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.

Non-transplantable Recurrence After Resection for Transplantable Hepatocellular Carcinoma: Implication for Upfront Treatment Choice

“…In fact, while recurrence following transplantation for HCC has been reported to be as low as 10-14%, recurrence after liver resection for early-stage HCC can be as high as 50-70%. [2][3][4][5][6] Liver transplantation is not, however, available to many patients due to limited services at certain medical centers, poor access to liver donors, and prolonged wait times. 19,20 In fact, a subset of patients with early-stage HCC and underlying chronic liver disease who are on the waiting list are at risk of tumor progression and drop out from the list.…”

“…However, the incidence of recurrence in the remnant liver can be as high as 50-70% among patients with concomitant chronic liver disease. 5,6 Salvage liver transplantation may be feasible for patients with transplantable recurrence (TR) after initial tumor resection with better long-term outcomes than re-resection or ablation. [7][8][9] Salvage transplantation is not feasible in all clinical situations, as some patients develop non-transplantable recurrence (NTR) despite strict surveillance after resection.…”

Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study

“…Previous studies have demonstrated that the recurrence patterns and survival outcomes of patients with LR are different from those of patients with ER. Compared with patients with ER, patients with LR often present with multiple lesions but have better survival outcomes (25,26). Therefore, identifying reliable and accurate markers for the early detection of LR of HCC is critical.…”

“…Recently, a novel HCC risk score, the age-male-ALBIplatelets (aMAP) score, was developed and validated in a global, multi-ethnic, multi-etiological, prospective cohort study of chronic hepatitis to accurately predict the risk of hepatitis-related HCC (29). Age and gender were shown to be related to HCC recurrence while platelet count, serum albumin and serum bilirubin levels were co-related with liver function in multiple studies (17,25,30,31). Therefore, this scoring system accurately stratifies the risk of HCC development for patients with hepatitis and can improve early HCC detection by developing personalized monitoring strategies.…”