Screening Patients With HCC Risk Factors Linked With Reduced Mortality

A study published in JAMA Network Open found that screening for hepatocellular carcinoma (HCC) is associated with reduced mortality, highlighting the need to promote HCC screening for patients with known risk factors.¹

One of the main prognostic factors for patients with HCC is the tumor stage and curative therapy eligibility at diagnosis, with 5-year survival rates significantly better with early-stage curative therapies vs palliative therapies in more advanced HCC.² Additionally, the American Association for the Study of Liver Diseases and European Association for the Study of the Liver both recommend screening for HCC with ultrasonography either with or without measuring α-fetoprotein (AFP) levels in patients with risk factors for HCC, which includes cirrhosis.¹

“Understanding the true benefit of HCC screening is important for determining its overall value, considering potential physical, financial, and psychological harms,” the authors wrote.¹ “Delayed evaluation of the risk-to-benefit ratio has led to controversies in other cancer screening programs, including prostate cancer, colorectal cancer in older individuals, and breast cancer in younger women.”

Liver cancer illustration | Image credit: Rasi - stock.adobe.com

In the retrospective study, the authors aimed to determine the benefits of screening in a cohort of patients with HCC after taking into account lead-time and length-time biases. The main outcome was screen-detected HCC, including abnormal screening-intent abdominal imaging or AFP levels in the 6 months prior to diagnosis.

A total of 1313 patients with HCC treated at UT Southwestern Medical Center in Dallas, Texas, and Parkland Health in Dallas were included in the study. The mean (SD) patient age was 61.7 (9.6) years, and the cohort comprised 75.6% male patients. Of the overall cohort, 56.3% of patients (n = 739) had Barcelona Clinic Liver Cancer stage 0/A disease. Data on patient demographics, insurance status, clinical characteristics, liver disease cause, ECOG performance status, and Child-Pugh class were collected from electronic health records.

In 42.3% of cases (n = 556), HCC was detected via screening, while 57.7% of cases (n = 757) were not screen detected. Among patients with screen-detected HCC, 70.7% (n = 393) had early-stage disease vs 45.7% (n = 346) of those whose cancer was not detected through screening (risk ratio [RR], 1.54; 95% CI, 1.41-1.70). Those with screen-detected HCC were also more likely to receive curative treatment vs patients with non–screen-detected HCC (51.1% (n = 283) vs 33.5% (n = 252); RR, 1.52; 95% CI, 1.34-1.74).

Mortality was significantly lower in patients with screen-detected disease (HR, 0.75; 95% CI, 0.65-0.87), and the association was persistent in fully adjusted models and after correcting for lead-time bias. While adjusting for length-time bias decreased estimated survival, the authors noted that 3-year and 5-year survivals among the screen-detected HCC cohort were still longer compared with the non–screen-detected HCC cohort. Tumor doubling times and proportions of indolent tumors were similar between the cohorts.

There were several limitations in the study, including that it was prone to ascertainment bias because the imaging studies were not done at the health systems, although a review of outside clinical records mitigated this risk. Misclassification bias for screen-detected vs non–screen-detected HCC classification is also possible, as is misclassification of symptomatic vs incidental presentation. The findings may not be generalizable to broader populations, although the 2 health centers where the study was conducted are large and diverse. Still, the study’s strengths outweigh the limitations, the authors said.

“Overall, these data highlight the importance of promoting HCC screening implementation in practice,” the authors wrote. “Several studies have demonstrated persistent underuse of screening, related to a combination of patient and practitioner barriers. Although most practitioners believe screening improves early detection and survival, many report a continued need for data evaluating the benefits and harms of HCC screening.”


References

1. Daher D, Seif El Dahan K, Rich NE, et al. Hepatocellular carcinoma screening in a contemporary cohort of at-risk patients. JAMA Netw Open. Published online April 29, 2024. doi:10.1001/jamanetworkopen.2024.8755

2. Dhir M, Lyden ER, Smith LM, Are C. Comparison of outcomes of transplantation and resection in patients with early hepatocellular carcinoma: a meta-analysis. HPB (Oxford). 2012;14(9):635-645. doi:10.1111/j.1477-2574.2012.00500.x