Mesothelioma Staging

There are four primary stages of mesothelioma doctors use to identify the seriousness of a mesothelioma diagnosis, labeled stage I, II, III or IV. The lower the number, the more treatment options you have, and the better your chances are for long-term survival.

Staging is an accepted way for cancer doctors to describe to patients – and to one another – how advanced the disease is, how prevalent tumors are and how far the cancer has spread. Given the aggressive nature of the cancer, mesothelioma staging is a key part of proper diagnosis and treatment.

Why is mesothelioma staging important? Because knowing where a cancer is in its development sets the table for treatment, which treatment options are available and which are not. For example, doctors use cancer stage as a guideline when deciding whether a patient is likely to benefit from surgery.

If a patient is healthy enough for aggressive treatment and doctors believe that all visible signs of cancer can be completely removed, they say the cancer is resectable and will likely recommend a treatment plan involving surgery. If the spread of cancer is too advanced, however, and can't be removed completely, the cancer is unresectable. In this situation, doctors will recommend other treatment options, including chemotherapy and experimental treatments.

Patient Advocate Karen Selby talks about the differences found among the stages of mesothelioma.

Stage I pleural mesotheliomas are generally resectable, as well as some diagnosed at stage II and III. But by stage IV, the cancer can't be removed completely with surgery. The cancer's subtype can also affect treatment options because most doctors agree surgery doesn't help with sarcomatoid mesotheliomas.

When peritoneal mesotheliomas have spread beyond the abdomen, surgery likely is not helpful. Doctors consider peritoneal mesothelioma unresectable when it has invaded certain areas within the abdomen, including:

  • The hepatoduodenal ligament
  • The retroperitoneal region
  • Root of the mesentery

If the cancer has spread to these locations, doctors typically deliver chemotherapy to the entire body or directly to the abdomen.

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Why Is Early Detection Vital?

The stage of cancer is vital information for oncologists (cancer doctors) who treat mesothelioma, but all experts agree universally on one principle: It's preferable to catch cancer, specifically mesothelioma, in the earliest stage possible.

Staging Methods Vary

Many specialists who treat these cancers — even some of the most respected ones in the field — don't agree on one staging system. Although many doctors agree that staging is a strong predictor of lifespan, not all do.

Learn More About Staging Methods

Getting a Second Opinion

If you are diagnosed with mesothelioma, you should seek a second opinion. Oncologists treat a variety of cancers, but they may not have experience with staging asbestos-related cancers. Always find a doctor who does.

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Stages of Cancer and What They Mean

Dr. Fontaine explains how the stage of mesothelioma affects the treatment options

Using one of three systems, doctors will assign your cancer a stage of I through IV. The stage varies depending on several factors, including the size and location of your tumor and whether it has spread to lymph nodes or distant organs.

There Are Three Main Staging Systems

Doctors use three primary systems for mesothelioma staging: Brigham, TNM, and Butchart. These systems are used primarily for pleural mesothelioma staging because there are currently no formal staging systems for the other types. TNM and Brigham are the most-used by mesothelioma specialists, although some doctors believe that none are accurate enough.

Stage I Is the Least Serious

Stage I typically offers the best chance for survival because of the potentially curative surgical treatments available for patients. Most stage I patients qualify for extrapleural pneumonectomy, an aggressive surgery that attempts to remove as much of the tumor growth as possible. Surgeons take out an entire diseased lung and other tissues, including the diaphragm, nearby lymph nodes and the linings of the chest and heart.

Stage IV Is the Most Serious

At this stage of progression, most doctors only recommend palliative treatments because the cancer has spread to many parts of the body. Trying to remove all the tumors is too difficult, and many patients are too weak to withstand aggressive treatments. Palliative treatments, which focus on symptoms rather than curing the disease, can ease pain and suffering and improve quality of life.

Because of the nature of mesothelioma and the way the cancer grows and spreads, most people are not diagnosed until stage III or IV. Doctors usually treat asbestos-related cancers with a combination of chemotherapy, radiotherapy and surgery. Depending on the progression and location of cancer cells, they may recommend different options.

