Tumor staging

Definition

Tumor staging is the process of defining at what point in the natural history of the malignant disease the patient is when the diagnosis is made. The organ and cell type in which the malignancy has developed defines the type of malignancy. For example, adenocarcinoma of the lung defines that the cancer originated in the mucus-secreting cells lining the airways of the lung. Staging is different than defining the type of cancer; it is the process of defining the degree of advancement of the specific type of malignancy in the patient at the time of presentation (the time when the diagnosis is made). Because there are many different types of malignancy arising from many different organs in body, the specifics of staging systems vary.

Purpose

Staging fulfills an organizational role that is central to treatment of cancer. After the tumor is staged, the treatment team knows to what degree the cancer has evolved in its natural history. This knowledge will provide the information necessary to formulate a plan of treatment and will allow an estimate of the success of that treatment (prognosis). Finally, by establishing uniform criteria for staging, people with the same type of malignancy presenting at the same stage can be treated equivalently. If a new treatment is tested that improves the long-term prognosis then that treatment will become the new standard of care. Thus, staging is vital to the processes of research and scientific reporting.

Prognosis

The first question that most patients want answered when they find they have cancer is "How am I going to do?" They want to know the ultimate outcome—their prognosis. Because of the existing research on the natural history, or progression, of the disease, this information is available on a statistical basis. Staging, then, helps define the patient's prognosis. Intuitively, one would think that those presenting with an earlier stage have a better prognosis. For the most part, that is correct.

Scientific reporting and research

When a patient develops a life-threatening disease such as cancer, the physicians and other members of the treatment team intervene in an effort to improve the prognosis. Treatment regimens are defined as good or bad based on how they influence the prognosis of the disease. Staging allows medical professionals to interpret whether or not their efforts are favorably influencing the natural history of the disease. Once a patient's cancer stage has been established, a baseline exists against which to measure the efficacy of the cancer treatment that follows for that patient.

Staging plays a similar "baseline" role when considering a large group of cancer patients. In order to gauge accurately the effectiveness of any cancer treatment, researchers must know if the patients' conditions really are comparable. If they are, comparisons between treatments are fair. If the patients' conditions vary at the outeset of a study, then comparing the outcomes of different treatments is not useful.

Staging provides that useful, objective standard so that researchers can accurately compare specific treatments in certain stages of particular cancers. Staging allows uniformity in treatment protocol and reporting of the data related to outcome. As new treatment protocols are developed, they can be tested on patients with the same type and stage of cancer and the two groups compared. If there is improvement with a new treatment protocol, that treatment regimen will be adopted as standard. Physicians can use these established best practices to determine treatments for their patients.

Criteria for staging

As it became apparent to medical professionals that staging of malignancies was necessary for accurate assessment of treatment regimens and defining the treatment recommendations themselves, criteria for staging needed to be developed. Initially this was done for individual tumors separately. Because of the need for uniformity, a universal set of criteria was desired. The TNM system of staging has been adopted for the most part for this reason. It has been developed and updated by The American Joint Committee on Cancer (AJCC). Some of the types of malignancy do not fit well into the TNM criteria and others have older systems that are still in use because they are effective and are deeply established in scientific literature.

TNM system

This system of staging is the general format used for staging cancer of all types and is updated and maintained by the AJCC. The "T" stands for tumor size. The "N" stands for spread to lymph nodes, (nodal metastasis ). The "M" stands for metastasis, (spread of the cancer to sites in the body other than the organ of origin. When the diagnosis of cancer is made, the physical examination along with laboratory testing and imaging studies will be performed to define the TNM status of the patient. The TNM status will define stage.

The tumor size, "T" will be assessed by physical examination or various imaging modalities depending on the accessibility of the tumor. The "T" value is generally defined as 1 through 4 on the basis of size and whether or not the tumor is invading structures that surround it. In cancer so early that it is felt to be incapable of spreading, it is assigned a "T" value of 0. The "T" value is, in essence, a description of the tumor in its local place of origin. As time passes and the staging system is updated, the "T" value is being subdivided in certain types of cancer. The subdivisions are indicated by letters "a" through "d" and also have a graduated value system. For example: T1 breast cancer is a tumor sized 2 cm or less in greatest dimension. T1a is less than 0.5 cm, T1b is 0.5 to 1.0 cm, and T1c is 1.0 to 2.0 cm.

