Hepatocellular Carcinoma Screening in a Contemporary Cohort of At-Risk Patients

Importance Cohort studies demonstrating an association of hepatocellular carcinoma (HCC) screening with reduced mortality are prone to lead-time and length-time biases. Objective To characterize the clinical benefits of HCC screening, adjusting for lead-time and length-time biases, in a diverse, contemporary cohort of at-risk patients. Design, Setting, and Participants This retrospective cohort study of patients with HCC was conducted between January 2008 and December 2022 at 2 large US health systems. Data analysis was performed from September to November 2023. Main Outcomes and Measures The primary outcome was screen-detected HCC, defined by abnormal screening-intent abdominal imaging or α-fetoprotein level within 6 months before diagnosis. Cox regression analysis was used to characterize differences in overall survival between patients with screen-detected and non–screen-detected HCC; lead-time and length-time adjustments were calculated using the Duffy parametric formula. Results Among 1313 patients with HCC (mean SD age, 61.7 9.6 years; 993 male 75.6%; 739 56.3% with Barcelona Clinic Liver Cancer stage 0/A disease), HCC was screen-detected in 556 (42.3%) and non–screen detected in 757 (57.7%). Patients with screen-detected HCC had higher proportions of early-stage HCC (393 patients 70.7% vs 346 patients 45.7%; risk ratio RR, 1.54; 95% CI, 1.41-1.70) and curative treatment receipt (283 patients 51.1% vs 252 patients 33.5%; RR, 1.52; 95% CI, 1.34-1.74) compared with patients with non–screen-detected HCC. The screen-detected group had significantly lower mortality, which persisted after correcting for lead-time bias (hazard ratio, 0.75; 95% CI, 0.65-0.87) in fully adjusted models. Both groups had similar tumor doubling times (median IQR, 3.8 2.2-10.7 vs 5.6 1.7-11.4 months) and proportions of indolent tumors (28 patients 35.4% vs 24 patients 38.1%; RR, 0.93; 95% CI, 0.60-1.43). Adjustment for length-time bias decreased survival estimates, although 3-year and 5-year survival for patients with screen-detected HCC remained longer than that for patients with non–screen-detected HCC. Conclusions and Relevance The findings of this cohort study suggest that HCC screening is associated with reduced mortality even after accounting for lead-time and length-time biases. However, these biases should be considered in future studies.