LI-RADS category 5 hepatocellular carcinoma: preoperative gadoxetic acid-enhanced MRI for early recurrence risk stratification after curative resection

Abstract

Objectives: To explore the role of preoperative gadoxetic acid-enhanced MRI in stratifying the risk of early recurrence in patients with LR-5 hepatocellular carcinoma (HCC) by LI-RADS v2018 after curative resection.

Methods: Between July 2015 and August 2018, this study evaluated consecutive treatment-naïve at-risk LR-5 HCC patients who underwent gadoxetic acid-enhanced MRI examination within 2 weeks before curative resection. The Cox regression analysis was performed to identify potential predictors of early recurrence. Disease-free survival (DFS) rates were analyzed and compared by using the Kaplan-Meier method and log-rank tests.

Results: Fifty-three of 103 (51.5%) patients experienced early recurrence. Three MRI findings were significantly associated with early recurrence: corona enhancement (hazard ratio [HR]: 2.116; p = 0.013), peritumoral hypointensity on hepatobiliary phase (HBP) (HR: 2.262; p = 0.007), and satellite nodule (HR: 2.777; p = 0.005). An additional risk factor was AFP level > 400 ng/mL (HR: 1.975; p = 0.016). Based on the number of MRI predictors, LR-5 HCC patients were stratified into three subgroups: LR-5a (60/103; no predictor), LR-5b (26/103; one predictor), and LR-5c (17/103; two or three predictors), with low, medium, and high risk of early recurrence, respectively. The 2-year DFS rate of LR-5a, LR-5b, and LR-5c patients was 65.0%, 38.5%, and 5.9%, respectively, while the corresponding median DFS was undefined, 17.1 months, and 5.1 months, respectively (p < 0.001).

Conclusions: In at-risk LR-5 HCC patients, corona enhancement, peritumoral hypointensity on HBP, and satellite nodule could be used to preoperatively stratify the risk of early recurrence after hepatectomy.

Key points: • Corona enhancement, peritumoral hypointensity on HBP, satellite nodule, and serum AFP level > 400 ng/mL were significant predictors of early recurrence in patients with LR-5 HCC after hepatectomy. • Based on the number of predictive MRI findings, LR-5 HCC patients could be preoperatively stratified into three subgroups: LR-5a, LR-5b, and LR-5c, with significantly different risk of early recurrence and disease-free survival. • Preoperative risk stratification is essential for the identification of patients at increased risk of postoperative early recurrence, which may contribute to risk-based personalized management for LR-5 HCC patients.

Keywords: Carcinoma, hepatocellular; Gadoxetic acid; Liver; Magnetic resonance imaging; Prognosis.

Fig. 1

Flow chart of the study population. HCC, hepatocellular carcinoma; NC, not categorizable

Fig. 2

A 47-year-old man with a 4.5-cm moderately differentiated LR-5 HCC in hepatic segment VIII and the serum AFP level was higher than 1210 ng/mL. a Mass shows non-rim hyperenhancement and mosaic architecture (arrow) on late arterial phase. b Mass shows hypointensity and non-smooth tumor margin (arrow) on hepatobiliary phase. This patient had none of the predictive MR imaging findings for early recurrence and was categorized as LR-5a. There was no early recurrence during follow-up after curative resection. The disease-free survival was 37.6 months

Fig. 3

a, b A 47-year-old woman with a 5.2-cm poorly differentiated LR-5 HCC in hepatic segment VI and serum AFP level of 1.38 ng/mL. a Mass shows non-rim hyperenhancement, nodule-in-nodule (asterisk), and mosaic architecture on late arterial phase. b Mass shows mixed intensity and peritumoral hypointensity (arrowhead) on hepatobiliary phase (HBP). This patient had one of the predictive MR imaging findings (peritumoral hypointensity on HBP) for early recurrence and was categorized as LR-5b. Early recurrence occurred in the liver during follow-up after curative resection. The disease-free survival was 23.7 months. c, d A 29-year-old man with a 7.0-cm moderately differentiated LR-5 HCC in hepatic segment VI and the serum AFP level was higher than 1210 ng/mL. c Mass shows non-rim hyperenhancement, nodule-in-nodule (asterisk), mosaic architecture, and corona enhancement (arrowhead) on late arterial phase. d Mass shows hypointensity and non-smooth tumor margin on hepatobiliary phase. This patient had one of the predictive MR imaging findings (corona enhancement) for early recurrence and was categorized as LR-5b. Early recurrence occurred in the liver during follow-up after curative resection. The disease-free survival was 8.5 months

Fig. 4

A 38-year-old man with a 10.0-cm poorly differentiated LR-5 HCC in hepatic segment V-VIII and serum AFP level of 5.06 ng/mL. a Mass shows non-rim hyperenhancement, nodule-in-nodule (asterisk), and mosaic architecture on late arterial phase. b Mass shows hypointensity, non-smooth tumor margin, and peritumoral hypointensity (arrowhead) on hepatobiliary phase. c A 1.7-cm satellite nodule (arrow) located in the peritumoral parenchyma shows non-rim hyperenhancement on late arterial phase. d The satellite nodule (arrow) shows non-peripheral “washout” on portal venous phase. This patient had two of the predictive MR imaging findings (peritumoral hypointensity on HBP and satellite nodule) for early recurrence and was categorized as LR-5c. Early recurrence occurred in the liver during follow-up after curative resection. The disease-free survival was 3.7 months

Fig. 5

Disease-free survival (DFS) curves of LR-5a (green), LR-5b (blue), and LR-5c (red) subgroups, with LR-5 HCC patients having no, one, and two or three significant MR imaging findings for predicting early recurrence, respectively. DFS differed significantly among three subgroups of LR-5 HCC patients according to the Kaplan–Meier method and log-rank tests

Fig. 6

Comparison of disease-free survival (DFS) according to the serum AFP level in LR-5a (a), LR-5b (b), and LR-5c (c) subgroups. There were no significant differences in DFS between patients with serum AFP level > 400 ng/mL and those with serum AFP level ≤ 400 ng/mL for three subgroups