Neoadjuvant ICI May Expand Surgical Options for HCC

Neoadjuvant immune checkpoint inhibitor (ICI) therapy may enable patients with high-risk hepatocellular carcinoma (HCC) to achieve outcomes similar to those undergoing upfront surgery. | Image Credit: Peakstock - stock.adobe.com

Administering immune checkpoint inhibitors (ICI) before surgery may allow patients with advanced hepatocellular carcinoma (HCC) who would normally not qualify for surgery to experience treatment outcomes similar to patients who undergo immediate surgical removal of the tumor, according to a recent study published in Cancer Research Communications.¹

Around 80% of all primary liver cancers are classified as HCC, and it is currently the fifth leading cause of cancer mortality in the US. The cancer growth begins slowly, often without symptoms from the tumor in the early stages.² As HCC progresses throughout the body, symptoms can include an enlarged liver or spleen, signs of jaundice, swollen stomach, loss of appetite, nausea, itching, and unexplained weight loss.

Tumor removal is often part of the treatment process, and in some cases, a liver transplant can be beneficial for patients in earlier stages of HCC. However, it is common for patients to not learn about the condition until it has advanced and spread, leading to liver failure.

Only about 30% of patients diagnosed with HCC are deemed suitable candidates for surgical removal of the liver (hepatectomy) under current Western guidelines.¹ This is often due to factors such as the spread of cancer beyond the liver, poor liver function, or complex tumor location that prevents complete removal without sacrificing healthy tissue. Surgical options for HCC include partial liver resection, where a portion of the liver is removed and eventually regrows, and liver transplantation, which involves complete removal of the diseased liver.³

Treatment given before and after surgery, known as perioperative systemic therapy, is being actively studied to reduce microscopic cancer spread and improve outcomes for patients with HCC.¹

In recent years, immunotherapy combinations have demonstrated improved outcomes for patients with high-risk HCC who undergo curative-intent surgery or ablation, proved through longer periods without disease recurrence. However, more time is needed to determine the overall survival impact of these treatments.

Methods

The retrospective study compared patients with HCC receiving neoadjuvant ICI therapy vs those undergoing immediate surgery. Researchers hypothesized that patients who received neoadjuvant ICI had more aggressive tumors but could potentially achieve similar survival rates.

Patients were required to have undergone a liver resection at the Johns Hopkins Hospital between January 1, 2017, through December 1, 2023.

Results

Overall, the clinical cohort included a total of 92 patients, 36 of whom received neoadjuvant ICI-based treatment. Both the neoadjuvant ICI and upfront surgery cohorts had a median age range in the 60s; the former cohort included more patients who identified as White (69.4% vs 50%) and male (58.3% vs 76.8%, respectively).

More than half of the patient population (61.1%) received neoadjuvant ICI–based therapy and were outside of standard resectability criteria. Furthermore, this patient group was more likely to exhibit risk factors for cancer recurrence, such as elevated α-fetoprotein levels (≥400 ng/mL; P = .02), larger tumor size (≥5 cm; P = .001), portal vein invasion (P < .001), and multifocality (P < .001).

Similar rates of margin-negative resection (P = .47) and recurrence-free survival (RFS) were identified among patients who received neoadjuvant immunotherapy and those who underwent upfront surgical resection (median RFS, 44.8 vs 49.3 months, respectively; log-rank P = .66).

The results found an insignificant trend toward superior RFS in the subset of patients with a pathologic response (tumor necrosis ≥ 70%) with neoadjuvant immunotherapy.

Limitations

Several factors limit the interpretation of these findings. The study comparison between low-risk surgery and high-risk neoadjuvant therapy may have masked potential treatment differences. Additionally, the disproportionate number of Black patients in the surgery group could influence outcomes.

Determining the true impact of neoadjuvant ICI therapy is challenging due to the lack of a comparable high-risk surgery group, a standard practice in HCC management. This study focused solely on patients who underwent resection and may not represent the overall experience of patients receiving neoadjuvant ICI. Moreover, the results might not be generalizable to other institutions due to variations in patient populations and treatment protocols.

“Our observations highlight the need for future prospective trials to further defined the role of neoadjuvant ICI therapy in both traditionally resectable and high-risk localized HCC populations,” the study authors concluded.

References

1. Nakazawa M, Fang M, Vong T, et al. Impact of neoadjuvant immunotherapy on recurrence-free survival in patients with high-risk localized HCC. Cancer Res Commun. 2024;1-10. doi:10.1158/2767-9764.CRC-24-0151

2. Hepatocellular carcinoma (HCC). Cleveland Clinic. February 13, 2024. Accessed August 14, 2024. https://my.clevelandclinic.org/health/diseases/21709-hepatocellular-carcinoma-hcc

3. Hepatectomy (liver resection). Cleveland Clinic. April 29, 2022. Accessed August 14, 2024. https://my.clevelandclinic.org/health/treatments/22930-hepatectomy-liver-resection