PATIENT-CENTERED SURVEILLANCE STRATEGIES FOR HEPATOCELLULAR CARCINOMA: A SOCIETAL PERSPECTIVE

Purpose: Hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related death in the United States, and its incidence has recently increased mainly due to hepatitis C infection.  Early detection of HCC through regular surveillance can improve prognosis. However due to a lack of any randomized clinical trial in hepatitis C patients, the benefit and optimal screening interval remains questionable. Our objective was to determine cost-effective patient-centered surveillance strategies, and compare them with the current recommendations.

Method: We developed a novel mathematical model to determine the optimal surveillance strategy maximizing the net benefit (NB). We allowed the screening interval to range from 3 months to 2 years. We considered one-size-fits-all policies, and policies with changing screening intervals after a long period of time, which we called the interval-switching policies. We also considered the possibility that the optimal surveillance strategy may be different depending on patients' age and stage of liver disease (advanced fibrosis [F3], compensated cirrhosis [CC], or decompensated cirrhosis [DC]). The baseline policy was a one-size-fit-all policy with the same screening interval (i.e., 6 or 12 months) as recommended by some guidelines. Our model's parameters were estimated from meta-analysis results and published clinical studies. Extensive sensitivity analyses were conducted on various model parameters, including risks of disease progression and treatment cost-effectiveness.

Result: The interval-switching policy with a cycle of 6 years had a higher NB ($560,353), in comparison with semiannual screenings (NB=$554,871) and annual screenings (NB=$553,166).  We found that (1) the surveillance frequency should be more aggressive in advanced stages of the liver disease, (2) surveillance frequency should become less aggressive as the population ages, and 3) surveillance is not cost-effective after mid-70's. We also found among the policies with no change in screening intervals, the optimal policy was every 3-month screening for patients in F3, semi-annual screening for CC, and annual screening for DC.

Conclusion: Current guidelines for HCC surveillance are controversial and mostly emphasize one-size-fit-all type surveillance strategies. We also find that rather than the one-size-fits-all type policies, surveillance strategies stratified by fibrosis stages can significantly improve cost-effectiveness. Lastly, we found that HCC surveillance is not cost effective in patients older than mid-70's.

Figure 1. Optimal interval-switching policies with cycle of 6 years.