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Impact of sequencing of different treatment modalities on survival outcomes among patients with non-metastatic hepatocellular carcinoma
Background
Hepatocellular carcinoma (HCC) is the most common type of liver malignancy and the third leading cause of cancer-related death in the world. Liver transplant is a cornerstone in treating non-metastatic disease, but a significant portion of patients miss the opportunity of upfront liver transplant giving the long waiting time for donor organs. Herein, we compare the survival outcome between upfront liver transplant, liver transplant with bridge systemic therapy and systemic therapy only.
Methods
The National Cancer Database was queried for patients diagnosed with non-metastatic HCC between 2004 and 2017. After including only patients with clinical N0 stage who received either systemic therapy alone, liver transplant alone or liver transplant with bridge systemic therapy, we split the cohort into three groups: systemic therapy only (including intra-arterial chemotherapy {e.g. TACE}) group, upfront liver transplant group and liver transplant with bridge systemic therapy group. We evaluated the overall survival (OS) between the three groups. We studied the OS using Kaplan-Meier estimates and multivariate cox regression analyses to evaluate factors associated with OS.
Results
A total of 29,691 patients with non-metastatic HCC were included for analysis of which 25,122 (84.6%) were treated with systemic therapy only, 2,513 (8.5%) were treated with bridge systemic therapy followed by liver transplant and 2,056 (6.9%) were treated with upfront liver transplant. We found that patients who were treated with bridge systemic therapy followed by liver transplant and patients who were treated with upfront liver transplant had a statistically significant better OS compared to patients who were treated with systemic therapy only (mean OS was 101.9 months and 98.2 vs 39.4 months, respectively with P On multivariate analysis, factors associated with worse OS were older age (HR 1.011; 95% CI 1.010 - 1.013; P < 0.001), Male gender (HR 1.048; 95% CI 1.014 - 1.084; P=0.006), White compared to African American race (HR 1.055; 95% CI 1.012 - 1.099; P=0.011), no insurance status (HR 1.155; 95% CI 1.079 - 1.237; P < 0.001), clinical T4 stage compared to T0 stage (HR 1.366; 95% CI 1.257 - 1.483, P < 0.001), and systemic therapy alone compared to upfront liver transplant and liver transplant with bridge therapy (HR for upfront liver transplant and transplant with bridge therapy vs systemic therapy was 0.202; 95% CI 0.184 – 0.223, and HR 0.194, 95% CI 0.178 - 0.212, respectively with P < 0.001 for all).
Conclusions
Patients with non-metastatic HCC who were treated with upfront liver transplant or liver transplant with bridge therapy had statistically significant improvement in OS compared to patients who were treated with systemic therapy only. While our study confirms the survival benefit of liver transplant among patients with non-metastatic HCC, these results raise the importance of proceeding with liver transplant after intra-arterial and/or systemic treatments in patients who are not initially eligible for or missed the opportunity of upfront liver transplant.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
O. Abdel-Rahman: Honoraria (self): Bayer, Roche; Advisory / Consultancy: Ipsen, Lilly, Eisai. The author has declared no conflicts of interest.
