What is a Metastasis and Why, How, and Where Do They Happen

Definition and Importance of Metastases With Cancer

diagram of caner cells spreading through tissue
What is the meaning of the term metastasis?. istockphoto.com

What does the word metastasis mean? How do cancers spread to other regions of the body, why do they spread (in contrast to benign tumors,) and what are the most common sites of metastases?

Definition of Metastasis

A metastasis is defined as the spread of cancer cells from their primary location (the organ in which the cancer began) to another region of the body. Cancer that has spread in this way is called metastatic cancer. 

Metastatic cancer is named based on the site where the cancer began. For example, if lung cancer spreads to the bones, it would not be called “bone cancer” but rather “lung cancer metastatic to the bones.” In this case, when the metastatic cells are looked at under the microscope they would be cancerous lung cells, not bone cells.

Some cancers are metastatic at the time of diagnosis, while others become metastatic after the cancer has progressed, or recurs. When a cancer is gone (or at least is unable to be detected by scans) and then later recurs at a site away from the original cancer, it is termed a "distant recurrence." In staging cancers, a tumor that has metastasized is usually considered stage 4.

Importance of Metastases

The ability to metastasize is one major characteristic that distinguishes malignant (cancerous) tumors from benign (non-cancerous) tumors. Some benign tumors can grow to be quite large, and cause significant problems, especially if they are in an enclosed space such as the brain. Yet these tumors do not spread to other regions of the body. 

Metastases are responsible for 90 percent of cancer deaths, and therefore significant research is in progress looking at both ways to treat metastases and ways to prevent this spread from occurring in the first place.                                                                     

How Do Cancers Metastasize (Spread)?

Cancer cells differ from normal cells in several ways, one of which is that cancer cells are able to detach from nearby cells in order to invade and spread to other tissues. Normal cells make adhesion molecules which act like glue, holding similar cells together. Cancer cells lack these adhesion molecules allowing them to break loose and travel. Another difference is that normal cells communicate with other nearby cells—in essence, being reminded of their boundaries. Cancer cells have devised ways to ignore these communication signals. Once a cancer cell is “loose” and mobile, it is able to travel. There are several different ways in which cancer cells spread:

  • Locally (regionally): When benign tumors grow they do so as a solid mass, as if there is a clear boundary containing them.  In contrast, cancer cells invade neighboring tissues in an invasive manner which can appear like tentacles.  It is, in fact, the claw-like extension of cancer into other tissues from which the name originates; cancer being derived from the Greek word for claw.
  • Through the bloodstream: Cancer cells can enter the bloodstream and travel to other regions of the body.
  • Through the lymphatic system: The lymphatic system is another network through which cancer cells can travel.
  • Through the airways (lung cancer): In addition to the methods of metastasis above, recent studies suggest that lung cancer, likely spreads through the airway of the lungs (aerogenous metastasis) as well, and this may be even more important than bloodstream metastasis for people with lung adenocarcinoma.

Once a cancer has spread, further steps are needed to ensure the cancer cells can continue to grow. One necessity is the formation of new blood vessels to feed the new tumor, a process called angiogenesis. Medications called angiogenesis inhibitors work to interrupt this process, making it difficult for tumors to establish themselves in new areas.

Where do Cancers Spread?

Most cancers have the ability to spread to any region of the body, but some sites of metastases are more common than others.

Sites of metastasis overall and with the most common types of cancers include:

  • The most common sites of metastasis overall include the bones, liver, and lungs.
  • The most common sites for breast cancer to metastasize are the bones, the brain, the liver, and the lungs.
  • The most common sites for lung cancer to spread are the adrenal glands, the bones, the brain, the liver, and elsewhere in the lungs. 
  • The most common sites for colon cancer to metastasize are the liver, the lungs, and the peritoneum.
  • The most common sites to which prostate cancer spreads are the adrenal glands, the bone, the liver, and the lungs.

Symptoms of Metastases

Symptoms of metastatic cancer can include those related to the presence of tumor in a particular area of the body to which a cancer has spread, as well as non-specific symptoms such as unintentional weight loss and fatigue. Some symptoms may include:

  • Lung metastases may cause a persistent cough, shortness of breath, or chest pain.
  • Brain metastases may cause headaches, vision loss, seizures, numbness or weakness of the arms or legs, and loss of balance.
  • Bone metastases may cause pain in the region where the affected bone is located, as well as an elevated calcium level in the blood (hypercalcemia of malignancy.) When cancer is present in a bone it can be more likely to fracture, and the first sign of a bone metastasis may be a pathologic fracture (fracture through a bone damaged by a tumor.)  When cancer spreads to the spine, it may cause spinal cord compression with resulting weakness of the legs and bowel or bladder dysfunction.
  • Liver metastases may cause jaundice (a yellow discoloration of the skin,) bloating, abdominal pain, and weight loss.
  • Metastases to the adrenal gland are often asymptomatic but important with regard to treatment.

Treatment of Metastatic Cancer

The treatment of metastatic cancer will depend upon the location of the primary tumor. Metastatic cancer cannot usually be cured, but it is treatable. Newer medications such as targeted therapies and immunotherapy are improving the survival rates for some people with metastatic cancer, and several medications are being studied in clinical trials which bring hope that further improvements in metastatic cancer treatment are near.

Some areas of metastases are, however, more difficult to treat than others. Due to a complex network of tightly knit cells referred to as the blood brain barrier, a barrier designed to prevent toxins from gaining access to the central nervous system, many chemotherapy drugs, and some targeted therapies are unable to reach areas of metastases in the brain. Studies are in progress looking at medications which are better able to penetrate into the brain, as well as other methods of treating these metastases. 

For some people who have one or only a few sites of metastases (oligometastases,) removing the metastasis with surgery or radiation may improve survival. The term metastasectomy is used to describe the removal of metastases and may be considered with some types of cancer with only a few metastases to the brain, liver, or lung.

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