Metastatic mesothelioma is mesothelioma that has spread to distant organs. It means that the mesothelioma is in an advanced stage. The mesothelioma survival rate is lower than that for many other types of cancer, particularly when it has metastasized.
Though the fine details of how a mesothelial cell (a cell in the membrane surrounding the lung, heart, abdomen, and in rare cases, the testicles) becomes malignant are unknown, the basics of how the disease develops are known. For example, researchers do not yet know whether the asbestos fibers directly interact with mesothelial cells directly or by the generation of toxic products that actually cause the cancer. But asbestos exposure is the only known cause of mesothelioma.
Asbestos fibers that are inhaled cause local irritation of the lung tissue in which they are lodged. This local irritation leads to the production of cytokines. Cytokines are chemicals that mediate various body processes. They induce cellular changes to the mesothelial and lung cells that lead to malignant transformation.
In a healthy state, genes that promote growth and suppress growth remain in balance so that cell division and cell growth only happen when needed. When those genes become damaged, the mechanism that suppresses unwanted cell division may be lost. If the growth-promoting genes are damaged, they can lose their ability to promote cell growth, or they can be damaged to increase growth promotion. If this happens, the growth-promoting mechanism stops responding to the growth suppressing genes and continue to multiply. If damage occurs to the genes that program cell death as well, the cell may turn malignant, becoming malignant mesothelioma in the case of asbestos exposure.
Malignant mesothelioma
With malignant mesothelioma, a tumor suppressor gene on chromosome 9 may play a role in the development of the disease. Growth stimulating genes may also play a role in the development of mesothelioma. Additionally, growth stimulation factors such as platelet derived growth factors (PDGF) may also be involved. Chromosome abnormalities on chromosomes 1, 3, 6, and 9 are commonly seen in mesothelioma patients, and sometimes loss of one copy of chromosome 22 is discovered in people with mesothelioma.
Mesothelioma is classified according to the site where the disease originated, such as malignant pleural mesothelioma (lungs), pericardial mesothelioma (the sac around the heart), malignant peritoneal mesothelioma (in the membrane around abdominal organs) or mesothelioma of the tunica vaginalis (the membrane around the testicles). The disease is also classified by mesothelioma stage. These characterizations will play a large role in determining the patient’s mesothelioma treatment options and eligibility for mesothelioma clinical trials.
Stages of mesothelioma
With malignant pleural mesothelioma there are three staging systems used, each according to different variables. The stage describes the extent of the disease based on the primary tumor and if and where it has spread in the body. Mesothelioma is evaluated based on whether it has invaded nearby organs or distant organs. The stage of the disease helps the patient’s medical team determine the best mesothelioma treatment plan, develop an prognosis and find clinical trials that the patient may be eligible for. The most common staging system for malignant mesothelioma is the TNM system, with T standing for primary tumor, N for regional lymph nodes, and M for distant metastasis.
The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program uses summary staging, which is used for all types of cancer. It has five main categories: in situ (only present in the cells where it began); localized (limited to the organ where it originated); regional (spread to nearby lymph nodes or organs); distant (spread to distant lymph nodes or organs); and unknown (cases in which there is not enough information to indicate stage).
Various types of testing may be done to help the medical team determine the stage of mesothelioma, such as physical examination, imaging like CT scans and MRI scans, laboratory tests of blood, urine, and other bodily fluids and tissues, pathology reports, and surgical reports on the observed appearance of a tumor and nearby lymph nodes or organs.
Other staging systems include the Burchart System (the oldest) based on the extent of primary tumor mass. The Brigham System is the latest system, and it stages mesothelioma by its resectability (ability to be removed surgically) and involvement of lymph nodes. Staging information, plus factors like the patient’s age, general health, and the patient’s wishes all go into determining the best mesothelioma treatment plan.
What is metastatic mesothelioma
Metastatic mesothelioma is disease that has spread from the original site of the tumor to distant organs of the body. Metastasis is the spread of the original cancer cells from the primary tumor to create new malignant tumors in other parts of the body. Mesothelioma becomes metastatic through the bloodstream and lymph nodes. Cancer cells can enter the bloodstream and travel throughout the body. Even though most cancer cells in the bloodstream are actually harmless, some can attach to other parts of the body and begin to grow. Lymph nodes in closer proximity to the original tumor site are more prone to becoming metastatic.
