01. Mesothelioma Metastasis Overview
What Is Mesothelioma Metastasis?
Metastasis happens when cells break off of a primary tumor, travel somewhere else and form a new tumor. This may occur if tumor cells travel through blood vessels or the lymph system, which includes lymph nodes.
Experts say metastasis occurs in mesothelioma in steps, including:
- Mesothelioma cancer cells form in areas of normal tissue.
- Cancer cells travel into lymph nodes or blood vessels.
- Blood or lymph vessels carry the cancer cells away from their source.
- Cancer cells get stuck in small blood or lymph vessels.
- Cancer cells move into the tissue near their stopping point.
- Cancer cells grow in their new location until a secondary tumor forms.
- The secondary tumor sends signals to grow new blood vessels.
- The new blood vessels form and help the tumor keep growing.
These steps may happen over a long or short period of time.
Some patients may think that metastatic mesothelioma has limited treatment options. This may be because they assume cancer only progresses in late stages. But metastasis can occur even in early stages of mesothelioma. That means patients who have metastatic mesothelioma have almost as many treatment options as those who do not.
How Are Mesothelioma Metastasis and Metastatic Mesothelioma Different?
Metastasis refers to the spread of cancer in general. This means mesothelioma metastasis can refer to any amount of spread. Metastasis can happen in early- or late-stage mesothelioma.
Metastatic mesothelioma generally refers to late-stage mesothelioma. Healthcare providers may consider stage 4 mesothelioma to be metastatic mesothelioma. Patients with advanced mesothelioma generally have a significant amount of metastasis.
When Does Mesothelioma Metastasize?
Metastasis may occur at nearly any stage of mesothelioma. Metastasis that occurs far from the origin (distant metastasis) generally happens in stage 3 or stage 4 mesothelioma. Stage 4 mesothelioma may even be referred to as metastatic mesothelioma.
Patients may think metastatic mesothelioma has few treatment options and a poor prognosis, but this is not the case. Mesothelioma research has led to multiple effective treatment options for patients in later stages.
What Is the Prognosis for Metastatic Mesothelioma?
Stage 4 mesothelioma may be called metastatic mesothelioma. Life expectancy for later stages can depend on treatment approach and mesothelioma type. With treatment, mesothelioma prognosis for stages 3 and 4 ranges from about 12 to 26 months.
02. Metastasis Locations
Where Does Mesothelioma Metastasize?
Doctors may describe mesothelioma as being locally advanced or having distant metastasis.
- Locally advanced mesothelioma: The cancer has spread to areas near the primary tumor.
- Distant metastasis: The cancer has spread to areas far from the primary tumor.
Mesothelioma tumors often progress in areas near the primary tumor. Common sites of mesothelioma metastasis include lymph nodes and the linings of nearby organs.
For example, in pleural mesothelioma, the primary tumor develops in the lung lining. If the cancer is locally advanced, tumors may surround the affected lung. But the cancer may be contained to just the area near the original tumor.
If the original tumor spreads to the bones or liver, that is distant metastasis. According to research, distant metastasis of malignant mesothelioma is rare. But it may happen even before the cancer is locally advanced.
Patients interested in these concepts can talk about them with a mesothelioma doctor. Doctors can help patients understand how they may be affected by local or distant spread of cancer.
What Are the Symptoms of Mesothelioma Metastasis?
Metastasis does not always cause symptoms. When symptoms do arise, they can depend on the site and extent of metastasis.
- Bone metastasis: If cancer spreads to the bones, it may cause bones to break during normal activity.
- Brain metastasis: If cancer spreads to the brain, patients may experience headaches or dizziness. They may also have speech difficulty, nausea, confusion or problems with walking.
- Liver metastasis: If cancer spreads to the liver, patients may experience pain, abdominal swelling or jaundice (yellowing of the skin and eyes). Other signs of liver metastasis include nausea, loss of appetite and weight loss.
- Lung metastasis: If cancer spreads to the lungs, the patient may have a cough, a bloody cough, chest pain or difficulty breathing.
Metastatic Pleural Mesothelioma
Pleural mesothelioma commonly metastasizes to sites near the original tumor, including the lymph nodes and chest wall. It can also spread to more distant sites, like the brain or liver.
Pleural Mesothelioma Metastasis Sites
- Adrenal glands
- Chest wall
- Lymph nodes
- Pericardium (lining around the heart)
- Peritoneum (abdominal lining)
- Pleura on the opposite side
Metastatic Peritoneal Mesothelioma
Peritoneal mesothelioma commonly metastasizes to lymph nodes near the original tumor. It may also spread to nearby organs like the liver or kidneys.
Peritoneal Mesothelioma Metastasis Sites
- Adrenal glands
- Lymph nodes
- Thyroid gland
Metastatic Pericardial Mesothelioma
Pericardial mesothelioma arises in the lining around the heart. It accounts for less than 1% of mesothelioma cases. This means information about pericardial mesothelioma metastasis is relatively sparse.
Available research shows pericardial mesothelioma metastasizes to nearby tissues like the lymph nodes and pleura. Case reports also indicate pericardial mesothelioma can spread to the following locations:
- Nearby lymph nodes
- Pleura (the lining around the lungs)
Quick Fact: Local metastasis reportedly occurs in 81% of pericardial mesothelioma cases.
Metastatic Testicular Mesothelioma
Testicular mesothelioma develops in the lining around the testis, the tunica vaginalis. It accounts for less than 1% of all mesothelioma cases. As such, little is known about testicular mesothelioma metastasis. Case reports indicate it may spread to the brain or spinal cord.
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03. Influencing Factors
Factors That Influence Mesothelioma Metastasis
Research has not yet determined what causes or encourages mesothelioma metastasis. But experts have suggested cell type and treatment may influence how mesothelioma cancer spreads.
