A Chance for Disease-Free Survival: Fudan Team’s Findings Published in The Lancet

Hepatocellular carcinoma (hereinafter referred to as "liver cancer") is a malignant tumor that seriously threatens the health of people in China. Most liver cancer patients are already in the intermediate and advanced stages when diagnosed and lose the chance of radical cure, resulting in a poor prognosis. Clinically, some patients with advanced liver cancer can have a chance of surgical resection after their tumors shrink or downstage after receiving systemic treatment. However, whether such patients should undergo surgical resection or continue medical treatment is a decision-making dilemma faced by clinicians, patients, and families. Surgery can remove remaining drug-resistant tumor cells, thereby providing patients with the opportunity for radical treatment; however, systemic treatment needs to be suspended before and after surgery, which may cause the tumor to lose control; surgical resection can also cause trauma to the patient. Whether surgical resection is superior to continuous systemic treatment requires high-level evidence-based medical research evidence.

On August 22, Beijing time, an investigator-initiated, nationwide multicenter Phase III randomized controlled study led by Academician Fan Jia’s team at Zhongshan Hospital, Fudan University, together with 24 major hepatobiliary cancer centers in China, was published online in The Lancet. Patients with locally advanced liver cancer and vascular tumor thrombus received four cycles of atezolizumab plus bevacizumab. Those whose imaging showed no tumor progression and whose tumors could be resected were then randomized: Group A underwent surgical resection followed by one year of atezolizumab and bevacizumab, while Group B continued systemic treatment. A total of 489 patients received systemic treatment in the study, of whom 201 were randomized. Compared with continued drug treatment alone, surgery followed by continued drug treatment significantly improved time to treatment failure. Preliminary survival analysis showed a trend toward better survival in Group A than in Group B (HR=0.67). However, surgery also increased adverse reactions: grade 3–4 treatment-related adverse events occurred in 39% and 21% of patients in the two groups, respectively.

Article published online (web version)

The results of this study suggest that surgical resection for patients with advanced liver cancer who have responded to treatment may provide patients with a chance of disease-free survival. This study potentially changes liver cancer clinical practice both in China and abroad. Patients with advanced liver cancer who receive systemic treatment must undergo regular imaging examinations to evaluate the efficacy of treatment. It is also necessary to undergo evaluation by a multidisciplinary team to evaluate whether surgical resection is possible and the benefit of resection.

Comments from the same period (from Professor Alejandro Forner, Spain)

The magazine invited Spanish liver disease research expert Professor Alejandro Forner to comment on this study at the same time. He said: "This study is the first multi-center, randomized, phase III trial to evaluate whether surgical resection can benefit patients with advanced liver cancer who have responded to systemic treatment. The results suggest that resection of the tumor and its macroscopic vascular tumor thrombus may help prevent systemic dissemination, thereby converting short-term systemic disease control into long-term disease remission."

In the field of conversion therapy for liver cancer, Academician Fan Jia, Academician Zhou Jian and Professor Sun Huichuan from Zhongshan Hospital and Fudan University have continued to conduct a number of retrospective and prospective studies. Previously, the team has led domestic experts in the field of hepatobiliary tumors to formulate two versions of the Chinese expert consensus in the field of conversion therapy for liver cancer (2021 and 2024 versions). There are currently a number of conversion therapy studies being carried out in order to give more patients with intermediate and advanced liver cancer the chance of surgical resection and disease-free survival.

Academician Fan Jia of Zhongshan Hospital, Fudan University is the corresponding author of this article; Professor Sun Huichuan and Deputy Chief Physician Zhu Xiaodong of Zhongshan Hospital, Fudan University, and Professor Shen Feng of the Third Affiliated Hospital of Naval Medical University are the co-first authors of this article.

Paper address: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)01252-3/fulltext