A multicenter clinical trial in China has demonstrated that surgical resection can significantly improve treatment outcomes for patients with advanced-stage liver cancer who respond to systemic therapies. The findings, published Saturday in The Lancet, offer new evidence supporting surgery following systemic treatment in select hepatocellular carcinoma cases.
The study was led by Zhongshan Hospital, affiliated with Fudan University in Shanghai, and involved 24 hepatobiliary tumor centers across the country. It focused on patients with advanced hepatocellular carcinoma characterized by macrovascular invasion but no metastasis beyond the liver. Traditionally, most liver cancer patients in China are diagnosed at intermediate or advanced stages, often precluding surgical options and resulting in poor prognosis.
In recent years, advances in systemic therapies such as immunotherapy and targeted agents—including the combination of atezolizumab and bevacizumab—have extended median survival for advanced liver cancer patients from about one year to nearly two years. However, the overall prognosis remains unsatisfactory, and it is unclear whether surgery offers additional benefit once a patient responds to systemic treatment.
To investigate this, researchers conducted a randomized, open-label phase 3 trial enrolling 489 treatment-naive hepatocellular carcinoma patients between April 2021 and July 2024. Following four cycles of induction systemic therapy, 201 patients achieved sufficient tumor shrinkage or downstaging to be eligible for surgery. These patients were randomly assigned to either a surgery group, which underwent surgical resection followed by one year of sequential atezolizumab and bevacizumab, or a maintenance therapy group that continued systemic treatment without surgery.
After a median follow-up of more than 18 months, the study found that patients who underwent surgical resection combined with systemic therapy experienced a nearly twofold extension in time to treatment failure, reaching 20.4 months on average. Preliminary survival analyses also suggest a trend toward improved overall survival in the surgery group, although follow-up is ongoing.
“This study rigorously confirms that about 40 percent of patients with advanced liver cancer can become candidates for surgery following systemic therapy,” said Sun Huichuan, first author and professor at Zhongshan Hospital. “Those patients derive greater benefits from surgery compared to maintenance therapy alone and may achieve tumor-free survival.”
The trial’s corresponding author, Fan Jia, an academician of the Chinese Academy of Sciences and honorary hospital president, noted the clinical dilemma the study sought to address: balancing the benefits of removing residual tumor cells through surgery against the risks of interrupting systemic treatment and surgical recovery.
Experts from abroad have acknowledged the study’s implications. Spanish professor Alejandro Forner highlighted that resecting both the tumor and visible vascular emboli may prevent further systemic spread, potentially transforming temporary disease control into longer-term remission. He also emphasized the study’s potential to inform treatment approaches for other advanced cancers such as cholangiocarcinoma, pancreatic, lung, and gastrointestinal tumors.
As systemic therapies continue to improve, this trial provides important evidence supporting surgical resection for select patients with advanced liver cancer, potentially expanding curative options beyond standard systemic strategies.