From February 20 to 22, 2025, the European Association for the Study of the Liver (EASL) hosted the Liver Cancer Summit in Paris, France. During this prestigious academic event, our publication had the honor of inviting two leading experts in liver cancer treatment—Dr. Feng Xia from The First Hospital Affiliated to TAMU in China and Dr. Vincenzo Mazzaferro from the National Cancer Institute of Milan, Italy—for an exclusive "Pinnacle Dialogue" discussion.The two experts provided an in-depth analysis of the latest advancements in surgical treatment based on the newly released 2024 EASL Clinical Practice Guidelines for Liver Cancer and China’s 2024 Primary Liver Cancer Diagnosis and Treatment Guidelines. They examined the key differences between the two sets of guidelines, underscoring the crucial role of surgery in comprehensive liver cancer treatment and the challenges it presents. Additionally, the discussion delved into topics such as post-surgical adjuvant therapies, innovative surgical techniques, and future trends in liver cancer treatment.
This dialogue offered valuable insights and expert perspectives to professionals in the field, providing a significant reference point for clinical decision-making and inspiring further advancements in liver cancer treatment.
Key Updates in the 2024 EASL Clinical Practice Guidelines for Liver Cancer
Oncology Frontier: Professor Mazzaferro, could you share the key updates or highlights regarding surgical treatment in the newly released 2024 EASL Clinical Practice Guidelines for Liver Cancer?
Dr. Vincenzo Mazzaferro (National Cancer Institute, Milan, Italy):
The 2024 edition of the EASL Clinical Practice Guidelines for Liver Cancer represents a significant milestone in the field. This is a long-awaited update—our last guideline revision was five years ago. Over this period, our understanding of hepatocellular carcinoma (HCC) and its treatment strategies has evolved substantially, making this update both timely and necessary.
From a surgical perspective, we have thoroughly reviewed and reassessed the indications for liver resection and transplantation to ensure that treatment decisions are based on the latest evidence-based medicine. These updated guidelines now provide more precise and comprehensive criteria for surgical interventions.
The revisions go beyond just surgical indications—they encompass liver cancer diagnosis, staging, and non-surgical treatment approaches as well. When discussing treatment strategies for patients, it is crucial to consider the full spectrum of surgical options, from transplantation to resection, ensuring that each patient receives the most appropriate therapeutic approach.
This comprehensive update aims to assist surgeons in making informed clinical decisions, ultimately enhancing the quality of care for patients with hepatocellular carcinoma.
Key Updates in the 2024 Chinese Guidelines for Primary Liver Cancer
Oncology Frontier: Thank you, Professor Mazzaferro, for your insightful sharing. In April 2024, China also released an updated version of the 2024 Chinese Guidelines for Primary Liver Cancer Diagnosis and Treatment. Now, we would like to invite Dr. Feng Xia to introduce the key updates in surgical treatment within the latest Chinese guidelines.
Dr. Feng Xia (The First Hospital Affiliated to TAMU):
Last year, the Chinese Society of Liver Cancer under the China Anti-Cancer Association released the 2024 edition of the Chinese Liver Cancer Diagnosis and Treatment Guidelines. This revision introduced significant updates in both content and structure, particularly in the field of surgical treatment. The updates can be broadly categorized into three key areas:
1. Conceptual Updates
One of the major changes is the refinement of surgical indications. In China, the criteria for liver resection tend to be broader, covering stages Ia to IIIa based on the Chinese liver cancer classification system. However, for stage IIIa patients, the preferred approach is now systemic therapy combined with locoregional treatments—such as transarterial chemoembolization (TACE) and immunotherapy—rather than immediate surgical resection. This reflects the growing adoption of the conversion therapy concept, where non-surgical treatments are used first to improve surgical eligibility and outcomes.
