Cancer Staging
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Cancer staging is the process of determining the extent to which a
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
has developed by growing and spreading. Contemporary practice is to assign a number from I to IV to a cancer, with I being an isolated cancer and IV being a cancer that has spread to the limit of what the assessment measures. The stage generally takes into account the size of a
tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, whether it has invaded adjacent
organs In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a f ...
, how many regional (nearby)
lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
it has spread to (if any), and whether it has appeared in more distant locations (
metastasized Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
). The staging system is not applicable to
astrocytoma Astrocytomas are a type of brain tumor. They originate in a particular kind of glial cells, star-shaped brain cells in the cerebrum called astrocytes. This type of tumor does not usually spread outside the brain and spinal cord and it does not usu ...
, which is instead expressed as "grade I–IV". Grade IV astrocytoma, more commonly referred to as
glioblastoma multiforme Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality cha ...
, is a universally fatal primary brain cancer most commonly seen in the seventh decade of life.


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). This staging system is used for most forms of cancer, except
brain tumor A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and seconda ...
s and
hematological malignancies Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid tissues (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system. Because these tissues are al ...
. * Clinical stage is based on all of the available information obtained before a surgery to remove the tumor. This stage may include information about the tumor obtained by
physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally consists of a series of questions about the pati ...
, blood tests,
radiologic Radiology ( ) is the medical discipline that uses medical imaging to diagnose diseases and guide their treatment, within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiatio ...
examination,
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a dise ...
, and
endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...
. * Pathologic stage adds additional information gained by examination of the tumor
microscopically Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...
by a
pathologist Pathology is the study of the causal, causes and effects of disease or injury. The word ''pathology'' also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when us ...
after it has been surgically removed. Because they use different criteria, clinical stage and pathologic stage often differ. Pathologic staging is usually considered to be more accurate because it allows direct examination of the tumor in its entirety, contrasted with clinical staging which is limited by the fact that the information is obtained by making indirect observations of a tumor which is still in the body. However, clinical staging and pathologic staging often complement each other. Not every tumor is treated surgically, so pathologic staging is not always available. Also, sometimes surgery is preceded by other treatments such as
chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
and
radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radi ...
which shrink the tumor, so the pathologic stage may underestimate the true stage.


Considerations

Correct staging is critical because treatment (particularly the need for pre-operative therapy and/or for adjuvant treatment, the extent of surgery) is generally based on this parameter. Thus, incorrect staging would lead to improper treatment. For some common cancers the staging process is well-defined. For example, in the cases of breast cancer and prostate cancer, doctors routinely can identify that the cancer is early and that it has low risk of metastasis., citing * * In such cases,
medical specialty A medical specialty is a branch of medical practice that is focused on a defined group of patients, diseases, skills, or philosophy. Examples include those branches of medicine that deal exclusively with children (paediatrics), cancer (oncology), ...
professional organizations A professional association (also called a professional body, professional organization, or professional society) usually seeks to further a particular profession, the interests of individuals and organisations engaged in that profession, and th ...
recommend against the use of
PET scans Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...
, CT scans, or bone scans because research shows that the risk of getting such procedures outweighs the possible benefits. Some of the problems associated with overtesting include patients receiving invasive procedures, overutilizing medical services, getting unnecessary radiation exposure, and experiencing misdiagnosis.


Pathologic

Pathologic staging, where a pathologist examines sections of tissue, 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 most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
can mean mistaging 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 A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...
happen not to be present in the slices of tissue viewed, incorrect staging and improper treatment can result.


Current research

New, highly sensitive methods of staging are in development. For example, the
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
for GCC ( guanylyl cyclase c), present only in the luminal aspect of
intestinal epithelium The intestinal epithelium is the single cell layer that form the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelial cells, it serves two main functi ...
, can be identified using molecular screening (
RT-PCR Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase ch ...
) with a high degree of sensitivity and exactitude. Presence of GCC in any other tissue of the body represents colorectal metaplasia. Because of its high sensitivity, RT-PCR screening for GCC greatly reduces underestimation of disease stage. Researchers hope that staging with this level of precision will lead to more appropriate treatment and better
prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...
. Furthermore, researchers hope that this same technique can be applied to other tissue-specific
proteins Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
.


