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Multicenter Study
. 2025 Sep;32(9):6312-6323.
doi: 10.1245/s10434-025-17673-3. Epub 2025 Jun 19.

Patterns of Site and Timing of Recurrence After Curative Resection in Single and Multiple Large Hepatocellular Carcinoma: A Multicenter International Comprehensive Analysis

Fabio Giannone  1   2   3 , Gianluca Cassese  4   5   6   7 , Antonio Cubisino  8 , Emanuele Felli  9 , Federica Cipriani  10 , Bruno Branciforte  11 , Rami Rhaiem  12 , Alessandro Tropea  13 , Edoardo Maria Muttillo  13 , Andrea Scarinci  14 , Bader Al Taweel  15 , Raffaele Brustia  16   17 , Ephrem Salame  9 , Daniele Sommacale  16   17 , Salvatore Gruttadauria  13   18 , Tullio Piardi  12 , Gian Luca Grazi  19 , Guido Torzilli  11 , Luca Aldrighetti  10 , Mickael Lesurtel  8 , Ho-Seong Han  7 , Fabrizio Panaro  4   5   6   15 , Patrick Pessaux  20   21
Affiliations
Multicenter Study

Patterns of Site and Timing of Recurrence After Curative Resection in Single and Multiple Large Hepatocellular Carcinoma: A Multicenter International Comprehensive Analysis

Fabio Giannone et al. Ann Surg Oncol. 2025 Sep.

Abstract

Background: Curative options for large hepatocellular carcinoma (LHCC) are limited because of the high risk of early and extrahepatic recurrence. However, only a few studies report data on long-term outcomes in large cohorts of resected LHCC. We therefore investigated timing and site of recurrence of LHCC and assessed factors strictly associated with adverse patterns.

Patients and methods: This was a retrospective, international, multicenter study of patients undergoing anatomic resection of HCC ≥ 5 cm at 12 hepatobiliary high-volume centers. Extrahepatic recurrence was defined as any distant site of metastasis, while recurrence within 2 years after surgery was classified as early recurrence.

Results: A total of 869 patients were included. Recurrence was observed in 487 (56%) cases. Patterns associated with reduced overall survival were early (p < 0.001) and simultaneous intrahepatic and extrahepatic recurrence (p = 0.038). Variables independently associated with early recurrence were age (p = 0.037), major hepatectomy (p = 0.023), microvascular invasion (p = 0.011), satellites nodules (p = 0.005), and open approach (p = 0.025). Variables correlated with simultaneous intra- and extrahepatic relapse were age (p < 0.001), preoperative transarterial chemoembolization (TACE) (p < 0.001), microvascular invasion (p < 0.001), and satellite nodules (p = 0.026).

Conclusions: Surgery for LHCC is associated with a high risk of early recurrence. Apart from pathological variables, factors independently associated with adverse patterns were open approach and age for the early recurrence and preoperative TACE and age for simultaneous intra-extrahepatic relapse. BCLC stage was not associated with timing nor with site of recurrence.

Keywords: BCLC score; Hepatocellular carcinoma; Outcomes; Patterns of recurrence; Surgical resection.

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Conflict of interest statement

Disclosure: The authors have no related conflicts of interest or fundings to declare.

References

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