Cancer staging
Encyclopedia
The stage of a cancer is a description (usually numbers I to IV with IV having more progression) of the extent the cancer
has spread. The stage often takes into account the size of a tumor
, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized
to (if any), and whether it has spread to distant organs. Staging of cancer is the most important predictor of survival, and cancer treatment is primarily determined by staging. Thus, staging does not change with progression of the disease as it is used to assess prognosis. Patients' cancer, however, may be restaged after treatment but the staging established at diagnosis is rarely changed.
Because they use different criteria, clinical stage and pathologic stage often differ. Pathologic staging is usually considered the "better" or "truer" stage because it allows direct examination of the tumor and its spread, contrasted with clinical staging which is limited by the fact that the information is obtained by making indirect observations at a tumor which is still in the body. However, clinical staging and pathologic staging should complement each other. Not every tumor is treated surgically, therefore pathologic staging is not always available.
Also, sometimes surgery is preceded by other treatments such as chemotherapy
and radiation therapy
which shrink the tumor, so the pathologic stage may underestimate the true stage.
This staging system is used for most forms of cancer, except brain tumor
s and hematological malignancies.
, can be particularly problematic for two specific reasons: visual discretion and random sampling of tissue. "Visual discretion" means being able to identify single cancerous cells intermixed with healthy cells on a slide. Oversight of one cell
can mean mistagging and lead to serious, unexpected spread of cancer. "Random sampling" refers to the fact that lymph nodes are cherry-picked from patients and random samples are examined. If cancerous cells present in the lymph node
happen not to be present in the slices of tissue viewed, incorrect staging and improper treatment can result.
New, highly sensitive methods of staging are in development. For example, the mRNA for GCC (guanylyl cyclase c
), present only in the luminal aspect of intestinal epithelium
, can be identified using molecular screening (RT-PCR) with an astonishing degree of sensitivity and exactitude. Presence of GCC in any other tissue of the body represents colorectal metaplasia. Because of its exquisite sensitivity, RT-PCR screening for GCC nearly eliminates the possibility of underestimation of true disease stage. Researchers hope that staging with this level of precision will lead to more appropriate treatment and better prognosis
. Furthermore, researchers hope that this same technique can be applied to other tissue-specific proteins.
and lung cancer
). Some cancers, however, do not have a staging system. Although competing staging systems still exist for some types of cancer, the universally-accepted staging system is that of the UICC
, which has the same definitions of individual categories as the AJCC
.
Systems of staging may differ between diseases or specific manifestations of a disease.
Staging. This system uses numerals I, II, III, and IV (plus the 0) to describe the progression of cancer.
Within the TNM system, a cancer may also be designated as recurrent, meaning that it has appeared again after being in remission or after all visible tumor has been eliminated. Recurrence can either be local, meaning that it appears in the same location as the original, or distant, meaning that it appears in a different part of the body.
).
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
has spread. The stage often takes into account the size of a tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
, how deeply it has penetrated, whether it has invaded adjacent organs, how many lymph nodes it has metastasized
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
to (if any), and whether it has spread to distant organs. Staging of cancer is the most important predictor of survival, and cancer treatment is primarily determined by staging. Thus, staging does not change with progression of the disease as it is used to assess prognosis. Patients' cancer, however, may be restaged after treatment but the staging established at diagnosis is rarely changed.
TNM staging system
Cancer staging can be divided into a clinical stage and a pathologic stage. In the TNM (Tumor, Node, Metastasis) system, clinical stage and pathologic stage are denoted by a small "c" or "p" before the stage (e.g., cT3N1M0 or pT2N0).- Clinical stage is based on all of the available information obtained before a surgerySurgerySurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
to remove the tumor. Thus, it may include information about the tumor obtained by physical examinationPhysical examinationPhysical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
, radiologicRadiologyRadiology is a medical specialty that employs the use of imaging to both diagnose and treat disease visualized within the human body. Radiologists use an array of imaging technologies to diagnose or treat diseases...
examination, and endoscopyEndoscopyEndoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
. - Pathologic stage adds additional information gained by examination of the tumor microscopically by a pathologist.
Because they use different criteria, clinical stage and pathologic stage often differ. Pathologic staging is usually considered the "better" or "truer" stage because it allows direct examination of the tumor and its spread, contrasted with clinical staging which is limited by the fact that the information is obtained by making indirect observations at a tumor which is still in the body. However, clinical staging and pathologic staging should complement each other. Not every tumor is treated surgically, therefore pathologic staging is not always available.
