Surgery More Effective Than Continued Drug Therapy for Advanced Liver Cancer Responding to Treatment

A large clinical trial found that even in patients with advanced liver cancer, removing the tumor surgically after it shrinks in response to combination targeted and immunotherapy provides longer-lasting treatment benefits than continuing drug therapy.

Surgery can eliminate residual drug-resistant cancer cells and offer a chance for curative treatment, but evidence has been lacking on which option is better because drug therapy must be stopped before and after surgery and the procedure itself carries a burden.

Results from an investigator-initiated phase 3 randomized controlled trial conducted by an academician Fan Jia’s team at Zhongshan Hospital, Fudan University, in collaboration with 24 major hepatobiliary tumor centers in China, were published Aug. 22 local time in the international journal The Lancet.

The researchers administered four cycles of atezolizumab plus bevacizumab to patients with locally advanced liver cancer accompanied by vascular invasion, then divided 201 patients whose tumors had not progressed on imaging and were resectable into two groups.

One group underwent surgical tumor resection followed by continued atezolizumab and bevacizumab treatment for 1 year, while the other continued drug therapy. A total of 489 patients received the combination therapy, of whom 201 were randomly assigned.

The group that continued drug therapy after surgery had a significantly longer “time to treatment failure” than the group that continued drug therapy alone. In the initial survival analysis, the surgery group also showed a tendency toward longer survival (hazard ratio, 0.67).

However, adverse events were more common in the surgery group. The incidence of grade 3-4 treatment-related adverse events was 39% in the surgery group, compared with 21% in the continued drug therapy group.

The researchers concluded that surgical resection in patients with advanced liver cancer who respond to treatment may provide an opportunity for tumor-free survival. This is the first multicenter, randomized phase 3 trial to evaluate whether surgery benefits patients with advanced liver cancer.

In a commentary published alongside the study in The Lancet, Spanish liver disease expert Alejandro Forner said, “Resecting the tumor and macroscopically visible vascular invasion could help prevent systemic spread and convert temporary systemic disease control into long-term disease remission.”

Based on these findings, the researchers proposed that patients with advanced liver cancer should undergo regular imaging to assess treatment response while also having a multidisciplinary team evaluate surgical feasibility and the potential benefits of resection.

Fan Jia is the corresponding author of the paper. Professor Sun Huichuan of Zhongshan Hospital, deputy chief physician Zhu Xiaodong, and Professor Shen Feng of the Third Affiliated Hospital of Naval Medical University are co-first authors.