Metastatic cancer is commonly found in the brain, bones, and liver. If it is caught soon enough, it can be treated before it causes permanent damage to these organs. Some cancers metastasize to predictable areas. For example, breast cancer metastasizes to the lungs, and colon cancer spreads to the liver. Knowing these tendencies can help doctors maintain close watch on organs that may be prone to metastases.
The biggest risk with metastatic cancer is when malignant tumors develop in vital organs. If a patient is unaware of existing cancer, it can become metastatic and travel to a part of the body where it can cause more damage. The person may only feel ill after experiencing symptoms from cancer in the new area. Because metastatic cancer often invades the bones and the brain, patients may only realize he or she is ill after experiencing seizures, delirium, or headaches, or when bones deteriorate and affect the spinal cord.
The mesothelioma survival rate with metastatic mesothelioma is, unfortunately, low. But the earlier it is discovered, the better the prognosis. When mesothelioma is advanced, it does not necessarily mean that the patient will only live a short while. Advanced cancer patients may live for longer periods with treatment by chemotherapy, radiation, or other types of therapy.
Determining stages of mesothelioma
To determine if a mesothelioma tumor is primary or metastatic, a pathologist examines a tissue sample and uses advanced diagnostic techniques like immunohistochemical staining and electron microscopy to determine where the cells originated. Sometimes metastatic cancer is found at the same time the primary tumor is found. Treatment goals for metastatic mesothelioma may be aggressive or more geared toward the patient’s quality of life, depending on the degree of metastasis, the mesothelioma treatments the patient has already received, and the patient’s age and wishes. But even for patients who have had the so-called first line treatments which were unsuccessful, there are often clinical trials available that they can be enrolled in.
When mesothelioma becomes metastatic, tumor cells detach and first end up in matrix surrounding the cell, a protein layer that insulates the tumor from adjoining tissue. The metastatic cells break down the layer of proteins, allowing them to escape. Once the tumor cells find a new location to latch onto, they emit cellular signals to tissue activating proteins that cause blood vessels to be created. The blood vessels then supply nutrients to and remove wastes from the new tumor, causing it to grow in its new site. For the tumor to be able to grow, it requires essential nutrients and the flow of oxygen. A substance called Vascular Endothelial Growth Factors (VEGF) induces blood vessels to grow to the area of the tumor to bring oxygen and nutrients to it.
VEGF is made up of a family of protein growth factors that stimulate survival and growth in the vascular system, including arterioles, arteries, veins, and capillaries. In many cases of mesothelioma, overproduction of VEGF can be found. The process of the building of a branch of the vascular system to feed a distant tumor is called angiogenesis. Angiogenesis is a natural process used in wound healing, but unfortunately it can fuel metastases of mesothelioma. There are now drugs that halt production of VEGF and prevent the formation of new blood vessels, and they are often used to treat mesothelioma.
This new tumor is called a secondary tumor or a metastatic tumor. The cells in it are the same as in the original tumor. So, even if a mesothelioma cell metastasizes to the chest wall, the new tumor is made of mesothelioma tumor cells rather than abnormal cells from the cell wall. Metastatic mesothelioma can metastasize to the lungs as well, creating a secondary layer of lung cancer.
New mesothelioma treatments
New mesothelioma treatments include anti-angiogenesis drugs, which target the tumor while sparing the normal cells of the body. Immunotherapy uses the body’s immune system to protect against disease. The immune system may be able to recognize the difference between cancer cells and healthy cells and get rid of the ones that become cancerous. The substances used in immunotherapy are called biological response modifiers (BRMs), and they alter the interaction between the immune system and cancer. BRMs can now be made in the laboratory and can imitate the body’s natural immune response.
Photodynamic therapy is based on the theory that single-cell organisms treated with certain photosensitive drugs will die when exposed to light of a certain wavelength. This technique destroys cancer cells by using a special wavelength light to activate photosensitizing drugs in the body tissues. Given intravenously, the drugs concentrate in diseased cells and are eliminated from normal cells. The diseased cells are exposed to laser light that activates the photosensitive drug at the cancer site. As the treated cells absorb the light, a form of oxygen destroys the cancer cells.
Gene therapy is another new course of mesothelioma treatment that is based on correcting the disease at the level of the DNA by compensating for abnormal genes. Complementary and alternative treatments are also used in treating metastatic mesothelioma. Many cancer patients choose to add these treatments to the course of their cancer treatment, and some patients say that they help them manage their mesothelioma symptoms or side effects better. These rapidly advancing treatments for mesothelioma are helping to increase the mesothelioma survival rate.