Also, sometimes surgery is preceded by other treatments such as chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
which shrink the tumor, so the pathologic stage may underestimate the true stage.
This staging system is used for most forms of cancer, except brain tumor
Brain tumor
A brain tumor is an intracranial solid neoplasm, a tumor within the brain or the central spinal canal.Brain tumors include all tumors inside the cranium or in the central spinal canal...
s and hematological malignancies.
Considerations in staging
Correct staging is critical because treatment is directly related to disease stage. Thus, incorrect staging would lead to improper treatment, and material diminution of patient survivability. Correct staging, however, can be difficult to achieve. Pathologic staging, where a pathologist examines sections of tissueTissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
, can be particularly problematic for two specific reasons: visual discretion and random sampling of tissue. "Visual discretion" means being able to identify single cancerous cells intermixed with healthy cells on a slide. Oversight of one cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
can mean mistagging and lead to serious, unexpected spread of cancer. "Random sampling" refers to the fact that lymph nodes are cherry-picked from patients and random samples are examined. If cancerous cells present in the lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...
happen not to be present in the slices of tissue viewed, incorrect staging and improper treatment can result.
New, highly sensitive methods of staging are in development. For example, the mRNA for GCC (guanylyl cyclase c
Guanylyl cyclase c
Guanylate cyclase 2C, also known as guanylyl cyclase C , intestinal guanylate cyclase, guanylate cyclase-C receptor, or the heat-stable enterotoxin receptor is an enzyme that in humans is encoded by the GUCY2C gene....
), present only in the luminal aspect of intestinal epithelium
Intestinal epithelium
The intestinal epithelium is the epithelium that covers the small and large intestine. It is simple columnar and nonciliated.They primarily take part in the digestive system. However, they also express TLR 4 receptors, and are thus a part of the immune system, both as a barrier and as a first-line...
, can be identified using molecular screening (RT-PCR) with an astonishing degree of sensitivity and exactitude. Presence of GCC in any other tissue of the body represents colorectal metaplasia. Because of its exquisite sensitivity, RT-PCR screening for GCC nearly eliminates the possibility of underestimation of true disease stage. Researchers hope that staging with this level of precision will lead to more appropriate treatment and better prognosis
Prognosis
Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...
. Furthermore, researchers hope that this same technique can be applied to other tissue-specific proteins.
Systems of staging
Staging systems are specific for each type of cancer (e.g., breast cancerBreast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
and lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
). Some cancers, however, do not have a staging system. Although competing staging systems still exist for some types of cancer, the universally-accepted staging system is that of the UICC
International Union Against Cancer
The International Union Against Cancer, or UICC is the only non-governmental organization dedicated exclusively to the global control of cancer. Its vision is of a world where cancer is eliminated as a major life-threatening disease for future generations...
, which has the same definitions of individual categories as the AJCC
American Joint Committee on Cancer
The American Joint Committee on Cancer is an organization best known for defining and popularizing cancer staging standards, officially the AJCC staging system....
.
Systems of staging may differ between diseases or specific manifestations of a disease.
Blood
- LymphomaLymphomaLymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
: uses Ann Arbor stagingAnn Arbor stagingAnn Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma and Non-Hodgkin lymphoma . It was initially developed for Hodgkin's, but has some use in NHL... - Hodgkin's Disease: follows a scale from I–IV and can be indicated further by an A or B, depending on whether a patient is non-symptomatic or has symptoms such as fevers. It is known as the "Cotswold System" or "Modified Ann Arbor Staging System".
Solid
For solid tumors, TNM is by far the most commonly used system, but it has been adapted for some conditions.- Breast cancerBreast cancerBreast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
: In breast cancer classificationBreast cancer classificationBreast cancer classification divides breast cancer into several categories according to multiple different schemes, each based on different criteria and serving a different purpose. A typical description usually considers each of these aspects in turn: the histolopathological type, the grade of the...
, staging is usually based upon TNM, but staging in I–IV may be used as well - Cervical and ovarian cancers: the "FIGOInternational Federation of Gynecology and ObstetricsThe International Federation of Gynaecology and Obstetrics, usually just FIGO as the acronym of its French name Fédération Internationale de Gynécologie et d'Obstétrique, is a worldwide NGO organisation representing obstetricians and gynaecologists in over one hundred territories...
