Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma

Abstract

Objective: The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). Background: LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study. Methods: Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression. Results: Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil–lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67). Conclusions: For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.

Embolotherapy for Hepatic Oncology: Current Perspectives and Future Directions

“…48 Pathologic response to locoregional techniques may also have important prognostic consequences: complete pathologic response (CPN) of the treated tumor on explant is associated with reduced HCC recurrence and improved posttransplant survival. 49,50 The use of specialized catheter delivery tools such as balloon and microvalve catheters may further augment tumor response for appropriate candidates in this setting. cTACE performed with microvalve catheters prior to transplant for HCC demonstrated significantly higher percentage tumor necrosis on explant, 89.0 AE 2.2%, compared with standard end-hole catheters, 56.1 AE 44.5% (p ¼ 0.006).…”

Recent advances in liver transplantation for cancer: The future of transplant oncology

“…Firl et al validated the hazard associated with LT in HCC (HALT-HCC) and demonstrated a significant heterogeneity by site and year, reflecting practice trends over the last decade.. 27 Response to locoregional therapies Response to locoregional therapies (LRT) such as ablation, transarterial chemoembolisation (TACE), selective internal radiation therapy and stereotactic body radiation therapy correlates with tumour biology. [28][29][30] Complete pathological response in the explant has been associated with a higher overall survival (OS) and DFS. 30 In patients within the Milan criteria, poor response to LRT was associated with HCC-dependent transplant failure.…”

“…[28][29][30] Complete pathological response in the explant has been associated with a higher overall survival (OS) and DFS. 30 In patients within the Milan criteria, poor response to LRT was associated with HCC-dependent transplant failure. Lai et al have shown that patients with progressive disease despite LRT had a higher risk of dropout or posttransplant HCC recurrence (subdistribution HR 5.62, 95% CI 4.10-7.69).…”

T2 Hepatocellular Carcinoma Exception Policies That Prolong Waiting Time Improve the Use of Evidence-based Treatment Practices

“… 16 Pretransplant radiologic response and complete pathologic response to pretransplant LRT significantly decrease post-LT HCC recurrence. 17 – 19 However, if expected LT waiting time is short, aggressive LRT may be less likely to be pursued. We hypothesized that the 2015 policy resulted in more aggressive pre-LT treatment for HCC, and as a result more prevalent complete pathologic response on LT explant, particularly in regions with shorter prepolicy wait-times.…”