Bridging and downstaging treatments for hepatocellular carcinoma in patients on the waiting list for liver transplantation

Abstract

Several therapeutic procedures have been proposed as bridging treatments for patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The most used treatments include transarterial chemoembolization and radiofrequency ablation. Surgical resection has also been successfully used as a bridging procedure, and LT should be considered a rescue treatment in patients with previous HCC resection who experience tumor recurrence or post-treatment severe decompensation of liver function. The aims of bridging treatments include decreasing the waiting list dropout rate before transplantation, reducing HCC recurrence after transplantation, and improving post-transplant overall survival. To date, no data from prospective randomized studies are available; however, for HCC patients listed for LT within the Milan criteria, prolonging the waiting time over 6-12 mo is a risk factor for tumor spread. Bridging treatments are useful in containing tumor progression and decreasing dropout. Furthermore, the response to pre-LT treatments may represent a surrogate marker of tumor biological aggressiveness and could therefore be evaluated to prioritize HCC candidates for LT. Lastly, although a definitive conclusion can not be reached, the experiences reported to date suggest a positive impact of these treatments on both tumor recurrence and post-transplant patient survival. Advanced HCC may be downstaged to achieve and maintain the current conventional criteria for inclusion in the waiting list for LT. Recent studies have demonstrated that successfully downstaged patients can achieve a 5-year survival rate comparable to that of patients meeting the conventional criteria without requiring downstaging.

Keywords: Hepatocellular carcinoma, Bridging treatment, Downstaging, Liver cirrhosis, Liver transplantation, Liver resection, Waiting list, Waiting time, Dropout rate

Core tip: The bridging treatments for patients with hepatocellular carcinoma within Milan criteria listed for liver transplantation are useful in decreasing dropout rate from the waiting list and the experiences reported to date suggest a positive impact on post-transplant tumor recurrence and patient survival. The response to treatments may represent a surrogate marker of tumor biological aggressiveness and could be evaluated to prioritize hepatocellular carcinoma candidates in the waiting list. Advanced hepatocellular carcinoma may be downstaged to achieve the current conventional criteria for inclusion in the waiting list and successfully downstaged patients can achieve an excellent 5-year survival rate.