The era of targeted immunotherapy has revolutionized liver cancer treatment, offering unprecedented therapeutic efficacy. Comprehensive approaches are emerging to enhance patient outcomes, prompting a reevaluation of traditional surgical concepts for liver cancer.

At the 2024 Chinese Congress of Holistic Integrative Oncology (CCHIO), Dr. Haitao Zhao from Peking Union Medical College Hospital led a discussion on the topic: “In the Era of Targeted Immunotherapy, Does Palliative Surgery for Responding Liver Cancer Patients Improve Survival Outcomes?” Following his presentation, Oncology Frontier conducted an exclusive interview to delve deeper into this critical subject.

Oncology Frontier: Your presentation at this conference focused on “Palliative Surgery for Responding Liver Cancer Patients in the Era of Targeted Immunotherapy.” Could you share the background and rationale for raising this issue?

Dr. Haitao Zhao: Liver cancer treatment has entered a transformative phase. Reflecting on the decade preceding five years ago, the only available option was targeted therapy, which offered limited efficacy. Consequently, surgery dominated liver cancer treatment during that era, with targeted drugs considered secondary options for inoperable cases.

However, the past five years, and especially the last three, have witnessed groundbreaking advancements. First-line immunotherapy combinations, such as atezolizumab + bevacizumab (T+A), sintilimab + bevacizumab (Double-Da), and camrelizumab + apatinib (Double-Ai), alongside innovative combinations like LEAP-012 (targeted therapy with localized treatments), have dramatically improved treatment efficacy. These advances have raised objective response rates (ORR) to as high as 70%, with tumor shrinkage achieved in 20–40% of patients even under typical conditions.

Drawing from experiences in treating metastatic cancers such as colorectal, cervical, and ovarian cancers, we’ve observed that palliative surgery (or cytoreductive surgery) in conjunction with effective drug therapies can significantly benefit patients. This insight led us to reconsider its application in liver cancer, especially for patients responding to immunotherapy but with residual metastases.

For these patients, a treatment plateau often ensues, where without further intervention, tumor resistance may develop. We hypothesized that removing primary drug-resistant tumors during this critical window could extend survival, similar to strategies in other cancers. Following surgery, systemic therapy could target remaining metastases, potentially achieving long-term tumor-free survival. This shift is facilitated by improvements in minimally invasive surgical techniques, which now impose impacts comparable to other local treatments while avoiding the trauma and systemic disruption of traditional open surgery.

Our clinical data supports this approach. Recent findings, which we are in the process of publishing, demonstrate that cytoreductive surgery during the bottleneck phase improves 18- and 24-month survival rates compared to immunotherapy or combined local therapy alone. These findings inspired our discussion topic at this conference, as we aim to identify which patients benefit most and refine optimal strategies for implementation.

Oncology Frontier: Palliative treatment is often equated with end-of-life care. How has the concept of palliative treatment evolved in the era of targeted immunotherapy, particularly for liver cancer?

Dr. Haitao Zhao: Palliative treatment traditionally referred to managing symptoms and improving quality of life when curative options were unavailable. It formed part of supportive care, focusing on comfort rather than cure or survival extension.

Today, with advances in medical science, our approach to these patients has shifted significantly. We now lean towards proactive strategies that include interventions like surgery. Rather than labeling such interventions as “palliative surgeries,” we refer to them as cytoreductive surgeries aimed at removing disease burden and optimizing subsequent treatments, with the ultimate goal of prolonging survival and, in some cases, achieving cure.

Looking ahead, the field of palliative care will likely bifurcate into distinct pathways. One group will remain within traditional supportive care frameworks, focusing on symptom management. Meanwhile, a growing number of patients may undergo interventions like cytoreductive surgery, falling into a category of active treatment aimed at survival extension and cure. The term “palliative surgery” may eventually give way to “cytoreductive surgery,” better reflecting its intent and goals.

In contrast, palliative treatment may revert to its original definition, focusing on patients who have exhausted all active treatment options due to poor physical condition or declining health after multiple therapy lines. In these cases, supportive care remains critical for maintaining quality of life.

Oncology Frontier: With targeted immunotherapy poised to dominate the future of liver cancer treatment, could you share your team’s ongoing explorations in this field and your key areas of focus for the future?

Dr. Haitao Zhao: As a multidisciplinary team (MDT) with a strong surgical focus, we have continuously explored and innovated within the realm of targeted immunotherapy. We pioneered the “Immunotherapy 3.0” model, emphasizing multidimensional comprehensive treatment. This strategy integrates PD-1/PD-L1 inhibitors as systemic therapy with localized treatments, significantly boosting overall ORR.

However, it’s important to note that increasing ORR doesn’t necessarily translate to prolonged overall survival (OS). Hence, during tumor shrinkage phases, we incorporate additional modalities like radiation, radiofrequency ablation, or surgery to push patients toward a No Evidence of Disease (NED) status. Clearing the primary tumor enhances immunotherapy’s ability to manage residual micro-metastases, especially in patients responding well to immunotherapy. These efforts have allowed us to sustain NED in many patients over the long term.

Our current priorities are twofold:

1. Expanding systemic and local treatment combinations, including new modalities to maintain and enhance NED status.
2. Overcoming resistance to targeted immunotherapy, exploring novel agents and cellular therapies to address this challenge.

Our ultimate goal remains the same: to help patients achieve and sustain NED while overcoming resistance throughout their treatment journey.

Dr. Haitao Zhao

• Administrative Deputy Director, Department of Hepatic Surgery, Peking Union Medical College Hospital
• Chief Physician and Ph.D. Supervisor
• National “Ten Thousand Talents Program” Expert (Leading Talent)
• Winner of the 23rd Wu Yang Award
• Founder of the China Social Welfare Foundation’s Tumor Precision Immunotherapy Fund
• Executive Member, CSCO Liver Cancer Expert Committee
• Secretary-General and Vice-Chair, Chinese Society for Microcirculation Hepatology Division
• Board Member, Peking University Alumni Association
• Associate Editor, Hepatobiliary Surgery and Nutrition (HBSN)
• Editorial Board Member, World Journal of Gastroenterology (WJG)
• Author of 177 SCI-indexed papers with an H-index of 54