Abstract
Background
Data on recurrence are important to inform surveillance and improve long-term surgical
outcomes for patients with hepatocellular carcinoma. We sought to identify risk factors
and long-term prognosis among patients who experienced beyond-Milan recurrence after
hepatectomy for early-stage hepatocellular carcinoma.
Methods
Patients who underwent hepatectomy for Barcelona Clinic Liver Cancer stage 0/A hepatocellular
carcinoma were identified from a multi-institutional database. Predictors of beyond-Milan
recurrence and risk factors associated with post-recurrence survival among patients
with beyond-Milan recurrence were assessed using univariate and multivariate Cox regression
analyses.
Results
Among 753 patients (median follow-up, 51.8 months), 138 (18.3%) developed beyond-Milan
recurrence. Regular surveillance (interval follow-up ≤3 months within 1 year and ≤6
months in subsequent years after surgery) was not carried out for 53 (38.4%) patients
who developed beyond-Milan recurrence. On multivariate analysis, increased risk of
beyond-Milan recurrence was independently associated with preoperative alpha-fetoprotein
level >400 ng/mL, tumor size >5.0 cm, multifocal disease, microvascular invasion,
and no/irregular recurrence surveillance. Median post-recurrence survival among patients
with beyond-Milan recurrence was only 8.4 months (95% confidence interval: 7.0–9.8
months). Among patients who developed beyond-Milan recurrence, Child-Pugh grade B/C,
early recurrence within 1 year after surgery, macrovascular invasion/distant metastasis,
and noncurative treatment of recurrence were independent risk factors associated with
worse post-recurrence survival.
Conclusion
Nearly 1 in 5 patients developed beyond-Milan recurrence after hepatectomy for early-stage
hepatocellular carcinoma. Patients with beyond-Milan recurrence had a median survival
of less than 1 year after diagnosis of the recurrence. Regular surveillance is an
important and actionable measure to decrease beyond-Milan recurrence and, in turn,
improve long-term survival among patients treated with hepatectomy for hepatocellular
carcinoma.
Graphical abstract
Graphical Abstract
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Article info
Publication history
Published online: July 19, 2022
Accepted:
May 20,
2022
Footnotes
The abstract of this study has been presented at the 31st APASL conference as a poster presentation (Mar 31–Apr 3, 2022, Seoul, Korea).
Zi-Han Feng, Ming-Da Wang, Zhong Chen, Li-Yang Sun, and Xiao Xu, contributed equally to this work. The authors contributed in the following ways: study concept and design: Z.-H. Feng, M.-D. Wang, Z. Chen, L.-Y. Sun, X. Xiao and T. Yang. Data collection: X. Xiao, Q.-Y. Kong, Z.-X. Chen, Y.-Y. Zeng, Y.-J. Liang, Z.-Y. Chen and H. Wang. Data analysis: Z.-H. Feng, M.-D. Wang, Y.-H. Zhou, T.-H. Chen and L.-Q. Yao. Draft writing: Z.-H. Feng and C. Li. Critical revision of the manuscript for important intellectual content: Z. Chen, Timothy M. Pawlik and Wan Yee Lau. Study supervision: F. Shen and T. Yang.
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