The challenges of liver transplantation for hepatocellular carcinoma on cirrhosis

Abstract

Summary Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and liver transplantation (LT) has potentials to improve survival for patients with HCC. However, expansion of indications beyond Milan Criteria (MC) and use of bridging/downstaging procedures to convert intermediate‐advanced stages of HCC within MC limits are counterbalanced by graft shortage and increasing use of marginal donors, partially limited by the use of donor‐division protocols applied to the cadaveric and living‐donor settings. Several challenges in technique, indications, pre‐LT treatments and prioritization policies of patients on the waiting list have to be precised through prospective investigations that have to include individualization of prognosis, biological variables and pathology surrogates as stratification criteria. Also, liver resection has to be rejuvenated in the general algorithm of HCC treatment in the light of salvage transplantation strategies, while benefit of LT for HCC should be determined through newly designed composite scores that are able to capture both efficiency and equity endpoints. Innovative treatments such as radioembolization for HCC associated with portal vein thrombosis and molecular targeted compounds are likely to influence future strategies. Accepting this challenge has been part of the history of LT and will endure so also for the future.

Milan criteria in liver transplantation for hepatocellular carcinoma: An evidence-based analysis of 15 years of experience

“…17,25,89,109,110 Nevertheless, the risk of dropout due to cancer progression in patients meeting the MC at the time of listing still exists and is as high as 30% if no treatment is pursued; however, bridging therapies during the waiting period (either ablation or locoregional approaches) are able to reduce the dropout rate into the range of 0% to 21%. 111,112 In general, the dropout risk increases as the waiting time progresses; in the case of HCC patients who are listed for more than 3 months, the dropout rate is greater than that observed for patients with nonmalignant diseases. 112 Although there is no proven posttransplant advantage in treating patients within the MC who are listed for transplantation, the available evidence (average NOS score ¼ 7) 17,22,23,35,80 indicates that listed patients within the MC who are treated while they are on the waiting list with ablation (preferred for single nodules < 3 cm) or transarterial chemoembolization (TACE; preferred for HCCs > 3 cm or with a multinodular pattern) have reduced dropout rates in comparison with historical untreated controls.…”

“…111,112 In general, the dropout risk increases as the waiting time progresses; in the case of HCC patients who are listed for more than 3 months, the dropout rate is greater than that observed for patients with nonmalignant diseases. 112 Although there is no proven posttransplant advantage in treating patients within the MC who are listed for transplantation, the available evidence (average NOS score ¼ 7) 17,22,23,35,80 indicates that listed patients within the MC who are treated while they are on the waiting list with ablation (preferred for single nodules < 3 cm) or transarterial chemoembolization (TACE; preferred for HCCs > 3 cm or with a multinodular pattern) have reduced dropout rates in comparison with historical untreated controls. 23 Although no RCTs have confirmed this, up to 65% of the HCC patients on the Organ Procurement and Transplantation Network waiting list currently receive locoregional treatments.…”

Avaliação do tratamento dos nódulos do hepatocarcinoma nos pacientes em lista de espera para transplante hepático

“…Studies comparing chemo-embolization with radioablation suggest better results for the latter, both in relation to nodule response and to dropout risk 21 . The bridge treatment is able to reduce the dropout by up to 21% 22 . On the other hand, an inadequate response to locoregional treatment was shown to be a predictive factor for dropout in Italian centers, as well as a relationship with relapse and death after transplantation, especially if it was associated with elevated AFP 21 .…”

The modernized treatment of hepatocellular cancer: time to think twice!

“…When expanding the inclusion criteria for LT, one should take care not to transform ''drop-out'' before LT (on the waiting list) into a high recurrence rate after LT. Mazzaferro and Majno [1] warned of this by launching the ''Metroticket'' concept: the further you go (the larger the inclusion criteria), the greater the price (the higher the number of recurrences)! The ''up to 7'' score, consisting of the sum of the largest tumor diameter and the number of tumors, represents a good guideline for the clinician in relation to the indication for LT in HCC.…”