Systems

Staging systems are specific for each type of cancer (e.g.,
breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
and
lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
), but some cancers 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 {{Short description, Organization standardising cancer staging The American Joint Committee on Cancer (AJCC) is an organization best known for defining and popularizing cancer staging standards, officially the AJCC staging system. The American Joi ...
. Systems of staging may differ between diseases or specific manifestations of a disease.


Blood

*
Lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...
: most use
Ann Arbor staging Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma (formerly designated Hodgkin's disease) and non-Hodgkin lymphoma (abbreviated NHL). It was initially developed for Hodgkin's, but has some use in NHL. It has roughly ...
*
Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition wa ...
: follows a scale from I to 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 cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...
: In
breast cancer classification Breast cancer classification divides breast cancer into categories according to different schemes criteria and serving a different purpose. The major categories are the histopathological type, the grade of the tumor, the stage of the tumor, and the ...
, staging is usually based on TNM, but staging in I–IV may be used as well. * Cervical and ovarian cancers: the " FIGO" system has been adopted into the TNM system. For premalignant dysplastic changes, the CIN (
cervical intraepithelial neoplasia Cervical intraepithelial neoplasia (CIN), also known as cervical dysplasia, is the abnormal growth of cells on the surface of the cervix that could potentially lead to cervical cancer. More specifically, CIN refers to the potentially precancerous t ...
) grading system is used. *
Colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
: originally consisted of four stages: A, B, C, and D (the Dukes staging system). More recently, colon cancer staging is indicated either by the original A-D stages or by TNM. *
Kidney cancer Kidney cancer, also known as renal cancer, is a group of cancers that starts in the kidney. Symptoms may include blood in the urine, lump in the abdomen, or back pain. Fever, weight loss, and tiredness may also occur. Complications can include sp ...
: uses TNM. *
Cancer of the larynx Laryngeal cancers are mostly squamous-cell carcinomas, reflecting their origin from the epithelium of the larynx. Cancer can develop in any part of the larynx. The prognosis is affected by the location of the tumour. For the purposes of staging ...
: Uses TNM. *
Liver cancer Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...
: Uses TNM. *
Lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissue (biology), tissues of the lung. Lung carcinomas derive from tran ...
: uses TNM. *
Melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...
: TNM used. Also of importance are the "Clark level" and "Breslow depth" which refer to the microscopic depth of tumor invasion ("Microstaging"). *
Prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...
: TNM almost universally used. *
Testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle, or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an u ...
: uses TNM along with a measure of
blood serum Serum () is the fluid and solute component of blood which does not play a role in clotting. It may be defined as blood plasma without the clotting factors, or as blood with all cells and clotting factors removed. Serum includes all proteins not u ...
markers (TNMS). *
Non-melanoma skin cancer Skin cancers are cancers that arise from the skin. They are due to the development of abnormal cells that have the ability to invade or spread to other parts of the body. There are three main types of skin cancers: basal-cell skin cancer (BCC ...
: uses TNM. *
Bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...
: uses TNM.


Overall stage grouping

Overall Stage Grouping is also referred to as
Roman Numeral Roman numerals are a numeral system that originated in ancient Rome and remained the usual way of writing numbers throughout Europe well into the Late Middle Ages. Numbers are written with combinations of letters from the Latin alphabet, eac ...
Staging. This system uses numerals I, II, III, and IV (plus the 0) to describe the progression of cancer. * Stage 0: carcinoma ''in situ'', abnormal cells growing in their normal place ("in situ" from Latin for "in its place"). * Stage I: cancers are localized to one part of the body. Stage I cancer can be surgically removed if small enough. * Stage II: cancers are locally advanced. Stage II cancer can be treated by chemotherapy, radiation, or surgery. *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 III can be treated by chemotherapy, radiation, or surgery. * Stage IV: cancers have often metastasized, or spread to other organs or throughout the body. Stage IV cancer can be treated by chemotherapy, radiation, or surgery. Despite treatment, a patient's mortality rate can be significantly higher with Stage IV cancer, e.g., the cancer can progress to become
terminal Terminal may refer to: Computing Hardware * Terminal (electronics), a device for joining electrical circuits together * Terminal (telecommunication), a device communicating over a line * Computer terminal, a set of primary input and output dev ...
. 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 is a change in the distribution of stages 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 Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...
scans). Stage migration can lead to curious statistical phenomena (for example, the Will Rogers phenomenon).


References


External links


"Staging: Questions and Answers" at the National Cancer Institute
{{Tumors Anatomical pathology