Doctors identify the extent of pleural mesothelioma at the time of its diagnosis by doing studies that allow them to assign it as stage 1, 2, 3 or 4. The cancer’s stage is a major factor in determining a patient’s prognosis and treatment options.
Early-stage patients may benefit from aggressive therapies with potential substantial prolongation of life. Late-stage patients usually benefit more from treatment primarily focused on symptom management to hopefully improve quality of life and sometimes duration of survival. Staging is a codified way for cancer doctors to describe to patients and other medical specialists how advanced the disease is, how prevalent tumors are and how far the cancer has spread.
MESOTHELIOMA STAGING FACTS
- Doctors classify pleural mesothelioma as stage 1, 2, 3 or 4.
- A higher stage number signifies more advanced cancer.
- Usually, more aggressive treatment options are available at earlier stages.
- The TNM staging system is preferred by most doctors.
Cancer staging is a key part of mesothelioma diagnosis and treatment. Knowing where the cancer is in its development helps specialists decide which treatment options are appropriate and which are not. For example, doctors use cancer stage as a guideline when deciding whether a patient is likely to benefit from surgery.
Resectable Mesothelioma
If a patient is healthy enough for aggressive treatment and doctors believe all visible signs of cancer can be completely removed, they say the cancer is resectable and will likely recommend a treatment plan involving a major surgery such as pleurectomy/decortication (P/D) or extrapleural pneumonectomy (EPP). Stage 1 pleural mesotheliomas are generally resectable as well as some diagnosed at stage 2 and 3.
Unresectable Mesothelioma
If the spread of cancer is too advanced, however, and can’t be removed completely, the cancer is unresectable. In this situation, doctors recommend other treatment options, including chemotherapy and experimental treatments. Such treatments are considered only palliative because they are focused on symptom control and rarely meaningfully prolong life.
Because early mesothelioma symptoms are easily mistaken for those of other illnesses, most patients are not diagnosed until stage 3 or 4. In addition to the stage, the cancer’s cell type and the patient’s overall health also affect treatment options.
The Four Stages of Mesothelioma
Doctors can use one of three systems for mesothelioma staging: TNM, Brigham and Butchart. These systems are used primarily for pleural mesothelioma, the most common type. There are currently no formal staging systems for the other types.
Stage 1
Initially, tumor growth is localized to a single area. The life expectancy associated with stage 1 mesothelioma is significantly better than those of later stages, but it is difficult to catch the cancer this early because people with this stage do not usually experience symptoms.
Major surgery to remove the tumor is considered the first line of treatment, and doctors usually recommend an aggressive multimodal approach including chemotherapy, radiation therapy or immunotherapy.
Median life expectancy at stage 1 is 21 months with surgery.
Stage 2
Stage 2 symptoms are vague and mild, and patients and doctors often mistake them for signs of other illnesses such as the flu. Patients with peritoneal mesothelioma may lose weight and yet feel bloated. The available treatment options are generally the same as for stage 1 mesothelioma.
Median life expectancy at stage 2 is 19 months with surgery.
Stage 3
Once the cancer progresses to stage 3, it may have spread to several tissues, organs and lymph nodes in the same region of the body where it originally formed.
Pleural mesothelioma patients may suffer from difficulty breathing and intense chest pain even when resting. Peritoneal mesothelioma usually involves abdominal pain and digestive problems. Discomfort may be felt in other parts of the body as well.
Some stage 3 cancer patients are ineligible for surgery and other aggressive treatments. At that point, doctors offer palliative options.
Median life expectancy at stage 3 is 16 months with surgery.
Stage 4
By stage 4, cancer has spread throughout the body via the bloodstream (a process called metastasis) and could be present in the liver, brain, bones or elsewhere. Patients may experience extreme difficulty breathing and swallowing, digestive problems and severe pain.
For stage 4 patients, doctors fall back on palliative treatments designed to ease pain and control other symptoms.
Median life expectancy at stage 4 is 12 months or less with surgery.
TNM Staging System
Also called the IMIG Staging System, this is the most widely used system for pleural mesothelioma. Doctors sometimes use it for other types of mesothelioma as well.
