Identifying risk for recurrent hepatocellular carcinoma after liver transplantation: Implications for surveillance studies and new adjuvant therapies

Abstract

The recurrence of hepatocellular carcinoma (HCC) is a major cause of mortality for patients transplanted with HCC. There currently exists no standard method for identifying those patients with a high risk for recurrence. Identification of factors leading to recurrence is necessary to develop an efficient surveillance protocol and address new potential adjuvant therapies. We Stepwise logistic regression identified 4 independent significant explant factors predictive of recurrence. Size of one tumor (Ͼ4.5 cm), macroinvasion, and bilobar tumor were positive predictors of recurrence, whereas the presence of only well-differentiated HCC was a negative predictor. Designating each significant factor with points in relation to its odds ratio, a Predicting Cancer Recurrence Score (PCRS) with results ranging from Ϫ3 to 6 was developed that accurately determined risk of recurrence. These findings were then applied to the two validation cohorts, which confirmed the high predictive value of this model. The recurrence of hepatocellular carcinoma (HCC) is a significant cause of mortality after liver transplantation.1,2 Even with the implementation of the Milan criteria, recurrence rates have been shown to be 8%-15% in most studies. [2][3][4] One reason for this is that diagnostic staging prior to transplantation relies on radiographic evaluation, which has been reported to understage tumors in 21%-43% of cases.5-8 Several case series reviews have identified tumor characteristics that may lead to a higher recurrence rate. Most of these reviews identified factors determined through pathological analysis of explanted livers.3,4,9-11 However, patients transplanted for HCC are usually not restaged, and all are still followed post-transplantation with

Tools for monitoring patients with hepatocellular carcinoma on the waiting list and after liver transplantation

“…The risk of recurrence in patients within the Milan criteria has been regularly reported to be 6% to 10%. 54 The inclusion of additional defining criteria such as pretransplant AFP levels or a risk factor analysis based on explant pathology findings should certainly be capable of reducing this risk. In the University of Alberta experience, although 2 of 4 of patients (50%) who were within the Milan criteria, had AFP levels > 400 ng/mL, and survived more than 6 months after liver transplantation experienced HCC recurrence, only 2 of 66 patients (3%) who were within the Milan criteria and had AFP levels < 400 ng/mL experienced recurrence.…”

Hepatocellular carcinoma: A comprehensive review

“…Different systems to stage HCC have been created and validated, in various degrees. The American Joint Committee on Cancer revised the tumor, lymph nodes, and metastasis (TNM) classification of malignant tumors staging system and tumor satellites, and tumorspecific biomarkers [36] . Tumor differentiation and microvascular invasion are also substantial risks, but these features are not determined until after the evaluation of the explant.…”

“…Further evidence suggests that independent variables beyond the size of the tumor and total number of tumors may be linked to a more aggressive tumor biology, resulting in an increased chance of HCC recurrence post-transplant [39,79] . The diagnostic accuracy of MRI and CT has shown to be in the range of 45%-60% and for cases with lesions under stage, noted for 21%-43% [36] . This is likely because the relationship comparing imaging criterion and histopathology for cirrhotic hepatic explants needs further investigation.…”

Management of Recurrent Hepatocellular Carcinoma in Liver Transplant Recipients: A Systematic Review

“…Conversely, the degree of tumor cell differentiation is inversely associated with recurrent disease in that well-differentiated HCC is associated with decreased risk for recurrence. 39 Cillo and associates studied 48 patients with HCC in a prospective manner and found that patients with moderately to well-differentiated tumors had a 75% actuarial survival rate and 92% recurrence-free survival rate. 40 Thus, the degree of tumor differentiation and presence of vascular invasion before LT are predictors of post-LT HCC recurrence, but both are determined on explant pathology and are not as useful clinically during the selection process.…”