Non-small cell lung cancer staging
Encyclopedia
Non-small-cell lung carcinoma (NSCLC) is any type of epithelial lung cancer
other than small cell lung carcinoma (SCLC). As a class, NSCLCs are relatively insensitive to chemotherapy
, compared to small cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy is increasingly being used both pre-operatively (neoadjuvant chemotherapy) and post-operatively (adjuvant chemotherapy).
, but there are several other types that occur less frequently, and all types can occur in unusual histologic variants and as mixed cell-type combinations.
Sometimes the phrase non-small-cell lung cancer [Not Otherwise Specified, or NOS] is used generically, usually when a more specific diagnosis cannot be made. This is most often the case when a pathologist examines a small amount of malignant cells or tissue in a cytology
or biopsy
specimen.
Lung cancer in never-smokers is almost universally NSCLC, with a sizeable majority being adenocarcinoma.
On relatively rare occasions, malignant lung tumors are found to contain components of both SCLC and NSCLC. In these cases, the tumors should be classified as combined small cell lung carcinoma (c-SCLC), and are (usually) treated like "pure" SCLC.Simon GR, Turrisi A, American College of Chest Physicians. Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132(3 Suppl):324S-39S.
is more common in men than in women. It is closely correlated with a history of tobacco smoking
, more so than most other types of lung cancer
. According to the Nurses' Health Study
, the relative risk
of SCC is approximately 5.5, both among those with a previous duration of smoking of 1 to 20 years, and those with 20 to 30 years, compared to never-smokers. The relative risk increases to approximately 16 with a previous smoking duration of 30 to 40 years, and approximately 22 with more than 40 years.
It most often arises centrally in larger bronchi
, and while it often metastasizes to locoregional lymph nodes (particularly the hilar nodes) early in its course, it generally disseminates outside the thorax somewhat later than other major types of lung cancer. Large tumors may undergo central necrosis, resulting in cavitation. A squamous cell carcinoma is often preceded for years by squamous cell metaplasia
or dysplasia
in the respiratory epithelium
of the bronchi, which later transforms to carcinoma in situ
. In carcinoma in situ, atypical cells may be identified by cytologic smear test of sputum, bronchoalveolar lavage
or samples from endobronchial brushings. However, squamous-cell carcinoma in situ is asymptomatic and undetectable on X-ray radiographs. Eventually, it becomes symptomatic, usually when the tumor mass begins to obstruct the lumen of a major bronchus, often producing distal atelectasis
and infection
. Simultaneously, the lesion invades into the surrounding pulmonary substance. On histopathology
, these tumors range from well differentiated, showing keratin pearls and cell junction
s, to anaplastic
, with only minimal residual squamous cell features.
Currently, four variants (papillary, small cell, clear cell, and basaloid) of squamous cell carcinoma of the lung are recognized. Of these variants, there is some evidence that the basaloid and poorly differentiated small-cell variants may have worse prognoses than "conventional" squamous cell carcinomas. The papillary variant occurs more frequently as a primarily superficial, endobronchial lesion, with a modestly better prognosis Very little data is currently available on the clear cell variant of squamous cell carcinoma, and no consensus has been reached on the prognostic implications of clear cell changes in lung cancer
Recently, four mRNA expression subtypes (primitive, basal, secretory, and classical) were identified and validated within squamous cell carcinoma. The primitive subtype correlates with worse patient survival. These subtypes, defined by intrinsic expression differences, provide a possible foundation for improved patient prognosis and research into individualized therapies.
is currently the most common type of lung cancer
in "never smokers" (lifelong non-smokers). Adenocarcinomas account for approximately 40% of lung cancers. Historically, adenocarcinoma was more often seen peripherally in the lungs than small cell lung cancer and squamous cell lung cancer, both of which tended to be more often centrally located. Interestingly, however, recent studies suggest that the "ratio of centrally-to-peripherally occurring" lesions may be converging toward unity for both adenocarcinoma and squamous cell carcinoma.
