Upfront Surgical Resection Versus Neoadjuvant Chemotherapy for HCC

While hepatocellular carcinoma (HCC) accounts for 80% of all primary liver cancers, only about 30% of patients are eligible for surgical resection due to favorable tumor features and anatomy.

Previous research has shown that the use of neoadjuvant chemotherapy may provide response rates of 20 to 33% in patients who were initially poor candidates for upfront resection, but it is unknown if this can improve the long-term survival outcomes of HCC.

A recent study by Mari Nakazawa, MD, and colleagues has compared the outcomes of patients with HCC who underwent upfront surgical resection with those who received neoadjuvant immunotherapy before the procedure.

Researchers retrospectively identified 95 patients with HCC who underwent liver resection between January 2017 and December 2023. Patient characteristics, demographics, and clinical features were reviewed prior to initiation of neoadjuvant immune checkpoint inhibitor (ICI)-based therapy or surgery.

The primary clinical endpoints included recurrence-free survival (RFS) – defined as time from curative-intent hepatectomy to radiographic disease recurrence or death due to any cause – and overall survival.

Of a total of 92 patients in the final clinical cohort, 36 underwent neoadjuvant ICI-based treatment. Most patients (61.1%) who received this therapy were more likely to have features known to be linked to disease recurrence, including α-fetoprotein ≥ 400 ng/mL (P=.02), tumor diameter ≥ 5 cm (P=.001), portal vein invasion (P<.001), and multifocality (P<.001).

Most patients who received neoadjuvant ICI were treated with anti-PD1-based therapy, either as monotherapy (27.8%), in combination with tyrosine kinase inhibitors (36.1%), or in combination with anti-LAG3 (16.7%).

Treatment with neoadjuvant immunotherapy and upfront surgical resection had similar rates of margin-negative resection (P=.47) and RFS (median RFS 44.8 months vs 49.3 months, respectively, log-rank P=.66).

There was a nonsignificant trend toward superior RFS in patients who had a pathologic response (tumor necrosis ≥ 70%) with neoadjuvant immunotherapy.

The use of neoadjuvant ICI-based therapy before surgical resection may allow high-risk patients, including those who are outside traditional resectability criteria, to achieve similar clinical outcomes to those who undergo upfront resection.