Early Versus Late Recurrence of Hepatocellular Carcinoma After Surgical Resection Based on Post-recurrence Survival: an International Multi-institutional Analysis

Abstract

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.

Early recurrence after radiofrequency ablation for hepatocellular carcinoma: a multicenter retrospective study on definition, patterns and risk factors

“…Patients with HCC who refused to undergo surgery, or those who were not feasible for surgery because of cirrhosis, poor hepatic reserve and portal hypertension received RFA after the diagnosis. The present study focused on HCC recurrence, and excluded patients who did not developed recurrence until the end of follow-up or death, similar to the previous studies on postsurgical early recurrence [8,9]. Inclusion criteria were: (1) HCC confirmed by histology or noninvasive diagnostic criteria according to the European Association for the Study of Liver (EASL) [18]; (2) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (3) patients with very early-stage (single tumor 2 cm, BCLC 0 stage) or early-stage HCC (up to 3 tumors 3 cm, BCLC A stage); (4) absence of extrahepatic metastasis or major vessel invasion; (5) patients who underwent RFA with complete tumor ablation.…”

“…Although the terms 'early recurrence' and 'late recurrence' of HCC are often mentioned in both the academic research and clinical practice, a scientific definition of early recurrence is still lacking [6]. Different cutoff values reported by previous studies ranged from 8 months to 24 months after radical therapies for HCC [8][9][10][11][12]. Some researchers have defined early and late recurrence by overall survival (OS) or disease free survival (DFS) [13,14].…”

“…Some researchers have defined early and late recurrence by overall survival (OS) or disease free survival (DFS) [13,14]. Post recurrence survival (PRS) has also been used as an indicator to distinguish early and late recurrence after surgical resection for HCC or pancreatic cancer, because it can objectively reflect the prognosis of tumor recurrence compared with OS [8,9,15]. However, the optimal cutoff time to differentiate early and late recurrence of HCC after RFA has not been studied.…”

“…Previous studies have shown that patients who develop early recurrence have poorer prognosis than those who develop late recurrence [8,9]. Many researchers have considered that early recurrence develops from intrahepatic micrometastasis, while late recurrence appears to be due to de novo carcinogenesis [11,12,16].…”

“…Many researchers have considered that early recurrence develops from intrahepatic micrometastasis, while late recurrence appears to be due to de novo carcinogenesis [11,12,16]. Previous studies reported early recurrence after hepatectomy to be associated with aggressive oncological features, such as large tumor size, high alpha-fetoprotein (AFP) level, high albumin-bilirubin (ALBI) ratio, poor differentiation, and microvascular invasion (MVI) [8,9,12,17]. However, the risk factors associated with scientific definition of 'early recurrence' after RFA for HCC have not been studied.…”