" system has been adopted into the TNM system. For premalignant dysplastic changes, the CIN (cervical intraepithelial neoplasiaCervical intraepithelial neoplasiaCervical intraepithelial neoplasia , also known as cervical dysplasia and cervical interstitial neoplasia, is the potentially premalignant transformation and abnormal growth of squamous cells on the surface of the cervix. CIN is not cancer, and is usually curable...
) grading system is used. - Colon cancer: originally consisted of four stages: A, B, C, and D (the Dukes staging systemDukes classificationIn 1932 the British pathologist Cuthbert Dukes devised a famous classification system for colorectal cancer. Several different forms of the Dukes classification were developed...
). More recently, colon cancer staging is indicated either by the original A-D stages or by TNM. - Kidney cancerKidney cancerKidney cancer is a type of cancer that starts in the cells in the kidney.The two most common types of kidney cancer are renal cell carcinoma and urothelial cell carcinoma of the renal pelvis...
: uses TNM - Cancer of the larynxCancer of the larynxLaryngeal cancer may also be called cancer of the larynx or laryngeal carcinoma. Most laryngeal cancers are squamous cell carcinomas, reflecting their origin from the squamous cells which form the majority of the laryngeal epithelium....
: Uses TNM - Liver cancer: uses Stages I–IV
- Lung cancerLung cancerLung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
: uses TNM - Melanoma: TNM used. Also of importance are the "Clark level" and "Breslow depth" which refer to the microscopic depth of tumor invasion ("Microstaging").
- Prostate cancerProstate cancer stagingProstate cancer staging is the process by which physicians categorize the risk of cancer having spread beyond the prostate, or equivalently, the probability of being cured with local therapies such as surgery or radiation. Once patients are placed in prognostic categories, this information can...
: outside of US, TNM almost universally used. Inside US, Jewett-Whitmore sometimes used. - Testicular cancerTesticular cancerTesticular cancer is cancer that develops in the testicles, a part of the male reproductive system.In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year. In the UK, approximately 2,000 men are diagnosed each year. Over his lifetime, a man's risk of...
: uses TNM along with a measure of blood serumBlood serumIn blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
markers. - Non melanoma skin cancerSkin cancerSkin neoplasms are skin growths with differing causes and varying degrees of malignancy. The three most common malignant skin cancers are basal cell cancer, squamous cell cancer, and melanoma, each of which is named after the type of skin cell from which it arises...
: uses TNM - Bladder cancerBladder cancerBladder cancer is any of several types of malignant growths of the urinary bladder. It is a disease in which abnormal cells multiply without control in the bladder. The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis...
: uses TNM
Overall stage grouping
Overall Stage Grouping is also referred to as Roman NumeralRoman numerals
The numeral system of ancient Rome, or Roman numerals, uses combinations of letters from the Latin alphabet to signify values. The numbers 1 to 10 can be expressed in Roman numerals as:...
Staging. This system uses numerals I, II, III, and IV (plus the 0) to describe the progression of cancer.
- Stage 0 carcinoma in situCarcinoma in situCarcinoma in situ is an early form of cancer that is defined by the absence of invasion of tumor cells into the surrounding tissue, usually before penetration through the basement membrane. In other words, the neoplastic cells proliferate in their normal habitat, hence the name "in situ"...
. - Stage I cancers are localized to one part of the body.
- Stage II cancers are locally advanced.
- Stage III cancers are also locally advanced. Whether a cancer is designated as Stage II or Stage III can depend on the specific type of cancer; for example, in Hodgkin's Disease, Stage II indicates affected lymph nodes on only one side of the diaphragm, whereas Stage III indicates affected lymph nodes above and below the diaphragm. The specific criteria for Stages II and III therefore differ according to diagnosis.
- Stage IV cancers have often metastasized, or spread to other organs or throughout the body.
Within the TNM system, a cancer may also be designated as recurrent, meaning that it has appeared again after being in remission or after all visible tumor has been eliminated. Recurrence can either be local, meaning that it appears in the same location as the original, or distant, meaning that it appears in a different part of the body.
Stage migration
Stage migration describes change in the distribution of stage in a particular cancer population induced by either a change in the staging system itself or else a change in technology which allows more sensitive detection of tumor spread and therefore more sensitivity in detecting spread of disease (e.g., the use of MRI scan). Stage migration can lead to curious statistical phenomena (for example, the Will Rogers phenomenonWill Rogers phenomenon
The Will Rogers phenomenon is obtained when moving an element from one set to another set raises the average values of both sets. It is based on the following quote, attributed to comedian Will Rogers:...
).