Metastatic Cancer

Metastatic Cancer

Also called: Metastatic Disease

Reviewed By:
Martin E. Liebling, M.D., FACP
Mark Oren, M.D., FACP

Summary

Metastatic cancer is cancer that has spread from its original site in the body to other parts of the body. It occurs when cells break free from a tumor and travel to other locations. These cells often form “colony” tumors and continue to grow in the new location. When cancer has spread to other tissues, it is known as metastasis.

Metastatic cancer should not be confused with cancer that has spread locally. Cancers that spread locally are found in nearby organs and tissues. For example, a tumor in the mouth may spread into the throat. With distant metastatic cancer, the disease spreads through the bloodstream or lymphatic system to other parts of the body.

In addition, metastatic cancer is not always the same as advanced cancer. An individual may be diagnosed with metastatic cancer even if only a small number of cells have spread. Minimally spread cancer may be treated successfully. However, if metastatic cancer has significantly invaded tissues and organs causing damage, it may advanced cancer.

Risk factors associated with metastatic cancer are the same as those for cancer in general. Lifestyle factors that can increase the risk of cancer include tobacco use, alcohol abuse, too little exercise and unhealthy diet. These factors contribute to the development of approximately two-thirds of all fatal cancers. Certain inherited genes also can increase a person’s risk for some cancers. The most common sites of metastasis include the bones, lungs, liver and brain.

Metastases are responsible for the majority of cancer-related deaths, according to the American Cancer Society (ACS). With the exception of non-melanoma skin cancer, about one-third of patients have metastasis at the time of their cancer diagnosis.

A great deal of research is devoted to the prevention of cancer metastasis. Currently, the only way to prevent cancer from spreading is early detection and effective treatment of the primary disease. There are a number of screening tests that can help detect early cancers, such as prostate, breast and colon cancer. These tests, however, cannot find all cancers and some may not be detected until after they have metastasized. In addition, there are some cancers that cannot be detected reliably with screening methods.

About metastatic cancer

Metastatic cancer is a form of the disease that spreads from one area of the body to another. Distant metastasis occurs when cancer cells break loose from a tumor and enter the bloodstream or the lymphatic system. These cells take root and grow in areas more or less distant from the primary site. Local metastsis occurs when the primary tumor grows into areas adjacent to the primary site.

Eventually, the cancer cells can take root in a new area of the body and begin to form another tumor. The cells in the new, metastatic tumor come from the original tumor site and are named for the area where that tumor originated. For instance, if a tumor spreads from the breast to the lungs, it is still considered breast cancer to the lungs, because the cancer cells are those that originated in the breast. If cancer has spread widely throughout the body, physicians may be unable to determine the primary site. This condition is referred to as cancer of unknown primary site or CUPS.

Risk factors associated with metastatic cancer are the same as those for cancer in general. Lifestyle risk factors include tobacco use, alcohol abuse, too little exercise and unhealthy diet. Together, these factors account for about two-thirds of fatal cancers, according the American Cancer Society (ACS). Some cancers have genetic risk factors, meaning individuals inherit genes that place them at higher risk for cancer. Genetic factors are associated with a lower number of cases, approximately 5 to 10 percent of all cancers.

Metastasis should not be confused with local spread. A cancer that spreads locally continues to grow in the same location that it originally developed. Local spread of a cancer may extend into nearby tissues and organs, but it does not spread to other parts of the body. Cancer that begins in the mouth and spreads to the throat is an example of local spread.

Cancer that has metastasized does not necessarily mean it is advanced cancer. Some tumors may spread only minimally but they will still be considered metastatic cancer. However, metastatic cancer that has invaded tissues and organs causing substantial harm is likely to be advanced cancer. Minimally spread metastatic cancer may be cured while advanced cancer will have a poorer prognosis. Each year, more than half a million people will die from advanced cancer in the United States, according to the ACS.

In metastasis, cancer cells spread to other areas, including the lymph nodes via the blood or lymph vessels (tubes that contain lymph cells and immune system cells). The lymph nodes are the bean-shaped collections of immune-system cells located throughout the body that help to fight infections and cancer. They are located throughout the body in areas sucj as the armpits, throat and groin. When cancer cells settle into the lymph nodes, they may continue to grow and the prognosis for survival becomes poorer.

When cancer spreads to the lymph nodes near the primary cancer site, doctors sometimes call this regional spread. For example, breast cancer may regionally spread into the lymph nodes under the arm. This is to differentiate it from distant metastasis, which generally occurs when the cells travel to other organs or tissues and develop new tumors.

In tubular body structures like the bronchi or colon, there may be so called drop metastases, where the malignant cells migrate down the tube and implant and grow, rather than travel through the blood and lymph vessels.

