Although the classification of tumors based on the preceding descriptive criteria helps the oncologist
determine the malignant potential of a tumor, judge its probable course, and determine
the patient’s prognosis, a method of discovering the extent of disease on a clinical basis and a
14 CANCER BIOLOGY universal language to provide standardized criteria
among physicians are needed. Attempts to develop an international language for describing
the extent of disease have been carried out by two major agencies—the Union Internationale
Contre le Cancer (UICC) and the American Joint Committee for Cancer Staging and End Results
Reporting (AJCCS). Some of the objectives of the classification system developed by these groups
are (1) to aid oncologists in planning treatment; (2) to provide categories for estimating prognosis
and evaluating results of treatment; and (3) to facilitate exchange of information.5 Both the
UICC and AJCCS schemes use the T, N, M classification system, in which T categories define
the primary tumor; N, the involvement of regional lymph nodes; and M, the presence or absence
of metastases. The definition of extent of malignant disease by these categories is termed
staging. Staging defines the extent of tumor growth and progression at one point in time; four
different methods are involved:
1. Clinical staging: estimation of disease progression based on physical examination,
clinical laboratory tests, X-ray films, and endoscopic examination.
2. Tumor imaging: evaluation of progression based on sophisticated radiography—for
example, CT scans, arteriography, lymphangiography, and radioisotope scanning;
MRI; and PET.
3. Surgical staging: direct exploration of the extent of the disease by surgical procedure.
4. Pathologic staging: use of biopsy procedures to determine the degree of spread,
depth of invasion, and involvement of lymph nodes.
These methods of staging are not used interchangeably, and their use depends on agreedupon
procedures for each type of cancer. For example, operative findings are used to stage certain
types of cancer (e.g., ovarian carcinomas) and lymphangiography is required to stage Hodgkin’s
disease. Although this means that different staging methods are used to stage different tumors,
each method is generally agreed on by oncologists, thus allowing a comparison of data from
different clinical centers. Once a tumor is clinically staged, it is not usually changed for that
patient; however, as more information becomes available following a more extensive workup,
such as a biopsy or surgical exploration, this information is, of course, taken into consideration
in determining treatment and estimating prognosis. Staging provides a useful way to estimate at
the outset what a patient’s clinical course and initial treatment should be. The actual course of
the disease indicates its true extent. As more is learned about the natural history of cancers, and
as more sophisticated diagnostic techniques become available, the criteria for staging will likely
change and staging should become more accurate. It is important to remember that staging does
not mean that any given cancer has a predictable, ineluctable progression.
Although some tumors may progress in a stepwise fashion from a small primary tumor to a larger primary tumor, and then spread to regional nodes and distant sites (i.e., progressing from stage I to stage IV),
others may spread to regional nodes or have distant metastases while the primary tumor is
microscopic and clinically undetectable. Thus, staging is somewhat arbitrary, and its effectiveness
is really based on whether it can be used as a standard to select treatment and to predict the
course of disease. Although the exact criteria used vary with each organ site, the staging categories listed below represent a useful generalization.6
Stage I (T1 N0 M0): Primary tumor is limited to the organ of origin. There is no evidence of
nodal or vascular spread. The tumor can usually be removed by surgical resection.
Long-term survival is from 70% to 90%.
Stage II (T2 N1 M0): Primary tumor has spread into surrounding tissue and lymph nodes
immediately draining the area of the tumor (‘‘first-station’’ lymph nodes). The tumor is
operable, but because of local spread, it may not be completely resectable. Survival is 45%
to 55%.
Stage III (T3 N2 M0): Primary tumor is large, with fixation to deeper structures. First-station
lymph nodes are involved; they may be more than 3 cm in diameter and fixed to underlying
tissues. The tumor is not usually resectable, and part of the tumor mass is left behind.
Stage IV (T4 N3 Mรพ): Extensive primary tumor (may be more than 10cm in diameter) is present.
It has invaded underlying or surrounding tissues. Extensive lymph node involvement has
occurred, and there is evidence of distant metastases beyond the tissue of origin of the primary
tumor. Survival is under 5%. Survival is 15% to 25%.
