Abstract
BackgroundLocoregional interventional bridging therapy (IBT) is an accepted neoadjuvant approach in liver transplant candidates with hepatocellular carcinoma (HCC). However, the prognostic value of IBT in patients with advanced HCC is still undefined.AimThe aim of this trial was to evaluate the impact of postinterventional tumor necrosis on recurrence-free long-term survival after liver transplantation (LT) in patients with HCC, especially focusing on those exceeding the Milan criteria on pretransplant radiographic imaging.Patients and MethodsA total of 93 consecutive liver transplant candidates with HCC were included in this trial. In 36 patients, tumors were clinically staged beyond Milan criteria prior LT. Fifty-nine patients underwent IBT by transarterial chemoembolization or radiofrequency ablation pretransplantation. Postinterventional tumor necrosis rate as assessed at liver explant pathology was correlated with outcome post-LT.ResultsThere was no significant difference in 5-year tumor-free survival rate between the IBT- and the non-IBT subpopulation (78% versus 68%, P = 0.25). However, tumor response following IBT (≥50% tumor necrosis rate at explant pathology) resulted in a significantly better outcome 5 years post-LT (96%) than tumor non-response to IBT (<50% tumor necrosis rate at explant pathology; 21%; P<0.001). Five-year recurrence-free survival rate was 80% in Milan Out patients with extended post-IBT tumor necrosis versus 0% in Milan Out patients without tumor response to IBT (P<0.001). None of macromorphological HCC features, but only the absence of increased 18F-fluoro-deoxy-glucose (18FDG) uptake on pretransplant positron emission tomography (PET) was identified as independent predictor of postinterventional tumor response (P<0.001).ConclusionOur results implicate that extended postinterventional tumor necrosis promotes recurrence-free long-term survival in patients with HCC beyond standard criteria. Pretransplant PET assessment may identify those patients with advanced HCC that will benefit from post-IBT tumor response and may, thereby, achieve excellent posttransplant outcome.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and its incidence is expected to rise continuously
There was no significant difference in 5-year tumor-free survival rate between the interventional bridging therapy (IBT)- and the non-IBT subpopulation (78% versus 68%, P = 0.25)
Our results implicate that extended postinterventional tumor necrosis promotes recurrence-free long-term survival in patients with hepatocellular carcinoma (HCC) beyond standard criteria
Summary
Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and its incidence is expected to rise continuously. The implementation of the Milan criteria (one tumor nodule up to 5 cm, maximum of 3 tumor nodules each up to 3 cm, no macroscopic vascular invasion or extrahepatic disease) in 1996 by Mazzafero et al has established LT as standard therapy in patients with early stage HCC in liver cirrhosis [3]. Patients with tumors selected according these standard criteria may achieve a 5-year recurrence-free survival rate about 70%, which is an extraordinary outcome data in oncological surgery [4,5]. They have been adopted by the United Network for Organ Sharing and by the Eurotransplant Foundation as standard criteria for listing patients with HCC. The prognostic value of IBT in patients with advanced HCC is still undefined
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