Neoadjuvant immunotherapy is emerging as a promising strategy to improve outcomes for patients with locally advanced liver cancer, specifically hepatocellular carcinoma. A recent study published in Cancer Research Communications, along with ongoing clinical trials, suggests that administering immunotherapy before surgery can shrink tumors, increase the likelihood of successful resection, and potentially reduce the risk of recurrence.
The Rationale Behind Neoadjuvant Immunotherapy
According to Mark Yarchoan, MD, an associate professor of oncology at the Johns Hopkins Kimmel Cancer Center, locally advanced liver cancers may be deemed unresectable due to multiple localized tumors, invasion into veins or arteries, or large tumor size. Neoadjuvant immunotherapy offers the potential to shrink these tumors, making them safer to remove.
Furthermore, studies indicate that administering immunotherapy while the tumor is still intact allows the immune system to generate a more robust response against a broader range of antigens. This heightened immune response may target micrometastases, reducing the likelihood of cancer recurrence after surgery.
Mari Nakazawa, MD, a clinical research fellow at Johns Hopkins Kimmel Cancer Center, emphasized the unmet need to expand surgical eligibility and improve long-term survival rates for liver cancer patients.
Impact on Long-Term Survival
Yarchoan, Nakazawa, and their colleagues conducted a study involving 92 patients who underwent curative resection for hepatocellular carcinoma at Johns Hopkins. Among them, 46 patients received neoadjuvant immune checkpoint inhibitors (ICIs), primarily within clinical trials. Notably, 61.1% of these patients would have been ineligible for curative resection based on standard criteria at the time of intake.
The study revealed that 94.4% of patients treated with neoadjuvant ICIs underwent successful resection with negative margins, which Yarchoan highlighted as particularly impressive given the initial ineligibility for surgery in most cases. However, the study also found that patients who received neoadjuvant ICIs had comparable recurrence-free survival compared to those who underwent upfront surgery. The median recurrence-free survival was 44.8 months for the neoadjuvant ICI group and 49.3 months for the upfront surgery group.
Study Limitations and Future Directions
Yarchoan and Nakazawa acknowledged that the study's findings are retrospective, derived from a single institution, and based on data from various clinical trials and standard-of-care treatments. They emphasized the need for further prospective trials to validate these results and identify the patients who would benefit most from this approach. Nakazawa stated that "Prospective trials that are thoughtfully designed in the right populations can help us understand which patients can benefit most from this approach."
Despite these limitations, the study suggests that current criteria for determining candidacy for curative therapy in liver cancer may be too restrictive. Systemic therapy, such as neoadjuvant immunotherapy, could potentially transform the treatment paradigm for patients with early-stage disease.