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Characteristics of the four primary stages of mesothelioma include:

  • Stage I

    Stage I Mesothelioma

    The cancer is localized and surgery is most effective.
    The survival rate is highest at stage I.

    At this point of early development, tumors are close to the original tumor, having only grown in one layer of the lining of the lungs (pleura). The cancer may also have grown into the covering of the heart and the diaphragm on the same side as it first formed.

    The life expectancy for someone with stage I mesothelioma is significantly better that those with later stages, and these patients may live three years or longer. However, it is difficult to catch the cancer this early because people with this stage do not usually have symptoms.

    Curative surgery to remove the tumor is considered the first line of treatment, and doctors usually recommend aggressive treatment that includes chemotherapy and radiotherapy.

    Median life expectancy at stage I is 21 months.

    Stage I Mesothelioma

    The cancer is localized and surgery is most effective.
    The survival rate is highest at stage I.

  • Stage II

    Stage II mesothelioma

    The cancer has started to spread. Surgery is still an option and the survival rate is close to that of stage I.

    Stage II symptoms are vague and mild. Patients — and even doctors — sometimes mistake them for signs of other illnesses like the flu. Patients with peritoneal mesothelioma may lose weight and yet feel bloated.

    Several treatment options are available, and doctors can usually offer curative surgery to remove tumors. In studies, some patients diagnosed at this point survive for years.

    Median life expectancy at stage II is 19 months.

    Stage II mesothelioma

    The cancer has started to spread. Surgery is still an option and the survival rate is close to that of stage I.

  • Stage III

    Stage III mesothelioma

    The cancer has progressed to an advanced stage of spreading. Surgery may still be an option and chemotherapy can extend survival.

    Once the cancer progresses to stage III, it may have spread to several locations on the same side of the body as it formed. These areas may include the lymph nodes, esophagus, muscles, ribs, heart and the chest wall.

    Pleural mesothelioma patients may suffer from more difficulty breathing and intense chest pain even when resting. Peritoneal mesothelioma usually involves some type of bowel obstruction and pain. Because the tumors have now spread to multiple areas of the body, discomfort may be felt in other parts of the body as well.

    Tumors typically do not respond to potentially curative treatment, and some stage III cancer patients will find themselves ineligible for surgery. At that point, doctors offer palliative options.

    Median life expectancy at stage III is 16 months.

    Stage III mesothelioma

    The cancer has progressed to an advanced stage of spreading. Surgery may still be an option and chemotherapy can extend survival.

  • Stage IV

    Stage IV mesothelioma

    The cancer has spread extensively and surgery is usually not effective. Chemotherapy, radiation therapy and palliative treatments can extend survival and provide symptom relief.

    About 30 percent of mesothelioma patients are not diagnosed until this stage. By stage IV, tumors have metastasized (spread) throughout the body via the bloodstream and could be present on the liver, in the brain, bones or elsewhere.

    Patients experience extreme difficulty breathing and suffer from severe chest pain. Tumors can spread to the esophagus or stomach, causing digestive problems and difficulty swallowing or eating.

    Doctor's don't recommend aggressive surgeries. Instead, they fall back on palliative treatments designed to ease pain and control symptoms.

    Median life expectancy at stage IV is 12 months or less.

    Stage IV mesothelioma

    The cancer has spread extensively and surgery is usually not effective. Chemotherapy, radiation therapy and palliative treatments can extend survival and provide symptom relief.

Medical Definitions
Parietal pleura: The lining of the chest cavity
Visceral pleura: The lining of the lungs
Lung parenchyma: Any form of lung tissue, including the bronchioles, bronchi, alveoli, interstitium and blood vessels
Mediastinal: Affecting the mediastinum, the area between the lungs containing the heart, aorta, trachea esophagus and thymus
Diaphragmatic pleura: The lining of the diaphragm, a primary breathing muscle
Peritoneum: The lining of the abdominal cavity
Endothoracic fascia: A layer of connective tissue that separates the ribs from the pleura
Pericardium: The lining of the heart
Myocardium: The muscle tissue of the heart
Diffuse: Spread across a wide area
Multifocal: Occurring in more than one location
Unresectable: Not capable of being removed with surgery
Nontransmural: Occurring not completely, but partially across the wall of an organ
Ipsilateral: On the same side of the chest as where the cancer formed
Contralateral: On the opposite side of the chest as where the cancer formed

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 the cancer has advanced.

