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.

Fig. 1

Kaplan–Meier estimates of disease-free and overall survival for patients with hepatocellular carcinoma within or outside the Milan criteria at listing based on imaging Disease-free survival for patients a within and b outside the Milan criteria (MC), and overall survival for patients c within and d outside the MC. a P = 0.002, b P = 0.490, c P < 0.001, d P = 0.726 (log rank test).

Fig. 2

Effect of progression during bridging on disease-free and overall survival in patients with hepatocellular carcinoma within the Milan criteria both at the time of listing and at transplantation a Disease-free and b overall survival. a P = 0.089, b P = 0.021 (log rank test).

Fig. 3

Kaplan–Meier model of disease-free and overall survival, according to behaviour of lesions during bridging/time on waiting list a Disease-free and b overall survival in relation to changes in Milan criteria status during therapy assessed by comparing listing imaging and explant histopathology. In, disease within limits of Milan criteria; out, disease outside limits of Milan criteria. a P < 0.050 (remaining in versus other subgroups; b P = 0.068 (remaining in versus remaining out), P < 0.050 (remaining in versus in-to-out and out-to-in subgroups) (log rank test).