Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma

Ye Rim Kim; Sung Won Chung; Min-Ju Kim; Won-Mook Choi; Jonggi Choi; Danbi Lee; Han Chu Lee; Ju Hyun Shim

doi:10.2147/JHC.S456093

Limited Generalizability of Retrospective Single-Center Cohort Study in Comparison to Multicenter Cohort Study on Prognosis of Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2024 Jul 1:11:1235-1249. doi: 10.2147/JHC.S456093. eCollection 2024.

Authors

Ye Rim Kim^#^{1

2}, Sung Won Chung^#^{1

2}, Min-Ju Kim³, Won-Mook Choi^{1

2}, Jonggi Choi^{1

2}, Danbi Lee^{1

2}, Han Chu Lee^{1

2}, Ju Hyun Shim^{1

2

4}

Affiliations

¹ Division of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
² Liver Cancer Center, Asan Cancer Institute, Asan Medical Center, Seoul, Republic of Korea.
³ Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
⁴ Digestive Diseases Research Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

^# Contributed equally.

Abstract

Introduction: We aimed to evaluate the generalizability of retrospective single-center cohort studies on prognosis of hepatocellular carcinoma (HCC) by comparing overall survival (OS) after various treatments between a nationwide multicenter cohort and a single-center cohort of HCC patients.

Methods: Patients newly diagnosed with HCC between January 2008 and December 2018 were analyzed using data from the Korean Primary Liver Cancer Registry (multicenter cohort, n=16,443), and the Asan Medical Center HCC registry (single-center cohort, n=15,655). The primary outcome, OS after initial treatment, was compared between the two cohorts for both the entire population and for subcohorts with Child-Pugh A liver function (n=2797 and n=5151, respectively) treated according to the Barcelona-Clinic-Liver-Cancer (BCLC) strategy, using Log rank test and Cox proportional hazard models.

Results: Patients of BCLC stages 0 and A (59.3% vs 35.2%) and patients who received curative treatment (42.1% vs 32.1%) were more frequently observed in the single-center cohort (Ps<0.001). Multivariable analysis revealed significant differences between the two cohorts in OS according to type of treatment: the multicenter cohort was associated with higher risk of mortality among patients who received curative (adjusted hazard ratio [95% confidence interval], 1.48 [1.39-1.59]) and non-curative (1.22 [1.17-1.27]) treatments, whereas the risk was lower in patients treated with systemic therapy (0.83 [0.74-0.92]) and best supportive care (0.85 [0.79-0.91]). Subcohort analysis also demonstrated significantly different OS between the two cohorts, with a higher risk of mortality in multicenter cohort patients who received chemoembolization (1.72 [1.48-2.00]) and ablation (1.44 [1.08-1.92]).

Conclusion: Comparisons of single-center and multicenter cohorts of HCC patients revealed significant differences in OS according to treatment modality after adjustment for prognostic variables. Therefore, the results of retrospective single-center cohort studies of HCC treatments may not be generalizable to real-world practice.

Keywords: BCLC; UICC; external validation; liver cancer; retrospective cohort.

Grants and funding

This study did not receive any funding or support from any commercial sources. This study was supported by grants from the Basic Science Research Program through the National Research Foundation of Korea (NRF-2022R1A2C3008956 and NRF-2021R1A6A1A03040260), a grant from Asan Institute for Life Sciences, Asan Medical Center (2022IT0013), and a grant from the “Elimination of Cancer Project Fund” of the Asan Cancer Institute of Asan Medical Center, Seoul, Republic of Korea. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of data; preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.