Brigham System

Stage I

Tumors are confined to the lining of the lungs and cancer has not spread to the lymph nodes.

Stage II

Tumors are confined to the lining of the lungs. Either the intraparenchymal or mediastinal lymph nodes are cancerous.

Stage III

Aggressive and unresectable tumors in the lining of the lungs have spread into the mediastinum or invaded the chest wall, diaphragm or contralateral lymph nodes.

Stage IV

Cancer has spread to other parts of the body and is unresectable.

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TNM Staging System

Doctors use the TNM system 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.

Microscope Icon

Also called the IMIG Staging System, this is the most widely used system for someone with pleural cancer. Doctors sometimes use it for other types as well. Earlier staging systems like the Butchart system and Brigham system were based largely on studies of patients who underwent extrapleural pneumonectomy.

The abbreviation TNM signifies three different parts of a diagnosis:
(T) describes tumor size and location.
(N) describes whether lymph nodes are affected.
(M) describes whether the tumors metastasized, or spread, to other parts of the body.

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.

  • Specifics of the TNM System

    After evaluating your case, doctors assign a value to each part of the TNM system. Next, they use this information to give your cancer a stage. For example, TNM staging guidelines say that a T1N1M0 mesothelioma is an example of stage III cancer.

  • Tumor

    T describes the size and location of the tumor:

    TX:

    The primary tumor cannot be assessed.

    T0:

    There is no evidence of a primary tumor.

    T1a:

    The tumor is limited to the ipsilateral parietal pleura as well as the mediastinal and diaphragmatic pleura. There is no involvement of the visceral pleura.

    T1b:

    The tumor has spread to the ipsilateral parietal and visceral pleura, along with the mediastinal and diaphragmatic pleura.

    T2:

    The ipsilateral pleural surfaces, which include the parietal, mediastinal, diaphragmatic and visceral pleura, have been invaded by tumors. At least one of the following features is also included in this stage:

    • Involvement of the diaphragm
    • Tumor has spread to the visceral pleura and underlying parenchyma of the lung

    T3:

    The tumor has expanded locally, but can potentially be removed with surgery. It has invaded all of the ipsilateral pleural surfaces, which include the parietal, mediastinal, diaphragmatic and visceral pleura. One or more of the following features will be displayed:

    • Cancer has spread to the endothoracic fascia
    • Cancer has spread to mediastinal fat
    • Cancer has spread to the soft tissues of the chest wall
    • Nontransmural cancer spread to the pericardium

    T4:

    The tumor is locally advanced and is unresectable. It has spread to all of the ipsilateral pleural surfaces including the parietal, mediastinal, diaphragmatic and visceral pleura. These tumors will also display at least one of the following features:

    • Diffuse cancer spread or multifocal masses on the chest wall, with or without rib destruction
    • Cancer has spread to the peritoneum through the diaphragm
    • Cancer has spread to the contralateral pleura
    • Cancer has spread to one or more organs of the mediastinum
    • Cancer has spread to the spine
    • Cancer has spread through the internal surface of the pericardium, with or without pericardial effusion
    • Cancer has spread to the myocardium
  • Nodes

    N describes whether the cancer has spread to glands of the immune system called lymph nodes:

    Node Classification Description
    NX The regional lymph nodes cannot be assessed.
    N0 Cancer has not spread to the regional lymph nodes.
    N1 Cancer has spread to the ipsilateral bronchopulmonary or hilar lymph nodes.
    N2 Cancer has spread to the subcarinal or the ipsilateral mediastinal lymph nodes, which include the ipsilateral internal mammary nodes.
    N3 Cancer has spread to the contralateral mediastinal, contralateral internal mammary, ipsilateral or contralateral supraclavicular lymph nodes.
  • Metastasis

    M indicates whether cancer has spread to other parts of the body. If the cancer has metastasized, that means it has spread, causing secondary tumors to grow in distant parts of the body away from where the first tumor formed.