Metastasis develops in several phases:

  • Phase one. As a tumor grows, cancer cells divide and are more likely to spread.

  • Phase two. In a process known as angiogenesis, the tumor creates new blood vessels that feed the cancer and cause it to grow.

  • Phase three. Additional cells develop in the tumor that are both faster growing and more likely to spread. Before spreading, these cells produce an enzyme that allows them to break loose from the tumor’s extracellular matrix, which acts like a mortar that holds together the cells in the tumor. These cancer cells must undergo several other changes that enable them to break through the walls of blood vessels or lymphatic vessels.

  • Phase four. Tumor cells enter the blood or lymph circulation. The immune system destroys most of these cells, but some have undergone changes that make them resistant to the immune system. This allows them to survive and travel to other parts of the body.

  • Phase five. The cells have the ability to travel to and grow in distant organs or lymph nodes.

  • Phase six. Tumors actually grow into another organ or lymph nodes by penetrating blood vessel and lymph vessel walls.

  • Phase seven. Angiogenesis must occur in the new environment.

  • Phase eight. The cancer cells must be able to grow in their new environment and avoid the body’s attempts to reject them.

Metastatic cancers are discovered in several ways. Sometimes they are found during the diagnosis of a primary cancer. In other cases, signs of the metastatic cancer – such as enlarged lymph nodes – may be found before a physician is even aware of the presence of a primary cancer. The ACS estimates that with the exception of non-melanoma skin cancers, about one-third of cancer patients have metastasis at the time of diagnosis.

Metastases are responsible for the majority of cancer-related deaths, according to the ACS. Though primary cancers in many organs (including the prostate, breast, colon and lungs) can be removed during surgery, it is metastasis of these cancers that causes the most serious consequences for the patient.

Types and differences of metastatic cancer

Metastasis is generally divided into two categories:

  • Regional spread. Also known as lymph node involvement, it occurs in lymph nodes close to the area where the primary cancer originally developed. Regional spread can also include non-lymphatic metastasis, such as the skin with breast cancer.
  • Distant spread. Also known as metastatic disease, it occurs when cancer cells travel through the bloodstream or lymphatic system to other organs. 

Once the cancer has spread to a new area of the body, it is still named for the area of the body where it originated.  breast cancer that spreads to the lungs is classified as breast cancer, not lung cancer.

In some cases, metastasis emerges after a cancer has been treated and the patient appears to be in remission. When the cancer reappears in the same organ or in another organ or tissue, it is known as recurrence. There are three types of recurrence:

  • Local recurrence. Cancer that returns to the original organ, or a nearby organ or tissue.
  • Regional recurrence. Cancer that returns to lymph nodes near the originally affected area, or to the area surrounding the lymph nodes.
  • Distant recurrence. Cancer that returns to any other part of the body not included in a local or regional recurrence.

Risk factors and causes of metastatic cancer

The risk factors associated with metastatic cancer are the same as those of any cancer. Genetic risk factors account for between 5 percent and 10 percent of all cancers, according to the American Cancer Society (ACS). The bulk of cancers are caused instead by factors related to lifestyle or the environment. These include:

  • Tobacco use
  • Unhealthy diet
  • Lack of exercise
  • Alcohol abuse
  • Radiation
  • Infectious agents such as certain viruses
  • Toxic chemicals or other environmental factors

Some types of primary cancers are especially prone to metastasizing to specific areas of the body. These include the following:

Primary SiteMetastases
BreastLymph nodes (underarm), lung, bone, liver, brain
Colon and rectumLymph nodes (next to bowels), liver, lung, bone
KidneyLymph nodes (next to kidney), lung, bone, liver, brain, skin
LungLymph nodes (next to lungs), other lung, adrenals, liver, bone, brain
OvaryLymph nodes (in pelvis), liver, lung, abdominal cavity
PancreasLymph nodes (in abdomen), liver, lung, bone, brain
ProstateLymph nodes (in pelvis), bone, lung, liver
Soft tissues (sarcoma)Lungs, bone, lymph nodes, brain
StomachLymph nodes (in abdomen), liver, lungs, brain, abdominal cavity
ThyroidLymph nodes (in neck), lungs, liver, bone

The risk of metastasis in an organ can sometimes depend on the specific type of cancer that is present. For example, squamous cell and basal cell skin cancers rarely spread. On the other hand, malignant melanoma skin cancers are more likely to spread to the lymph nodes, lungs, liver, brain and other organs.

In addition, most cancer cells that break free of a tumor are trapped in the next “downstream” capillary bed or set of lymph nodes. This is why metastatic cancers usually appear near the original cancer site. In addition, cancers frequently spread to the lungs because the heart pumps blood from all parts of the body through the lung’s blood vessels. The liver is also a common site of metastasis because cancers in the stomach and intestines are carried through blood to the liver. Despite these general patterns, some metastases are able to find and invade specific sites in various locations throughout the body.