(AJCC) and the International Union Against Cancer
(UICC) recommend TNM staging, using a uniform scheme for non-small cell lung carcinoma, small-cell lung carcinoma and broncho-pulmonary carcinoid
tumors. AJCC has provided an accessible poster version of these copyrighted TNM descriptors to which readers are directed. Extensive presentation of prognostic data for both 6th and 7th edition individual TNM descriptors and overall groups is available.
involving cisplatin
. Other treatment choices are chemotherapy
, radiation therapy
(radiotherapy), and targeted therapy
.
New methods of giving radiation treatment allow doctors to be more accurate in treating lung cancers. This means less radiation affects nearby healthy tissues. New methods include Gamma knife, Cyberknife
and stereotactic radiosurgery
(SRS).
Other treatments are radiofrequency ablation
and chemoembolization
.
are used in advanced (metastatic) NSCLC.
Some patients with particular mutations in the EGFR
gene respond to EGFR tyrosine kinase inhibitors such as gefitinib
.
There are many phase III clinical trials of new therapies for advanced NSCLC, including intedanib
(BIBF 1120).
s which are in clinical trials. Crizotinib
gained FDA approval in Aug 2011.
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...
other than small cell lung carcinoma (SCLC). As a class, NSCLCs are relatively insensitive to chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, compared to small cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy is increasingly being used both pre-operatively (neoadjuvant chemotherapy) and post-operatively (adjuvant chemotherapy).
Types
The most common types of NSCLC are squamous cell carcinoma, large cell carcinoma, and adenocarcinomaAdenocarcinoma
Adenocarcinoma is a cancer of an epithelium that originates in glandular tissue. Epithelial tissue includes, but is not limited to, the surface layer of skin, glands and a variety of other tissue that lines the cavities and organs of the body. Epithelium can be derived embryologically from...
, but there are several other types that occur less frequently, and all types can occur in unusual histologic variants and as mixed cell-type combinations.
Sometimes the phrase non-small-cell lung cancer [Not Otherwise Specified, or NOS] is used generically, usually when a more specific diagnosis cannot be made. This is most often the case when a pathologist examines a small amount of malignant cells or tissue in a cytology
Cytopathology
Cytopathology is a branch of pathology that studies and diagnoses diseases on the cellular level. The discipline was founded by Rudolf Virchow in 1858. A common application of cytopathology is the Pap smear, used as a screening tool, to detect precancerous cervical lesions and prevent cervical...
or biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
specimen.
Lung cancer in never-smokers is almost universally NSCLC, with a sizeable majority being adenocarcinoma.
On relatively rare occasions, malignant lung tumors are found to contain components of both SCLC and NSCLC. In these cases, the tumors should be classified as combined small cell lung carcinoma (c-SCLC), and are (usually) treated like "pure" SCLC.Simon GR, Turrisi A, American College of Chest Physicians. Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132(3 Suppl):324S-39S.
Squamous cell lung carcinoma
Squamous cell carcinoma (SCC) of the lungLung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
is more common in men than in women. It is closely correlated with a history of tobacco smoking
Tobacco smoking
Tobacco smoking is the practice where tobacco is burned and the resulting smoke is inhaled. The practice may have begun as early as 5000–3000 BCE. Tobacco was introduced to Eurasia in the late 16th century where it followed common trade routes...
, more so than most other types of 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...
. According to the Nurses' Health Study
Nurses' Health Study
The Nurses Health Study, established in 1976 by Dr. Frank Speizer, and the Nurses' Health Study II, established in 1989 by Dr. Walter Willett, are the most definitive long-term epidemiological studies conducted to date on older women's health. The study has followed 121,700 female registered...
, the relative risk
Relative risk
In statistics and mathematical epidemiology, relative risk is the risk of an event relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group....
of SCC is approximately 5.5, both among those with a previous duration of smoking of 1 to 20 years, and those with 20 to 30 years, compared to never-smokers. The relative risk increases to approximately 16 with a previous smoking duration of 30 to 40 years, and approximately 22 with more than 40 years.
It most often arises centrally in larger bronchi
Bronchus
A bronchus is a passage of airway in the respiratory tract that conducts air into the lungs. The bronchus branches into smaller tubes, which in turn become bronchioles....
