Editor's note
Liver cancer, as a major "invisible killer", often develops rapidly to an advanced stage in the asymptomatic incubation period, posing a severe challenge to the life and health of mainland people and bringing a heavy burden to patients and their families. In recent years, a series of major breakthroughs have been made in the field of liver cancer treatment with systemic therapy. A few days ago, at the 2024 Asia-Pacific Association for the Study of the Liver (APASL) Oncology Conference held in Chiba, Japan, the latest "APASL Liver Cancer Systematic Treatment Guidelines" was released. The contents are organized below for the benefit of readers.
01
Could you briefly describe the key updates and highlights of the new APASL Guidelines for Systemic Therapy of Liver Cancer released at this conference?
Prof. Liu Ka-kit: More than 900,000 people suffer from liver cancer and about 830,000 people die every year in the world, and various sources predict that this number will increase by another 55% by 2040. About 70% of liver cancer patients in the world are concentrated in the Asia-Pacific region, and 45% are in China.
Two years ago, the APASL Academic Patient Council established a Liver Cancer Systemic Treatment Group, which brought together more than 60 liver cancer experts from 14 countries to develop the APASL Guidelines for Liver Cancer Systemic Treatment. The guidelines are designed to address the following three key clinical issues: for patients who are partially unresectable, or who do not respond to interventional therapy, and who face recurrence after surgery or other treatments:
Which patients with liver cancer should be considered for systemic therapy?
Which systemic approach should be used?
How are patients scheduled for systemic therapy managed and monitored?
The expert group has fully discussed the problems faced by the clinical management of liver cancer and the focus of the guidelines, and continues to accept opinions from all parties for updates, which have been reviewed by the journal Hepatology International and will be published in the near future. The guidelines make 8 recommendations:
01
Who should treat patients with liver cancer, that is, how to manage systemic treatment of patients with liver cancer? Because the systemic treatment of liver cancer is complex, with various curative effects and side effects, the guidelines recommend that a multidisciplinary and multi-expert team is needed to deal with the problem.
02
Which staging system should be used? Guidelines recommend staging systematic therapy for patients with HCC following the ASAPL 2017 version (Figure 1).
Figure 1. Decision Tree for Staging Treatment for Hepatocellular Carcinoma (from Speaker's Slide)
03
What kind of patients should receive systemic therapy? Guidelines recommend that patients with CPT-A and B who cannot undergo surgical resection and who have adequate liver function, with or without portal vein occlusion, can be treated systematically.
For patients without bleeding risk, the preferred first-line regimen is dual immune checkpoint inhibitors (ICIs) with anti-VEGF + anti-PD-1/anti-PD-L1 or anti-CTLA-4 plus anti-PD-1/PD-L1, such as atezolizumab, bevacizumab, or sintilimab. For immunotherapy in patients at risk of bleeding or financially limited, lenvatinib or sorafenib should be considered.
After 8~12 weeks of first-line treatment, if there is disease progression, second-line treatment should be considered, and there are new data to support the use of other drugs in second-line treatment. For patients who have failed anti-VEGF+ anti-PD-1/anti-PD-L1, considered second-line therapies include dual ICIs of anti-CTLA-4 and anti-PD-1/anti-PD-L1 or lenvatinib; For patients who have failed dual ICIs of anti-CTLA-4 and anti-PD-1/anti-PD-L1, anti-VEGF+ anti-PD-1/anti-PD-L1 or lenvatinib should be considered.
04
Management of immune-mediated adverse events. For patients with single immunotherapy, observe the patient's clinical liver function every 2~4 weeks, because there are many side effects, the most critical treatment plan is early detection and early treatment, so it is recommended to observe once every 1~2 weeks. Immune-related adverse events (irAEs) can be determined based on the Common Terminology Criteria for Adverse Events (CTCAE) to the exclusion of other possibilities.
