Multicenter Study of Staging and Therapeutic Predictors of Hepatocellular Carcinoma Recurrence Following Transplantation

Abstract

Orthotopic liver transplantation (OLT) and resection are effective treatments for hepatocellular carcinoma (HCC). However, optimizing OLT and limiting HCC recurrence remains a vexing problem. New HCC Model for End-Stage Liver Disease and allocation algorithms provide greater observation of HCC patients, many while receiving local-regional treatments. Potential benefits of local-regional treatment for limiting HCC recurrence after OLT remain incompletely understood. Therefore, we aimed to define HCC-specific prognostic factors affecting recurrence in a contemporary, multicenter cohort of HCC patients undergoing OLT and specifically whether local-regional therapies limited recurrence. We identified 441 patients undergoing OLT for HCC at 3 major transplant centers from 2008 to 2013. Cox regression was used to analyze covariate-adjusted recurrence and mortality rates after OLT. "Bridging" or "downstaging" therapy was used in 238 (54%) patients with transarterial chemoembolization (TACE) being used in 170 (71%) of treated patients. The survival rate after OLT was 88% and 78% at 1 and 3 years, respectively, with HCC recurrence (28% of deaths) significantly increasing the mortality rate (hazard ratio [HR], 19.87; P < 0.001). Tumor size, not tumor number, either at presentation or on explant independently predicted HCC recurrence (HR, 1.36 and 1.73, respectively; P < 0.05) with a threshold effect noted at 4.0-cm size. Local-regional therapy (TACE) reduced HCC recurrence by 64% when adjusting for presenting tumor size (HR, 0.36; P < 0.05). Explant tumor size and microvascular invasion predicted mortality (HR, 1.19 and 1.51, respectively; P < 0.05) and pathologic response to therapy (TACE or radiofrequency ablation) significantly decreased explant tumor size (0.56-1.62 cm diameter reduction; P < 0.05). In conclusion, HCC tumor size at presentation or explant is the most important predictor for HCC recurrence after OLT. Local-regional therapy to achieve a pathologic response (decreasing tumor size) can limit HCC recurrences after OLT. Liver Transplantation 00 000-000 2018 AASLD.

Hepatocellular carcinoma recurrence after liver transplantation: Risk factors, screening and clinical presentation

“…Another meta-analysis showed that the risk of TR was proportional to the diameter of the larger nodule, with no association with the number of nodules, probably because multiple nodules, however small, did not present higher frequency of vascular invasion[9]. These findings were confirmed in a retrospective cohort study that showed an increase of 36% in the risk of TR for each extra centimeter in the diameter of the larger nodule, with no association with the number of nodules[10].…”

Stereotactic Radiofrequency Ablation of Hepatocellular Carcinoma: a Histopathological Study in Explanted Livers

“…Locations of tumors included all liver segments. The median number of coaxial needles per lesion was three (range, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17], and in lesions ≥3 cm five.…”

“…Neoadjuvant locoregional therapy (LRT) is an established treatment option in HCC patients considered for LT to both decrease the waiting list dropout rate and downstage tumors to meet transplant eligibility . Presence of partial necrosis after LRT has been identified as a major risk factor for tumor recurrence after LT …”

“…(1) Neoadjuvant locoregional therapy (LRT) is an established treatment option in HCC patients considered for LT to both decrease the waiting list dropout rate (2,3) and downstage tumors to meet transplant eligibility. (3)(4)(5)(6) Presence of partial necrosis after LRT has been identified as a major risk factor for tumor recurrence after LT. (7)(8)(9)(10)(11)(12) A large, monocenter study (13) reported a very low HCC recurrence rate (<3% within 5 years) in patients with complete histological response after LRT compared to 10%-15% of tumor recurrence observed in patients meeting Milan criteria at explant pathology. These results were confirmed by a recent multicenter study, where only 5% of patients with no evidence of residual vital tumor (RVT) in explant histopathological exams showed a 5-year HCC recurrence compared to 40% of recurrences observed in patients having an RVT ≥2 cm.…”

Liver transplantation for hepatocellular carcinoma: Management after the transplant

“…The presence of MVI on explant is strongly associated with HCC recurrence and reduced survival after LT 51,52 (Table 2). The incidence of MVI is almost twice as high in tumors larger than 5 cm compared to smaller tumors.…”