In many cancers, there seems to be a progression from the place of primary origin, then to the regional lymph nodes, and then throughout the body. Lymph nodes can be thought of as filters that drain tissue fluid coming from a particular organ. If that organ has developed a cancer and some of the cells flow away with the tissue fluid to the lymph node filter that is draining that organ, the cancer may begin to grow there also. Assessment of lymph node involvement thus becomes the next step in staging and defines the "N" value. Since the word metastasis means that the cancer has spread from its point of origin to somewhere else in the body and the lymph nodes are in the region, the "N" value defines presence of regional metastasis. The assessment is performed by physical examination and imaging studies of the region involved. "N" is assigned a value of 0 for no nodes involved, or depending on the anatomic nature of the region, values 1 through 3.

"M" stands for distant metastasis. As mentioned previously, metastasis is the spread of the primary tumor to elsewhere in the body. When that spread or metastasis is outside the region of the primary tumor, the patient has distant metastasis. The "M" value is assessed by physical exam, laboratory studies, and imaging studies. Different cancers have different typical patterns of metastasis. Common areas of metastatic involvement are lung, liver, bone, and brain. The "M" value is assigned either 0 or 1. Another term used to describe the patient who has distant metastasis is that of having systemic disease. In the TNM system virtually all patients with an "M" value of 1 have stage IV disease. The "M" value may also have a subscript defining the organ of metastatic involvement.

After the values for TNM have been determined as accurately as possible, the values are grouped together and a stage value is assigned. The stage value is usually I through IV, (and is written in roman numerals). Each stage may be subdivided, (A, B, C…), if it is useful for treatment recommendations and reporting. In general, stage I implies the tumor is confined to its source of origin and stage IV implies distant metastasis or systemic disease. Because of different anatomical, prognostic, and treatment considerations, the intermediate stages are defined by different tumor sizes, the presence or absence of local invasion of the tumor into surrounding structure, or the number and/or presence of involved lymph nodes. Treatment recommendations and expected outcome are both defined to a large extent by stage. The specific criteria for each stage are contained in the AJCC Cancer Staging Manual.

An example of TNM staging follows. This example is the staging criteria for non-small-cell lung cancer.

• Stage 0: A small group of cancerous cells have been found in one location in the lung.
• Stage I: The cancer is only in the lung and has not spread anywhere else.
• Stage II: The cancer has spread to nearby lymph nodes.
• Stage III: The cancer has spread to more distant lymph nodes, and/or other parts of the chest like the diaphragm.
• Stage IV: The cancer has spread to other parts of the body (distant metastasis).

Special staging systems

In the development of staging systems it has been recognized that some malignancies do not fit well into the scheme of the TNM system or that the system in place reflects the same information as the TNM system. Thus there are a few special staging systems in use for specific organs of involvement. The goal is the same for these schema as for TNM; to define the point in the natural history at presentation, to allow establishment of prognosis and treatment recommendations, and to facilitate scientific research and reporting.

COLON CANCER: DUKE'S STAGING.

The Duke's staging system is similar to the TNM system when describing colo-rectal cancer. This was the original staging system for colon and rectal cancers; however, the TNM staging sytem has begun to replace the Duke's system for colon and rectal cancers.

OVARIAN CANCER: FIGO SYSTEM.

FIGO stands for the International Federation of Gynecology and Obstetrics. This organization developed staging criteria for the various gynecologic malignancies and the one for cancer of the ovary is still used somewhat though the TNM criteria are gradually replacing the FIGO system. In the FIGO system, ovarian cancer is staged I through IV similar to the TNM scheme then each stage is subdivided into A, B, or C, depending on defined criteria.

LYMPHOMA: ANN-ARBOR STAGING.

Anatomically, the lymph system and its nodes are found throughout the body. Malignancies involving the lymph system (lymphomas), do not fit the typical TNM scheme well. The Ann Arbor staging criteria are instead utilized to classify this group of malignancies. The goals of the Ann Arbor lymphoma staging system are to define the degree of advancement of the disease so that treatment recommendations can be made and prognosis can be estimated, and to facilitate consistent reporting and research.

The Ann Arbor system classifies lymphoma into four stages based on anatomic lymph nodal group involvement. Disease confined to one nodal group or location defines stage I. Disease limited to one side of the diaphragm, (the muscle separating the chest from the abdomen), defines stage II. Stage III patients have disease on both sides of the diaphragm and stage IV patients once again have disseminated disease. Consideration of involvement of the liver, spleen, and bone marrow are also considered in this system. Finally, the stage is subdivided into categories of A and B depending on the presence of symptoms of itching , weight loss , fever , and night sweats . Those having symptoms receive the designation "B" and have a worse prognosis.

LEUKEMIA: THE FAB AND RAI/BINET STAGING SYSTEMS.

