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. 2024 Apr 1;7(4):e248755.
doi: 10.1001/jamanetworkopen.2024.8755.

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

Darine Daher  1 , Karim Seif El Dahan  1 , Nicole E Rich  1 , Nabihah Tayob  2 , Vincent Merrill  1 , Daniel Q Huang  3 , Ju Dong Yang  4 , Anand V Kulkarni  5 , Fasiha Kanwal  6   7 , Jorge Marrero  8 , Neehar Parikh  9 , Amit G Singal  1
Affiliations

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

Darine Daher et al. JAMA Netw Open. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Rich reported receiving personal fees from AstraZeneca, Eisai, and Exelixis outside the submitted work. Dr Huang reported serving on the Gilead advisory board outside the submitted work. Dr Kanwal reported receiving personal fees from Madrigal outside the submitted work. Dr Marrero reported serving as a consultant for Glycotest and serving on a data safety monitoring board for Astra Zeneca outside the submitted work. Dr Parikh reported receiving grants and personal fees from Exact Sciences and Exelixis, and personal fees from Fujifilm Medical, Astra Zeneca, Gilead, and Sirtex outside the submitted work. Dr Singal reported receiving personal fees from Genentech, AstraZeneca, Eisai, Bayer, Exelixis, FujiFilm Medical Sciences, Exact Sciences, Roche, Glycotest, Freenome, GRAIL, Boston Scientific, Sirtex, HistoSonics, and Merck outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Tumor Growth Patterns Among Early-Stage Group
Screen-detected hepatocellular carcinoma (HCC) had a median (IQR) tumor doubling time of 3.8 (2.2-10.7) months vs 5.6 (1.7-11.4) months for non–screen-detected HCC (P = .40).
Figure 2.
Figure 2.. Kaplan-Meier Curves Comparing Patients With Non–Screen-Detected vs Screen-Detected Hepatocellular Carcinoma, With Lead-Time Bias Adjustments for Various Sojourn Times
See this image and copyright information in PMC

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