Early treatment is the key to improving the survival rate of liver cancer patients. At the 58th Annual Meeting of the European Association for the Study of the Liver (EASL 2023) and the EASL Congress 2023, Doctor Fabio Piscaglia from the University of Bologna, Italy, presented the latest developments in the treatment of early-stage hepatocellular carcinoma (HCC) in a special session titled “Treatment of early stage HCC in 2023.” Hepatology Digest had the privilege of inviting Professor Fabio Piscaglia to share insights into HCC treatment strategies, strategies for preventing HCC recurrence, and the current status and prospects of emerging technologies for tumour molecular characterization.
Hepatology Digest: There are many treatment options for early hepatocellular carcinoma (HCC), so how do clinicians select the best treatment plan for patients? Could you please elaborate on this?
Dr. Fabio Piscaglia: Currently, there are several treatment options available for small, early-stage HCC to help extend patients’ survival. Determining the best treatment plan involves three steps.
First, treatment should aim for complete tumour clearance, achieving complete remission.
Second, it is essential to maintain the patient’s liver function during treatment, as most HCC patients also have chronic liver diseases such as cirrhosis. If tumour clearance leads to impaired liver function, it may negatively impact the patient’s survival. Our goal is to maximize survival while providing the best quality of life for the patient.
Third, the choice of the best treatment plan involves balancing the benefits of complete remission and liver function preservation while understanding the risk of recurrence. Even in cases where histological complete tumour response is achieved, early-stage patients with intermediate to high risk still have a recurrence rate of up to 50% within three years. Therefore, assessing the risk of recurrence is a crucial factor in determining the best treatment plan. Typically, we assess this based on criteria such as the presence of satellite nodules, microvascular invasion (MVI), and tumour grading (if histological information is available). Consequently, it is challenging to predict the prognosis accurately before surgical resection or ablation therapy, and we usually rely on tumour size and alpha-fetoprotein (AFP) levels for evaluation.
Additionally, the patient’s liver function status, including whether they are in Child-Pugh Class A compensation and any prior compensation in Child-Pugh Class A5, A6, or B7, must be taken into consideration. A multidisciplinary team comprising surgeons, transplant surgeons, interventional radiologists, hepatologists, oncologists, and radiation therapists discusses each patient’s case, taking into account factors such as tumour size, AFP levels, and liver function, to determine the best treatment plan. It is important to remember that patients often require multiple treatments and may need additional therapies in the event of recurrence. Therefore, long-term strategies must be developed to maximize patient survival.
Hepatology Digest: Molecular profiling of liver cancer is advancing. How do you assess the value and limitations of these tools, and what benefits can they bring to clinical practice?
Dr. Fabio Piscaglia: Molecular characterization of tumours is a relatively new field. Due to molecular abnormalities, such as changes in inflammatory molecules, different subtypes of high-density hepatocellular carcinoma (HCC) can be classified into at least four distinct molecular subtypes.
Currently, this technology is still in the research phase and has not been widely applied in clinical practice because treatment decisions and prognosis cannot be solely based on molecular characteristics. Additionally, we often only have access to this information from the tumour itself. Therefore, in most cases, patients undergo tumour resection surgery without direct guidance from molecular characteristics.
However, this field is quite intriguing because by identifying different tumour types, we may discover new drug targets. If these research results prove successful, it may be possible to determine the best treatment plan based on molecular characteristics, especially when selecting the most suitable drugs for different patients. But I must admit that this is currently a research direction.
Hepatology Digest: Liver cancer has a high recurrence rate. What research strategies are worth considering for preventing recurrence? Could you share your clinical experiences and insights on preventing HCC recurrence?
Dr. Fabio Piscaglia: For patients with early-stage tumours who have achieved complete tumour remission, the recurrence rate within three years remains relatively high, ranging from 40% to 60%, and it increases to 60% to 70% within five years. Recurrence can be categorized into two types. Typically, the initial recurrences observed within the first few years are micro-metastases of the initial tumour. However, if the initial tumour lesion is within a cirrhotic liver, other independent tumours may also develop, referred to as de novo cancers. Therefore, we have two goals in reducing recurrence.
