What is cancer staging?

Quick Answer
The process in which the location, extent, and degree of metastasis (spread) of the primary, or original, cancerous tumor is determined.
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Cancers diagnosed or treated: Essentially all solid tumor cancer diagnoses are staged similarly. Nonlocalized leukemias are staged in unique ways according to the specific diagnosis. The diagnostic processes used to stage a specific case vary somewhat according to cancer type and location.

Why performed: Cancer staging plays an integral role in determining overall disease prognosis as well as influencing treatment modality choices. Stage assessment also plays an important role in assuring effective communication among the patient’s medical team and accurate disease surveillance and epidemiology efforts.

Patient preparation: Patient preparation will vary according to the technique, or supporting procedures, used to help stage the cancer. These procedures range from physical examination and imaging X-rays, ultrasounds, computed tomography (CT), magnetic resonance imaging (MRI) scans to laboratory tests, biopsies, and surgical excisions with subsequent pathological examination of the tumor. Any preparation normally required of these supporting procedures will apply to the process.

Types of staging: There are four different types of cancer staging: clinical staging, pathological staging, post-therapy staging, and restaging. Clinical staging is accomplished by nonpathologic means based on physical examination and imaging technology such as X-ray, MRI, and CT, as well as immunologic and molecular blood tests to detect and measure cancer markers where applicable.

Pathological staging is accomplished following tissue removal by biopsy in which surgical tumor excision is assessed as a sound treatment option. The biopsied tissue and/or removed tumor, surrounding tissue, and nearby lymph nodes are examined microscopically and histologically to determine the type and extent of the cancer from a pathologic perspective. Because treatment considerations and survival statistics are based on the stage of a patient’s cancer, the initial stage assessment remains static throughout the course of the disease regardless of progression and/or response to treatment.

Post-therapy staging is completed after the patient receives an initial treatment such as chemotherapy, hormone therapy, or radiation therapy prior to surgery or in cases where surgery is not performed. Post-therapy staging is assessed using clinical staging guidelines.

Should a cancer patient enter remission but subsequently present with a recurrence, restaging may be accomplished if additional treatment is planned. The restaging process is identical to the original one, including both clinical and pathological staging, but is now designated with a lowercase r. For example, a restaged Stage IV grouping would be recorded as Stage rIV.

In order to maintain terminology consistency, a limited number of classification systems are utilized, and efforts toward additional interpretive continuity are ongoing. Although the type of cancer dictates which specific categorization is applied, common elements include tumor location, size and number, lymph node involvement, and degree of metastasis (spread). The most prevalent systems used include tumor-node-metastasis (TNM) staging and overall group staging.

The tumor-node-metastasis (TNM) classification is adapted by the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control.

The category T, for tumor, provides information about the original tumor such as measurement (in millimeters, centimeters) at the site of origin and its degree of invasion into nearby tissues and organs.

  • TX: Cannot be measured/evaluated
  • T0: No evidence of primary tumor
  • Tis: In situ tumor (tumor limited to cell layers of the original site)

Beyond Tis, numerical tumor categorization offers a relative degree of severity, with higher numbers reflecting a larger tumor and/or more aggressive invasion.

  • T1: Smaller tumor, least aggressive
  • T2
  • T3
  • T4: Larger tumor, most aggressive

The tumor grade is the degree of abnormality (amount of differentiation from normal cells) and is determined pathologically by microscopic analysis. Typically, well-differentiated, or low-grade, tumors are considered the least aggressive and are associated with the best outcomes overall.

  • GX: Cannot be determined
  • G1: Tumor cells well differentiated from surrounding tissue
  • G2: Tumor cells moderately well differentiated from surrounding tissue
  • G3: Tumor cells poorly differentiated from surrounding tissue
  • G4: Tumor cells undifferentiated from surrounding tissue

Special cases are prostate cancer and central nervous system (CNS) cancers. The most common approach to classification of prostate cancer is the Gleason system, which is based on the degree of glandular change, including size, shape, and pathologic differentiation. The Gleason Score or Sum (GS) represents the sum of the primary and secondary grade of the prostate tumor. Based on a ranking from G2 (least aggressive, best prognosis) to G10 (most aggressive, poorest prognosis), the higher the sum is, the more severe is the disease. There are several, similar classification systems used to grade CNS/brain cancers: World Health Organization (WHO), Kernohan, or Ringertz. Rather than tumor size, grading is based on tissue differentiation and degree of vascularity and necrosis. Classification is made based on a three- or four-grade system, with the higher number associated with more aggressive cancer.

The category N, for node, describes the degree that lymph nodes have been affected by cancer. This is typically accomplished by a process termed “sentinal node biopsy.” The (nearby) sentinal node or nodes are detected by injection of a radioactive or colored dye solution at the tumor site. The indicator solution will travel a path within the lymph system that circulating cancer cells would be expected to follow. The area is then scanned to detect the presence of the indicator solution in nearby, or sentinal, lymph nodes. One or more lymph nodes are then removed and examined pathologically for the presence of cancer cells. Positive findings will typically result in further removal and testing of nearby lymph nodes to determine extent.

  • NX: Cannot be measured/evaluated
  • N0: Nearby lymph nodes are clear of cancer

Beyond N0, numerical categorization describes the size, location, and number of lymph nodes affected. The higher the number, the more lymph nodes are involved.

