What is metastasis? Definition

Cancer that spreads from its place of origin to other regions of the body is called metastatic cancer and the process is called metastasis, the plural of which is metastases. It is referred to as stage 4 cancer.

Metastasis is defined as the formation of secondary and tertiary tumors in body tissues and organs away from the primary cancer site.

When examined under the microscope, metastatic cancer cells exhibit characteristics of the primary cancer cells and are not like the cells in the tissue where the metastasis has occurred. This is how doctors can detect the primary cancer source.

However, sometimes when metastatic cancer is diagnosed, it is not possible to detect the primary source of cancer. This type of cancer is called cancer of unknown primary origin, or CUP.

Virtually all cancers spread to other parts of the body. Chances of survival decrease once cancer spreads or has metastasized.

Death more often than not occurs due to metastasis and not from the primary tumor or primary cancer, which is cancer that first originates in the body. For example, in a patient where stomach cancer has given rise to metastasis in the liver, the patient will die of liver failure and not stomach cancer.

Metastasis often occurs during the late stages of cancer and accounts for 90 percent of all cancer–related deaths.

Metastatic cancer is named after primary cancer. For example, breast cancer that has spread to the lung is called metastatic breast cancer, not lung cancer. Oncology treats it as stage IV breast cancer and not as lung cancer.

How does cancer spread?

In the early stages, the cancer cells are confined to the primary tumor site. As the disease progresses, the cancer cells undergo genetic changes. They become more aggressive and breach the surrounding cells to invade the neighboring tissues and travel via the vascular, lymphatic, and transcoelomic routes to distant organs of the body.

Any type of cancer can undergo metastasis. This can happen in five ways:

1) Local metastasis or direct invasion

This is metastasis where the cancer cells of the malignant tumor spread and invade the neighboring tissues. The cancer cells have grown outside the body part it started in but have not yet spread to other parts of the body.

2) Lymphatic spread

Lymphatic spread of cancer is also called embolization and is the more common type of metastasis. The detached cancer cells from the primary cancer tumor, travel via the lymphatic system and get lodged in the immediate and then far-off lymph nodes to form the growth of a secondary tumor.

The lymphatic system is a distribution channel of fluid called lymph, which consists of lymphatic vessels and lymphatic nodes. The lymph carries among other things, the lymphocytes, to the various parts of the body. Lymphocytes are the immune cells responsible for the immunity of our body.

3) Metastasis through the blood circulation system

Once the primary malignant tumor grows and invades a neighboring blood vessel, the detached cancer cells travel through the bloodstream and get lodged in another organ or body tissue.

All the cancer cells that travel through the blood do not survive our immune system. But, just one cancer cell is enough to grow into a secondary malignant growth.

Metastasis through blood takes place through the veins and not the arteries. This metastasis through the blood is called the hematogenous spread of cancer or hematogeneous metastasis.

4) Transcoelomic spread

Transcoelomic type of metastasis occurs across cavities such as:

  • through the bronchi, which are the airways in the lungs,
  • across the pleural cavity, which is the cavity present between the two layers of the pleural sac and contains the pleural fluid. The pleural sac is the covering sac of the lungs.
  • through the pericardium, which is the sac covering the heart and contains the pericardial fluid. This spread of cancer cells through the pericardium is rare.
  • Transcoelomic spread through the peritoneal cavity. The peritoneal sac that covers the abdominal cavity and contains the peritoneal fluid forms the peritoneal cavity.

Examples of transcoelomic metastasis include:

  • An ovarian tumor that spreads through the peritoneal cavity
  • Mesothelioma is a malignant tumor seen in the pleura that spreads through the pleural cavity. This malignancy is an occupational hazard, caused by regular and over-exposure to asbestos or glass fragments and powder.
  • Other examples include cancers of the pancreas, colon, ovaries, stomach, intestines, and cervix.

5) Spread of cancer cells by transplantation.

Transplantation occurs by the mechanical transfer of cancer cells through surgical instruments during surgery or through a needle during an investigative biopsy.

Primary cancer sites and their common areas of metastasis

The most common sites for metastasis are the lung, liver, brain, and bone. Given below are some primary cancer sites followed by the most tissues/organs in the body where secondaries can travel.

