Surgical resection for hepatocellular carcinoma (HCC), one of the forms of liver cancer, is typically reserved only for those patients with single tumors without vascular invasion, but new research from a retrospective study by investigators at the Johns Hopkins shows that neoadjuvant immunotherapy could allow high-risk HCC patients, including those who currently fall outside standard surgery criteria, to undergo margin-negative resection. These findings, published recently in the journal Cancer Research Communications, noted that these patients can achieve comparable positive long-term outcomes and highlight the need for prospective studies on the possible benefits of neoadjuvant therapy in HCC.
“There’s a strong unmet need to expand the number of patients who may be eligible for surgery and, further, to transform more patients with early-stage liver cancer into long-term survivors of this disease,” said the study’s first author Mari Nakazawa, MD, a clinical research fellow at the Johns Hopkins Kimmel Cancer Center.
Immunotherapy has become a common treatment for patients with metastatic liver cancer, but the main method of treating HCC remains tumor resection. Unfortunately, only about 30% of patients are eligible for surgery due to safety concerns related to the size of the tumor, proximity to critical structures and the presence of multiple tumor sites. The current study, by Nakazawa and colleague Mark Yarchoan, MD, an associated professor of oncology and senior author, sprang from the knowledge that neoadjuvant immunotherapy has shown positive results for other forms of cancer.
For this research, Nakazawa, Yarchoan, and team conducted a retrospective study of 92 patients who underwent surgical resection for HCC at Johns Hopkins between 2017 and 2023. Among this group were 36 patients who had received a neoadjuvant immune checkpoint inhibitor (ICI). Many of the patients given ICI therapy were treated under clinical protocols to assess the feasibility of providing an immunotherapy prior to surgery. Of those in that group, more than 60% would not have met surgical resection criteria based on their physiology.
Compared with patients who qualified and received surgery as a first-line therapy, patients who received the ICIs more commonly showed high-risk disease features including high serum alpha fetoproteins, tumors larger than 5 cm, portal vein invasion, and multiple tumor foci. All of these features have previously been associated with worse outcomes than patients who undergo tumor resection.
Yet, the ICI patients in this study had comparable outcomes to the patients who received upfront surgery. Among the neoadjuvant immunotherapy patients, 94.4% had successful margin-negative resection with a median recurrence-free survival (RFS) of 44.8 months, just five months shorter than the RFS of those who received upfront surgery.
The authors said that limitations of the study were the relatively small cohort size, the fact it was retrospective, and that it was based on patient data from a single center, Johns Hopkins.
“Despite these limitations, this is the largest retrospective cohort to report on the outcomes of neoadjuvant ICI–treated and untreated patients in a rapidly evolving landscape of ICI-based treatments available in HCC,” the investigators stated.
They also noted that prior studies have examined the feasibility of resection on patients with large tumor sizes, multinodular disease, and with major vascular invasion, as a means of expanding the pool of HCC patients eligible for resection, but these showed poor outcomes.
Their study seems to have moved the needle: “Our observation that RFS was comparable in the ICI-treated and untreated cohorts provides initial evidence that neoadjuvant ICI–based therapy may be effective in transforming the natural histories of these patients postresection to that of one comparable with those who received upfront surgery for lower-risk HCC,” the researchers wrote.
The findings of this retrospective analysis now point the way for future prospective trials that can further define the role and parameters of neoadjuvant therapy with ICIs for patients with both resectable tumors, as defined under current guidelines, and those with high-risk, localized HCC.
