The spread of cancer in any part of the body from the tissue of origin to another tissue is called metastasis. Metastasis is an indication that the cancer is in a more aggressive behavior and at an advanced stage. Even after cancer cells have spread to another organ, it is still referred to by the name of the organ or tissue where it first developed. For example, colon cancer that has spread to the liver is not defined as liver cancer, it is expressed as colon cancer with liver metastases and is treated according to the colon cancer treatment principles.
What is Metastatic Cancer?
Metastasis becomes detectable when cancer cells spread from their origin to another part of the body via the bloodstream or lymphatic vessels and form new tumor foci.
Cancer can spread in one of three ways:
- Via tissue: The spread of cancer from the place where it first formed to nearby tissues through the neighborhood.
- Via the lymphatic system: Cancer cells can spread through the lymphatic vessels to other parts of the body.
- Via blood: Cancer cells can move through blood vessels to other parts of the body.
The most common place where cancer metastasizes is the lymph nodes. Cancer cells may also tend to spread to different organs such as the liver, brain, lungs, and bones. Some types of cancer are more likely to spread to certain organs, for example prostate cancer often spreads to the bones. Cancer cells originating from bone tissue also tend to settle in lung tissue.
What Are the Symptoms of Metastatic Cancer?
Complaints (ie symptoms) caused by metastatic cancer vary depending on the type of cancer and where it has spread. For example, common symptoms of cancer that has spread to the brain may be headaches, seizures, vision problems (such as blurred vision, double vision, visual field defects), and dizziness. Symptoms related to liver metastases include loss of appetite, bloating, indigestion, early satiety, jaundice (yellowing of the skin or eyes).
In some cases, cancer cells can spread even after the primary cancer has been treated. Metastatic tumors can occur months or even years after initial cancer treatment.
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What are the Distinctive Features of Metastasis?
In order for a cancerous cell to be “metastatic”, it must have the following characteristics:
Mobility and Invasion
The defining feature of malignancy is the tumor cells’ capacity to disrupt the basement membrane (a thin, fibrous, extracellular tissue matrix that separates the lining of an inner or outer body surface from the underlying connective tissue) and pass through the underlying connective tissue, the connective tissue of the tumor. Motility, that is, the ability of cancer cells to move, is not sufficient for metastasis alone. If a cancer cell can successfully break away from a tumor focus but does not subsequently survive, it will not metastasize.
Ability to Change Secondary Regions
Cancer cells recruit new cells to the local microenvironment, mobilize immune/inflammatory cells, remodel other tissues, cause alterations in the metabolism of the surrounding stroma, inhibit all antitumor actions of the immune system, and reconstruct the normal behavior of the extracellular matrix and other cells.
Plasticity
Primary or secondary tumors are not static. It is actually very dynamic at the cellular level. Cancer cells must adapt their metabolism to meet the demands that accompany rapid growth of the primary tumor and colonization of different metastatic sites. It is possible for neoplastic cells to alter the growth rates, drug resistance, and metastatic capacity of other cells.
Ability to Colonize Secondary Tissues
Colonization of secondary tissues is the hallmark of metastatic cancer. In the Hurst-Welch study, if a tumor cell or cells break off from the primary tumor and survive but cannot take root elsewhere in the body, it cannot metastasize.
What are the Treatment Options in Metastic Cancer?
Metastatic cancer is more difficult to treat than early-stage cancer. Treatment options vary greatly for each type of cancer. As a matter of fact, there is no single treatment method defined for cancer or metastasis. As researchers advance in treatment, certain types of metastatic cancer may be cured.
In some clinical situations, metastases can be treated in certain ways.
For Brain Metastases;
Depending on the number of tumors and the extent of disease in the rest of the body, treatment options may include surgery (in very specific cases), radiotherapy, gamma knife surgery, smart treatments, chemotherapy, and/or steroids.
