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Hepatocellular carcinoma screening is associated with survival benefit in silico but needs confirmation in an in vivo analysis

Hepatocellular carcinoma (HCC) is the fastest-growing cause of cancer deaths in the United States. The overall prognosis of patients with HCC remains dismal except for a small subset of patients in whom HCC is detected at an early stage and who receive curative therapies, including liver transplant (LT), surgical resection, and, possibly, local ablation. Therefore, for patients at increased risk of HCC (i.e., primarily those with cirrhosis), clinical practice guidelines recommend regular HCC surveillance using liver ultrasound and/or a-fetoprotein measurements to increase the likelihood of detecting early-stage cancer. Despite these guidelines, long-term benefits of HCC surveillance are not known. To address this evidence gap, a large randomized, controlled trial is needed to compare long-term outcomes of screening and no-screening arms; such a trial could take decades to complete and may even be considered by some as unethical for patients in the no-screening arm. Under such a situation, mathematical disease modeling is a useful method for weighing the risks and benefits of cancer screening strategies and gaining insight into the main variables affecting this balance. Yang et al. performed a multistate Markov simulation model (in silico study) to evaluate the possible efficacy of HCC surveillance on both HCC-specific as well as overall mortality. The model incorporated cirrhosis stages, progression and decompensation rates, stage of HCC at diagnosis, sensitivity of screening tests, treatment-related complications, recurrence posttreatment, and probability of LT listing, among others. In a simulated cohort of 50-year-olds followed for up to 15 years, 68.2% of the cohort members died (25.1% from HCC and 43.6% from cirrhosis decompensation). With HCC surveillance, median survival improved from 10.4 to 11.2 years. The numbers needed to screen to avoid one death from all causes and one HCCspecific death over 15 years were 28 and 18 patients, respectively. The researchers put these estimates in context by drawing comparison with the number needed to screen of 550 men for prostate-specific antigen over 12 years of follow-up, and between 233 and 746 women for mammography over lifetime. The model addresses an important issue, provides a long-time horizon, and, at least in the sensitivity analyses, covers some of the recently changing estimates such as HCC risk in patients treated successfully for hepatitis C virus (HCV) or hepatitis B virus (HBV). Collectively, the findings offer a rather optimistic view Abbreviation: CT, computed tomography; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LT, liver transplant; MRI, magnetic resonance imaging; NAFLD, nonalcoholic fatty liver disease.