Primary cancer site ——Main sites of metastasis

  • Breast —– Lungs, liver, bones
  • Colon —— Liver, peritoneum, lungs
  • Kidney —- Lungs, liver, bones
  • Lungs —–Adrenal gland, liver,
  • Melanoma —Lungs, skin, muscle, liver
  • Ovary ——  Peritoneum, liver, lungs
  • Pancreas —-Liver, lungs, peritoneum
  • Prostate —-  Bones, lungs, liver
  • Rectum —–  Liver, lungs, adrenal gland
  • Stomach —  Liver, peritoneum, lungs
  • Thyroid —–  Lungs, liver, bones
  • Uterus ——  Liver, lungs, peritoneum

Symptoms and signs of metastasis

Symptoms and signs of cancer metastasis vary and depend on the organ involved to which cancer has spread. Few examples include:

  • Cough, hemoptysis (blood in sputum), and dyspnea (shortness of breath) are the presenting symptoms when metastasis occurs to the lungs
  • An enlarged liver (hepatomegaly)  and jaundice ( yellowish discoloration of the eyes) are present when cancer spreads to the liver.
  • Headache, seizures (fits), and vertigo(a feeling of dizziness) are symptoms of metastasis that occurs in the brain.
  • Fracture of the affected bone and bone pain are symptoms of bone metastasis.
  • Lymph node metastasis shows an enlarged lymph node that is recognized on touch and local examination. This is called lymphadenopathy.

Diagnostic criteria of metastasis

Pathologically, a secondary tumor formed because of metastasis is similar to the primary tumor. For example, a primary malignant tumor in the breast will metastasize in the lung. The tissue of this secondary tumor in the lung will be similar to the tissue of the primary tumor in the breast and will not resemble the tissue of a primary lung cancer tumor. This helps the doctor or the oncologist to diagnose and locate primary cancer.

It is, therefore, that the cancer is named not according to the site of metastasis but according to the site of origin of cancer. For example, testicular cancer that has metastasized to the lungs is called testicular cancer and not lung cancer.

At times, when the patient presents himself late in the disease, a secondary tumor may be seen at the time of identification of the primary tumor.  At other times, the secondary tumor may be seen much later, even months or years later.

Nearly, in half the cancer patients, metastasis is detected, while in a large number of patients diagnosed with cancer, micrometastasis remains undetected with the currently available diagnostic techniques.

Sometimes, the secondary tumor is detected and diagnosed, while its source, the primary tumor is never found. This is called Cancer of Unknown Primary Origin or CUP.

Treatment options for metastasis

In spite of extensive and vigorous research in the last few decades, studies are far from conclusive. The one single factor that makes clinical management of cancer challenging is cancer’s property of “metastasis.”

The aim of treating metastatic cancer is to stop or slow its growth. There are several treatment options and each has its indications. Your doctor will decide which option is best for you.

What your doctor will choose depends on the type and location of your primary cancer, where it has spread, your past treatments, and the condition of your general health.

Your oncologist might start with one type of treatment and at times may switch to another option if the first treatment stops giving satisfactory results. He could start with a combination of therapies.

Treatment for metastasis often differs from that given for the original tumor. Besides treating the primary malignancy, treatment options for metastatic cancer include:

1.Local therapy concentrates on the local area of the tumor and options include:.

  • Surgery
  • Radiotherapy

2. Systemic therapy targets the entire body and options include:

  • Palliative or supportive treatment improves the quality of life of the patient by controlling the symptoms
  • Chemotherapy
  • Immunotherapy
  • Hormone therapy
  • Targeted therapy

3. Combination of the above

At times, the oncologist will put the patient on a combination of therapies when one therapy is not giving satisfactory results.

The rationale behind a combination therapy is to administer drugs that work by different modes of action. This reduces the chances of the cancer cells developing resistance. This enables the doctor to administer each drug at its optimal dose without serious side effects.

Forskolin

The incidence of metastasis is curtailed by the administration of forskolin or its analogs. Forskolin is a potent inhibitor of platelet aggregation. It is administered alone or with other drugs, which inhibit the aggregation of platelets.

It should be known here that platelet aggregation or clumping plays an important part in the formation of the secondary tumor that has metastasized through the blood.


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