Metastasis

ALSO KNOWN AS: Metastatic disease, metastatic cancer

RELATED CONDITIONS: Bone cancer, lung cancer, nodal involvement

DEFINITION: Metastasis is the movement or spreading of cancer cells from their original site to other areas of the body. The capacity to metastasize is a characteristic of all malignant tumors. Cancer cells can enter the bloodstream and flow to any part of the body, making a new home for themselves. Different cancers have different patterns of spreading. When cancer comes back in a patient at a site distant from the original location, although the patient appears to be free of cancer, this is called metastatic recurrence.

Risk factors: Whether cancer cells will metastasize to other parts of the body depends on many factors, including the type of cancer, the stage of the cancer, and the original location of the cancer. Tumors are usually classified as either benign or malignant. Malignant tumors can spread by invasion and metastasis, while benign tumors just grow locally. Often, the term “cancer” is used only in reference to malignant tumors, not benign ones.

Etiology and the disease process: Metastasis can occur through the circulatory system, the lymphatic system, or both routes. Common sites for metastasis are the adrenals, the liver, the brain, and the bones. Different cancer types have different metastatic tendencies; that is, the origin of the cancer can often predict the location of metastatic tumor formation. For example, colon cancer will often metastasize to the liver, while prostate cancer tends to metastasize to the bones. Similarly, in women, stomach cancer will often metastasize to the ovaries. It is believed that the migrating cancer cells attempt to find new organs that resemble the local environment of the primary (original) tumor, where they can engraft and thrive. Breast cancer cells, in a high-calcium environment due to the proximity of calcium-containing breast milk, will often metastasize to the bone marrow (also a site of high calcium content).

Cancer will often spread to neighboring lymph nodes; however, this may be referred to as “nodal involvement” or “regional disease” rather than metastasis. Cancers that are highly metastatic (and therefore particularly dangerous) have been found to secrete proteins that degrade the extracellular matrix that connects cells and separates the organs. Such cells may have a greater ability to leave the primary tumor location, migrate into the blood vessels, and then leave the circulation at a remote site. Once cancer cells engraft at a new location, they must induce the growth and infiltration of new microscopic blood vessels to grow in size. Some treatment approaches have attempted to target and interfere with the ability of metastatic tumors to induce new blood vessel growth.

Incidence: Metastatic disease is common in many late-stage cancers. Cancers that frequently are the source of metastasis are melanomas and cancers of the lung, breast, colon, kidney, prostate, and pancreas. Therefore, the incidence of metastatic cancer is similar to the incidence of these common cancers after they progress to a metastatic stage.

Symptoms: The exact symptoms experienced by patients with metastatic cancer depend on the type of disease. For instance, lung metastasis can cause coughing or shortness of breath. Brain metastasis can cause symptoms of confusion, seizures, or even coma. Liver metastasis can reveal itself as abdominal pain or jaundice. Bone metastasis is associated with pain in the bones.

Screening and diagnosis: Early metastatic disease may have no signs at all. The more advanced a cancer, the easier it usually is to detect. Each diagnosis of metastasis must be evaluated individually and with care. The extent of each cancer must be determined, and all the potential sites of metastasis must be studied. Metastatic tumors are quite common in the late stages of cancer. Cells collected from a secondary metastatic tumor, when examined under a microscope, can often be identified as cells of the type found in the primary cancer. Therefore, an appropriate treatment regimen may be one that is known to be effective in treating the primary tumor type. The terminology used to describe a metastatic tumor refers to the primary tumor type. For example, breast cancer cells that metastasize to the bone are referred to as “metastatic breast cancer” instead of “bone cancer.”

Advances have been made in the diagnosis of metastatic cancers. Liquid biopsies can detect tumor-related DNA in patients' blood, and devices that can detect cancer biomarkers in bodily fluids can also allow for earlier detection of metastatic cancer. Artificial intelligence is also increasingly deployed to analyze imaging and determine the extent of cancer spread. 

Treatment and therapy: Treatment of metastatic cancer varies widely, depending on the type of cancer and where it has metastasized. Common treatment options include surgery, radiation, and chemotherapy. Biological therapy, radiosurgery, hormone therapy, and laser-immunotherapy can also be treatment options for specific types of metastatic cancer. Treatment must address the symptoms of the metastatic disease along with the primary cancer. Other factors that must be considered in selecting the most appropriate treatment include the size of the metastatic tumor and the patient’s age and well-being.

Advances have been made in treating specific types of metastatic cancers in the twenty-first century. For the treatment of metastatic pancreatic cancer, the US Food and Drug Administration approved a new chemotherapy called NALIRIFOX, which extended patients' lifespans by two months. New drug combinations were also approved for metastatic prostate cancer as well. For the treatment of metastatic melanoma, medical researchers developed the first cell-based therapy for solid tumors. This therapy involved injecting lymphocytes from a patient’s tumor back into the patient, allowing them to attack the cancer cells. In clinical trials, one-third of participants saw their tumors shrink. 

Prognosis, prevention, and outcomes: When a patient is diagnosed with cancer, it is important to determine whether the disease is local or has spread to other locations. The tendency of cancer to spread to secondary organs is what makes the disease potentially life-threatening.

Bibliography

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