A pioneering Chinese study has established that surgical resection can offer additional survival benefit in patients with advanced-stage liver cancer who respond to systemic therapy.

The study, published on Saturday in the journal The Lancet, focused on addressing the question of whether patients with advanced-stage liver cancer, or hepatocellular carcinoma, should undergo surgical resection after systemic therapy or continue with the therapy.

Led by Zhongshan Hospital, affiliated with Fudan University in Shanghai, the trial involved 24 hepatobiliary tumor centers across China. With high-quality evidence supporting the procedure, the findings suggested that surgical resection — removal of part of the organ — in patients with advanced liver cancer who respond to systemic therapy can greatly extend their time to treatment failure, and may offer them the opportunity for tumor-free survival.

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Liver cancer poses a serious threat to the health of many Chinese people. Most liver cancer patients are found in the intermediate or advanced stages at the time of diagnosis, having lost the opportunity for resection and curative treatment, which often results in a poor prognosis.

In recent years, with continuous advances in systemic therapies, such as immunotherapy and targeted therapies represented by the combination of atezolizumab and bevacizumab, the median survival of patients with advanced liver cancer has increased from about one year to nearly two years. But the overall therapeutic efficacy still remains unsatisfactory.

Clinically, some patients with advanced liver cancer see tumor shrinkage or tumor downstaging after systemic therapy, making them eligible for surgical resection. However, whether such patients should undergo surgery or maintain the therapy presents a difficult decision for clinicians, patients and their families.

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Although surgery can remove residual drug-resistant tumor cells to offer patients the opportunity for curative treatment, patients are usually left with surgical incisions that are challenging to recover from. Additionally, systemic therapy has to be suspended before and after surgery, which may also lead to loss of tumor control. Thus, whether surgical resection is superior to continued systemic therapy requires evidence from high-level evidence-based medical studies.

To address this question, Fan Jia, an academician with the Chinese Academy of Sciences and honorary president of the hospital, led a team to start the randomized, open-label, multicenter, phase 3 trial about seven years ago.

Between April 2021 and July 2024, the team enrolled 489 treatment-naive patients with hepatocellular carcinoma, macrovascular invasion and no extrahepatic metastasis from 24 hospitals across China. They were first treated in the induction phase with systemic therapies for four cycles, and 201 of them entered the next stage.

They were later randomly assigned to two groups. Patients in the surgery group underwent surgical resection followed by one year of sequential treatment with atezolizumab and bevacizumab, while those in the other group received maintenance therapy.

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After a median follow-up of over 18 months, the team found that the combination of resection and systemic therapy can significantly extend patients' time to treatment failure, with a nearly twofold increase to 20.4 months. Survival follow-up for this study is ongoing, and preliminary survival analyses indicate that survival in the surgery group also shows a trend toward superiority over the maintenance therapy group.

"The results indicate the success of our study," said Sun Huichuan, a first author of the article and professor at the hospital.

"We have rigorously demonstrated that about 40 percent of patients with advanced liver cancer can meet the criteria for surgery following systemic therapy. Patients in the surgical resection group derive greater benefits than those in the maintenance therapy group, and have the opportunity for curative surgical resection."

In a commentary on this article in the same issue, Spanish professor Alejandro Forner spoke highly of the team's work. He noted that the study suggested that resection of the tumor and its visible vascular emboli may help prevent systemic dissemination, thereby transforming temporary systemic disease control into long-term disease remission.

"Resection is agreed to be the best way to treat liver cancer. Clinical solutions for its treatment have been advancing step by step, bringing new opportunities to patients in the advanced stage.

"Despite interpatient heterogeneity, the study is expected to provide new insights into the treatment of overseas patients with advanced liver cancer. It can also inspire the treatment of other tumors such as cholangiocarcinoma, pancreatic cancer, lung cancer, gastrointestinal tumors and more," said Fan, corresponding author of the article.

Contact the writer at wangxin2@chinadaily.com.cn