Liver cancer develops when cells in the liver grow or reproduce uncontrollably. When they become particularly advanced or aggressive, they can spread to other organs.

Healthcare professionals consider any cancer that starts in the liver as liver cancer, even if it spreads to other areas of a person’s body.

“Metastasis” is a term doctors use to describe the spread of cancer from one part of the body to another. When diagnosing cancer, a doctor will classify its stage with a number from 1–4. For example, if a person has stage 4 liver cancer, it means the cancer has spread beyond the liver to nearby lymph nodes or organs further away.

Doctors may also categorize liver cancer as resectable (surgically treatable) or unresectable (too advanced for surgical operation).

This article explores how liver cancer spreads and the stages of liver cancer in more detail. It also discusses treatment and outlook for stage 4 liver cancer.

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Cancer develops when genetic changes stop cells from dying when they typically would or cause cells to grow or spread too quickly. This can lead to tumors.

During metastasis, cells can break away from the original tumors and travel to other parts of the body in the blood or lymphatic system. They may then form new tumors.

Hepatocellular carcinoma, which develops in the cells that make up the liver, is the most common type of liver cancer. Other rare types of liver cancer, such as hemangiosarcoma and angiosarcoma, develop in the cells that line the blood vessels in the liver. These rare types often grow rapidly.

Most of the time, when a doctor finds cancer in a person’s liver, it is a different type of cancer that has spread to the liver from another organ. A doctor may refer to this as “liver metastases.”

A doctor will assign a stage to a person’s cancer to determine:

  • how far it has spread
  • how quickly it has grown
  • the best way to try and treat it
  • the likely outlook

The stages mean the following in terms of tumor size and liver cancer spread:

  • Stage 1: A person has one tumor measuring around 2 centimeters (cm). Cancer has not spread to nearby lymph nodes or distant tissues.
  • Stage 2: A person has one large tumor (over 2 cm) that has grown into nearby blood vessels. Alternatively, a person may have more than one tumor, none of which is larger than 5 cm. The cancer has not yet spread to distant tissues or nearby lymph nodes.
  • Stage 3: A person has multiple tumors, with at least one that is larger than 5 cm. Alternatively, a person might have at least one tumor that has grown into a major vein in the liver (either the hepatic or portal vein). At this stage, it has not yet spread to distant tissues or nearby lymph nodes.
  • Stage 4: Cancer has spread from the liver to nearby lymph nodes or distant organs. Healthcare professionals may refer to this as metastatic liver cancer.

It is important to note that some healthcare professionals may use other staging systems that determine a person’s liver health.

It is often not possible to treat stage 4 liver cancer using surgery. In this case, healthcare professionals may describe it as “unresectable.”

However, a doctor may recommend nonsurgical treatments at this stage.

At first, doctors may treat advanced liver cancer with an immunotherapy drug, atezolizumab (Tecentriq), and a targeted therapy drug called bevacizumab (Avastin). They might also treat liver cancer with either sorafenib (Nexavar) and lenvatinib (Lenvima), which are also targeted therapy drugs.

Immunotherapy aims to trigger an individual’s immune system into attacking cancer directly. Targeted therapy locates cancer cells through specific proteins on their surface and attempts to kill them.

If initial treatment with these drugs does not work as intended, a doctor may recommend other targeted therapy drugs, including:

  • cabozantinib (Cabometyx)
  • regorafenib (Stivarga)
  • ramucirumab (Cyramza)

They might also try different immunotherapy drugs, including a combination of pembrolizumab (Keytruda) or nivolumab (Opdivo) with ipilimumab (Yervoy).

In some cases, they may recommend a person join a clinical trial to find out whether newer forms of treatment could help with their condition.

A medical team bases a person’s outlook on individual factors, such as:

  • age
  • overall health
  • the response of the cancer to treatment
  • treatments available at the time of diagnosis

They can use the 5-year relative survival rate to form a picture of how likely it is that treatment will work as intended. This figure shows how many people with the cancer in question were alive 5 years later, compared with how many people without the cancer survived for 5 years.

The 5-year relative survival rate for stage 4 liver cancer is 3%. This means that people with advanced or metastatic liver cancer are 3% as likely as those without the condition to live for another 5 years.

However, treatment methods advance all the time, and the 5-year survival rate comes from older data. This means a person receiving a diagnosis now may have a better outlook than the 5-year survival rate suggests. Additionally, the 5-year survival rate does not take someone’s individual health factors, such as age, into account.

Liver cancer spreads when cells break away from a tumor in the liver and move to other parts of the body. This is a feature of stage 4 liver cancer, which doctors may also refer to as metastatic liver cancer.

Healthcare professionals often recommend immunotherapy and targeted therapy to treat stage 4 liver cancer. A person should speak with a doctor about which treatments may work best for their condition and their individual outlook.