2. Advances in Surgical Techniques
The latest clinical research evidence supports laparoscopic liver resection (LLR) as a viable alternative to traditional open liver resection for early-stage liver cancer. Studies show that the five-year overall survival (OS) rates for patients undergoing LLR and open surgery are comparable. Moreover, for elderly patients with liver cancer, laparoscopic resection has demonstrated better surgical outcomes, including a lower complication rate and a shorter hospital stay. That being said, laparoscopic surgery has specific indications and contraindications, which surgeons need to carefully consider.
3. Updates in Treatment Strategies
A significant emphasis has been placed on conversion therapy for intermediate and advanced-stage patients (stages IIa–IIIb). At these stages, surgery alone is often insufficient due to the high risk of recurrence. The guidelines now recommend systemic therapy in combination with surgery, which has been shown to reduce recurrence rates and improve prognosis.
Notably, immunotherapy combined with locoregional treatments has proven effective in downstaging tumors, making previously unresectable cases surgically eligible. Some experts have even introduced the concept of “dual conversion”, where a combination of oncological and surgical approaches allows a wider group of patients to become eligible for resection.
Additionally, the 2024 Chinese guidelines now include recommendations for postoperative adjuvant therapy, which is a distinctive feature compared to other international guidelines. For patients at high risk of recurrence, adjuvant treatments are suggested to prevent early relapse and improve long-term outcomes.
These are some of the major updates in the surgical section of the 2024 Chinese Liver Cancer Guidelines.
Innovative Surgical Techniques in the 2024 EASL Guidelines
Oncology Frontier: Thank you, Professor Xia, for your insightful interpretation of the guidelines. With advancements in medical technology, surgical techniques continue to evolve. Professor Mazzaferro, could you share some of the new surgical techniques or methods recommended in the EASL guidelines and their potential applications in hepatocellular carcinoma (HCC) treatment?
Dr. Vincenzo Mazzaferro (National Cancer Institute, Milan, Italy):
In the field of liver resection, we have made significant strides, particularly in minimally invasive surgery. With rapid advancements in medical technology, we can now perform liver surgeries using laparoscopic and robotic-assisted techniques. These approaches offer greater precision, significantly reducing surgical trauma and post-operative pain, while also improving safety and success rates.
By leveraging laparoscopy and robotic surgery, we can precisely locate and target liver tumors, enabling more refined surgical procedures. This has led to better post-operative outcomes, including reduced risk of liver failure, shorter hospital stays, lower recurrence rates, and fewer complications.
However, when it comes to liver transplantation, there is still considerable progress to be made. In this regard, we greatly admire and actively learn from our Chinese colleagues, who have accumulated extensive expertise in living donor liver transplantation. China has made remarkable advancements in this area, not only in surgical techniques but also in post-operative management, significantly improving both patient survival rates and quality of life.
From a technical perspective, achieving optimal outcomes in liver transplantation requires a high degree of surgical precision and preparation. One crucial innovation is the use of 3D reconstruction technology, which allows for a detailed virtual simulation and precise donor-recipient matching. This ensures that every aspect of the surgical procedure is meticulously planned, ultimately leading to better outcomes.
Moreover, global collaboration and knowledge exchange are essential. By learning from the latest advancements in transplantation techniques worldwide, we can continue refining our surgical approaches and improving treatment outcomes. The goal is to make liver transplantation as effective as possible, bringing hope and better prognoses to more patients.
Commonalities and Differences in Surgical Treatment of Liver Cancer Between Chinese and European Guidelines
Oncology Frontier: Professor Mazzaferro, in your opinion, what are the shared principles between the Chinese and European guidelines regarding the surgical treatment of liver cancer? Additionally, where do the key differences lie?
Dr. Vincenzo Mazzaferro (National Cancer Institute, Milan, Italy):
Despite regional differences in patient demographics and disease patterns, the fundamental principles of liver cancer treatment share many similarities between China and Europe.
