Survival After Treatable Hepatocellular Carcinoma Recurrence in Liver Recipients: A Nationwide Cohort Analysis

Abstract

BackgroundSurvival after post-transplant recurrence of HCC is dismal, and almost all treatments for recurrent HCC are off-labeled, without an extensive large-scale analysis. We aimed to delineate their post-recurrence courses and define benchmarks for comparing future treatment effectiveness.MethodsThree national databases, including health insurance, catastrophic illness, and the cause of death, were linked for cohort establishment and data collection during the period from 2005 to 2016. Patients with HCC recurrence ≥6 months after transplant surgery and under treatment were recruited for survival analysis. Selection of treatment strategies for HCC recurrence after liver transplant was based on the same criteria for those without liver transplant.ResultsOf 2,123 liver transplant recipients, 349 developed HCC recurrence ≥6 months after liver transplant, and the median recurrence time was 17.8 months post-transplant. Within 2 years of treatment, 61% patients showed recurrence (early recurrence group), and survival in these patients was poorer than in the late recurrence group. According to a multivariable analysis, the transplant era before 2008 and radiofrequency ablation were associated with good prognosis, whereas receiving sorafenib and radiotherapy was associated with poor prognosis. The effect of transplant era became insignificant after stratification by recently receiving pretransplant transarterial chemoembolization.ConclusionTiming of recurrence and interventions used were associated with the outcomes of patients with post-transplant HCC recurrence. These data provide the benchmark and indicate the critical period and high-risk factors for further therapeutic trial consideration.

The management of post-transplantation recurrence of hepatocellular carcinoma

“…HCC recurrence occurs most frequently (60%) in the first 2 years post-transplant [ 12 , 33 , 37 ], and this early recurrence is predictive of worse prognosis, often with the increased disease burden and extrahepatic metastases [ 17 , 19 , 38 ], One recent study by Kim et al [ 35 ], demonstrated median timing of recurrence for single intrahepatic (20.6 months; interquartile range [IQR], 9.8–32.1), multiple intrahepatic (9.6 months; IQR, 5.2–14.4), single extrahepatic (11.1 months; IQR, 4.6–19.0), and single lung recurrence (21.4 months; IQR, 10.4–41.1). Late recurrence (beyond 2 years) have also been reported and may have more favorable tumour biology, with better response to locoregional treatments [ 33 , 39 ].…”

“…Late recurrence (beyond 2 years) have also been reported and may have more favorable tumour biology, with better response to locoregional treatments [ 33 , 39 ]. Given the greater proportion of early recurrences and the observed worse prognosis, current data supports intense surveillance for the first 2 years post-transplant, to identify early recurrences [ 29 , 33 , 37 ].…”

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive Models

“…Studies have shown that the average survival time until recurrence is diagnosed ranges between 10.1 and 12.4 months [ 7 , 28 , 121 – 122 ] and depends on various factors. Based on these factors, several scales of risk of death for patients diagnosed with recurrence have been created.…”

“…The average survival in the low-risk, average-risk, and high-risk groups were 70.6, 12.2, and 3.4 months, respectively [ 120 ]. Other authors also reported poor prognosis for patients with early recurrence [ 122 ] and not qualifying for radical treatment, while 1-year and 2-year survival after radical recurrence resection was 93.8% and 52.6%, respectively [ 127 ]. Some authors indicate the benefits of immunosuppression conversion to sirolimus in patients who are not treated surgically [ 121 , 127 , 128 ].…”

Editorial: Transplant Oncology of Liver Malignancies

“…As the expansion of eligible criteria to liver transplantation for HCC, the outcomes of liver transplantation for primary, recurrent, or down-staged HCCs might be different. Downstaging of HCC to reduce post liver transplant recurrence is another hotspot for investigation [ Bhatti et al , ( 5 )]. Bhatti et al reported their data that LDLT without prior downstaging could reach comparable survival for T2-T4a HCC with lower AFP.…”