Hepatocellular Carcinoma (HCC) is the most prevalent form of primary liver cancer, often developing in individuals with underlying chronic liver disease, particularly cirrhosis. Treating HCC requires a personalized strategy due to the tumor’s diverse characteristics and varying patient health statuses.
Types of HCC Treatments
Various treatment modalities exist for HCC, designed to address different stages and presentations of the disease. These treatments are broadly categorized into surgical interventions, locoregional therapies, and systemic therapies, with the choice depending on the specific clinical scenario.
Surgical Interventions
Surgical approaches offer the potential for cure in selected patients. These methods aim to either remove the tumor directly from the liver or replace the entire diseased organ.
Liver Resection involves surgically removing the portion of the liver containing the tumor, along with a margin of healthy tissue. This procedure is considered for patients with a single tumor confined to the liver, without vascular invasion, and with good overall liver function. The extent of the resection depends on the tumor’s size and location, ranging from a small segment to an entire lobe.
Liver Transplantation replaces the diseased liver with a healthy organ from a donor. This option is considered for patients with early-stage HCC who may not be suitable for resection due to underlying liver disease or specific tumor characteristics. Standard criteria, such as the Milan criteria, allow for a single tumor up to 5 centimeters in diameter or up to three tumors, each 3 centimeters or less, without evidence of vascular invasion or spread beyond the liver. Liver transplantation can offer high long-term survival rates.
Locoregional Therapies
Locoregional therapies deliver treatment directly to the liver, targeting the tumor while minimizing impact on the rest of the body. These procedures are often performed by interventional radiologists.
Ablation techniques, such as Radiofrequency Ablation (RFA) and Microwave Ablation (MWA), use heat to destroy tumor cells. RFA involves passing high-frequency electrical currents through a needle electrode inserted into the tumor, generating heat that coagulates and destroys the cancer cells. MWA utilizes electromagnetic waves in the microwave spectrum to produce heat, which also leads to the destruction of tumor tissue. Both RFA and MWA are suitable for small liver tumors, typically less than 1.5 inches (approximately 3.8 cm) in diameter.
Embolization procedures, including Transarterial Chemoembolization (TACE) and Transarterial Radioembolization (TARE, also known as Yttrium-90 or Y90), work by blocking the blood supply to the tumor and/or delivering therapeutic agents directly. TACE involves injecting a mixture of chemotherapy drugs and an oily medium directly into the arteries feeding the liver tumor, followed by particles to block blood flow, thus starving the tumor. TARE delivers tiny radioactive microspheres containing yttrium-90 (Y90) directly to the tumor via the hepatic artery, where they emit localized radiation to destroy cancer cells. HCC tumors receive approximately 90% of their blood supply from the hepatic artery, making these targeted approaches effective while sparing healthy liver tissue.
Radiation Therapy, such as Stereotactic Body Radiation Therapy (SBRT) and Proton Therapy, delivers high-dose radiation precisely to the tumor. SBRT uses advanced imaging to target tumors with high accuracy, delivering strong doses of radiation in fewer treatment sessions. Proton therapy utilizes protons instead of photons to deliver radiation, which allows for a highly focused dose to the tumor while minimizing radiation exposure to surrounding healthy tissues, due to a property called the Bragg peak. These advanced radiation techniques are employed for unresectable HCC, offering effective local tumor control.
Systemic Therapies
Systemic therapies circulate throughout the body to treat cancer cells wherever they may be present. These are often used for more advanced stages of HCC or when locoregional treatments are not suitable.
Targeted Therapy involves medications that block specific molecular pathways involved in cancer growth and progression. For instance, drugs like sorafenib and lenvatinib are multi-tyrosine kinase inhibitors that interfere with processes such as angiogenesis (new blood vessel formation) and tumor cell proliferation. These therapies aim to be more selective than traditional chemotherapy by interfering with molecules that are aberrantly activated in cancer cells.
Immunotherapy uses medications to enhance the body’s own immune system to recognize and destroy cancer cells. Immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies, work by releasing the “brakes” on immune cells, allowing them to mount a stronger attack against the tumor. The combination of atezolizumab and bevacizumab has emerged as a first-line treatment for unresectable HCC, leveraging synergistic mechanisms to boost immune response and reduce immunosuppression within the tumor microenvironment.
Chemotherapy, while a common treatment for many cancers, is less frequently used as a primary systemic therapy for HCC due to the liver’s natural resistance to many traditional chemotherapy drugs. HCC cells often express a multidrug resistance gene protein, which actively pumps chemotherapeutic agents out of the cells. However, certain regimens, such as FOLFOX4, may be considered for advanced HCC, especially in specific clinical trial settings or when other options are limited.
Factors Guiding Treatment Decisions
Decisions regarding HCC treatment are complex and involve careful consideration of several patient and tumor characteristics. A multidisciplinary team of specialists collaborates to determine the most appropriate course of action.
The stage of the cancer is a primary determinant, encompassing the size, number, and spread of tumors. Staging systems, such as the Barcelona Clinic Liver Cancer (BCLC) classification, categorize HCC from very early to advanced stages, guiding initial treatment recommendations. For instance, surgical options like resection or transplantation are reserved for early-stage disease.
The patient’s overall liver function and health are equally important. Liver function is assessed using tools like the Child-Pugh score, which helps determine the liver’s ability to tolerate various treatments. Patients with well-compensated liver function may be candidates for more aggressive therapies compared to those with impaired function.
A patient’s overall health and performance status, reflecting their ability to tolerate treatment, influence decisions. This includes assessing their physical condition and the presence of other medical conditions. The availability of specific treatment options and the expertise of the medical center play a role, as certain advanced procedures may only be offered at specialized facilities.
Finally, patient preferences and their goals of care are integrated into the decision-making process. Open discussions about potential benefits, risks, and expected outcomes of each treatment option ensure that the chosen path aligns with the individual’s values and priorities.
Supportive Care During Treatment
Beyond direct anti-cancer treatments, supportive care is an important part of managing HCC, focusing on alleviating symptoms and enhancing the patient’s quality of life throughout their journey. This holistic approach addresses the physical, emotional, and psychological challenges associated with the disease and its treatment.
Pain management is a frequent need, as HCC can cause abdominal discomfort or other types of pain due to tumor growth or treatment side effects. Nutritional support is important, as liver disease and cancer can lead to muscle wasting and malnutrition; dietary adjustments and supplements may be recommended to maintain strength and overall health. Managing fatigue, a common symptom, involves strategies such as energy conservation techniques and addressing underlying causes.
Emotional and psychological support, including counseling and participation in support groups, helps patients and their families cope with the emotional burden of a cancer diagnosis and treatment. Addressing specific treatment side effects, such as nausea, skin reactions, or other adverse events, is managed with appropriate medications and interventions. Palliative care integration, which can be offered at any stage of illness alongside active cancer treatment, provides comprehensive symptom relief and support focused on improving comfort and well-being.