Mesothelioma Metastasis

Metastasis occurs when cancer from an initial site, such as the pleura, travels to a distant location within the body and forms new tumors. Mesothelioma patients should be aware of how their cancer spreads and the risk factors that affect the rate of metastasis.

Mesothelioma commonly spreads throughout the cavity where it initially forms. Cancer develops locally or regionally up to stage 3. Distant metastasis occurs in end-stage mesothelioma for about 10% to 50% of patients.

Metastasis can affect a patient’s eligibility for surgery and other treatment options. Mesothelioma has a long latency period of 20 to 40 years, and many patients do not have symptoms until the disease is in its later stages, when metastasis is more likely to occur.

Doctors can make a metastatic mesothelioma diagnosis through radiology imaging scans such as MRI, CT or PET. Symptoms or abnormalities not consistent with the initial site of cancer may indicate metastatic progression, prompting the treating physician to order a biopsy or additional tests.

Cancer cells spread through the body using lymph nodes in the lymphatic system or through blood vessels in the circulatory system. Metastatic mesothelioma can travel through these structures and establish new cancer sites on distant organs and tissues such as the liver or kidneys.

Malignant mesothelioma is also prone to spreading locally, within the immediate area of its origin. Pleural mesothelioma, for example, will typically progress within the pleura on the same side of the affected lung. Regional metastasis signifies tumor involvement of deeper tissues within the region such as lymph nodes or fatty tissue.

The initial site of mesothelioma can affect where metastatic cancer sites might develop. If tumors are close to large blood vessels or lymph nodes, distant metastasis may be more likely to occur. Pleural mesothelioma that forms close to the middle of the chest could progress into the protective structures that surround the heart.

Secondary sites of cancer often depend on the initial type and location of the disease. The most common pleural mesothelioma metastasis sites include the:

Peritoneal mesothelioma metastasizes most often to the following sites:

Researchers have only recently discovered the potential of malignant pleural mesothelioma to spread to other parts of the body. Importantly, doctors also consider mesothelioma that travels to the opposite lung as distant metastasis.

The most common site of metastasis for pleural mesothelioma is the liver, occurring in 55.9% of late-stage metastatic patients. The next most common areas are the kidneys and adrenal glands, which sit on the top of the kidneys, both occurring in about 30% of cases.

The peritoneal cavity houses the abdominal organs such as the liver, spleen, kidneys, intestines and others. As mesothelioma progresses within the peritoneal tissue that surrounds the abdomen, many of these organs are at risk of metastatic disease.

Approximately 50% of malignant peritoneal mesothelioma patients develop distant metastasis, most commonly in the liver. Cancer can also spread into the brain and central nervous system, though this only occurs in roughly 3% of patients. Other less common sites include the thyroid, heart, pancreas, appendix, skin and bone.

Pericardial mesothelioma is a rarer subtype of the disease and metastatic trends are not yet well known. As cancer spreads, the most likely sites of regional metastasis include the lungs, pleura, lymph nodes and mediastinum, the area between the lungs. Less commonly, pericardial mesothelioma can also metastasize to the kidneys.

The mesothelioma cell types that make up tumors include epithelial, sarcomatoid and biphasic, which is a mixture of both. Patients have different cellular makeups that define the structure of their tumors.

Epithelial tumors grow slower than other types and are more responsive to treatment. Patients with epithelial type tend to have a longer mesothelioma life expectancy. Conversely, sarcomatoid and biphasic cancer cells spread more rapidly to distant sites in the body, limiting treatment options and worsening prognosis.

The most recognized pleural mesothelioma staging system is the TNM method. TNM measurements include tumor size and location, lymph node involvement and the presence of metastasis. Doctors use the Peritoneal Cancer Index to stage peritoneal mesothelioma, which tracks the presence of tumors in sectors throughout the abdomen.

Early-stage mesothelioma includes stage 1 and stage 2, which have a lower risk of metastasis and the most treatment options. Late-stage, or end-stage, mesothelioma includes stages 3 and 4, where distant metastasis is more likely to occur. Treatment options are limited to palliative therapies that control symptoms.

The risk of metastasis decreases significantly for early-stage patients who undergo an aggressive treatment such as mesothelioma surgery. Adjuvant chemotherapy or radiation can slow or prevent new tumor growth. Patients who respond well to early therapies have the best prognosis and a mesothelioma life expectancy of about two to three years.

Newer mesothelioma treatments are also showing potential for controlling metastasis and prolonging survival. Immunotherapy is a targeted treatment that can potentially circulate anti-cancer antibodies for many years. Tumor Treating Fields are adhesive arrays applied by the patient that use painless electrical fields to limit cancer growth.

When mesothelioma metastasizes to another site in the body, symptoms may not always be noticeable. When signs and symptoms of metastasis do appear, they typically relate to the area of new tumor growth. Doctors use imaging scans and physical examinations to detect metastatic sites as early as possible.

In some cases, symptoms of metastasis may mimic the expected effects of the primary mesothelioma site. Cancer does not spread distantly until the later stages of the disease, when mesothelioma symptoms may already be severe.

The most common site of mesothelioma metastasis is the liver. Symptoms of new tumor sites on the liver can include jaundice, abdominal pain and edema, or swelling of the legs. If cancer spreads to the kidneys or adrenal glands, patients may experience low back pain, blood in the urine and anemia.

While rare, metastatic spread to the brain is possible and can cause many different neurological symptoms. Metastatic brain cancer can cause changes in memory, vision and personality. Tumors in the brain are also responsible for poor coordination, seizures and severe headaches.

Once the cancer has spread to other sites in the body, mesothelioma treatment options are limited and focus on palliative care. Palliative care options aim to reduce symptom severity, prolong survival and improve quality of life.

Doctors will prescribe traditional treatments, such as chemotherapy and radiation, in an attempt to manage the spread of cancer and decrease the risk of further metastasis. Radiation is useful for preventing recurrence within an area after surgical resection. Mesothelioma specialists determine the best course of treatment based on many factors.

Researchers are exploring many different types of therapies to combat mesothelioma metastasis. Anti-angiogenesis drugs, for example, combat tumor growth by limiting vascular growth and blood supply on new tumors.

Newer treatments involve the expanded use of targeted therapies, treatments that only affect cancer sites, as opposed to chemotherapy or radiation, which can damage healthy cells. Immunotherapy is significantly growing in popularity as an additional option in a multimodal treatment plan.

Many types of immunotherapy use antibodies that target cancer and direct the immune system to attack tumor cells in the same way as an infection, such as a virus. For immunotherapy to be most effective, the cancer cells must express specific biomarkers on their surface.

Gene therapy is another type of targeted therapy that manipulates the DNA within cells to prevent defects in cellular replication, which could lead to metastasis.

Proton therapy is a safer alternative to traditional radiation therapy for mesothelioma, allowing radiation oncologists greater control in treating metastatic sites without damaging healthy tissue.

Another option for metastatic patients is Tumor Treating Fields, a personal device that delivers painless, alternating electrical fields to slow tumor growth.

Mesothelioma clinical trials are frequently enrolling metastatic patients as researchers attempt to learn more about preventing the spread of cancer. These trials offer experimental therapies that may provide improved patient survival and increased effectiveness against mesothelioma metastasis.

This study is a first-in-human trial investigating the use of an artificial antibody that targets a death receptor on tumor cells, inciting cancer cells to kill themselves.

Another first-in-human trial, this study is testing the use of an experimental anti-tumor injection for safety, efficacy and tolerability in mesothelioma patients.

Researchers are studying the preliminary effectiveness of investigational drug SO-C101 in combination with anti-PD1 immunotherapy, pembrolizumab.