Complete pathologic response to pretransplant locoregional therapy for hepatocellular carcinoma defines cancer cure after liver transplantation: analysis of 501 consecutively treated patients.

Abstract

OBJECTIVES:

To evaluate the rate, effect, and predictive factors of a complete pathologic response (cPR) in patients with hepatocellular carcinoma (HCC) undergoing locoregional therapy (LRT) before liver transplantation (LT).

BACKGROUND:

Eligible patients with HCC receive equal model for end-stage liver disease prioritization, despite variable risks of tumor progression, waitlist dropout, and posttransplant recurrence. Pretransplant LRT mitigates these risks by inducing tumor necrosis.

METHODS:

Comparisons were made among HCC recipients with cPR (n = 126) and without cPR (n = 375) receiving pre-LT LRT (1994-2013). Multivariable predictors of cPR were identified.

RESULTS:

Of 501 patients, 272, 148, and 81 received 1, 2, and 3 or more LRT treatments. The overall, recurrence-free, and disease-specific survival at 1-, 3-, and 5 years was 86%, 71%, 63%; 84%, 67%, 60%; and 97%, 90%, 87%. Compared with recipients without cPR, cPR patients had significantly lower laboratory model for end-stage liver disease scores, pretransplant alpha fetoprotein, and cumulative tumor diameters; were more likely to have 1 lesion, tumors within Milan/University of California, San Francisco (UCSF) criteria, LRT that included ablation, and a favorable tumor response to LRT; and had superior 1-, 3-, and 5-year recurrence-free survival (92%, 79%, and 73% vs 81%, 63%, and 56%; P = 0.006) and disease-specific survival (100%, 100%, and 99% vs 96%, 89%, and 86%; P < 0.001) with only 1 cancer-specific death and fewer recurrences (2.4% vs 15.2%; P < 0.001). Multivariate predictors of cPR included a favorable post-LRT radiologic/alpha fetoprotein tumor response, longer time interval from LRT to LT, and lower model for end-stage liver disease score and maximum tumor diameter (C-statistic 0.75).

CONCLUSIONS:

Achieving cPR in patients with HCC receiving LRT strongly predicts tumor-free survival. Factors predicting cPR are identified, allowing for differential prioritization of HCC recipients based on their variable risks of post-LT recurrence. Improving LRT strategies to maximize cPR would enhance posttransplant cancer outcomes.

• Authors: Vatche G Agopian, Maud M Morshedi, Justin McWilliams, Michael P Harlander-Locke, Daniela Markovic, Ali Zarrinpar, Fady M Kaldas, Douglas G Farmer, Hasan Yersiz, Jonathan R Hiatt, Ronald W Busuttil
• Journal: Annals of surgery (Ann Surg) Vol. 262 Issue 3 Pg. 536-45; discussion 543-5 (Sep 2015) ISSN: 1528-1140 [Electronic] United States
• PMID: 26258323 (Publication Type: Comparative Study, Evaluation Study, Journal Article)

Topics

• Adult
• Aged
• Biopsy, Needle
• Carcinoma, Hepatocellular (mortality, pathology, surgery, therapy)
• Databases, Factual
• Disease-Free Survival
• Female
• Follow-Up Studies
• Graft Rejection
• Graft Survival
• Humans
• Immunohistochemistry
• Liver Neoplasms (mortality, pathology, surgery, therapy)
• Liver Transplantation (methods, mortality)
• Logistic Models
• Male
• Middle Aged
• Multivariate Analysis
• Neoadjuvant Therapy (methods)
• Predictive Value of Tests
• Preoperative Care (methods)
• Retrospective Studies
• Statistics, Nonparametric
• Survival Analysis
• Time Factors
• Treatment Outcome