Cancer Stages and Grading
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INTRODUCTIONBack to top
In order to have a uniform way of describing where cancer is situated and if or where it has spread (in other words, how much cancer is present in a person’s body), we make use of what is called a cancer staging system. [1,2] Making use of such a universal staging system assists clinicians in many ways. In particular, it helps them to:
- Discuss the diagnosis with everyone in the healthcare team in a clear, concise language without the need to go into lengthy explanations and/or discussions.
- Formulate a treatment plan – for example, deciding whether surgery is warranted or appropriate and/or whether chemotherapy or radiation therapy is required.
- Estimate the chance of recovery.
- Determine how well cancer responded to treatment.
- Estimate the chance of cancer recurring (coming back) after the initial treatment, and
- Evaluate how effective new treatments are in a large number of people with the same diagnosis. 
A staging system is mostly used for cancers that form tumours. Cancers involving blood cells (i.e., leukaemia) are usually not staged in a similar way. 
The TNM staging system
The special investigations or diagnostic tests (e.g., x-rays, biopsies, surgical excision, etc.) that were performed to assist with the diagnosis of cancer, may also help doctors with the staging of that cancer. Sometimes additional special investigations, such as imaging studies (computed tomography or CT, magnetic resonance imaging or MRI, or positron emission tomography or PET scans, or sonars) are also used to further assist with accurately determining the stage of cancer. The results of these and other tests, including blood tests, help doctors to determine the size of the primary (original or main) tumour and its location, whether cancer has spread to lymph nodes and/or to other parts of the body and to find out whether there are any tumour markers that indicate whether the cancer is more or less likely to spread (or metastasise). [1,2,3]
Once the above is known, doctors can use a staging system of their choice. One of the most widely used cancer staging systems is the TNM system that was developed by the American Joint Committee on Cancer (AJCC).  Here the letters donate the following:
- T stands for the size and the extent of the primary/main Tumour.
- N refers to the number of nearby lymph Nodes that have been invaded by cancer.
- M refers to whether cancer has Metastasised/spread to other parts of the body.
The primary tumour (T)
The primary or main tumour is where cancer first started. The cancer is named after this location (i.e., lung, liver, or colon cancer) and, apart from its location, doctors also need to determine the tumour’s size and to check whether it has spread into nearby organs or areas. The following letters and numbers help to describe their findings:
- TX = there is no information about the primary tumour or it cannot be measured
- T0 = the primary tumour cannot be found or there is no evidence of a primary tumour
- Tis = the primary tumour is in situ – this means that the cancer is only growing in the layer of cells where it originated, but that it has not penetrated into deeper layers (it is also called pre-cancer)
- T1, T2, T3, T4 = these numbers might describe the tumour size and/or the amount of penetration into nearby organs or tissues so that the higher the number, the larger the tumour and/or the more it has grown into nearby tissues. [2,3]
Lymph nodes (N)
With the help of imaging studies and/or biopsies (where a sample of the tissue is obtained with the use of a needle or small surgical excision), doctors will determine whether cancer has spread to nearby lymph nodes. The lymphatic system is one of the body’s major defence systems and cancer cells, which are recognised as abnormal, may become lodged in lymph nodes. Many types of cancer may reach nearby lymph nodes before they spread to more distant areas or organs. The following letters and numbers are used to describe the N category of the TNM system:
- NX = there is no information about the nearby lymph nodes or they cannot be assessed
- N0 = there are no cancerous cells in nearby lymph nodes (i.e., cancer is not present in the nearby lymph nodes)
- N1, N2, N3 = these numbers might describe the size, location, and/or a number of nearby lymph nodes that contain cancer cells. Higher numbers indicate greater spread to nearby lymph nodes.
When cancer cells from the primary tumour spread to distant organs it is called metastasis (plural: metastases). The following numbers indicate the presence or absence of metastases:
- M0 = no distant metastases have been identified
- M1 = cancer has spread to distant organs. 
Important points to remember
Not all cancers are staged in exactly the same manner because different cancers tend to behave differently. This means that letters and numbers may have slightly different meanings for different types of cancer and the above is just to provide a general understanding of how staging works. Sometimes staging is further subdivided so that a stage may be denoted as T3a or T3b. A patient’s oncologist (doctor specialised to treat cancer) is the best person to ask about cancer staging. 
