Hepatocellular carcinoma is the most common type of primary liver cancer, accounting for about 80% of all primary liver cancers in the United States, and is currently the sixth most common cancer and the fourth most common cause of cancer-related deaths. Although immunotherapy is now a mainstay for the treatment of advanced liver cancer, the primary curative treatment protocol for patients with early-stage disease is surgery alone. However, only approximately 30% of patients with the cancer are eligible for resection by current Western guidelines due to the presence of extrahepatic and vascular extension, poor hepatic reserve, and/or anatomical considerations (including multinodular disease) that preclude adequate resection margins. Even in patients who undergo curative-intent resection, the vast majority will experience cancer recurrence within 5 years of surgery.
Results from a retrospective study found that neoadjuvant immunotherapy may allow patients with high-risk localized liver cancer—including those who would not have been eligible for surgery by standard resection criteria—to successfully undergo margin-negative resection and achieve comparable long-term clinical outcomes compared to patients who received upfront resection. Prospective trials are needed to further define the role of neoadjuvant immune checkpoint inhibitor therapy in both traditionally resectable and high-risk localized hepatocellular carcinoma, concluded the study authors.
The study by Nakazawa et al was published in Cancer Research Communications.
Study Methodology
The researchers retrospectively examined the outcomes of 92 patients who had undergone liver resection at The Johns Hopkins Hospital between January 2017 and December 2023. Thirty-six of the patients had undergone immune checkpoint inhibitor–based treatment, many of whom were treated under clinical trial protocols assessing the feasibility and efficacy of immunotherapy prior to surgery. Prior to the receipt of immunotherapy, 61% of these patients would not have been candidates for curative surgery based on traditional surgical resection criteria.
The overall patient cohort was mostly male (69%) and White (57.6%), with preserved liver function (98.9%).
Results
Compared with patients who received surgery upfront, patients who received neoadjuvant immune checkpoint inhibitors more commonly exhibited high-risk disease features, including high serum alpha fetoprotein, tumors larger than 5 cm (P = .001), portal vein invasion (P = .001), and multifocality (P < .001). Patients who received neoadjuvant immunotherapy had similar rates of margin-negative resection (P = .47) and recurrence-free survival as those who underwent upfront surgical resection (median recurrence-free survival = 44.8 months compared to 49.3 months, respectively; P = .66). There was a nonsignificant trend toward superior recurrence-free survival in the subset of patients with a pathologic response (tumor necrosis ³ 70%) with neoadjuvant immunotherapy.
“Neoadjuvant immune checkpoint inhibitor–based therapy may allow high-risk patients, including those who are outside traditional resectability criteria, to achieve comparable clinical outcomes to those who undergo upfront resection,” concluded the study authors.
Clinical Significance
“This study shows that the criteria by which we classify patients as being candidates for curative therapy is too narrow for this disease,” said senior study author Mark Yarchoan, MD, Associate Professor of Oncology at the Johns Hopkins Medicine Sidney Kimmel Comprehensive Cancer Center, in a statement. “Our findings demonstrate that systemic therapy may not only be useful for patients with advanced disease but can potentially be paradigm-changing in patients with early-stage disease. There is a group of patients with high-risk liver cancer who, in a contemporary era, may have long-term survival through aggressive treatment with systemic therapy followed by surgery.”
Disclosure: Funding for this study was provided by the National Institutes of Health, the Lou and Nancy Grasmick Fellowship, the Linda Rubin Pancreatic Cancer Fellowship, and the James and Frances McGlothin Fellows to Faculty Award. For full disclosures of the study authors, visit aacrjournals.org/cancerrescommun.
