Downstaging Hepatocellular Carcinoma before Transplantation Role of Immunotherapy Versus Locoregional Approaches

HCC continues to be a leading cause of cancer-related death in the United States. With advances in locoregional therapy for unresectable HCC during the last 2 decades and the recent expansion of transplant criteria for HCC, as well as ongoing organ shortages, patients are spending more time on the waitlist, which has resulted in increased usage of locoregional therapies. This changing landscape is well displayedin Fig. 1, which demonstrates the number of treatments per patient by year of listing (A) and the proportion of locoregional therapy type by year of treatment (B).91 Less than half of liver transplant candidates on the waiting list underwent locoregional therapy before listing in 2003, whereas 92.4% underwent some form of locoregional therapy in 2018.91 Although TACE is the current preferred modality for liver-directed therapy as a bridge to transplant in patients with HCC, recent evidence suggests that radioembolization may prolong time to progression when compared with chemoembolization. In just the last 5 years, the proportion of radioembolization performed for HCC has increased significantly, from less than 5% in 2013 to 19% in 2018.91 Expanding on the proven value of locoregional therapies, the plethora of molecularly targeted therapies and ICIs under investigation represent the new horizon of treatment of HCC not only in advanced stages but also potentially at every stage of diagnosis and management. Although data remain sparse in the pretransplantation population, the possibility of downstaging patients previously considered unresectable or initially outside of transplant criteria is an extremely alluring strategy, which may prove vital in establishing transplant candidacy for an expanded host of patients. Combination therapies have already begun to show promise in maintaining disease control and may ultimately prove lifesaving in patients who are able to undergo liver transplant. Although it will be critical in the coming years to determine timing of therapy and appropriate postoperative immunosuppression strategies, both locoregional techniques and immunomodulation will change the history of liver transplant for HCC as we currently know it.