Impact of Local Therapy on Outcomes in Patients with Recurrent Hepatocellular Carcinoma after Liver Transplantation

Abstract

Patients with hepatocellular carcinoma (HCC) who recur after liver transplantation have limited systemic therapy options in part due to ineligibility for immune checkpoint inhibition. Thus, assessing the benefit of local, metastasis-directed therapy (MDT) is imperative. We aimed to evaluate the impact of MDT on outcomes in patients with post-transplant HCC recurrence. Patients at a single center with recurrent HCC after liver transplant were identified. Recurrence/progression were assessed via RECIST criteria. At initial recurrence, patients with < = 3 metastases (mets) were considered oligorecurrent (oligoM1); those with >3 mets were polyrecurrent. Progression was defined as growth of existing mets or appearance of new mets. Poly-progression-free survival (polyPFS) was the time from oligorecurrence to polyprogression (>3 progressive mets) or death. Survival was estimated with the Kaplan-Meier method. Univariable Cox regression was used to identify covariates associated with outcomes; those with p<.05 were included in multivariable regression. From 2005-2022, 43 patients with HCC who underwent liver transplantation experienced recurrence; 27 (63%) had oligoM1 disease at the time of recurrence. The most common sites of recurrence were liver (N = 14), abdominal nodes (N = 14), and lungs (N = 11). Low AFP (<400 ng/mL) and oligoM1 disease were associated with a favorable OS (P<.05) and these associations remained significant in multivariable analysis. Among patients with oligoM1 recurrence, 15/27 received MDT to all sites of disease (MDT-All). MDT consisted of stereotactic ablative radiotherapy (N = 6), intensity-modulated radiotherapy (N = 2), TACE (N = 1), microwave ablation (N = 3), cryoablation (N = 2), and surgery (N = 2). Among oligoM1 patients, more patients with MDT-All had liver involvement than those who did not have MDT-All (33% vs 0%, P = .047), but there was no difference in performance status, AFP, or systemic therapy receipt. Among oligoM1 patients, MDT-All was associated with improved polyPFS (median 11.7 vs 4.8 mos; P = .025), and OS (38.4 vs 16.1 mos; P = .021) compared to those who did not receive MDT-All. Two patients who received MDT-All remained alive at >4 years of follow-up from recurrence, while 1 patient remained alive at >14 years of follow-up. Local therapy in patients with post-transplantation oligorecurrence (<3 mets) of HCC may delay disease progression and improve survival.