Oldhafer et al. (15) carried out a case-control study (level 3b) comparing 21 liver transplant patients with HCC who underwent pretransplant TACE with 21 matched pair historical controls. Sixty percent of the patients had a stage I or II tumor according to the modified International Union Against Cancer (UICC) (32) in both groups. Marked tumor necrosis (>50%) was found in 66% of the patients in the TACE group. However, there was no difference in overall survival between the groups with or without pretransplant TACE at 1 year (60.8% vs. 61.5%, NS) and at 3 years (48.4% vs. 53.9%, NS). Survival in the TACE group was penalized by three cases of pneumonia thought related to TACE, a complication not observed in other reports. In a retrospective analysis (level 3b), Majno et al. (14) compared 54 liver transplant patients with HCC who underwent preoperative TACE with 57 patients who underwent an OLT for HCC in the same period but without preoperative TACE. Both groups received postoperative systemic chemotherapy with doxorubicin and 5-fluorouracil, when their general condition allowed it. There was no difference between the groups in terms of tumor size or number. Downstaging (tumor reduction >50%) occurred in 52% of the patients treated with TACE. Overall, there was no difference in survival between the groups with versus without TACE (55% vs. 62% at 5 years, p = 0.77). However, patients with large tumors (>3 cm) that were downstaged by TACE had a significantly better disease-free survival in comparison with patients in whom the regimen failed to achieve significant downstaging (71% vs. 28% at 5 years, p = 0.01). On the other hand, there was no significant difference in term of disease-free survival between downstaged patients and patients who did not undergo TACE (71% vs. 49% at 5 years, p = 0.09). More recently, two European teams carried out comparative studies still in a retrospective way (level 3b). Perez Saborido et al. (22) compared 18 liver transplant patients with HCC who underwent preoperative TACE with 28 patients who underwent an OLT for HCC in the same period but without preoperative TACE. Seventy percent of the patients had a stage I–III tumor in both groups. All patients with TACE underwent only one pretransplant procedure. Patients who underwent TACE had a lower recurrence rate (16%) than patients without TACE (36%), but the difference did not reach statistical significance (p = 0.16). There was no difference in 1-, 3-, 5-year actuarial survival rates between the groups with versus without TACE (83%, 60% and 60% vs. 77%, 58% and 38%, respectively, p = 0.56). The French multicentric case-control study by Decaens et al. (21), compared 100 patients who received TACE before OLT with 100 control patients without TACE. Patients and controls were matched for the pre-OLT tumor characteristics, the period of transplantation, the time spent on the waiting list and the pre- and posttransplantation treatments. With a mean waiting period of 4.2 months in both groups, and one TACE procedure in the TACE group, overall 5-year survival was 59% in both groups (p = 0.7). The patients in the TACE group in which more than 80% of the tumor was necrotic at the time of transplantation and their matched controls had 5-year survival rate of 63% and 54%, respectively (p = 0.9). It is noteworthy that 28% of the patients in both groups received pretransplantation treatments other than TACE for HCC.
Two prospective and two retrospective studies (level 4) selected patients who met the Milano criteria (one single lesion <5 cm or three lesions <3 cm) corresponding to stages I and II (UICC) (18–20,31). In this setting, overall survival reached 90% at 3 or 5 years in the prospective (18,31) but only 60% at 5 years in the retrospective studies (19, 20). However, the very good results of the two prospective studies have not been compared with the same selected patients who would not have received preoperative TACE. Unfortunately, only the three most recent studies (18–20) reported the survival on an intent-to-treat basis. Therefore, these figures cannot be compared with the older data, which did not report the survival data on an intent-to-treat basis.
We conclude that there is insufficient evidence that TACE prior to liver transplantation for HCC does improve long-term survival (recommendation grade C). However, studies with higher level of evidence, reporting survival on an intent-to-treat basis, are urgently needed to clarify this question.