Hepatocellular carcinoma (HCC) is the most prevalent type of primary liver cancer. For those diagnosed, the term “unresectable” indicates that the cancer cannot be entirely removed through a surgical operation at the time of diagnosis. However, an unresectable diagnosis is not the same as an untreatable one. A wide array of advanced medical interventions are available to manage the disease. This determination marks a shift in strategy from curative removal to a non-surgical path focused on long-term control of the cancer.
Factors Determining Unresectability
The decision to classify HCC as unresectable is based on several factors, starting with the tumor’s characteristics. If there are numerous tumors scattered throughout the liver or if a single tumor is excessively large, surgical removal may not be feasible. The location is also a determinant; a tumor situated too close to major blood vessels, such as the portal vein, can make a safe surgical procedure impossible. Invasion of the tumor into these vascular structures is a common reason for this classification.
Another element is the health of the surrounding liver tissue. Most HCC cases develop in livers already damaged by chronic conditions like cirrhosis from hepatitis B or C infection, which impairs the liver’s ability to regenerate. If liver function is poor, the patient may not tolerate the removal of a significant portion of the organ, as the remaining liver would be insufficient to sustain life. Doctors use scoring systems, such as the Child-Pugh score, to assess the degree of liver dysfunction.
The patient’s general health status is also taken into account. Major surgery places immense stress on the body, and a patient’s performance status—a measure of their ability to perform daily activities—helps doctors determine if they can withstand the intervention. Medical comorbidities, such as severe heart or lung disease, can also render a patient ineligible for surgery.
Locoregional Therapies
For unresectable HCC confined to the liver, locoregional therapies attack the cancer directly. These treatments focus on destroying tumors within the liver while minimizing damage to the rest of the body.
- Transarterial chemoembolization (TACE): Involves injecting chemotherapy drugs directly into the hepatic artery supplying the tumor and then blocking that artery. This dual-action approach traps the drugs at the tumor site while cutting off its blood supply.
- Transarterial radioembolization (TARE): Delivers millions of microscopic radioactive beads through the hepatic artery. These beads lodge in the small vessels feeding the tumor and emit radiation over a short distance, delivering a high dose directly to cancer cells while sparing healthy tissue.
- Thermal Ablation: Uses a needle-like probe to destroy smaller, well-defined tumors with intense heat. Radiofrequency ablation (RFA) uses high-frequency electrical currents, while microwave ablation (MWA) uses microwaves to create heat more rapidly over a larger area.
- Stereotactic Body Radiation Therapy (SBRT): A precise form of external beam radiation that uses advanced imaging to deliver a very high dose to the tumor in just a few treatments. This precision maximizes the dose to the cancer while minimizing exposure to the surrounding healthy liver and other organs.
Systemic Treatments
When hepatocellular carcinoma has advanced, spread beyond the liver, or is not controlled by locoregional therapies, doctors turn to systemic treatments. These therapies circulate through the bloodstream to treat cancer cells throughout the body and represent a significant advance over traditional chemotherapy.
Immunotherapy is a foundational treatment for advanced HCC. It uses drugs called immune checkpoint inhibitors to help the body’s immune system recognize and destroy cancer cells. Cancer cells can produce proteins that act as a “brake” on the immune system; checkpoint inhibitors release this brake, allowing immune cells to attack the cancer.
Targeted therapy is another pillar of systemic treatment. These drugs interfere with specific molecules involved in the growth and spread of cancer cells. For HCC, tyrosine kinase inhibitors (TKIs) are frequently used to block signals that promote cancer cell growth and the formation of new blood vessels that tumors need to survive.
Current strategies often combine these two approaches. A standard of care for advanced HCC is the combination of an immune checkpoint inhibitor with a targeted therapy agent. This dual attack on the cancer’s growth pathways and its ability to hide from the immune system is more effective than using either drug alone. While traditional chemotherapy has a role in some cases, it is less common as a first-line treatment due to the efficacy of these newer therapies.
Prognosis and Evolving Strategies
The prognosis for unresectable HCC is influenced by the extent of the cancer, liver function, and treatment response. The modern approach emphasizes long-term disease control and quality of life, aiming to transform HCC into a manageable condition. Palliative care, which focuses on managing symptoms and improving comfort, is an integral part of this strategy from the start.
A development in treatment is the concept of “downstaging.” This strategy uses locoregional and systemic therapies to shrink tumors within the liver. In some cases, tumors that were initially unresectable can be reduced enough that a patient becomes eligible for curative treatments like surgical resection or a liver transplant. This shows that an initial unresectable diagnosis is not necessarily permanent.
The field of HCC treatment is continuously evolving through ongoing research. Clinical trials provide patients with access to the next generation of treatments before they are widely available, investigating novel drug combinations and new therapeutic agents. This progress offers more personalized options for managing unresectable HCC, aiming to extend survival while maintaining quality of life.