Leukemia is the type of malignancy that begins in the cells of the marrow that produce the cellular components of blood, the progenitor cells. These malignancies are truly systemic from their outset and do not fit any form of the TNM system. Still there is need to categorize the presenting features of the patients with these diseases to help make treatment recommendations, estimate prognosis, and to facilitate scientific research and reporting. The acute leukemias are staged by the FAB (French, American, British) system, and chronic lymphocytic leukemia is classified by the Rai/Binet system.

LUNG CANCER, SMALL CELL.

Unlike other types of lung cancer, the staging of small cell lung cancer is relatively simple. This is because approximately 70% of patients already have metastatic disease when they are diagnosed, and small differences in the amount of tumor found in the lungs do not change the prognosis. Small cell lung cancer is usually divided into three stages:

• Limited stage: The cancer is found only in one lung and in lymph nodes close to the lung.
• Extensive stage: The cancer has spread beyond the lungs to other parts of the body.
• Recurrent stage: The cancer has returned following treatment.

Defining the stage

The process of defining stage is quite simple. First, the diagnosis is established by study of the patient and by tissue biopsy . Once the cell type and organ of origin are established, the staging criteria are reviewed. The patient will undergo a series of diagnostic tests to define the various parameters of the staging criteria. The results of these tests define the extent of the disease and establish the stage. The known typical natural history of the disease dictates the types of testing done. The tests differ for each type of malignancy.

Special concerns

Clinical vs. pathological stage

The stage of the patient's disease may be categorized into clinical or pathological. As has been mentioned, the known natural history of the disease and the staging criteria are utilized to define the stage of the patient at the time of presentation. The investigations performed often involve an initial degree of uncertainty when they are based on clinical grounds alone. For example, the physical exam or the imaging of a particular group of lymph nodes may show that they are enlarged but the enlargement may not accurately define whether they are truly involved with cancer. This issue may only be resolved by removing some or all of the suspect enlarged nodes, sometimes by biopsy before treatment or sometimes by the removal of the questionable nodes at the time of definitive treatment. The evaluation under the microscope of the clinically enlarged nodes will define whether they are really involved with cancer or merely enlarged. When staging criteria are based on clinical assessment alone, it is referred to as the clinical stage. Once the results of the microcopic evaluation are known the true stage or pathologic stage may be assigned.

Stage is uniform and accurate

One of the main goals of staging is to facilitate communication so that like patients are compared to like patients. It is imperative that the adopted staging criteria are rigidly adhered to or inaccurate comparisons may be made and the results of research to develop better treatment regimens will be difficult to interpret.

Tumor grade

When the tissue obtained for diagnosis is evaluated under the microscope for cell type, often another index called grade is defined. As the pathologist analyzes the malignant cells, attention will be given to how close to a normal cell the malignant cells appear to be. If they are very similar, the malignant cells are not felt to be too aggressive and a low grade value is assigned. The more atypical the malignant cells appear to be, the more aggressive the tumor is and a higher grade value is assigned. Grade is usually assigned a value of I through IV though more levels can be assigned depending on theparticular cancer.

The estimate of grade is just that—an estimation. It is subjective in nature and cannot be determined quantitatively. Though useful in predicting prognosis, the correlation is not exact. Rather, grade is included as only one of the factors influencing prognosis. Grade may be included as part of the actual staging criteria; however, it usually is not part of the scheme.

Tumor boards

A tumor board is a body of specialists in the treatment of cancer that convenes to discuss the aspects of patients presenting with cancer. The AJCC encourages the development of tumor boards throughout the nation to facilitate the use of staging and reporting of cancer statistics from region to region throughout the country. In addition to allowing the collection of vital cancer statistics, local tumor boards create a forum where the clinical aspects of a patient's cancer may be discussed to provide recommendations or to play a role in education.

See Also Tumor grading; Individual cancer entries for specific staging information for each cancer.

Resources

BOOKS

Abelhoff, Armitage, Lichter, Niederhuber. Clinical Oncology Library. Philadelphia: Churchill Livingstone 1999.

AJCC Cancer Staging Manual, Fifth Edition. Philadelphia:Lippincott-Raven, 1997.

Richard A. McCartney, M.D.

KEY TERMS

Disseminated disease

—The presence of widespread malignancy implying a stage of IV.

Malignancy

—A general term for cancers of all tissue types, sarcomas, and leukemias.

Metastasis

—The spread of malignancy to another site within the body. To regional lymph nodes: regional metastasis. To distant sites: distant metastasis.

Prognosis

—The expected outcome

Systemic disease

—Disease that is widely metastatic or present throughout the body.