Diagnosis methods for metastatic cancer

A physician will review a complete medical history and conduct a physical examination as the initial steps in the diagnosis of cancer. In many cases, this exam will be combined with imaging tests or blood tests if the physician suspects the spread of cancer. However, confirmation of cancer can usually be confirmed only with a biopsy of the suspected tissue. This helps determine whether an abnormality is the result of cancer, or another illness such as infection.

Once a patient’s primary cancer has been diagnosed, the physician will try to determine how far it has spread. This is known as staging. The tumor’s exact type and size will help the physician to determine the risk of metastasis.

Tests used to diagnosed metastatic cancer include:

  • X-rays. Creates an image of part of the body by using low doses of radiation. Chest x-rays and bone x-rays can help spot masses and evidence of their growth. However, they are not effective in determining the type of cancer present or where it began.

  • Computed axial tomography (CAT) scan. Uses multiple x-ray images, taken from different angles, to create three-dimensional images of body structures. CAT scans can identify signs of metastatic cancer such as enlarged lymph nodes or masses in internal organs.
  • Magnetic resonance imaging (MRI). Produces clear cross-sectional or three-dimensional images of the body’s tissues, even through bone and other obstructions. This produces images similar to those of a CAT scan and, for some areas, with better detail. MRI may be completed with dye (contrast medium) that can help highlight tissues and organs.

  • Ultrasound. Sends and receives high-frequency sound waves to create images of internal organs or tissues. It can reveal masses in some organs, such as the breast or uterus in women.

  • Radionuclide bone scan. Test in which tiny amounts of radioactive materials (tracers) are introduced into the patient’s body. The tracers emit a type of energy called gamma rays, which are detected by special devices and converted to images. This scan can help reveal whether a cancer has metastasized to bones.

  • Positron emission tomography (PET) scan. A glucose substance is combined with small amounts of radioactive material and injected into a patient’s vein. Cancer cells in the body absorb the substance and they appear as hot spots on th image. PET scan is frequently used to determine the location and extent of cancer metastasis in the body.

  • Tumor markers. Some types of cancer release substances into the bloodstream that can be detected through blood tests. These substances, known as tumor markers, sometimes suggest the presence of metastatic cancers, especially when levels of the substance are very high.

  • Other blood chemical tests. Metastasis to certain organs can damage their cells or alter their metabolism. When this occurs, it may cause certain substances to be released into the bloodstream that can then be detected during blood testing.

  • Biopsy. Procedure to obtain a sample of suspected tissue or bone that is sent to a laboratory for analysis. The analysis is done by a specialized physician known as a pathologist. Biopsy is the definitive way to diagnose cancer and is necessary to determine the presence of the disease.

  • Laparotomy. Surgical technique that involves small incisions in the abdomen to allow a suspicious area to be viewed and biopsied if necessary.

  • Examination of body fluids. Cancer cells discovered in the cerebrospinal fluid indicate that cancer has spread to the brain or spinal cord. Cancer cells can sometimes be found in the space around the lungs (pleural fluid) or in the abdomen (peritoneal fluid). The presence of such cells indicates metastasis in those organs or in their lining membranes.

If cancer appears in more than one area of the body, physicians will try to diagnose whether the second cancer is directly related to the first, or if it developed separately. This is important, because treatment options and the patient’s ultimate prognosis varies depending on whether a cancer is primary or metastatic.

Treatment options for metastatic cancer

The precise treatment method for metastatic cancer will depend on where the cancer started and where it has spread. As a general rule, primary, localized cancers are treated with surgery or radiation therapy while metastatic cancers are treated with chemotherapy, hormone therapy or another form of systemic therapy. These treatments are usually taken by mouth or injected so they can enter the bloodstream. This allows the medicine to reach cancer cells that have spread throughout the body.

Treatments for metastatic cancer include:

  • Chemotherapy. Powerful drug treatment that targets fast-dividing cancer cells and kills them or interferes with their ability to reproduce and spread throughout the body. It is used as a primary therapy in treating metastatic cancers such as lymphomas and germ cell tumors of the ovaries, testicles or uterus. Chemotherapy may be used before or after other treatments, such as surgery or radiation therapy, to prevent the spread of cancer.