05
Application of interventional therapy combined with immunotherapy. Interventional therapy is now widely used in patients with liver cancer, and the latest data show that the combination of immunotherapy after receiving interventional therapy can greatly prolong the progression-free survival (PFS) of patients. Patients at the end of interventional therapy may be considered for improvement in PFS with dvalumab and bevacizumab.
06
The use of adjuvant therapy after surgery. The IMbrave050 study, which explored the use of the "T+A" regimen in adjuvant postoperative therapy, showed a significant benefit in recurrence-free survival (RFS) in the adjuvant atezolizumab plus bevacizumab group compared with active follow-up (HR=0.72, P=0.012), with 12-month RFS rates of 78% and 65%, respectively (Fig. 2). The study was published in The Lancet and received extensive attention around the world, but the follow-up time of the current study is still short, so the APASL guidelines have limited recommendations for atezolizumab combined with bevacizumab in postoperative adjuvant therapy, and we look forward to more new developments in the future.
Figure 2. IMbrave050 Research Results (Sourced from Speaker's Slideshow)
07
Use of systemic therapy in liver transplant patients. Whether the waiting period for liver transplantation can be treated systematically, whether it will affect liver transplantation, and whether there will be rejection after transplantation are relatively few international reports on these issues, and there is no large-scale clinical research support. Based on the limited data available, guidelines recommend that patients treated with ICIs need to undergo a 6-week washout period before undergoing transplantation.
08
After liver transplantation, sorafenib and lenvatinib can be used to treat recurrence of HCC, and ICIs are not recommended. ICIs may be considered as salvage therapy for HCC recurrence in liver transplant patients after weighing the individual immune risks and benefits, but very caution is required.
Systemic therapy has just begun to be used effectively, and it is hoped that there will be more evidence-based medical data on how to use systemic therapy to improve the current situation of liver cancer patients, and how to use systemic therapy to prolong the life of patients through big data management, and even successfully transform it into surgery to cure liver cancer, and artificial intelligence may be able to help deal with complex problems in all aspects in the future.
02
What specific impact do you think this guideline update will have on clinical practice in HCC in the Asia-Pacific region and around the world?
Prof. Liao Jiajie: In Europe and United States, there are European Society for Medical Oncology (ESMO) liver cancer guidelines and United States Society of Clinical Oncology (ASCO) liver cancer guidelines as guidance. However, in the Asia-Pacific region, there has been a lack of systematic guidelines to guide the systematic treatment of liver cancer for a long time. As the first and only authoritative guide in the Asia-Pacific region, this new guide is groundbreaking.
The guidelines brought together the wisdom of more than 60 experts from 14 countries around the world, and spent two years to comprehensively integrate all the situations and needs of systemic liver cancer treatment in the entire Asia-Pacific region. The issuance of this guideline will greatly help doctors in oncology, surgery, transplantation and other departments to enable them to treat liver cancer more systematically. The release of this guideline will also strongly promote the development and application of systemic treatment of liver cancer in the Asia-Pacific region, and lay a solid foundation for the subsequent realization of standardized and systematic diagnosis and treatment models.
03
Looking ahead, what do you think are the key research directions and challenges in the field of systemic therapy for liver cancer? How will the publication of the new guidelines advance these studies?
Prof. Liu Jiajie: In the past four to five years, significant progress has been made in the field of systemic treatment of liver cancer, which has brought good news to patients with liver cancer that cannot be removed by surgery, not only greatly extending their life cycle, but also significantly improving their quality of life. While this emerging field is promising, it also comes with its many challenges.
At present, in the face of the choice of many therapeutic drugs, how to scientifically and reasonably arrange the sequence of medication, when to replace drugs, and how to effectively monitor and respond to the side effects of drugs are all problems that need to be solved urgently. As an important means in the comprehensive treatment of liver cancer, how to synergize with other treatment methods such as surgery, interventional therapy, radiofrequency ablation and liver transplantation to achieve the best treatment effect is also an important direction of current research.