For bone metastases
If bone metastases are not causing pain or risk of fracture, they can be treated with medication. If there is severe pain or the bone is fragile, surgery and/or radiotherapy may be done at the site of the injury. There are non-chemotherapy drugs that are known to reduce the risk of pain and fractures due to bone metastases.
For Lung Metastases
Depending on the number and size of the metastases and the treatment status of the primary cancer, the treatment of lung metastases is carried out. In most scenarios, it is treated in the same way (with the same drugs) as the primary cancer. If the metastasis causes fluid to form around the lung, an operation (thoracentesis) is performed to facilitate breathing and to remove the fluid. In order to prevent the formation of fluid again, the gluing of the lung membranes (pleurodesis) can be performed.
For Liver Metastases
There are several ways to treat liver metastases, depending on the type and extent of the primary cancer, as well as the number and size of liver metastases. In most cases, liver metastases are treated in the same way (with the same drugs) as the primary cancer.
In cases of limited disease, both primary and metastatic, there are different new approaches, such as surgery and radiofrequency ablation (RFA), radio or chemoembolization (such as TARE, TAKE), microsphere therapy, and liver transplantation is usually not an option for metastatic disease.
Note: In cases where the cancer is incurable, the mainstay of treatment is to slow the growth of the cancer, reduce or alleviate the symptoms it causes.
What Are the Stages of Metastasis?
The spread of cancerous cells to new parts of the body occurs through the following stages:
- Separation from primary tumor
- Invasion of tissues around the initial lesion and penetration of basement membranes
- Entry into blood vessels and survival in blood. (It is called hematogenous spread that spreads through blood vessels)
- Entry into the lymphatics or peritoneal cavity. (Spreading through lymph channels is called lymphatic spread)
- Lungs, liver, brain bone, etc. reach distant organ
- Formation of a new lesion with new blood vessels feeding the tumor. (The formation of new blood vessels is called angiogenesis.)
How Is Metastasis Controlled?
Some cancers are metastatic at diagnosis, while others become metastatic after the cancer has progressed or recurred. Physicians use different medical tests to help check for metastasis:
Laboratory tests involve checking body tissues, blood, urine, or other substances in the body. These tests help the care team know how the person’s organs are working.
It uses x-rays, magnets, radio waves, and computer technology for imaging tests, which create detailed images of bones and internal organs and structures to check for cancer.
Why is Metastasis Dangerous?
Metastasis is of paramount importance, as most cancer deaths result from the spread of primary cancer to distant sites. In most cases, cancer patients with localized tumors have a better chance of survival than metastatic tumors.
The new findings show that 60 percent to 70 percent of patients initiate the metastatic process at the time of diagnosis. In addition, even patients who have no evidence of tumor spread at the time of diagnosis are at risk of metastasis.
What is the Seed and Soil Theory of Metastasis?
Some organs are more prone to metastasis from primary tumors than others. This was first discussed by Stephen Paget as the ‘seed and soil’ theory when the dates were 1889. For example, bones are the preferred site for prostate cancer, colon cancer spreads to the liver, stomach cancer can metastasize to the ovaries. The theory in question states that it is difficult for cancer cells to survive outside their primary focus. In other words, in order for cancer cells to spread, they must find an area with similar characteristics. For example, breast cancer cells require calcium ions from breast milk to multiply. Therefore, since the bones are rich in calcium, there may be an area of spread.
Malignant melanoma supports melanocytes and nerves, and so can spread to the brain as neural tissue and melanocytes originate from the same cell line in the embryo.
In 1928, the ‘seed and soil’ theory was challenged by James Ewing; Ewing suggested that metastasis occurs by purely anatomical and mechanical means, suggesting that the cancer cells spread through lymphatic channels and blood vessels, noting that cancer cells affect regional lymph nodes close to the primary tumor.
Can Metastasis Be Prevented?
The risk of developing secondary cancer depends on many factors, such as the type of cancer and the age of the patient whose cancer develops. It is possible to prevent metastasis in a significant group of patients, but unfortunately it is not yet possible to prevent it completely.
