Mailing invitations for hepatocellular carcinoma (HCC) surveillance screening to patients with cirrhosis increased ultrasound uptake by 13 percentage points, but the majority of patients still did not receive the recommended semiannual screenings, according to findings published in Clinical Gastroenterology and Hepatology.
“These data highlight the need for more intensive interventions to further increase surveillance,” wrote Amit Singal, MD, of University of Texas Southwestern Medical Center and Parkland Health Hospital System in Dallas, and colleagues. “The underuse of HCC surveillance has been attributed to a combination of patient- and provider-level barriers, which can serve as future additional intervention targets.” These include transportation and financial barriers and possibly new blood-based screening modalities when they become available, thereby removing the need for a separate ultrasound appointment.
According to one study, more than 90% of hepatocellular carcinoma cases occur in people with chronic liver disease, and the cancer is a leading cause of death in those with compensated cirrhosis. Multiple medical associations therefore recommend an abdominal ultrasound every 6 months with or without alpha-fetoprotein (AFP) for surveillance in at-risk patients, including anyone with cirrhosis of any kind, but too few patients receive these surveillance ultrasounds, the authors write.
The researchers therefore conducted a pragmatic randomized clinical trial from March 2018 to September 2019 to compare surveillance ultrasound uptake for two groups of people with cirrhosis: 1,436 people who were mailed invitations to get a surveillance ultrasound and 1,436 people who received usual care, with surveillance recommended only at usual visits. The patients all received care at one of three health systems: a tertiary care referral center, a safety net health system, and a Veterans Affairs medical center. The primary outcome was semiannual surveillance in the patients over 1 year.
The researchers identified patients using ICD-9 and ICD-10 codes for cirrhosis and cirrhosis complications, as well as those with suspected but undocumented cirrhosis based on electronic medical record notes such as an elevated Fibrosis-4 index. They confirmed the diagnoses with chart review, confirmed that the patients had at least one outpatient visit in the previous year, and excluded those in whom surveillance is not recommended, who lacked contact information, or who spoke a language besides English or Spanish.
The mailing was a one-page letter in English and Spanish, written at a low literacy level, that explained hepatocellular carcinoma risk and recommended surveillance. Those who didn’t respond to the mailed invitation within 2 weeks received a reminder call to undergo surveillance, and those who scheduled an ultrasound received a reminder call about a week before the visit. Primary and subspecialty providers were blinded to the patients’ study arm assignments.
“We conducted the study as a pragmatic trial whereby patients in either arm could also be offered HCC surveillance by primary or specialty care providers during clinic visits,” the researchers wrote. “The frequency of the clinic visits and provider discussions regarding HCC surveillance were conducted per usual care and not dictated by the study protocol.”
Two-thirds of the patients (67.7%) were men, with a median age of 61.2 years. Just over a third (37.0%) were white, 31.9% were Hispanic, and 27.6% were Black. More than half the patients had hepatitis C (56.4%), 18.1% had alcohol-related liver disease, 14.5% had nonalcoholic fatty liver disease, and 2.4% had hepatitis B. Most of the patients had compensated cirrhosis, including 36.7% with ascites and 17.1% with hepatic encephalopathy.
Nearly a quarter of the patients in the outreach arm (23%) could not be contacted or lacked working phone numbers, but they remained in the intent-to-screen analysis. Just over a third of the patients who received mailed outreach (35.1%; 95% confidence interval, 32.6%-37.6%) received semiannual surveillance, compared to 21.9% (95% CI, 19.8%-24.2%) of the usual-care patients. The increased surveillance in the outreach group applied to most subgroups, including race/ethnicity and cirrhosis severity based on the Child-Turcotte-Pugh class.
“However, we observed site-level differences in the intervention effect, with significant increases in semiannual surveillance at the VA and safety net health systems (both P < .001) but not at the tertiary care referral center (P = .52),” the authors wrote. “In a post hoc subgroup analysis among patients with at least 1 primary care or gastroenterology outpatient visit during the study period, mailed outreach continued to increase semiannual surveillance, compared with usual care (46.8% vs. 32.7%; P < .001).”
Despite the improved rates from the intervention, the majority of patients still did not receive semiannual surveillance across all three sites, and almost 30% underwent no surveillance the entire year.
The research was funded by the National Cancer Institute, the Cancer Prevention Research Institute of Texas, and the Center for Innovations in Quality, Effectiveness and Safety. Dr. Singal has consulted for or served on the advisory boards of Bayer, FujiFilm Medical Sciences, Exact Sciences, Roche, Glycotest, and GRAIL. The other authors had no industry disclosures.
