What is metastatic cancer?

Metastasis means that the cancer has spread to a distant region from the organ from which it originated. 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: Cancer can spread from where it started to nearby areas by growing 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.

Lymph nodes are the most common place where cancer metastasizes. Cancer cells 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 most often spreads to the bones. Cancer cells originating from bone tissue tend to settle in the lung tissue most frequently.

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, that is, brain metastases; Headache , seizures, vision problems (such as blurred vision, double vision, visual field defects), dizziness may occur, while there may be complaints such as loss of appetite, bloating, early satiety, indigestion, jaundice (yellowing of the skin or eyes) due to liver metastases. 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.

What are the distinguishing features of metastatic cancer?

In order for a cancerous cell to be "metastatic", it must have the following characteristics:

Mobility and invasion

Invasion, the defining feature of malignancy, is the capacity of tumor cells 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 (connective tissue of the tumor). Motility, that is, the ability of cancer cells to move, is not sufficient alone for metastasis; If a cancer cell can successfully break away from a tumor focus but cannot subsequently survive, it cannot metastasize.

Ability to switch secondary zones

Cancer cells recruit new cells to the local microenvironment, mobilize immune/inflammatory cells, remodel other tissues, alter the metabolism of the surrounding stroma, inhibit all antitumor actions of the immune system, manipulate and alter the behavior of other cancer cells. It reconstructs the normal behavior of the extracellular matrix and other cells.

Plasticity

Primary or secondary tumors are not static; They are 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. Moreover, neoplastic cells can alter the growth rates, drug resistance, and metastatic capacity of other cells.

Ability to colonize secondary tissues

Colonization of secondary tissues is the prominent feature 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 for metastatic cancer?

Metastatic cancer is more difficult to treat than early-stage cancer. Treatment options are vastly different for each type of cancer. As a matter of fact, there is no single treatment method defined for cancer or metastasis. As researchers continue to make progress in treatment, certain types of metastatic cancer are increasingly curable. In some clinical situations, metastases can be treated in certain ways.

For brain metastases

Depending on the number of tumors and the extent of the 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 do not cause pain or risk of fracture, they can be monitored during systemic therapy or treated with medication. If severe pain is present or the bone is fragile, surgery and/or radiotherapy may be used for 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

Treatment of lung metastases depends on the number and size of the metastases and the extent to which the primary cancer is treated. In most scenarios, they will be treated in the same way (with the same drugs) as the primary cancer. If the metastasis is causing fluid to build up around the lung, an operation to remove the fluid (thoracentesis) to facilitate breathing and gluing of the lung membranes (pleurodesis) to prevent re-fluid may 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 will be treated in the same way (with the same drugs) as the primary cancer.

​In cases where there is 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. Liver transplantation is not usually 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 or 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.

Doctors 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.

Imaging tests use x-rays, magnets, radio waves, and computer technology. These tests create detailed images of bones and internal organs and structures to check for cancer.

Why is metastasis dangerous?

Metastasis is of great importance as most cancer deaths are due to the spread of primary cancer to distant sites. In most cases, cancer patients with localized tumors have a higher chance of survival than those with metastatic tumors.

Recent evidence suggests that between 60 percent and 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 a century ago, when the dates were 1889, as the 'seed and soil' theory. For example, bones are the preferred site for prostate cancer, colon cancer spreads to the liver, stomach cancer can metastasize to the ovaries. In the theory in question, it is stated that it is difficult for cancer cells to survive outside their primary foci. In other words, in order for cancer cells to spread, they need to find a place with similar characteristics. For example, breast cancer cells need calcium ions from breast milk to multiply. Therefore, since the bones are rich in calcium, there may be a bone spreading area.

Malignant melanoma supports melanocytes and nerves and therefore can spread to the brain as neural tissue and melanocytes originate from the same cell line in the embryo.

The 'seed and soil' theory was challenged by James Ewing in 1928. Ewing suggested that metastasis occurs by purely anatomical and mechanical means. Ewing suggested that the cancer cells spread through the lymphatic channels and blood vessels, noting that the cancer cells affect the 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. While it is possible to prevent metastasis in a significant group of patients, it is unfortunately not possible to prevent it completely.