Grading of cancer
Apart from staging, cancers are usually also graded. The grade is a measure of how abnormal the cancer cells appear when examined under a microscope – this is known as a histological examination. The more abnormal the cells are (in other words, the more different they appear from the cells from which they originated) the more likely they are to grow and spread faster. [1,2]
As with staging, the grade is usually assigned the letter G with a number from 0 to 4 with lower numbers indicative of lower-grade cancers. Low-grade cancers are cancers where the cells are well differentiated so that they closely resemble the cells of the organ where they originated. Generally speaking, these cancers tend to grow slowly and to have a better prognosis. High-grade cancers consist of poorly differentiated cells that appear abnormal under the microscope and they may require different treatments from low-grade cancers. [1,2]
OTHER FACTORS AFFECTING PROGNOSIS AND/OR TREATMENTBack to top
While both staging and grading are important factors in determining treatment and prognosis, there are other factors to consider. Once again, these are different for different cancers and not all of these may be relevant to each and every cancer. Depending on the type of cancer, it may also be important to determine the following:
All cancers originate from a specific cell type within an organ or structure and sometimes these different cell types within the same organ require different treatments and/or carry different prognoses. For example, cancers of the oesophagus may originate from either squamous cells that line the inside of the oesophagus (called squamous cell carcinoma) or from cells within glands in the oesophagus, the so-called adenocarcinomas. Adenocarcinomas and squamous cell carcinomas are staged differently.
In some instances, the exact location of the primary tumour affects outlook and therefore it should be taken into consideration when staging is performed. For example, the stage of cancer of the oesophagus depends on whether the primary tumour is located in the upper, middle, or lower part of the oesophagus.
Tumour markers are substances produced by certain cancers and for which blood levels (the amount present in the bloodstream) might correlate with prognosis. Hence the number of such tumour markers should be taken into consideration when staging is performed.
A person’s age at the time the cancer is discovered may also impact the overall outlook, so it may have to take into account when staging is performed.
Results from blood tests
Some cancers are dependent on growth factors for their survival and such growth factors may include hormones that occur naturally in the human body. Examples of such cancers are certain forms of breast cancer that have oestrogen receptors on their surface. Oestrogen stimulates their growth. These cancers may be staged differently from those breast cancers that do not have oestrogen receptors and that grow independently of the amount of oestrogen in the body. 
Once the TNM staging has been completed and all of the above (and sometimes also other) factors have been taken into consideration, most cancers are assigned an overall stage by making use of the Roman numerals I to IV. 
The higher the number, the more advanced cancer typically is; in other words, these cancers usually have spread further or had other worrisome characteristics. Stage 0 cancer refers to very superficial cancer called “cancer in situ”, which means that the cancer is confined to the upper layers of the area where it started, and it has not penetrated into deeper tissues. Such cancers are usually completed cured by surgical removal. Stage I cancers are no longer confined to just the superficial layers, but have not grown deeply into nearby tissues and have not spread to lymph nodes or other parts of the body. While Stage II and III cancers have penetrated more deeply into surrounding tissues and may have spread to the lymph nodes, these cancers have not spread to distant parts of the body. Stage IV means that cancer has metastasised to other organs or parts of the body that is remote from where cancer originated. [1,2]
Depending on cancer, oncologists sometimes subdivide the stage further by making use of capital letters, e.g., Stage IIIA or IIIB. 
Sometimes staging is repeated during the course of treatment. If staging is done prior to surgery and only with the help of the findings during a physical examination and the results from the special investigations (like imaging studies), we refer to it as “clinical” staging. This is donated by making use of a lowercase “c” in front of the TNM classification. “Pathological” staging is performed based on the findings during surgery – surgery often provides the best information pertaining to the spread of cancer. Staging done after surgery is donated with a lowercase “p” in front of the TNM classification. 
If staging is done after a person has received radiotherapy, chemotherapy, hormone therapy or immunotherapy, it is called post-therapy staging. Such therapies are sometimes given prior to surgery to shrink the primary tumour and make surgery easier. In this case, we use a lowercase “y” in front of the TNM classification. 
CONCLUSIONBack to top
Cancers that form tumours (lumps) are usually staged according to internationally set criteria for specific cancer. Several factors are taken into consideration when cancer is staged and these may vary according to the cancer present. By staging cancer, doctors know at a glance how much cancer is present. This is important because it helps to determine the most appropriate treatment. In addition, it may also provide useful information about the patient’s outlook and prognosis.
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