Cancer Staging

What is cancer staging and its importance?

The stage of cancer gives an idea of how much the disease has spread. In other words, it describes the severity of the disease. Cancer staging is the process of determining the stage of cancer in a patient. It is important to know the stage of cancer or the following reasons:

  • Initiation of proper treatment by the doctor
  • Estimation of a patient’s prognosis or chances of survival
  • Helps doctors and researchers to group patients with similar prognosis and study them to find out new methods of treatment and prevention of the disease and comparing their studies to analyze
  • Information on the results of clinical trials on patients with similar cancer stages gives the scope to analyze them statistically. This helps in predicting the outcome of the disease even better.

Elements of staging system

With the development in research in the field of cancer in the last decade staging systems have improved immensely. There are different types of staging systems, some of which focuses on a specific category while others cover most of them. The elements used in most staging systems are:

  • Position of the primary tumor
  • Number and size of the tumors
  • Spread of cancer to lymph nodes
  • Type of cells and grade of tumor
  • Metastasis

Although staging system covers most types of cancer, leukemia is an exception. Since leukemia involves the circulating blood it cannot be localized anatomically. But, staging can be done for some forms of leukemia, which measures the extent of the disease. The staging system is mostly limited to solid tumors, since anatomical localization is possible for them. There staging system for solid tumors can be divided into:

  • The TNM system
  • The Overall Stage Grouping

The TNM system of cancer staging

The American Joint Committee on Cancer (AJCC) and the TNM committee of the International Union against Cancer (UICC) have immensely contributed in the field of cancer staging. The current procedures and understanding of the TNM system of cancer staging is completely based on their ideas and hard work. In addition, the Japanese Committee on Cancer has also played an important part in developing the present concepts on cancer staging.

The TNM system is built on the idea that the patterns of growth and outcomes are same for cancers of the same site and histology. According to the TNM system of classification,

T : size, extent or penetration of tumor

N : number and location of cancerous lymph nodes

M : distant metastasis (extent of the spread of cancer cells to other parts of the body)

Numerical subsets refer to the advancement of the disease.

The  Alphabets

The numbers

Indications

T X Unanalysable
is Carcinoma in situ
0 No evidence of tumor (primary)
1 Size/ Extent
2 Size/ Extent (more than 1)
3 Size/ Extent (more than 2)
4 Size/ Extent (more than 3)

N

X Unanalysable
0 No evidence of involvement of lymph nodes
1 Number/ Extent of Regional lymph nodes
2 Number/ Extent of Regional lymph nodes (more than 1)
3 Number/ Extent of Regional lymph nodes (more than 2)

             M

X Unanalysable
0 No evidence of metastasis
1 Distant metastasis detected

For example, liver cancer T2, N0, M0 indicates the involvement of nearby blood vessels by the tumor, but has not yet spread to the regional lymph nodes or other tissues and organs.

The overall group staging

Once the TNM categories have been determined the next step is to group them into different stages. Stages indicate the severity of cancers. Determining the stage of a given cancer helps in prognosis, treatment plans and communication with other doctors.

Multiple staging scales are in use. The most common one is given below:

Stages

Indications

0

Small localized cancers involving just a few cells or carcinoma in situ; usually curable

I

Small and did not spread from the organ it started in

II

Larger in size, locally advanced and/or with involvement of local lymph nodes

III

Larger than stage II cancer, locally advanced and/or with involvement of local lymph nodes (has spread more than II)

IV

Secondary or metastatic cancer; inoperable

The combination of both TNM system and overall group staging makes it easier to understand the condition of the patient. But, the staging system varies with the type of cancer.

There are further subdivisions of the TNM system providing more specificity if needed.

Cancer staging with TNM and stage grouping cannot be the only way to decide the prognosis of the patient. The health and age of the patient should also be considered. In the near future genetics will play an important role in prognosis of cancer.

TNM staging cannot be applied to types of cancer. Staging of brain and spinal cord cancers are based on the type of cell involved. A different staging system (Ann Arbor staging classification) is required for lymphomas. No proper staging system exists for leukemia.

Summary staging

SEER of the National Cancer Institute uses this system to stage cancer. The system includes-

  • In situ: Cancer cells are only detected in the specific site of origin.
  • Localized: Cancer cells have spread only within the affected organ.
  • Regional: Cancer has metastasized to nearby lymph nodes or organs.
  • Distant: Cancer has metastasized to distant lymph nodes or organs.
  • Unknown: Enough information is lacking.

Tumor Grading

Tumor grading is done on the basis of appearance of the cell under a microscope. The results of tumor grading will be available in a biopsy report. A higher grade is indicative of more aggressive cancer cells. Tumors are typically classified from least to most aggressive as grade I through IV. Tumor grading is given importance according to the type of cancer. It is very important for brain cancer, prostate cancer and lymphomas. It is normally treated as a secondary factor in most other cases.

Tests to determine stage of cancer

  • Physical exams: Doctors examine the patient physically to understand the symptoms and the position of tumor.
  • Imaging studies: There are many instruments, which gives images of the affected organs.  X-rays, ultrasound, CT, MRI and PET scans are usually employed for staging cancer.
  • Laboratory tests of fluids:  Blood, urine and other fluids collected from the patient can be used to analyze the presence of certain proteins or other molecules, which can indicate the development of cancer. For example, Prostatic acid phosphatase (PAP) can be detected in patients having prostate cancer.
  • Pathology reports: These reports mainly include information obtained by studying cells and tissues under microscope. Such samples, which are analyzed, are collected from the patients by biopsy. It may also contain information based on visual examinations of the tumor such as size, type and grade. Information on the extent of spread of a tumor into other tissues is also given in the report.
  • Surgical reports: These reports are based on the findings from surgery. Information mainly includes the site of tumor, the appearance of tumor and the extent of spread to lymph nodes and other organs.

The new staging system: Molecular staging systems

Multiple genetic alterations are the prerequisite for carcinogenesis. These genes and the related proteins can be used as biomarkers or molecular markers in staging and diagnosing cancer. According to the National Cancer Institute, biomarker is “a biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process or of a condition or disease.” Recent advancement in genetics and molecular pathology has generated many candidate biomarkers, which can help in cancer staging.

Uses of biomarker:

  • Risk Stratification
  • Screening
  • Chemoprevention
  • Diagnosis and Classification
  • Prognosis
  • Prediction of treatment
  • Therapy Tracking and Post-treatment Surveillance

Although there are several biomarkers associated with different stages of cancers, the selection of the appropriate biomarkers is essential.

References

  1. Joseph A. Ludwig & John N. Weinstein (2005) Biomarkers in Cancer Staging, Prognosis and Treatment Selection Nature Reviews. Cancer 5, 845-856
  2. Vathany Kulasingam and Eleftherios P Diamandis (2008) Strategies for discovering novel cancer biomarkers through utilization of emerging technologies Nature Clinical Practice Oncology ; 5, 588-599
  3. This article was originally published on September 3, 2012 and last revision and update was 9/4/2015.