One of the major differences is the underlying cause of liver cancer in each region. In China, hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) accounts for the vast majority of cases. In contrast, Europe sees a higher prevalence of metabolic-associated liver cancer, often linked to non-alcoholic fatty liver disease (NAFLD). These variations are influenced by factors such as lifestyle, dietary habits, and genetic predispositions.
However, despite these epidemiological differences, liver transplantation remains a cornerstone treatment for HCC in both regions. It is universally recognized as the most effective therapy for eligible patients with severe disease who cannot be adequately treated by resection or locoregional therapies. The scarcity of donor organs, however, remains a major challenge worldwide. This has led both China and Europe to explore alternative treatment strategies to improve patient survival and quality of life.
One of the key divergences in treatment approaches lies in systemic therapy. In Europe, there is a strong emphasis on immunotherapy, which is being actively integrated into liver cancer treatment protocols. Immunotherapy is not only gaining prominence as a standalone treatment but is also being explored in combination with surgical interventions like liver transplantation and resection. Emerging evidence suggests that immunotherapy can enhance surgical outcomes, improve post-transplant recovery, and increase long-term survival rates.
Ultimately, while both China and Europe prioritize liver transplantation as a core treatment, the evolving landscape of systemic therapies, particularly immunotherapy, is driving new treatment paradigms, shaping the future of HCC management worldwide.
Differences in Postoperative Adjuvant Therapy for Liver Cancer Between Chinese and European Guidelines
Oncology Frontier: Thank you, Professor Mazzaferro, for sharing insights into emerging surgical techniques and the differences between Chinese and European guidelines. Now, Professor Xia, do you think there are differences in the recommendations for postoperative adjuvant therapy in liver cancer between the two guidelines? What are the reasons behind these differences? Additionally, what unique experiences or explorations has China made in this area?
Dr. Feng Xia (The First Hospital Affiliated to TAMU):
Yes, there are significant differences between China and Europe when it comes to postoperative adjuvant therapy for liver cancer.
The EASL guidelines acknowledge the findings of the IMbrave050 trial, which initially suggested that adjuvant immunotherapy may help reduce postoperative recurrence. However, as the follow-up period extended, the study failed to demonstrate a clear long-term survival benefit, meaning it did not meet its pre-defined endpoints. As a result, the European guidelines generally do not strongly recommend systemic adjuvant therapy after liver cancer surgery. That said, antiviral therapy remains a universally accepted recommendation for patients with HBV-related HCC.
China’s Approach to Postoperative Adjuvant Therapy
In contrast, China has adopted a broader approach to postoperative adjuvant therapy, as reflected in the 2024 Chinese Liver Cancer Guidelines. Several adjuvant treatment options are included, such as:
- Targeted therapy + immunotherapy for patients with portal vein tumor thrombus (PVTT)
- Locoregional treatments like transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC)
- Traditional Chinese medicine (TCM)-based therapies, which are a unique feature of Chinese guidelines
Reasons Behind These Differences
These differences stem from fundamental variations in clinical practice and evidence evaluation between China and Europe:
- Evidence-Based Standards European guidelines rely heavily on large Phase III randomized controlled trials (RCTs). If a treatment lacks robust evidence demonstrating universal benefit, it is not included in the recommendations. Chinese guidelines, on the other hand, consider a broader range of clinical data, including real-world studies, retrospective analyses, and small cohort studies, which have suggested that certain adjuvant therapies may help reduce recurrence.
- Surgical Treatment Criteria In China, surgical indications for liver cancer are more inclusive, meaning that a higher proportion of intermediate and advanced-stage patients undergo resection. As a result, postoperative recurrence and metastasis become major concerns. In Europe, liver resection tends to be more selective, primarily for early-stage patients, reducing the perceived necessity for adjuvant therapy.
- Practical Considerations and Clinical Experience While large-scale RCTs are still lacking, China has accumulated substantial real-world experience, with many studies indicating that adjuvant therapy may help lower recurrence risk in high-risk patients. The Chinese guidelines thus provide more recommendations for postoperative adjuvant therapies, along with detailed follow-up strategies.
