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.

Strategies to improve outcome of patients with hepatocellular carcinoma receiving a liver transplantation

“…It has been hypothesized an increased risk of arterial and biliary complications after LT in patients with a previous TACE due to an endothelial damage, but this was not confirmed in a recent study with 456 HCC transplanted patients [88] . The use of TACE with drug eluting beads has improved the performance of the technique with complete tumour necrosis rates as high as 76.2%, and with a better safety profile [67,89] . In spite of this, RFA is preferred for single tumours less than 5 cm [80] .…”

The Evolution of Criteria for Liver Transplantation for Hepatocellular Carcinoma: From Milan to San Francisco and All Around the World!

“…It is also generally accepted that the patient's response to such treatments may be associated with the aggressiveness of the disease and thus could possibly be utilized as a surrogate marker for prognosis. Despite the fact that no firm conclusions can yet be made, data suggest that this process can increase patient survival and decrease tumor recurrence post-OLT 50 .…”

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“…However, the idea for using these therapies to downstage patients from extra-Milan to within-Milan criteria is beginning to gain traction, although the results for long-term survival and tumor-free survival are not yet clear. [33][34][35][36][37] The recent, large Adjuvant Sorafenib for Hepatocellular Carcinoma After Resection or Ablation (STORM) trial, however, failed to meet its hoped-for endpoints 38 and showed no benefit to survival for adjuvant sorafenib after resection. More effective anti-HCC agents are awaited.…”