Advanced liver cancer: Symptoms, treatment, and outlook

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According to the American Cancer Society, advanced or metastatic liver cancer is liver cancer that has spread to the lymph nodes or other organs.

There are different staging systems for diagnosing the stage of liver cancer. The American Joint Committee on Cancer (AJCC) TNM staging system is the most common in the United States.

The TNM system uses the following information to stage the cancer:

• Tumor: Doctors look at the size of a tumor and whether it has grown, the number of tumors, and whether the cancer has spread to nearby blood vessels.
• Lymph nodes: Doctors check whether the cancer has spread to nearby lymph nodes.
• Metastasis: Doctors check whether the cancer has spread to distant areas of the body, such as distant lymph nodes, organs, or the bones.

The TNM staging system also uses numbers to provide further detail. Higher numbers indicate the cancer is more advanced. Doctors refer to this as stage “grouping.”

The stage grouping also has an AJCC stage. For advanced liver cancer, it includes the stages 4A and 4B:

• 4A stage: One or multiple tumors of any size that have spread to nearby lymph nodes but not to any distant areas.
• 4B stage: One or multiple tumors of any size that may or may not have spread to nearby lymph nodes but have spread to distant areas, such as the lungs or bones.

Symptoms of liver cancer may not appear in its early stages. They typically show up in later stages.

Symptoms may include:

• loss of appetite
• unintended weight loss
• feeling full after not eating much
• nausea
• vomiting
• enlarged liver, which can feel like fullness under the ribs on the right side of the abdomen
• enlarged spleen, which can feel like fullness on the left side of the abdomen
• abdominal pain
• pain near the right shoulder blade
• abdominal swelling or fluid buildup
• itching
• jaundice, which is a yellowing of the skin and eyes
• fever
• enlarged veins on the abdomen
• abnormal bruising or bleeding

Liver tumors can produce hormones that may also cause:

• high levels of calcium in the blood, which may cause:
  • confusion
  • nausea
  • weakness
  • muscle problems
  • constipation
• low blood sugar, which may cause:
  • dizziness
  • fainting
  • fatigue
• high cholesterol
• breast enlargement
• testicle shrinkage
• high red blood cell count, which may make a person appear red or flushed

If cancer has spread to other areas of the body, people may also experience other symptoms, such as bone pain or respiratory symptoms.

Where does liver cancer spread to?

Liver cancer can spread to nearby structures, such as the lymph nodes, as well as distant organs in the body.

According to a 2018 analysis, the most common areas for liver cancer to spread to are the:

• lungs
• bones
• adrenal glands

Risk factors for liver cancer include:

• hepatitis B virus (HBV) infection
• hepatitis C virus (HCV) infection
• cirrhosis, which is a scarring of the liver
• heavy alcohol consumption
• cigarette smoking
• aflatoxin B1, a poison that can grow on certain foods stored in hot, humid places
• nonalcoholic steatohepatitis (NASH), a severe type of nonalcoholic fatty liver disease

Certain genetic conditions can also increase the risk of liver cancer, including:

• untreated hereditary hemochromatosis
• alpha-1 antitrypsin deficiency
• Wilson disease
• glycogen storage disease
• porphyria cutanea tarda

To diagnose liver cancer, doctors may perform and order the following tests:

• physical examination and medical history
• liver function tests, which are blood tests to check for abnormal levels of substances in the blood
• tumor marker tests to measure levels of alpha-fetoprotein (AFP)
• CT scan or MRI scan to examine the liver and nearby areas
• ultrasound
• biopsy to take a tissue or cell sample to examine for signs of cancer
• PET scan, which can help doctors stage liver cancer

In most cases, surgery is not suitable for treating advanced liver cancer because the cancer is widespread. Instead, doctors may prescribe medications to target the cancer.

If the liver is still functioning well enough, treatment options may include atezolizumab (Tecentriq), an immunotherapy drug, with bevacizumab (Avastin), a targeted therapy drug.

Doctors may also prescribe sorafenib (Nexavar) or lenvatinib (Lenvima), which are targeted therapy drugs.

If the options above are no longer effective, other drugs may include:

• other targeted drugs, such as:
  • regorafenib (Stivarga)
  • cabozantinib (Cabometyx)
  • ramucirumab (Cyramza)
• other immunotherapy drugs, such as:
  • pembrolizumab (Keytruda)
  • nivolumab (Opdivo) combined with ipilimumab (Yervoy)

People may also want to discuss the option of clinical trials with a healthcare professional. Clinical trials look at new forms of targeted therapy, immunotherapy, chemotherapy, and radiation therapy, which may have promise.

Doctors may also prescribe radiation therapy to help manage any pain symptoms.

Various factors can affect the outlook of a person with advanced liver cancer, including:

• tumor size and how much of the liver it affects
• where in the body the cancer has spread to
• how well the liver is functioning
• overall health
• whether cirrhosis is present

The American Cancer Society provides the following 5-year relative survival rates for people who received a liver cancer diagnosis between 2012 and 2018:

• Regional: 13%
• Distant: 3%

Regional means the cancer has spread outside of the liver to the lymph nodes or other nearby structures. Distant means the cancer has spread to distant areas, such as the bones or lungs.

Current survival rates may have improved due to advances in research and treatments.

Life expectancy without treatment

According to a 2018 analysis of cases from the Surveillance, Epidemiology, and End Results (SEER) database, the survival time of metastatic liver cancer without treatment was rarely longer than 62 days.

However, this research is from 2018, so figures may have changed since then. Survival rates and life expectancy may also vary depending on other factors, such as age, overall health, and where the cancer has spread.

Below are some common questions about advanced liver cancer.

Is it terminal?

Doctors may not be able to cure advanced liver cancer, but treatments may help manage symptoms and prolong life while aiming to improve quality of life.

How long can a person live with metastatic liver cancer?

Life expectancy may vary depending on many factors, such as a person’s age, sex, and overall health, where the cancer has spread, and the cancer’s response to treatment.

According to the SEER database, between 2000 and 2019, the relative 5-year survival rate for liver and intrahepatic bile duct cancer was 4.3% for females and 2.8% for males.

Advanced liver cancer is cancer that begins in the liver but has spread to nearby structures, lymph nodes, or distant areas in the body, such as the lungs or bones.

Surgery is not usually an option for advanced liver cancer. Treatments may include immunotherapy, targeted therapy drugs, and radiation therapy.