  • N1: One to two lymph nodes affected
  • N2: Three to six lymph nodes affected
  • N3: Seven or more lymph nodes affected

The M category, for metastasis, describes the degree to which the primary tumor has spread (metastasized) into surrounding tissues and/or organs.

  • M0: No cancer metastasis detected
  • M1: Cancer metastasis detected

Although the TNM metrics are relatively universal, each cancer type has a customized version of this classification system. In some instances, there may be many additional subcategories to refine tumor classification and offer additional prognostic information to the provider. In other cases, the staging classification may be simplified by means of truncated categorization.

Based on the established TNM categories, an overall cancer group stage is determined. Although criteria for stage assignment varies somewhat according to cancer type, the following provides a top-level overview of stage groupings:

  • Stage 0: Carcinoma in situ (cancer is limited to the site of origin)

Stages I through III classify cancer where higher numbers indicate more extensive and aggressive disease. Some cancers types utilize subcategories in staging to provide more specific information about type, behavior, and prognosis.

  • Stage IV: Distant metastatic cancer (cancer has spread to another, distant organ)

Special cases are female reproductive cancers, Hodgkin disease/lymphoma, colorectal cancer, and leukemia. Female reproductive cancers are stage according to the International Federation of Gynecologists and Obstetricians (FIGO). Although FIGO staging classification guidelines generally follow the general TNM/group staging approach, many of the female reproductive cancers, including those of the ovary, breast, cervix, and uterus, are subclassified in great detail.

Hodgkin disease and other cancers of the lymphoid system are staged using the Ann Arbor classification system. Stages I through IV are defined by the anatomical location of affected lymph nodes. The higher the stage number, the more lymph nodes are affected and the more aggressive is the disease. Each stage assignment is then subclassified as either “A” (asymptomatic) or “B” (symptomatic).

Colorectal cancer uses the Dukes’ staging classification, an older system that corresponds closely to group staging. Dukes’ A through D colorectal cancer stages effectively translate to group Stages I through IV.

Because leukemia involves the bone marrow and has often affected many organs, including the liver, spleen, and lymph nodes, staging is based primarily on the patient’s survival outlook according to disease progression. Although not all forms of leukemia utilize a formal staging system, each form that does has a dedicated staging classification system. For example, chronic myelogenous leukemia (CML) is classified into three phases (as opposed to stages):

  • Chronic: Fewer than 5 percent immature cells in circulation/bone marrow; mildly symptomatic, readily responsive to treatment
  • Accelerated: 5 to 30 percent immature cells in circulation/bone marrow; more symptomatic, less responsive to treatment
  • Acute/blast phase: Less than 30 percent immature cells in circulation/bone marrow; very aggressive, acute disease

Additional staging classifications, such as Rai (Stages 0-IV; U.S. predominant) and Binet (Stages A, B, and C; European predominant), are used for chronic lymphocytic leukemia (CLL). Still other systems are applied to different leukemia types such as the Stage 1 through Stage 3 classification based on level of anemia and spleen size for hairy cell leukemia (HCL).

In addition to providing information on the size, extent, and prognostic status of each cancer case, staging plays a vital role in epidemiology and treatment studies. The National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program and other cancer registries such as the National Program of Cancer Registries (NPCR) use summary staging classification in their surveillance and epidemiology efforts. For these purposes, all cancers are grouped into one of the following five summary categories:

  • In situ: Early-stage cancer, present only in the cell layers where first detected
  • Localized: Cancer localized to tissue/organ where first detected; no evidence of metastasis
  • Regional: Cancer metastasized to nearby lymph nodes, tissues, organs
  • Distant: Cancer metastasized to distant lymph nodes, tissues, organs
  • Unknown: Insufficient data available to classify

Data collected are made available to clinical and research professionals so that they may better understand and address the cancer burden according to a variety of demographics and metrics, including cancer stage.

Results: Cancer staging is a vital component of the diagnostic process. Accurate stage assessment will guide the medical team in making optimal treatment recommendations for patient care according to prognostic expectations. Because the epidemiologic value of the original stage is significant, the classification remains constant throughout the course of disease. Restaging occurs only if treatment is planned following a recurrence.

Bibliography

Baatrup, Gunnar, ed. Multidisciplinary Treatment of Colorectal Cancer: Staging, Treatment, Pathology, and Palliation. Berlin: Springer, 2014. Print.

Benedet, J. L., et al. “FIGO Staging Classifications and Clinical Practice Guidelines in the Management of Gynecologic Cancers.” International Journal of Gynecology and Obstetrics 70 (2000): 209–62. Print.

Greene, F. L. “Updates to Staging System Reflect Advances in Imaging, Understanding.” Journal of the National Cancer Institute 22 (2002): 1664–66. Print.

Greene, F. L. “Updating the Strategies in Cancer Staging.” American College of Surgeons Bulletin 87 (2002): 13–15.

Greene, F. L., et al., eds. American Joint Committee on Cancer Staging Manual. 7th ed. New York: Springer, 2011. Print.

O’Dowd, G. J., et al. “The Gleason Score: A Significant Biologic Manifestation of Prostate Cancer Aggressiveness on Biopsy.” PCRI Insights 4.1 (2001). Print.

"What Is Cancer Staging?" American Joint Committee on Cancer. American Joint Committee on Cancer, n.d. Web. 21 Jan. 2015.

Wittekind, C., et al. “TNM Residual Tumor Classification Revisited.” Cancer 94 (2002): 2511–16. Print.

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