Hepatocellular Carcinoma

Resection versus Transplantation

Truman M. Earl; William C. Chapman


Semin Liver Dis. 2013;33(3):282-292. 

In This Article

Resection With Salvage Transplantation

Several reports now document the use of "salvage transplantation" for intrahepatic recurrence or hepatic failure following resection.[36,80,85] This practice has not gained a tremendous foothold in the United States due to the MELD priority given to HCC; however, it has become a commonly debated topic as the number of patients waiting on transplantation is increasing as is the prevalence of HCC. The implications of this approach, especially for patients within the Milan criteria, is far reaching and is affected by numerous factors including waiting time and regional deceased-donor organ availability. The theoretical advantage of this approach is that a substantial portion of early-stage patients could be spared the inherent morbidity of liver transplantation and immunosuppression and an increase in the number of allografts available to patients with advanced liver disease. Salvage transplantation, however, is restricted to patients who develop recurrence with the Milan criteria and are otherwise candidates for transplantation and thus some candidates who may have been cured through transplantation may be converted to nontransplantable by a resection-first approach. Several series have utilized this approach in transplant candidates and demonstrated differing results. A study by Belghiti et al did not reveal inferior survival results, morbidity, or early mortality for those who underwent secondary liver transplantation after resection compared with patients who underwent primary liver transplantation.[86] A second study by Adam et al found that secondary liver transplantation after resection was associated with a much higher operative mortality, tumor recurrence, and lower 5-year posttransplant survival rates (41% vs. 61%;p = 0.03).[87] Ninety-eight patients who underwent resection were transplant eligible and tumor recurred in 69 (70%). Notably, only 17 patients (25%) of the 69 had transplantable tumor recurrence. The 5-year overall survival rate of those who underwent resection of transplant eligible tumors was significantly less than that of patients who underwent primary transplantation (50% vs. 61%;p = 0.05). A Markov model evaluating the harm and benefit of primary liver resection with salvage transplantation for HCC found that primary transplantation offered a greater life expectancy as long as 5-year posttransplant survival rates remained greater than 60%.[88] Based on an estimated 10% proportion of patients on the waiting list with HCC and a median time to transplant of 3 months, the harm caused to resected patients was higher than the benefit of having those livers reallocated to the waitlisted population.

An intention-to-treat analysis in the Bologna series demonstrated similar 5-year survival rates in the resection with salvage transplant group compared with patients listed for primary transplant. Similar analysis from Fuks et al in Paris found that 1- and 5-year survival rates were not different following primary transplantation versus resection with the possibility of salvage transplantation (1-year: 60% vs. 77%; 5-year: 56% vs. 40%).[69] The two groups were subject to selection bias inherent to retrospective studies with patients receiving primary transplantation having more advanced liver disease and those undergoing primary resection having more advanced tumors. Of the 138 patients undergoing resection, recurrence developed in 90 (65%) with 30 (33%) of these recurring beyond Milan. Twenty-one (35%) of the 60 patients recurring within Milan criteria were not eligible for transplantation for nontumor-related reasons and 39 (43.3%) of the 90 patients that recurred following resection were transplanted. Factors associated with recurrence beyond Milan included presence of cirrhosis, tumor diameter > 3 cm, vascular invasion, satellite nodules, and poor differentiation (Table 2). It is concluded that a resection-first strategy saved 22 allografts and precluded transplantation in these patients who were cured with resection. However, difficulty remains in predicting which patients, eligible for curative transplantation, will either develop advanced recurrence or become transplant ineligible for nontumor reasons—as occurred in 51 (45%) of the 112 patients resected for HCC in this study. Several studies have documented increase risk of recurrence with increased risk of recurrence beyond Milan criteria precluding salvage transplantation for tumors > 3 cm indicating that patients with these early-stage tumors may best be served by primary transplantation due to low rates of salvage transplantation in this group.[69,70]