The abbreviation TNM signifies three different parts of a diagnosis. Doctors add a number after each letter to describe how far the cancer has advanced. As tumor size increases and the cancer invades more structures, the number increases.
- T describes tumor size and location, ranging from T0 to T4.
- N describes whether lymph nodes are affected, ranging from N0 to N3.
- M describes whether the tumors have metastasized (spread through the bloodstream to other parts of the body), ranging from M0 to M1.
Doctors use the TNM framework to stage many different types of cancer. In 1995, the International Mesothelioma Interest Group (IMIG) modified this system specifically for asbestos-related cancers because of the lack of a universally accepted staging system.
After evaluating a case, doctors assign a value to each part of the TNM system. Next, they use this information to give the cancer a stage. For example, TNM staging guidelines say a T1N1M0 mesothelioma is a stage 3 cancer.
Brigham Staging System
The Brigham staging system was created by Dr. David Sugarbaker at the Brigham and Women’s Hospital in Boston. With this system, doctors examine organs, tissues and other structures to learn how far pleural mesothelioma has advanced.
Stage 1
Tumors are confined to the lining of the lungs and cancer has not spread to the lymph nodes.
Stage 2
Tumors are confined to the lining of the lungs. Lymph nodes near the tumors are cancerous.
Stage 3
Aggressive and unresectable tumors in the lining of the lungs have spread into the area between the lungs or invaded the chest wall, diaphragm or distant lymph nodes.
Stage 4
Cancer has spread to distant parts of the body.
Butchart Staging System for Pleural Mesothelioma
The Butchart system is the oldest method of determining someone’s pleural mesothelioma stage. Dr. Eric Butchart proposed this system in 1976 to help identify which patients are good candidates for aggressive treatment.
Stage 1
The cancer affects the pleura on only one side of the chest and may have spread to the heart sac (pericardium) and breathing muscle (diaphragm).
Stage 2
Cancer has spread to the chest wall and may affect both sides of the pleura. It may have spread to the esophagus, heart or lymph nodes of the chest.
Stage 3
Cancer has spread to the breathing muscle (diaphragm) or abdominal lining (peritoneum). Mesothelioma cells have also traveled through the lymphatic system to lymph nodes outside the chest.
Stage 4
The cancer has spread through the bloodstream to distant parts of the body. Tumors may now be present in the bones, liver, brain or other organs.
Tumor Grading
Doctors can also classify cancer based on how the cells appear under a microscope. Researchers have confirmed that cellular features of tumors can help doctors better predict survival rates among mesothelioma patients.
Aside from determining the cancer’s cell type, there is another approach called nuclear grading. The process classifies the size and shape of the nuclei in tumor cells and examines other factors such as nucleolus size, chromatin patterns and the rate of cell division. These variables play central roles in cancer cell genetics, and ongoing studies are exploring their clinical value as indicators of prognosis.
The nuclear grading system developed at Cleveland Clinic inspired other studies that investigated the connection between tumor grade and mesothelioma survival. In what turned out to be the strongest evidence supporting this relationship to date, researchers at Memorial Sloan-Kettering Cancer Center analyzed 232 cases of epithelioid diffuse malignant pleural mesothelioma for the following features:
Indicators of Prognosis
- Nuclear atypia
- Nuclear/cytoplasmic ratio
- Chromatin pattern
- Intranuclear inclusions
- Prominence of nucleoli
- Mitotic count
- Atypical mitoses
The analysis proved nuclear atypia (variations in cell nucleus appearance) and mitotic count (the number of cells actively dividing) were directly related to a patient’s prognosis.
Severe nuclear atypia was found to drastically reduce overall survival. A low mitotic count, which means few cells are dividing and spreading, indicated the highest overall survival.
The results of this study also linked tumor cell chromatin, which is a combination of nuclear DNA and protein, to survival.
Not only was nuclear grading found to be a simple, cost-effective prognostic tool for determining overall survival, but it also helped predict the time to mesothelioma recurrence among patients treated with surgery. Patients with a low mitotic count averaged 67 months before their cancer returned, and those with a high mitotic count averaged 14 months.