First, we should make every effort to prevent the development of de novo cancers. This is primarily achieved by treating underlying liver diseases, such as achieving sustained virological response by treating hepatitis C, suppressing hepatitis B virus replication and reducing viral load to zero, implementing lifestyle changes, and managing non-alcoholic fatty liver disease or alcohol cessation. By improving the underlying liver condition, we can reduce stimuli for regeneration and the development of new liver lesions.
Second, when the initial tumour spreads to other sites, even if the initial tumour is cured, tumour cells may still exist in other locations. Therefore, we need to provide anti-tumour treatment capable of killing these cells to prevent their progression to liver metastases. Currently, we have attempted drugs that have been effective for advanced tumours, hoping that they would also be effective for these micro-tumours, which are not visible to the naked eye, as they consist of scattered cells. These micro-tumours may progress in the coming months or years.
However, the initial attempt using sorafenib for targeted therapy unfortunately failed to improve patients’ recurrence-free survival (RFS). More recently, the combination therapy of atezolizumab and bevacizumab has shown a significant improvement in median RFS. This is an important development, but it is not the final goal. We await the final data and ongoing studies, including combinations of immune checkpoint inhibitors and anti-angiogenic drugs or the use of immune checkpoint inhibitors alone. We eagerly anticipate the results of these studies.
By combining the results of various trials, we may even distinguish the roles of anti-angiogenic drugs and immunotherapy in preventing metastasis and hope to cure these tiny circulating tumour cells. Furthermore, we must consider designing new trials because sometimes, when starting treatment immediately after tumour resection, the number of circulating tumour cells is too low to trigger an immune response. Therefore, a new approach to preventing recurrence is to initiate drug treatment before oncological treatment, known as perioperative adjuvant treatment. This field is very exciting and holds significant potential.
In summary, the prevention and management of liver cancer recurrence require a personalized approach, taking into account the patient’s individual characteristics and the best available treatment options.
Hepatology Digest: Overall, what clinical approach do you recommend for the diagnosis and treatment of liver cancer?
Dr. Fabio Piscaglia: There are some regional differences in the diagnosis of liver cancer, partly due to variations in the guidelines in different regions of the world. For example,
in Europe, most liver cancers are diagnosed based on contrast-enhanced imaging. In contrast, in Asia, where hepatitis B is prevalent, surveillance programs using alpha-fetoprotein (AFP) and ultrasound are common.
In terms of treatment, early diagnosis is key to achieving a good prognosis. Patients with small HCC lesions, even those in a very early stage (BCLC 0), have a survival advantage when diagnosed early and treated appropriately. For early-stage HCC, various treatment options are available, including surgical resection, liver transplantation, percutaneous ablation, and local regional therapies such as transarterial chemoembolization (TACE). It is crucial to identify the most suitable treatment for each patient by considering factors such as tumour size, location, and the patient’s liver function status. A multidisciplinary team comprising various specialists can provide the best treatment recommendations for patients.
Additionally, it’s important to emphasize that liver cancer is often associated with underlying liver diseases, such as hepatitis B or C, fatty liver disease, or alcohol-related liver disease. Therefore, managing these underlying conditions is equally important in preventing liver cancer and its recurrence.
In summary, early diagnosis, multidisciplinary collaboration, and personalized treatment plans tailored to the patient’s specific condition are key to improving the prognosis and outcomes of liver cancer patients.
Hepatology Digest: Thank you, Professor Piscaglia, for sharing your valuable insights on the treatment of early hepatocellular carcinoma (HCC) and strategies for preventing HCC recurrence, as well as the potential role of molecular technologies in tumour analysis. Your expertise is greatly appreciated.
This interview provides a comprehensive overview of the challenges and strategies involved in the treatment of early hepatocellular carcinoma (HCC) and the prevention of HCC recurrence. Professor Fabio Piscaglia highlights the importance of a multidisciplinary approach, personalized treatment plans, and ongoing research efforts to improve the outcomes of HCC patients. Additionally, he discusses the emerging field of tumour molecular characterization and its potential impact on treatment decisions in the future.
