultrasound with or without α-fetoprotein tumor marker (AFP). However, he stated, a systemic review of literature showed that ultrasound alone has relatively poor sensitivity for early HCC detection due to its operator-dependent nature. A pooled analysis indicated that 1 in 5 ultrasounds resulted in suboptimal visualization, particularly among patients with obesity, NASH, and alcohol cirrhosis, which are “populations we’re seeing with greater and greater frequency in our practices,” Dr Singal said.

“I, by no stretch, think that AFP is a perfect biomarker, but available data do suggest it is helpful when used in combination with ultrasound” and provides higher sensitivity as well as cost-effectiveness in detecting HCC. He added that novel biomarkers that can increase sensitivity of ultrasound are being investigated, and that a study in South Korea showed that magnetic resonance imaging (MRI) has much greater sensitivity than ultrasound for use in HCC surveillance among patients with hepatitis B.

Dr Singal noted that the preferred interval for HCC surveillance is semiannual. “It results in better survival over annual surveillance, but a study of quarterly screening did not improve detection.”

Patients with primary sclerosing cholangitis (PSC) comprise “a truly high-risk population for CCA,” Dr Singal stated. “The risk of CCA is 1.4 cases per 100 patient-years for these patients, and even higher, 2.8 per 100 patient-years, in first year after PSC diagnosis.” The risk is significantly higher among older patients, men, and patients with inflammatory bowel disease.

The American Gastroenterological Association recommends that patients with PSC be screened for CCA every 6 to 12 months. Early detection of CCA is associated with improved outcomes, Dr Singal said, noting that a retrospective cohort study revealed that half of the patients who had CCA that was detected at an early stage had much lower lymph node involvement (17% vs 54%), and higher 5-year survival (68% vs 20%) than patients with PSC and CCA whose cancer was found at a later stage. The surveilled patients also had higher transplant eligibility. Both transplant and surgical resection are available curative therapies, with transplant preferred in certain patients. Recent protocols suggest patients with PSC have 5-year survival of 60% or greater, Dr Singal said.

As with HCC, MRI has shown higher sensitivity and similar specificity to ultrasound for CCA surveillance, Dr Singal stated, and its use was associated with reduced mortality among asymptomatic patients. In regard to the use of the biomarker cancer antigen 19-9, there is debate regarding its utility. “This is likely an area where we need more study to see if biomarkers improve detection of CCA.”

Dr Singal stated that AASLD will update its guidelines on surveillance of patients with PSC for CCA in 2021.

—Rebecca Mashaw

Reference:

Singal AG. Surveillance for hepatocellular carcinoma and cholangiocarcinoma in patients with liver disease. Talk presented at: American Association for the Study of Liver Diseases annual meeting. November 14, 2020. Virtual.