Hepatocellular carcinoma progression during bridging before liver transplantation

Abstract

Background Recipient selection for liver transplantation in hepatocellular carcinoma (HCC) is based primarily on criteria affecting the chance of long-term success. Here, the relationship between pretransplant bridging therapy and long-term survival was investigated in a subgroup analysis of the SiLVER Study. Methods Response to bridging, as defined by comparison of imaging at the time of listing and post-transplant pathology report, was categorized into controlled versus progressive disease (more than 20 per cent tumour growth or development of new lesions). Results Of 525 patients with HCC who had liver transplantation, 350 recipients underwent pretransplant bridging therapy. Tumour progression despite bridging was an independent risk factor affecting overall survival (hazard ratio 1.80; P = 0.005). For patients within the Milan criteria (MC) at listing, mean overall survival was longer for those with controlled versus progressive disease (6.8 versus 5.8 years; P < 0.001). Importantly, patients with HCCs outside the MC that were downsized to within the MC before liver transplantation had poor outcomes compared with patients who never exceeded the MC (mean overall survival 6.2 versus 6.6 years respectively; P = 0.030). Conclusion Patients with HCCs within the MC that did not show tumour progression under locoregional therapy had the best outcomes after liver transplantation. Downstaging into the limits of the MC did not improve the probability of survival. Prognostic factors determining the long-term success of liver transplantation in patients with hepatocellular carcinoma are still under discussion. A subgroup analysis of the SiLVER trial showed that disease control under bridging therapy is strongly associated with improved prognosis in terms of overall survival. However, in tumours exceeding the limits of the Milan criteria, downstaging did not restore the probability of survival compared with that of patients within the Milan criteria.

How important is the role of iterative liver direct surgery in patients with hepatocellular carcinoma for a transplant center located in an area with a low rate of deceased donation?

“…The United Network of Organ Sharing (UNOS) guidelines suggest a downstaging protocol for patients beyond MC, focusing on their response to bridge therapy (41). Also, a recent study demonstrated that disease progression after bridging therapy is an independent risk factor for recurrence and mortality (42).…”

“…Another relevant data emerging from our multivariate analysis is the "protective role" of the minimally invasive approach. If patients develop RHCC much more time after the first IDLS, it is possible to experience longer tumor-free survival even after subsequent surgical treatments (42)(43)(44)(45)(46). The clinical entity of RHCC can be developed in different settings, and it depends on which first-line therapy was chosen.…”

Role of Pretransplant Treatments for Patients with Hepatocellular Carcinoma Waiting for Liver Transplantation

“…On the other hand, Oligane et al [ 40 ] reported that the overall survival rate was higher, and the recurrence rate was lower in the BT group with T2 tumors that received MELD exceptions in a study using the UNOS database in the USA. Renner et al [ 41 ] from Germany reported that patients whose HCC progressed from within the Milan to outside the Milan criteria despite BT had lower overall survival and recurrence-free survival than those controlled within the Milan criteria. On the other hand, Ogawa et al [ 42 ] from Kyoto, Japan, reported that if LT was performed within the Kyoto criteria (≤10 lesions ≤5 cm, DCP ≤400 mAU/mL), results of LT were relatively good.…”

Liver Transplant Oncology: Towards Dynamic Tumor-Biology-Oriented Patient Selection

“…Success rates for downstaging are acceptable and can be predicted by normalization of AFP levels prior to LT as well as wait times longer than 12 months [ 18 ]; recurrence rates after LT are satisfactory. However, tumor progression during waiting time for LT despite locoregional bridging appears to be an independent risk factor for increased recurrence and decreased outcome as shown in the SiLVER study [ 19 ]. Importantly, sufficiently long observation periods to identify favorable tumor biology need to be provided for successful LT outcomes [ 20 , 21 , 22 ].…”