Retrospective Cohort Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 21, 2023; 29(47): 6122-6137
Published online Dec 21, 2023. doi: 10.3748/wjg.v29.i47.6122
Impact of guideline adherence on the prognosis of Barcelona clinic liver cancer stage B hepatocellular carcinoma
Ji Eun Han, Hyo Jung Cho, Jae Youn Cheong, Sun Gyo Lim, Min Jae Yang, Choong-Kyun Noh, Gil Ho Lee, Soon Sun Kim
Ji Eun Han, Hyo Jung Cho, Jae Youn Cheong, Sun Gyo Lim, Min Jae Yang, Choong-Kyun Noh, Gil Ho Lee, Soon Sun Kim, Department of Gastroenterology, Ajou University School of Medicine, Suwon 16499, Gyeonggi-do, South Korea
Author contributions: SS Kim conceived the study and planned the statistical analysis; JE Han and SS Kim conducted statistical analysis; JE Han, SS Kim, HJ Cho, and JY Cheong contributed to the interpretation of the results; JE Han and SS Kim drafted the original manuscript; SS Kim supervised the conduct of the study; All authors reviewed the draft manuscript and revised it critically on intellectual content; All authors approved the final version of the manuscript to be published.
Supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, No. HR21C003000021.
Institutional review board statement: The study was approved by the Institutional Review Board of Ajou University Hospital, Suwon, South Korea (Approval No. AJOUIRB-EX-2023-085).
Informed consent statement: The requirement for informed consent was waived by the Institutional Review Board of Ajou University Hospital, Suwon, South Korea.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
STROBE statement: The authors have read the STROBE Statement, and the manuscript was prepared and revised according to the STROBE checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Soon Sun Kim, PhD, Professor, Department of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, South Korea. cocorico99@gmail.com
Received: August 28, 2023
Peer-review started: August 28, 2023
First decision: September 23, 2023
Revised: October 23, 2023
Accepted: December 1, 2023
Article in press: December 1, 2023
Published online: December 21, 2023
Processing time: 112 Days and 17.9 Hours
Abstract
BACKGROUND

Patients with Barcelona clinic liver cancer (BCLC) stage B hepatocellular carcinoma (HCC) are considerably heterogeneous in terms of tumor burden, liver function, and performance status. To improve the poor survival outcomes of these patients, treatment approaches other than transarterial chemoembolization (TACE), which is recommended by HCC guidelines, have been adopted in real-world clinical practice. We hypothesize that this non-adherence to treatment guidelines, particularly with respect to the use of liver resection, improves survival in patients with stage B HCC.

AIM

To assess guideline adherence in South Korean patients with stage B HCC and study its impact on survival.

METHODS

A retrospective analysis was conducted using data from 2008 to 2016 obtained from the Korea Central Cancer Registry. Patients with stage B HCC were categorized into three treatment groups, guideline-adherent, upward, and downward, based on HCC guidelines recommended by the Asian Pacific Association for the Study of the Liver (APASL), the European Association for the Study of the Liver (EASL), and the American Association for the Study of Liver Diseases (AASLD). The primary outcome was HCC-related deaths; tumor recurrence served as the secondary outcome. Survival among the groups was compared using the Kaplan-Meier method and the log-rank test. Predictors of survival outcomes were identified using multivariable Cox regression analysis.

RESULTS

In South Korea, over the study period from 2008 to 2016, a notable trend was observed in adherence to HCC guidelines. Adherence to the EASL guidelines started relatively high, ranging from 77% to 80% between 2008 and 2012, but it gradually declined to 58.8% to 71.6% from 2013 to 2016. Adherence to the AASLD guidelines began at 71.7% to 75.9% from 2008 to 2010, and then it fluctuated between 49.2% and 73.8% from 2011 to 2016. In contrast, adherence to the APASL guidelines remained consistently high, staying within the range of 90.14% to 94.5% throughout the entire study period. Upward treatment, for example with liver resection, liver transplantation, or radiofrequency ablation, significantly improved the survival of patients with BCLC stage B HCC compared to that of patients treated in adherence to the guidelines (for patients analyzed according to the 2000 EASL guidelines, the 5-year survival rates were 63.4% vs 27.2%, P < 0.001), although results varied depending on the guidelines. Progression-free survival rates were also significantly improved upon the use of upward treatments in certain groups. Patients receiving upward treatments were typically < 70 years old, had platelet counts > 105/μL, and serum albumin levels ≥ 3.5 g/dL.

CONCLUSION

Adherence to guidelines significantly influences survival in South Korean stage B HCC patients. Curative treatments outperform TACE, but liver resection should be selected with caution due to disease heterogeneity.

Keywords: Hepatocellular carcinoma; Barcelona clinic liver cancer stage B; Guideline adherence; Liver neoplasms; Transarterial chemoembolization; Liver resection

Core Tip: The current hepatocellular carcinoma (HCC) guidelines do not recommend curative treatments, except liver transplantation, for patients with Barcelona clinic liver cancer stage B HCC. Our study suggests survival benefits for selected patients aged < 70 years, with platelet counts > 105/μL and albumin levels ≥ 3.5 g/dL, even if the liver function corresponds to Child-Pugh score B7, beyond the Milan criteria and outside the up-to-7 criteria. As for the B2 group of the Kinki criteria, which presents a highly diverse population of patients with stage B HCC, curative strategies should be considered with caution through a multidisciplinary approach.