At present, in-depth research on these aspects is just beginning, and more real-world data needs to be collected to explore more effective treatments for liver cancer. Our goal is to prolong the life cycle of patients and even achieve a radical cure for liver cancer by continuously optimizing treatment options. We look forward to a more active role in the treatment of liver cancer in the Asia-Pacific region, especially in China, with the continuous promotion of academic and professional fields. We hope to bring more hope and well-being to liver cancer patients around the world by sharing and promoting our treatment experience and methods.
04
With a series of breakthroughs in the clinical treatment of liver cancer in recent years, what changes have occurred in the status and importance of surgical treatment in advanced liver cancer? How do you see the role of surgery in the treatment of advanced liver cancer in the future?
Prof. Liao Jiajie: In real-world medical practice, surgery still occupies a core position in the field of liver cancer treatment. Surgical methods such as surgical resection, radiofrequency ablation, and liver transplantation have the fundamental goal of curing the patient and eradicating the tumor completely. Systemic therapy, on the other hand, plays an important role in activating the immune system and reducing the size of tumors, making tumors that are difficult to remove become operable or eliminating metastases other than the liver, thus creating more treatment opportunities for patients. The close integration of surgery and internal medicine can not only significantly improve the success rate of surgery, but also effectively reduce the risk of secondary recurrence and further improve the cure rate. This treatment strategy, which is both internal and external, fully demonstrates the comprehensive treatment concept of modern medicine.
However, to find the optimal medical and surgical strategy to maximize the life cycle of patients, we need to invest more energy in future academic and clinical research. Through continuous in-depth exploration, we can better understand the interaction between surgical and internal medical treatments, and provide patients with more accurate and personalized treatment plans, so that they can go further and more steadily on the road of fighting cancer.
Resumes of experts
廖家杰教授Prof. George Lau
- Bachelor of Medicine and Bachelor of Surgery (MBBS), University of Hong Kong (1987)
- Fellow of the Royal College of Physicians of United Kingdom (MRCP) (1990)
- Fellow of the Hong Kong College of Physicians (FHKCP) (1995)
- Fellow of the Hong Kong Academy of Medicine (Gastroenterology and Hepatology) (FHKAM) (1995)
- Ph.D., University of Hong Kong (2001)
- Fellow of the Royal College of Physicians of Edinburgh (FRCP) (2004)
- Fellow of the Royal College of Physicians of the University of London (FRCP) (2006)
- Member, United States Society for the Study of Liver Diseases (FAASLD) (2015)
- He was the Assistant Dean of the Li Ka Shing Faculty of Medicine, the University of Hong Kong, China, the Clinical Professor of Gastroenterology and Hepatology, and the President of the Asia-Pacific Society of Hepatology.
- He has won the Ten Outstanding Young Persons of Hong Kong, the Outstanding Research Output Award of the Faculty of Medicine of the University of Hong Kong, the Second Prize of the People's Liberation Army General Logistics Medical Achievement Award, the Second Prize of the National Science and Technology Progress Award, the Chief Executive's Community Service Award of the Hong Kong S.A.R. Region, and the Okuda-Omata Outstanding Achievement Award, the highest honor award of the Asia-Pacific Association for the Study of Liver Diseases (APASL).
- 是目前国际上研究消化道及肝病的权威之一，在New Engl J Med，Lancet，Gastroenterology，Hepatology，Lancet Gastroenterol Hepatol等杂志上发表论文300多篇, H指数为95。
- International Academic Appointments:
- He is currently a senior standing committee member of the Asia-Pacific Association for the Study of Liver Diseases (APASL).
- Chair of the Asia-Pacific Association for the Study of Liver Diseases (APASL) Hepatitis B Reactivation Guidelines Committee and COVID-19 Working Expert Group, Co-Chair of the Hepatitis B Guidelines Committee, Member of the Hepatitis C and Liver Cancer Guidelines Committee, and Webinar Program Leader;
- He is currently a member of the Governing Committee of the Asia-Pacific Alliance for Digestive Diseases (APDWF).
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