Second Opinion on Liver cancer

Liver cancer is a malignant disease of liver cells. It can develop from the epithelium of the intrahepatic bile ducts (cholangiocarcinoma) or from blood vessels (angiosarcoma), but the most common type is hepatocellular carcinoma (HCC), which arises from hepatocytes, the main functional cells of the liver.

What symptoms may indicate liver cancer?

Hepatocellular carcinoma does not cause any specific symptoms. Even in advanced stages, the manifestations may be limited to highly nonspecific symptoms such as:

• general weakness;
• loss of appetite and unintentional weight loss;
• a feeling of pressure and pain in the upper abdomen, particularly on the right side;
• yellowing of the skin and eyes (jaundice).

Liver cancer is often detected incidentally during routine diagnostic tests for other diseases or during a preventive medical examination.

Liver cancer diagnosis

When a liver tumor is suspected, the doctor first takes the patient’s medical history and performs a physical examination. Previous and chronic liver diseases, viral hepatitis, alcohol consumption, previously diagnosed cirrhosis, and other possible risk factors are assessed.

Ultrasound examination

One of the main methods for the initial detection of focal liver lesions is ultrasound. It can identify the presence of a lesion and determine its location and approximate size. When necessary, specialized ultrasound techniques are used, such as color Doppler imaging or contrast-enhanced ultrasound.

For patients at increased risk, regular ultrasound examinations are particularly important for the early detection of tumor-related changes.

Blood tests and alpha-fetoprotein

Laboratory tests help assess liver and other organ function and detect signs of viral hepatitis. When HCC is suspected, the level of alpha-fetoprotein (AFP), a tumor marker that may be elevated in liver cancer, may also be measured. However, AFP alone cannot establish the diagnosis. In clinical practice, it is used mainly in combination with imaging methods and for monitoring disease dynamics and follow-up after treatment.

MRI and CT

After a suspicious lesion has been detected, its characteristics and extent need to be clarified. Contrast-enhanced computed tomography and magnetic resonance imaging are used for this purpose.

MRI provides a detailed assessment of the liver structure, the size and location of the tumor, and its relationship to blood vessels and surrounding tissues. In some situations, MRI provides greater diagnostic information than CT. CT is also used to assess the extent of the disease and to search for distant lesions, particularly in the chest.

Doctors need to establish the number and size of tumor lesions, their location, vascular involvement, and the presence of lymph node involvement or metastases. This information helps determine whether surgical removal, liver transplantation, local tumor treatment, or systemic therapy may be appropriate.

Biopsy and histological examination

In some cases, HCC can be diagnosed based on characteristic findings on imaging, so a biopsy is not always required.

If imaging findings are insufficient or another type of tumor is suspected, a needle biopsy may be performed. Under ultrasound or CT guidance, a tissue sample is obtained from the suspicious lesion using a fine needle. The sample is then subjected to histological examination. This can confirm the malignant nature of the lesion, determine its morphological type, and distinguish a primary liver tumor from metastatic disease. When innovative cellular therapies are being considered, examination of tumor tissue may have additional importance. For example, CAR-T therapy requires confirmation that the tumor cells express the relevant molecular target.

Treatment of Liver Cancer

The treatment strategy depends on the stage of the disease, the number and location of tumor lesions, the presence of vascular invasion and metastases, and the functional reserve of the liver. One of the key differences between HCC and many other solid tumors is that the physician must simultaneously control the tumor and preserve the remaining function of the affected organ.

For early-stage liver cancer, the main potentially curative treatments are surgical resection and liver transplantation. In selected cases, local tumor-destroying treatments are used.

Surgical resection

If the tumor is confined to the liver and can be removed without critically reducing the amount of functioning liver tissue, surgical resection may be considered. The extent of surgery depends on the size and location of the lesion, the number of lesions, the condition of the blood vessels, and the functional status of the liver.

In patients with cirrhosis, the possibility of removing part of the liver must be assessed particularly carefully, because even a technically feasible operation may place excessive stress on an organ whose functional reserve is already reduced.

Liver transplant

For some patients with HCC, liver transplant can address two problems simultaneously: removing the tumor and replacing a liver severely damaged by cirrhosis. The possibility of transplantation depends on the extent of the tumor, the patient's overall condition, and whether established selection criteria are met.

Local treatment methods

If surgery is not possible or direct treatment of the tumor is required, locoregional methods may be used. These include, among others, radiofrequency ablation and microwave ablation, in which tumor tissue is destroyed through thermal energy.

Another widely used approach is transarterial chemoembolization (TACE). A therapeutic agent is delivered directly to the tumor through the vascular system while its blood supply is simultaneously blocked. This makes it possible to target the tumor while reducing systemic exposure to the chemotherapeutic agent. TACE is particularly important in certain forms of unresectable HCC. However, its feasibility and appropriateness depend on the extent of the tumor and the functional status of the liver.

Other locoregional approaches may be used in selected clinical situations, including selective internal radiation therapy and stereotactic radiotherapy. The choice of a particular method depends on the tumor anatomy and the overall treatment plan.

Systemic Drug Therapy

For advanced or unresectable liver cancer, when surgery and local treatment cannot adequately control the disease, systemic medications are used.

Historically, targeted therapies such as tyrosine kinase inhibitors, particularly sorafenib, played an important role in the treatment of advanced hepatocellular carcinoma. Today, the range of systemic treatment options has expanded considerably. Depending on the individual situation, modern immunotherapies targeting immune checkpoints, as well as combinations of immunotherapy and targeted therapy, may be used.

The choice of first-line and subsequent treatments depends on liver function, the patient's overall condition, the extent of the tumor, and previous treatment.

Thus, liver cancer therapy cannot be reduced to a single universal approach. For one patient, the goal may be complete removal of the tumor; for another, preservation of liver function and disease control through a local intervention; while in advanced disease, the primary approach may be systemic therapy followed by other available treatment options.

CAR-T Therapy for Liver Cancer

CAR-T therapy is a form of cellular immunotherapy in which a patient's own T lymphocytes are genetically modified so that they can recognize a specific antigen on the surface of tumor cells.

The use of CAR-T therapy for solid tumors, including hepatocellular carcinoma, remains an active area of research. One of the main challenges is the complex tumor microenvironment of liver cancer, which can interfere with the penetration and activity of immune cells. Therefore, the results of current CAR-T studies in HCC cannot yet be equated with the established efficacy of standard treatments.

It is therefore being investigated as a potentially suitable antigen for targeted cellular therapy.

China is one of the most active centers for research into CAR-T therapy for solid tumors. Various GPC3 CAR-T approaches are currently being investigated, including constructs designed to improve the activity and persistence of T cells within the tumor microenvironment. oncology  Using CAR-T therapy not only as a standalone therapy but combining it with local procedures, such as transarterial chemoembolization, ablation, and stereotactic radiotherapy is one of the current trends in Chinese cancer care.

However, the final decision depends on a much broader range of factors.

At present, CAR-T therapy for liver cancer should primarily be regarded as an innovative cellular therapy option whose availability depends on the specific clinical program, tumor characteristics, and patient eligibility criteria. For patients with advanced HCC for whom standard treatments no longer provide adequate disease control, a remote consultation with a specialized center may help determine whether experimental treatment options are potentially available, including GPC3-directed CAR-T therapy in China.