Conclusion
The differences between Chinese and European postoperative adjuvant therapy recommendations reflect distinct clinical philosophies and patient demographics. While Europe emphasizes high-level RCT evidence, China prioritizes practical treatment strategies based on real-world clinical needs. Moving forward, further research—especially large-scale international trials—will be crucial to refining global liver cancer treatment guidelines and optimizing patient outcomes.
Future Directions in Liver Cancer Surgery: Challenges and Opportunities
Oncology Frontier: Thank you, Professor Xia, for your insightful analysis. Now, Professor Mazzaferro, could you share your thoughts on the future of surgical treatment for liver cancer? What challenges must we overcome, and what opportunities can we seize?
Dr. Vincenzo Mazzaferro (National Cancer Institute, Milan, Italy):
In the field of liver cancer treatment, we face two contrasting challenges.
1. The Challenge of Reducing the Need for Liver Transplantation
One of the biggest dilemmas in liver cancer management is the scarcity of donor organs. Given this limitation, there is a growing push to explore non-surgical treatment strategies—such as systemic therapy, locoregional therapy, and selective liver resection—that can control the disease without requiring transplantation.
A key question that has emerged is: For patients who achieve a complete response with non-surgical treatments, is liver transplantation still necessary? If a patient achieves tumor-free status through immunotherapy, targeted therapy, or a combination of locoregional approaches, should they still undergo a transplant? This is an area that requires deeper investigation, as avoiding unnecessary transplants could help preserve donor organs for those who truly need them.
2. Expanding Liver Transplantation Eligibility
At the other end of the spectrum, there is another major challenge: ensuring that more patients can access liver transplantation as a curative option. Many patients with advanced liver cancer currently do not meet the criteria for transplantation, leaving them without access to this potentially life-saving procedure.
One promising approach is downstaging therapy—using systemic and locoregional treatments to shrink tumors or improve their characteristics until they become eligible for transplantation. This concept, sometimes called “super downstaging,” involves aggressive pre-transplant treatments to optimize patient outcomes. By integrating multidisciplinary treatment strategies, we can broaden transplant eligibility and improve survival rates for a wider patient population.
The Path Forward
The future of liver cancer surgery lies in finding the right balance between surgical and non-surgical approaches. Through advancements in immunotherapy, targeted therapy, and precision medicine, we may be able to reduce the need for transplantation in some cases, while simultaneously expanding access to transplantation for those who need it most. Collaboration across disciplines and global research efforts will be essential in shaping the next era of liver cancer treatment.
China’s Success in Promoting the Multidisciplinary Treatment (MDT) Model for Liver Cancer
Oncology Frontier: Thank you, Professor Mazzaferro, for sharing your insights on the future of liver cancer surgery. In the multidisciplinary treatment (MDT) model, the integration of surgical intervention with targeted therapy and immunotherapy is becoming increasingly important. Finally, Professor Xia, could you share some of China’s successful experiences in promoting the MDT approach for liver cancer treatment?
Dr. Feng Xia (The First Hospital Affiliated to TAMU):
Surgical treatment remains the gold standard for liver cancer and is globally recognized as the most effective curative option. However, surgery has limitations, particularly concerning its eligibility criteria.
- In Europe, surgical indications are relatively narrow, meaning only a select group of early-stage patients qualify for resection.
- In China, surgical indications are broader, allowing a larger number of patients, including those with intermediate-stage disease, to undergo surgery.
Given that China accounts for over 40% of the world’s liver cancer cases, maximizing patient benefit is a key priority. In recent years, systemic therapies—particularly immunotherapy-based combinations—have significantly advanced, providing new opportunities for integrating surgery with systemic treatments.
Innovations in Surgical and Systemic Therapy Combinations
China has been actively exploring new ways to enhance surgical outcomes through systemic therapy. A prime example is our research on radiofrequency ablation (RFA) combined with immunotherapy, which was recently published in BMC.
