1 Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
2 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
3 Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner, Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
4 Department of Surgery, University of Verona, Verona, Italy.
5 Department of Surgery, Ospedale San Raffaele, Milan, Italy.
6 Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal.
7 Department of Hepatobiliopancreatic Surgery, APHP, Beaujon Hospital, Clichy, France.
8 Department of Surgery, Westmead Hospital, Sydney, Australia.
9 Department of Surgery, Stanford University, Stanford, CA, USA.
10 Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania.
11 Department of Surgery, University of Ottawa, Ottawa, Canada.
12 Department of Surgery, The University of Sydney, School of Medicine, Sydney, Australia.
13 Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner, Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA. Tim.Pawlik@osumc.edu.
BACKGROUND: To define early versus late recurrence based on post-recurrence survival (PRS) among patients undergoing curative resection for hepatocellular carcinoma (HCC).
METHODS: Patients who underwent curative-intent resection for HCC between 2000 and 2017 were identified from an international multi-institutional database. The optimal cut-off time point to discriminate early versus late recurrence was determined relative to PRS.
RESULTS: Among 1004 patients, 443 (44.1%) patients experienced recurrence with a median recurrence-free survival time of 12 months. A cut-off time point of 8 months was defined as the optimal threshold based on sensitivity analyses relative to PRS for early (n = 165, 37.2%) versus late relapse (n = 278, 62.8%) (p = 0.008). Early recurrence was associated with worse PRS (median PRS, 27.0 vs. 43.0 months, p = 0.019), as well as overall survival (OS) (median OS, 32.0 versus 74.0 months, p < 0.001) versus late recurrence. In addition, patients who recurred early were more likely to recur at extra- ± intrahepatic (35.5% vs. 19.8%, p = 0.003) sites and were less likely to have the recurrence treated with curative intent (33.8% vs. 45.7%, p = 0.08). Patients undergoing curative re-treatment of late recurrence had a comparable OS with patients who had no recurrence (median OS, 139.0 vs. 140.0 months); patients with early recurrence had inferior OS after curative re-treatment versus patients with no recurrence (median OS, 69.0 vs. 140.0 months, p = 0.036), yet still better than patients who received palliative treatment for early recurrence (median OS, 69.0 vs. 21.0 months, p < 0.001).
CONCLUSIONS: Eight months was identified as the cut-off value to differentiate early versus late recurrence. Curative-intent treatment for recurrent intrahepatic tumors was associated with reasonable long-term outcomes.