Late recurrence of hepatocellular carcinoma after radiofrequency ablation: a multicenter study of risk factors, patterns, and survival.

objectiveThis study aims to determine the risk factors, patterns, and long-term survival outcomes of late recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within the Milan criteria and develop a nomogram to predict the recurrence-free survival (RFS). MATERIALS AND

methodsThis retrospective study included patients with HCC within the Milan criteria, who received RFA at three hospitals in China from January 2011 to December 2016. The clinical variables were assessed by univariate and multivariate Cox regression analyses.

resultsA total of 398 patients were included. The median follow-up was 58.7 months (range: 24.1-96.0). Ninety-eight patients had late recurrence. Furthermore, 14 patients (14.29%) had local tumor progression (LTP) alone, 43 patients (43.88%) had intrahepatic distant recurrence (IDR) alone, 15 patients (15.31%) had extrahepatic recurrence (ER) alone, three patients (3.06%) had both LTP and IDR, six patients (6.12%) had both LTP and ER, and 17 patients (17.35%) had both IDR and ER. Patients without late recurrence had better long-term overall survival (OS) compared to those with late recurrence (p < 0.001). Male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence. A well-discriminated and calibrated nomogram was constructed to predict the probability of RFS.

conclusionMale gender, multiple tumors, and cirrhosis are the independent risk factors of late recurrence after RFA for HCC within the Milan criteria. Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. An individualized surveillance and prevention strategy for HCC patients after RFA should be developed. KEY POINTS: • In the present retrospective study of 398 patients, male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence (> 2 years) of HCC after RFA. • The most common pattern of late recurrence was intrahepatic distant recurrence alone (n = 43, 43.88%). Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. • A prognostic nomogram was built to predict the individualized recurrence-free survival after RFA, which achieved good calibration and discriminatory ability with a concordance index of 0.763.