Bridging therapies for patients with hepatocellular carcinoma awaiting liver transplantation: A systematic review and meta‐analysis on intention‐to‐treat outcomes

Abstract

Introduction:Locoregional therapies are commonly used as bridging strategies to decrease the drop-out of patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). The present paper aims to assess the outcomes of bridging therapies in patients with HCC considered for LT according to an intention-to-treat (ITT) survival analysis. Material and methods: Medline and Web of Science databases were searched for reports published before May 2021. Papers assessing adult patients with HCC considered for LT and reporting ITT survival outcomes were included. Two reviewers independently identified, extracted the data, and evaluated the papers according to Newcastle-Ottawa criteria. Outcomes analyzed were: drop-out rate; time on the waiting list; 1-, 3-, and 5-year survival after LT and based on an ITT analysis. Results:The search identified 3106 records; six papers (1043 patients) met the inclusion criteria. Patients with HCC, listed for LT and submitted to bridging therapies presented a longer waiting time before LT (MD 3.77, 95% CI 2.07-5.48) in comparison with the non-interventional group. However, they presented a raised post LT after 1-year (OR 2.00, 95% CI 1.18-3.41), 3-years (OR 1.47, 95% CI 1.01-2.15), and 5-years (OR 1.50, 95% CI 1.06-2.13) survival. Conclusion:Patients submitted to bridging procedures, despite having a longer interval on the waiting list, presented better post-LT survival outcomes. Bridging therapies for selected patients at low risk of post-procedural complications and long expected intervals on the waiting list should be encouraged. However, further clinical trials should confirm the survival benefit of bridging therapies in patients with HCC listed for LT.

Results of transarterial chemoembolization of hepatocellular carcinoma as a bridging therapy to liver transplantation

“…Locoregional therapy has been offered to waitlisted patients to avoid dropout ( 5 - 7 , 13 ) . Nevertheless, there is no consensus regarding this approach in the literature, mainly because of the difficulty of performing randomized, controlled prospective studies ( 5 , 12 , 21 , 22 ) .…”

“…However, their analysis included patients with tumors that had been downstaged. The most recent systematic review and meta-analysis on the topic in question ( 12 ) , using the concept of intention-to-treat in an original way, concluded that patients undergoing bridging therapy before liver transplantation, despite being on the waiting list for longer than those who did not undergo the procedure, had better post-transplant survival. Nevertheless, when the intention-to-treat analysis was performed, there was no difference between those two groups in terms of the one-, three-, or five-year survival rate.…”

“…Locoregional therapies, such as transarterial embolization, transarterial chemoembolization (TACE), transarterial radioembolization, local ablation therapies, stereotactic body radiation, and combinations of those strategies, have been considered for use as bridging therapies. As a rule, those pre-transplant therapies do not provoke severe adverse events, although minor complications reportedly occur in 2.3-8.3% of cases (12,13) . No superiority has been demonstrated among the proposed methods (5) .…”

Pushing the limits of treatment for hepatocellular carcinoma

“…Furthermore, they found no difference in successful downstaging between treatment modalities, but did note higher rates of tumor necrosis with Y-90. Tumor size and AFP stability/decrease over a period of 6 months has previously been shown to predict good outcomes post-LT [23,24]. Complete pathologic response to LRT is also a predictor of good outcomes [25].…”

A valuable tool for the treatment of hepatocellular carcinoma

“…Although their use is still controversial, locoregional treatment techniques such as percutaneous thermal ablation (by radiofrequency or microwave) and transarterial chemoembolization (TACE) are now in the toolbox of the interventional radiologist, being routinely applied at transplant centers to cure or inhibit the growth of HCC. This strategy, known as bridging therapy, is indicated when the time on the waiting list exceeds six months, and its use can avoid acquired ineligibility, thus improving LT efficacy and excluding patients with neoplasia that is more aggressive ( 6 ) .…”