    Metastasis Classification Description
    MX The presence of metastasis cannot be assessed.
    M0 The tumor has not metastasized to other parts of the body.
    M1 Metastasis to other parts of the body has occurred.
  • TNM Stage Grouping

    TNM stage grouping combines the tumor, node and metastasis values to reveal the cancer's stage.

    Stage Primary Tumor (T) Regional Lymph Nodes (N) Metastasis (M)
    I T1 N0 M0
    IA T1a N0 M0
    IB T1b N0 M0
    II T2 N0 M0
    III T1,T2 N1 M0
    T1,T2 N2 M0
    T3 N0,N1,N2 M0
    IV T4 Any N M0
    Any T N3 M0
    Any T Any N M1
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An Example Using the TNM System

A former shipyard worker visits his doctor and complains of relatively mild symptoms including difficulty breathing and a feeling of heaviness in the chest. Because the patient presents with a history of exposure to asbestos on the job, the doctor suspects mesothelioma.

After conducting a series of tests, the doctor finds a tumor that involves the supporting tissues of the lung and the diaphragm (T2), but finds no evidence that the tumor has spread to the lymph nodes (N0) or other areas of the body (M0). The doctor would likely diagnose the patient with stage II mesothelioma.

Butchart Staging System

The Butchart system is the oldest method of staging pleural mesothelioma. Eric Butchart proposed this system in 1976 in an article for Thorax medical journal.

The Butchart system classifies tumors as stage I through IV using the same basic parameters as the TNM and Brigham systems.

Butchart intended his system to help identify which patients are good candidates for radical treatment. Again, only patients with stage I or II cancer are candidates for curative treatment, and palliative treatment is offered to patients in the two late stages.

This system also may help doctors determine prognosis. In four multivariate studies, early stage is listed as a sign of good prognosis. Two of the studies cited stage I disease as a highly favorable factor for survival.

Butchart Staging System

Stage I

The cancer affects the pleura on only one side of the chest, and may have spread to the pericardium and diaphragm. Curative surgery is considered a first-line treatment.

Stage II

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. Butchart primarily recommends high-dose radiation therapy to most patients with stage II mesothelioma.

Stage III

Cancer has spread to the diaphragm or peritoneum. Mesothelioma cells have also traveled through the lymphatic system to lymph nodes outside the chest. These tumors are generally unresponsive to curative therapies, so patients are introduced to their palliative options. Butchart suggests tube drainage for pleural effusions and delivery of chemotherapy drugs directly to the chest.

Stage IV

The cancer has spread through the bloodstream to distant parts of the body. Tumors may now be present on the liver, brain or bones, among other organs. Patients with stage IV mesothelioma are considered terminal and Butchart recommends solely palliative treatments.

Tumor Grading

Imig staging system

Through a process known as tumor grading, doctors classify cancerous cells based on how they appear under a microscope. Researchers confirmed that cellular features of tumors can offer signs to help doctors better predict survival among mesothelioma patients.

One of several approaches to tumor grading is nuclear grading. The process classifies the size and shape of the nuclei in tumor cells while examining other factors, including 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 that 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, and a low mitotic count, which means that few cells are dividing and spreading, indicated the highest overall survival. Using this information, the researchers developed a three-tier nuclear grade score that divides patients into the following prognostic groups:

Grade Median Overall Survival
Grade 1 28 months
Grade 2 14 months
Grade 3 5 months

The results of this study also showed tumor cell's chromatin, which is a combination of nuclear DNA and protein, was also linked to survival.

Not only was nuclear grade 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.

Additional Resources


Karen Selby is a registered nurse and a Patient Advocate at The Mesothelioma Center. She worked in several subspecialties within nursing before joining Asbestos.com in 2009.

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  11. Cancer.org. (2013, December 19). Survival Statistics for Mesothelioma. Retrieved from http://www.cancer.org/cancer/malignantmesothelioma/detailedguide/malignant-mesothelioma-survival-statistics
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  15. NYU Langone Medical Center. (n.d.). Is Your Patient a Candidate? Retrieved from http://hipec.med.nyu.edu/physicians/your-patient-candidate

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