A dual-action approach to preventing hepatocellular carcinoma

Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide, largely due to its high rate of recurrence after surgery. Even after complete tumor removal, microscopic residual disease and early dissemination frequently lead to relapse within the first two years.

Postoperative transarterial chemoembolization is commonly used to reduce this risk, but its benefit is often limited in patients with aggressive tumor characteristics. At the same time, targeted systemic therapies have shown strong antitumor activity in advanced disease but remain underexplored in postoperative settings. Because of these challenges, more effective postoperative combination strategies are urgently needed.

Reporting (DOI: 10.1016/j.hbpd.2025.03.001) on March 26, 2025, in Hepatobiliary & Pancreatic Diseases International, researchers led by Huashan Hospital of Fudan University, together with teams from Mengchao Hepatobiliary Hospital of Fujian Medical University, Ningbo Medical Center Lihuili Hospital of Ningbo University, and several other major hepatobiliary centers in China, found that adding lenvatinib to postoperative transarterial chemoembolization significantly prolonged disease-free survival in hepatocellular carcinoma patients at high risk of recurrence.

The prospective multicenter cohort study assessed whether combining systemic targeted therapy with standard postoperative care could better prevent relapse after curative surgery, and demonstrated a clear advantage over transarterial chemoembolization alone.

The study included 297 patients who underwent complete surgical resection for hepatocellular carcinoma and were classified as high risk for postoperative recurrence based on clinical and pathological features. Participants received either postoperative transarterial chemoembolization alone or the same procedure combined with lenvatinib.

Patients treated with the combination therapy achieved a substantially longer median disease-free survival than those receiving standard treatment. This benefit remained consistent after multiple statistical adjustments designed to reduce baseline bias, strengthening the reliability of the findings. Subgroup analyses further showed that the benefit extended across several high-risk categories, including patients with vascular invasion and extensive microvascular involvement.

Safety outcomes were acceptable. Most treatment-related adverse events were mild to moderate and manageable through dose modification or supportive care. Severe adverse events occurred in a minority of patients and were consistent with the known safety profile of lenvatinib. Overall, the results demonstrate that integrating targeted systemic therapy into postoperative management can meaningfully delay recurrence without introducing unexpected toxicity.

"Preventing recurrence after surgery remains one of the biggest challenges in liver cancer treatment," said an expert in hepatobiliary oncology not involved in the study. "This research shows that combining systemic targeted therapy with locoregional treatment can deliver a tangible clinical benefit for patients at the highest risk. The strategy is biologically sound and feasible in routine practice. While randomized trials are still required, these findings provide strong real-world evidence to inform postoperative treatment decisions."

The findings support a more proactive, risk-adapted approach to postoperative management in hepatocellular carcinoma. For patients with a high likelihood of recurrence, combining systemic targeted therapy with transarterial chemoembolization may represent a new strategy to extend recurrence-free survival after surgery.

If confirmed in randomized trials, this approach could shift postoperative care from passive surveillance to active recurrence prevention. More broadly, the study highlights the growing importance of combination adjuvant therapies in oncology, emphasizing that durable postoperative disease control may require coordinated local and systemic intervention.