Impact of Pretransplant Bridging Locoregional Therapy for Patients With Hepatocellular Carcinoma Within Milan Criteria Undergoing Liver Transplantation: Analysis of 3601 Patients From the US Multicenter HCC Transplant Consortium.

Ann Surg

*Dumont-UCLA Liver Transplant and Cancer Centers, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA †Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX ‡Recanati/Miller Transplantation Institute, Mount Sinai Medical Center, New York, NY §Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA ¶Department of Transplantation, Mayo Clinic, Jacksonville, FL ||New York Presbyterian Hospital, Columbia University, New York, NY **New York Presbyterian Hospital, Weill Cornell, New York, NY ††Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA ‡‡Cleveland Clinic Foundation, Cleveland, OH §§Section of Transplantation, Department of Surgery, Washington University in St. Louis, St. Louis, MO ¶¶Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA ||||Department of Surgery, Stanford University, Palo Alto, CA ***Division of Transplant Surgery, Department of Surgery, University of Colorado School of Medicine, Denver, CO †††Sherrie & Alan Conover Center for Liver Disease & Transplantation, Houston Methodist Hospital, Houston, TX ‡‡‡Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA §§§Department of Surgery, University of Nebraska Medical Center, Omaha, NE ¶¶¶Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of California, San Diego, San Diego, CA ||||||Department of Surgery, Duke University Medical Center; Durham, NC ****Division of Transplant Surgery, Department of Surgery, Medical College of Wisconsin, Milwaukee, WI ††††Department of Surgery, Baylor College of Medicine, Houston, TX ‡‡‡‡Section of Hepatobiliary and Transplant Surgery, University of Louisville School of Medicine, Louisville, KY §§§§Medstar Georgetown Transplant Institute, Georgetown University, Washington, District of Columbia.

Published: September 2017

Objective: To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC).

Summary Background Data: Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited.

Methods: Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013).

Results: Compared with 747 LT recipients not receiving LRT, 2854 receiving LRT had similar 1, 3, and 5-year recurrence-free survival (89%, 77%, 68% vs 85%, 75%, 68%; P = 0.490) and 5-year post-LT recurrence (11.2% vs 10.1%; P = 0.474). Increasing LRT number [3 LRTs: hazard ratio (HR) 2.1, P < 0.001; 4+ LRTs: HR 2.5, P < 0.001), and unfavorable waitlist alphafetoprotein trend significantly predicted post-LT recurrence, whereas LRT modality did not. Treated patients achieving complete pathologic response (cPR) had superior 5-year RFS (72%) and lower post-LT recurrence (HR 0.52, P < 0.001) compared with both untreated patients (69%; P = 0.010; HR 1.0) and treated patients not achieving cPR (67%; P = 0.010; HR 1.31, P = 0.039), who demonstrated increased recurrence compared with untreated patients in multivariate analysis controlling for pretransplant and pathologic factors (HR 1.32, P = 0.044).

Conclusions: Bridging LRT in HCC patients within MC does not improve post-LT survival or HCC recurrence in the majority of patients who fail to achieve cPR. The need for increasing LRT treatments and lack of alphafetoprotein response to LRT independently predict post-LT recurrence, serving as a surrogate for underlying tumor biology which can be utilized for prioritization of HCC LT candidates.

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