  • Hormone therapy. Used to treat certain cancers that depend on hormones to grow and spread. Patients who undergo this treatment sometimes take medications that reduce the levels of certain hormones, such as estrogen (in women) and testosterone (in men). In other cases, patients may take drugs that prevent cancer from receiving the hormones they need to grow. Hormone therapy medications may be used to treat metastatic cancers of the breast, prostate, ovaries or endometrial tissue.
  • Radiation therapy. Uses a specific type of radiation to kill or shrink cancer cells. Radiation targets fast-dividing cancer cells and disrupts or destroys their genetic material, preventing the cells from continuing to grow and spread throughout the body. Radiation therapy is often used to keep primary cancers from metastasizing, or to relieve symptoms once the cancer has spread too far to be cured. Radiation therapy may be provided from an external machine or internally through the use of tiny implanted radioactive “seeds”.

  • Biological therapy. Biological therapy drugs are medications that stimulate the body’s immune system to better recognize and attack cancer cells. These medications repair, stimulate or enhance the immune system or, in some cases, target the cancer cells directly.

  • Surgery. In many cases, surgery is not an option for metastatic cancers that have spread too far to be completely removed. However, in some cases, surgery may help patients live longer with fewer symptoms.

The following therapies are most effective in treating various forms of metastatic cancer, according to the American Cancer Society (ACS):

MetastasesTreatments
BoneSystemic chemotherapy and/or hormonal therapy for cancers likely to be sensitive to these treatments

External beam radiation therapy

Radiopharmaceuticals (radioactive drugs)

Bisphosphonates (for bone strengthening)

Surgery to prevent or repair fractures

Clinical trials of new drugs, radiation techniques or other types of treatment (immunotherapy, gene therapy, etc.)
Brain and spinal cordSystemic chemotherapy and/or hormonal therapy for cancers likely to be sensitive to these treatments

External beam radiation therapy

Surgery

Clinical trials of new drugs, radiation techniques or other types of treatment
LiverSystemic chemotherapy and/or hormonal therapy for cancers likely to be sensitive to these treatments

Surgery

Ablative therapy to destroy the cancer without removing it. Treatment may include freezing, heating or injecting concentrated alcohol to kill cells, embolization (plugging up blood supply to the cancer)

Internal radiation therapy

Clinical trials of new drugs, radiation techniques or other types of treatment
LungSystemic chemotherapy and/or hormonal therapy for cancers likely to be sensitive to these treatments

External beam radiation therapy

Surgery

Clinical trials of new drugs, radiation techniques or other types of treatment

Prevention methods for metastatic cancer

The best way to prevent metastatic cancer is to detect, treat and remove primary cancers before they spread. For this reason, the American Cancer Society (ACS) recommends that individuals receive routine screening for certain cancers. For patients of certain ages or in high-risk categories, screening examinations may occur at an earlier age or more frequently. Screening tests are available for several cancers, including cancers of the skin, breast, prostate, colorectal and cervix.

Patients can also help prevent metastatic cancer by making the basic lifestyle choices that help prevent primary cancers. These include not using tobacco products, limiting alcohol consumption, getting regular exercise and eating a nutritious diet. However, despite all of these steps, people may still develop metastatic cancer.

Ongoing research

Researchers are presently studying a number of areas related to metastatic cancer. Scientists are focusing on the process that causes cells to break off from tumors and spread throughout the body. The areas of research include:

  • Drugs. Researchers are examining a class of drugs known as bisphosphonates, which may help reduce the production of growth factors in both cancer cells and normal bone cells. These drugs are currently used to strengthen bones and help relieve bone pain. Scientists are investigating their role in lowering bone metastasis.  In addition, researchers are developing and testing new chemotherapy drugs and drug combinations for cancer treatment.
  • Immunotherapy. Commonly used for metastatic melanoma, researchers are hoping to expand the use of this type of treatment for other cancers, such as lymphoma, breast and prostate cancer.
  • Angiogenesis. Angiogenesis is the formation of blood vessels, which can further develop cancer cells. Researchers are examining ways to prevent angiogenesis through drugs to prevent cancer cells from receiving nourishment for growth. Several of these drugs are being tested in clinical trialsand some, such as thalidomide and newer chemicals are being used clinically.
  • Gene therapy. Scientists continue to study gene changes that promote the metastasis of cancer. They are developing technology to eliminate abnormal genes and place new, healthy genes inside cancer cells.

Questions for your doctor about metastasis

Preparing questions in advance can help patients to have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about metastatic cancer:

  1. What is the primary site of my cancer?
  2. What is the likely location for my cancer to metastasize?
  3. What can be done to help reduce the chance of metastasis?
  4. Can any test predict the likelihood of metastasis?
  5. What tests will be used to determine if my cancer has metastasized?
  6. Do I have local, regional or distant metastasis?
  7. Which organs or areas of my body has the cancer invaded?
  8. What are my treatment options?
  9. What are the risks of these treatments?
  10. What is the prognosis for my type and stage of cancer?
  11. Am I a candidate for clinical trials?
  12. Can you recommend a support group for me and othe family members?
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