Key Findings of the Study
For unresectable liver cancer, combining immunotherapy with RFA proved more effective than systemic therapy alone. The mechanism behind this success is:
- Tumor Debulking Effect: RFA can reduce tumor burden by more than 50%, leading to extensive tumor cell necrosis.
- Enhancing the Immune Response: The necrotic tumor cells release tumor antigens, which in turn stimulate antigen presentation and modulate the tumor microenvironment.
- Increased Lymphocyte Infiltration: The localized immune response attracts more lymphocytes into the tumor site, significantly boosting the effectiveness of systemic immunotherapy.
These findings highlight how surgical techniques, when integrated with systemic therapy, can amplify treatment efficacy, paving the way for more effective combination strategies in liver cancer management.
The Future of MDT in Liver Cancer
Moving forward, a crucial question is: Can we further enhance treatment outcomes through optimized surgery and systemic therapy combinations?
China’s MDT approach is evolving to:
- Refine patient selection criteria for surgical-systemic therapy combinations
- Develop new treatment protocols integrating surgery, ablation, targeted therapy, and immunotherapy
- Continue clinical research to establish evidence-based guidelines for combination treatments
In summary, China’s MDT success lies in its proactive integration of surgical and systemic treatments, ensuring maximum therapeutic benefit for a wider range of liver cancer patients. Further research will determine how to optimize these strategies, shaping the future of liver cancer treatment worldwide.
- MD, PhD, Professor, Chief Surgeon, Doctoral Supervisor
- Southwest Hospital, Chongqing, China
Academic and Research Background
- Postdoctoral Researcher, Department of Surgery, University of Oxford
- Honorary Clinical Research Fellow, Department of Surgery, University of Hong Kong
- Adjunct Professor, Chongqing University & Southwest University
Professional Affiliations
- Vice Chairman, Chinese Chapter of the International Hepato-Pancreato-Biliary Association (IHPBA China)
- Chairman, Liver Hemangioma Committee
- Standing Committee Member, Liver Tumor Committee
- Chinese Representative, China-Africa Hepato-Pancreato-Biliary Alliance
- Council Member, Chinese Society of Clinical Oncology (CSCO)
- Standing Committee Member, CSCO Liver Cancer Expert Committee
- Standing Committee Member, Accelerated Recovery Oncology Surgery Committee of the Chinese Anti-Cancer Association
- Committee Member, Liver Cancer and Tumor Metastasis Committee of the Chinese Anti-Cancer Association
- Committee Member, Chinese Medical Doctor Association Liver Cancer Committee
- Standing Committee Member & Head of Liver Cancer Group, Hepato-Pancreato-Biliary Surgery Committee of the Chinese Research Hospital Association
- Standing Committee Member, Clinical Surgery Committee of Digital Medicine
- Vice President, Surgical Technology Innovation and Promotion Branch of the National Health Industry Enterprise Management Association
- Committee Member, International Education and Training Committee of the Chinese Medical and Healthcare International Exchange Promotion Association
- Committee Member, Hepato-Pancreato-Biliary Surgery Committee of the Chinese Medical Education Association
- Vice Chairman, Liver Cancer Committee of the Chongqing Anti-Cancer Association
Government and Expert Consultation Roles
- Expert Reviewer, Ministry of Science and Technology of China & Ministry of Education of China
- Consulting Expert, Xiangshan Science Conference
Editorial Roles
- Deputy Editor-in-Chief, Mini-invasive Surgery
- Editorial Board Member, Oncology and Translational Medicine
- Director, Gastrointestinal Surgery and Liver Transplantation
- National Cancer Institute, University of Milan, Italy
Professional Affiliations
- Founding Member, International Liver Cancer Association (ILCA)
- Member, European Association for the Study of the Liver (EASL)
- Member, American Association for the Study of Liver Diseases (AASLD)
- Editorial Board Member, EASL Clinical Practice Guidelines for Liver Cancer
