Abstract

Simple SummaryThe effectiveness of surgical resection and radiofrequency ablation in early hepatocellular carcinoma is still controversial because previous studies show conflicting results. In addition, previous studies did not consider the antiviral treatment-related factors, even though there is now robust evidence that antiviral therapy is crucial for determining the prognosis of patients with chronic hepatitis B-related liver cancer. After adjusting for the antiviral treatment, we demonstrated that radiofrequency ablation may provide comparable overall survival to resection in the treatment of very early or early hepatocellular carcinoma, although recurrence-free survival is marginally shorter than in the resection group.It remains controversial whether surgical resection, compared to radiofrequency ablation (RFA), improves overall survival (OS) in patients with early hepatocellular carcinoma (HCC). This study aimed to compare OS after RFA with that after resection for HCC. This retrospective study included patients who underwent RFA or surgical resection as initial treatment for hepatitis B virus (HBV)-related HCC at a very early or early stage. A total of 761 patients (RFA, n = 194; resection, n = 567) from Seoul National University Hospital (Seoul, South Korea) and 1277 patients (RFA, n = 352; resection, n = 925) from the Korean Primary Liver Cancer Registry were included in the hospital and nationwide cohorts, respectively. Primary and secondary endpoints were OS and recurrence-free survival (RFS), respectively. Additional analysis was performed when the history of the antiviral treatment and the type of prescribed nucleos(t)ide analogue were confirmed. The rate of complications was compared between the two treatment groups in the hospital cohort. Baseline characteristics were balanced, using inverse probability of treatment weighting (IPTW). In the hospital cohort, the RFA group had a smaller mean tumor size (1.7 vs. 3.9 cm) but a higher proportion of cirrhotic patients than the resection group (85.6% vs. 63.1%) (both p < 0.01). During 81.0 (interquartile range, 62.3–107.1) months of follow-up, there was no difference in OS (adjusted hazard ratio (aHR) = 0.870, 95% confidence interval (CI) = 0.400–1.897, p = 0.73) and RFA was associated with shorter RFS (aHR = 1.562, 95% CI = 1.099–2.219, p = 0.01) after employing IPTW. Antiviral treatment was independently associated with longer OS (aHR = 0.444, 95% CI = 0.251–0.786, p = 0.01) as well as RFS (aHR = 0.544, 95% CI = 0.391–0.757, p < 0.01) in the hospital cohort. In the nationwide cohort, there was no difference in OS (aHR = 0.981, 95% CI = 0.661–1.456, p = 0.92) between the two treatment groups when adjusted for antiviral treatment, which was a negative independent risk factor for mortality (aHR = 0.655, 95% CI = 0.451–0.952, p = 0.03) after IPTW. Among patients treated with tenofovir (n = 96) or entecavir (n = 184) in the hospital cohort, there was no difference in either OS (aHR = 0.522, 95% CI = 0.058–4.724, p = 0.56) or RFS (aHR = 1.116, 95% CI = 0.738–1.688, p = 0.60). The overall incidence of complications was higher in the resection group (26.3%) than in the RFA group (13.9%) (p < 0.01). RFA may provide comparable OS to resection in the treatment of very early or early HCC with a lower rate of complications, although RFS is marginally shorter than in the resection group after adjusting for antiviral treatment. Regardless of the type of NA, antiviral treatment in patients with HBV-related HCC is strongly associated with both OS and RFS.

Highlights

  • Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality globally, with more than 850,000 patients newly diagnosed each year [1]

  • Among a total of 761 patients in the hospital cohort, 567 (74.5%) patients were treated with surgical resection and 194 (25.5%) patients were treated with radiofrequency ablation (RFA)

  • The two groups differed in many baseline characteristics, including age, Child–Pugh score, BCLC stage, tumor size, cirrhosis, hepatitis B virus (HBV) e antigen (HBeAg) positivity, platelets, total bilirubin, albumin, and prothrombin time

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality globally, with more than 850,000 patients newly diagnosed each year [1]. The use of local therapy, such as radiofrequency ablation (RFA) for early HCC with curative intent, has been growing, with several studies showing that RFA has therapeutic effectiveness compared to that of surgical resection in these patients [3,4,5,6]. In an RCT comparing surgical resection and RFA to treat HCC with a diameter of less than 4 cm and up to two nodules, there was no difference in either OS or RFS [10]. Another RCT performed in patients with HCC satisfying the Milan criteria showed that surgical resection provided better OS as well as RFS than RFA [8]. The number of patients enrolled in those trials was insufficient

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