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.
Göran Klintmalm M.D.
Agopian, V. G., M. P. Harlander-Locke, R. M. Ruiz, G. B. Klintmalm, S. Senguttuvan, S. S. Florman, B. Haydel, M. Hoteit, M. H. Levine, D. D. Lee, C. B. Taner, E. C. Verna, K. J. Halazun, R. Abdelmessih, A. D. Tevar, A. Humar, F. Aucejo, W. C. Chapman, N. Vachharajani, M. H. Nguyen, M. L. Melcher, T. L. Nydam, C. Mobley, R. M. Ghobrial, B. Amundsen, J. F. Markmann, A. N. Langnas, C. A. Carney, J. Berumen, A. W. Hemming, D. L. Sudan, J. C. Hong, J. Kim, M. A. Zimmerman, A. Rana, M. L. Kueht, C. M. Jones, T. M. Fishbein and R. W. Busuttil (2017). “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 266(3): 525-535.
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.