Downstaging Prior to Liver Transplantation for Hepatocellular Carcinoma: Advisable but at the Price of an Increased Risk of Cancer Recurrence – A Retrospective Study

Clinical question Does the original HCC stage have an impact on post-transplant outcome after successful downstaging?

Take-away point 
Despite an increase in post-transplant HCC recurrence in downstaged patients, similar survivals can be achieved to patients who do not require downstaging. Therefore, downstaging should be continued to be performed.

Reference
Toso, Christian et al. “Downstaging Prior to Liver Transplantation for Hepatocellular Carcinoma: Advisable but at the Price of an Increased Risk of Cancer Recurrence - a Retrospective study.(Report).” Transplant International 32.2 (2019): 163–172.

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Study design: Retrospective review

Funding source: Self-funded or unfunded

Setting: Multi-institution 

Figure 1. Disease-free survival according to downstaging based on TTV115/AFP400 (47% versus 80% at 5 years, =0.95).

Summary

Studies have shown that patients with advanced HCC can benefit from transplantation after downstaging, however, most of these studies used Milan criteria as the downstaging goal and most of the patients were marginally outside of Milan criteria. The authors of this retrospective review of a prospectively maintained database of patients from 2 institutions included patients within the total tumor volume (TTV)/alpha fetoprotein (AFP) criteria (TTV <115 cm3 and AFP < 400 ng/mL; included approximately 20% more patients compared to Milan criteria) and those with advanced HCC but who were successfully downstaged to and stable within this criteria for 3 months. 455 patients were listed for transplantation, 286 of whom were transplanted according to the TTV115/AFP400 criteria. 257 of the transplanted patients underwent a locoregional HCC treatment prior to transplantation which included TACE, RFA, alcohol ablation, SIRT, and resection. TACE, RFA, and alcohol ablation were the most commonly performed procedures. 29 patients were successfully downstaged. Downstaged patients demonstrated similar disease-free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 criteria. Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Of note, patients treated by RFA or microwave ablation versus TACE prior to transplantation showed showed similar DFS (78.9% vs. 77.2% at 5 years, P = 0.74), and similar rates of post-transplant HCC recurrence (4/73, 5.5% vs. 13/164, 7.9%, P = 0.50).

Commentary

This paper suggests that patients with advanced HCC outside of expanded transplant criteria should have hope of achieving similar survival after transplantation compared to patients with lower AFP. The higher risk of recurrence is modest (~11%) and it does not appear that this should impact the decision to offer transplant versus palliation only for advanced HCC patients. Further study will need to be performed to determine which patients would benefit most from downstaging, especially considering the relatively small number of patients who were ultimately downstaged, but these results are promising for those patients for whom downstaging is successful.

Post author: Zagum Bhatti, MD
Assistant Professor
Department of Radiology, Interventional Radiology Division
University of Texas Health Science Center at Houston, Houston, TX
@ZagumBhatti