Mesothelioma occurs in three main cell types: epithelioid, sarcomatoid and biphasic. It has been suggested that certain cell types spread faster than others. But medical literature is inconclusive about these claims.
There is no proof that certain cell types spread more quickly. But some studies suggest certain cell types may be more likely to spread than others. The studies do not agree on which cell type is more likely to spread, though.
- 2008 report: A study investigated lymph node metastasis in 53 pleural mesothelioma patients. Sarcomatoid and biphasic cell types had a higher rate of metastasis than epithelioid.
- 2020 report: A study investigated general metastasis in 164 pleural mesothelioma patients. Of the three cell types, epithelioid cells were more likely to spread to the abdominal lining than biphasic or sarcomatoid.
Additional mesothelioma research may help scientists learn more about cell types and metastasis.
Response to Treatment
Treatment success may have some influence on metastasis. For instance, if a given treatment kills every mesothelioma cell, there would be no cancer left to spread. A highly effective treatment could therefore prevent later metastasis of the original cancer.
On the other hand, if a given treatment leaves behind many mesothelioma cells, later metastasis may be possible. This concept may help explain why some treatments extend survival more effectively than others.
It may also help explain why earlier stages tend to have better survival. In earlier stages of mesothelioma, there may be less cancer to fight. This could hypothetically allow a treatment to kill a larger percentage of cancer cells. Fewer remaining cells might decrease the risk of later metastasis. The following studies demonstrate some of these concepts.
Early-Stage Pleural Mesothelioma Study
Pleural mesothelioma patients with little to no metastasis received chemotherapy followed by extrapleural pneumonectomy surgery. The study patients had a median progression-free survival of 16.5 months. Two patients lived at least three years without any evidence of metastasis or recurrence.
What does it mean? In this case, the patients started with a smaller amount of mesothelioma tumors. They also received aggressive, combination treatment. This approach may have killed most of the existing cancer cells, helping keep tumors at bay for nearly 1.5 years.
Late-Stage Pleural Mesothelioma Study
Researchers treated pleural mesothelioma patients with multimodal therapy. Nearly 90% of the study patients had stage 3 or 4 mesothelioma. They underwent surgery, photodynamic therapy and chemotherapy. This treatment kept mesothelioma from spreading or returning for about a year.
What does it mean? These study patients had a significant amount of cancer and metastasis. Doctors addressed this with aggressive, trimodal therapy. This approach killed enough cancer cells to delay further progression for about a year.
Does Mesothelioma Stage Affect Metastasis?
Mesothelioma stage does not necessarily affect metastasis. However, metastasis does impact stage.
Doctors determine a patient’s mesothelioma stage to help understand their prognosis and treatment options. Many physicians use some form of the TNM staging system to do this. The TNM system accounts for the number of tumors (T), lymph node spread (N) and distant metastasis (M). This means metastasis can strongly affect a patient’s stage at diagnosis.
Patients with more metastasis tend to have a higher stage of mesothelioma and vice versa.
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04. Treating Metastasis
How Is Mesothelioma Metastasis Treated?
Mesothelioma treatments do not differ substantially between patients with and without metastasis. However, doctors may treat patients with slight metastasis differently than those with extensive metastasis.
Depending on the degree of metastasis, patients may qualify for radiation or some forms of surgery. Stage 3 or 4 mesothelioma patients may not be eligible for aggressive surgery. But they commonly qualify for systemic treatments like chemotherapy and immunotherapy.
Some patients with metastasis may benefit from heated local chemotherapy, such as HIPEC or HITHOC. HIPEC stands for hyperthermic intraperitoneal chemotherapy. It may be used to treat peritoneal mesothelioma. HITHOC stands for hyperthermic intrathoracic chemotherapy. It may be used to treat pleural mesothelioma.
Treatments for Mesothelioma Patients With Metastasis
Chemotherapy drugs kill fast-growing cells to treat cancer. Mesothelioma patients with little metastasis may receive heated, local chemotherapy like HIPEC or HITHOC. Patients with more extensive metastasis may receive systemic chemotherapy.
Immunotherapy equips the immune system to attack cancer cells. Mesothelioma patients with metastasis may receive checkpoint inhibitor immunotherapy. Patients may also receive other immunotherapies through a clinical trial.
Multimodal treatment combines two or more therapies in a single plan. Mesothelioma patients with little metastasis may undergo aggressive surgery and radiation. Patients with more extensive metastasis may receive palliative surgery and chemotherapy.
Surgery attempts to remove mesothelioma tumors. Patients with little metastasis may undergo aggressive surgery aimed at removing all cancer tissue. Patients with more extensive metastasis may have surgery to improve symptoms and quality of life.
Radiation therapy uses special forms of energy to kill cancer cells. Mesothelioma patients with substantial metastasis generally do not qualify for radiation. Patients with little metastasis may undergo radiation as part of a multimodal plan.
Palliative care aims to improve quality of life for patients with any level of metastasis. This may involve managing mesothelioma symptoms or treatment side effects. Palliative care plans may address the patient’s emotions and mind as well as the body. This can help address the psychological, social and spiritual challenges of cancer.
Timely treatment may impact prognosis for patients with any stage of metastasis. But they must receive an accurate diagnosis first. Patients should discuss their mesothelioma risk factors, like asbestos exposure, with a doctor. This information can help the doctor order appropriate tests. This may enable a timely and accurate diagnosis.
Mesothelioma patients with metastasis have effective treatment options. Patients with new or worsening symptoms should discuss these with their doctor. Catching metastasis early may allow for more aggressive treatment and a better prognosis.