The Key Role of Staging Definitions for Assessment of Downstaging for Hepatocellular Carcinoma

Abstract

The success of liver transplant (LT) for hepatocellular carcinoma (HCC) is dependent on accurate tumor staging using validated imaging criteria, and adherence to acceptable criteria based on tumor size and number. Other factors including α-fetoprotein (AFP) and response to local regional therapy (LRT) have now played a larger role in candidate selection. Tumor downstaging is defined as reduction in the size of viable tumors using LRT to meet acceptable criteria for LT, and serves as a selection tool for a subgroup of HCC with more favorable biology. The application of tumor downstaging requires a structured approach involving three key components in tumor staging—initial tumor stage and eligibility criteria, tumor viability assessment following LRT, and target tumor stage prior to LT—and incorporation of AFP into staging and treatment response assessments. In this review, we provide in-depth discussions of the key role of these staging definitions in ensuring successful outcome.

Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti‐VEGF/TKI and immunotherapy

“…Higher pre-LRT AFP has been identified as a negative prognostic biomarker for successful downstaging after LRT. [30,97] Pre-LRT AFP >1000 ng/mL was associated with a more than 3-fold risk of LRT treatment failure (HR, 3.3; p < .001). Similarly, Child-Pugh class B/C was associated with LRT downstaging failure (HR, 1.6; p < .001).…”

“…Similarly, Child-Pugh class B/C was associated with LRT downstaging failure (HR, 1.6; p < .001). [30,97] In fact, patients with Child-Pugh class B or C with pre-LRT AFP >1000 had 100% LRT downstaging treatment failure at 2 years from first LRT treatment. [30] Moreover, lower AFP reduction following LRT has been identified as a negative prognostic marker for successful downstaging.…”

Sequential treatment after transcatheter arterial chemoembolization for patients with single large hepatocellular carcinoma

“…Sequential treatment and on-treatment prognostic factors are sometimes mentioned. Downstaging for curative treatments such as transplantation has been reported without consistent results, 7,8 while TACEfailure has been discussed in this era of targeted therapy. 9 The concept of sequential treatment was firstly documented in treatment algorithms in the latest EASL guidelines 10 where recommendations for sequential treatments for BCLC stage B and C were included.…”

“…Patients beyond Milan criteria were downstaged by TACE to become candidates of transplantation. 7,8 Post-TACE resection extended the indication of surgical resection. Combination of TACE and radiofrequency or microwave ablation was proven to increase benefit in mediansized HCC.…”

“…TACE has been reported as a downstage modality to meet the inclusive criteria for curative treatment. Patients beyond Milan criteria were downstaged by TACE to become candidates of transplantation 7,8 . Post‐TACE resection extended the indication of surgical resection.…”