, and while it often metastasizes to locoregional lymph nodes (particularly the hilar nodes) early in its course, it generally disseminates outside the thorax somewhat later than other major types of lung cancer. Large tumors may undergo central necrosis, resulting in cavitation. A squamous cell carcinoma is often preceded for years by squamous cell metaplasia
Metaplasia
Metaplasia is the reversible replacement of one differentiated cell type with another mature differentiated cell type. The change from one type of cell to another may generally be a part of normal maturation process or caused by some sort of abnormal stimulus...
or dysplasia
Dysplasia
Dysplasia , is a term used in pathology to refer to an abnormality of development. This generally consists of an expansion of immature cells, with a corresponding decrease in the number and location of mature cells. Dysplasia is often indicative of an early neoplastic process...
in the respiratory epithelium
Respiratory epithelium
Respiratory epithelium is a type of epithelium found lining the respiratory tract, where it serves to moisten and protect the airways. It also functions as a barrier to potential pathogens and foreign particles, preventing infection and tissue injury by action of the mucociliary escalator.-...
of the bronchi, which later transforms to carcinoma in situ
Carcinoma in situ
Carcinoma 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"...
. In carcinoma in situ, atypical cells may be identified by cytologic smear test of sputum, bronchoalveolar lavage
Bronchoalveolar lavage
Bronchoalveolar lavage is a medical procedure in which a bronchoscope is passed through the mouth or nose into the lungs and fluid is squirted into a small part of the lung and then recollected for examination. BAL is typically performed to diagnose lung disease...
or samples from endobronchial brushings. However, squamous-cell carcinoma in situ is asymptomatic and undetectable on X-ray radiographs. Eventually, it becomes symptomatic, usually when the tumor mass begins to obstruct the lumen of a major bronchus, often producing distal atelectasis
Atelectasis
Atelectasis is defined as the collapse or closure of alveoli resulting in reduced or absent gas exchange. It may affect part or all of one lung. It is a condition where the alveoli are deflated, as distinct from pulmonary consolidation.It is a very common finding in chest x-rays and other...
and infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
. Simultaneously, the lesion invades into the surrounding pulmonary substance. On histopathology
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
, these tumors range from well differentiated, showing keratin pearls and cell junction
Cell junction
A cell junction is a type of structure that exists within the tissue of a some multicellular organism . Cell junctions consist of protein complexes and provide contact between neighbouring cells or between a cell and the extracellular matrix...
s, to anaplastic
Anaplasia
Anaplasia refers to a reversion of differentiation in cells and is characteristic of malignant neoplasms . Sometimes, the term also includes an increased capacity for multiplication. Lack of differentiation is considered a hallmark of aggressive malignancies. The term anaplasia literally means "to...
, with only minimal residual squamous cell features.
Currently, four variants (papillary, small cell, clear cell, and basaloid) of squamous cell carcinoma of the lung are recognized. Of these variants, there is some evidence that the basaloid and poorly differentiated small-cell variants may have worse prognoses than "conventional" squamous cell carcinomas. The papillary variant occurs more frequently as a primarily superficial, endobronchial lesion, with a modestly better prognosis Very little data is currently available on the clear cell variant of squamous cell carcinoma, and no consensus has been reached on the prognostic implications of clear cell changes in lung cancer
Recently, four mRNA expression subtypes (primitive, basal, secretory, and classical) were identified and validated within squamous cell carcinoma. The primitive subtype correlates with worse patient survival. These subtypes, defined by intrinsic expression differences, provide a possible foundation for improved patient prognosis and research into individualized therapies.
Large-cell lung carcinoma
Large cell lung carcinoma (LCLC) is a heterogeneous group of undifferentiated malignant neoplasms originating from transformed epithelial cells in the lung. LCLC's have typically comprised between around 10% of all NSCLC in the past, although newer diagnostic techniques seem to be reducing the incidence of diagnosis of "classic" LCLC in favor of more poorly differentiated squamous cell carcinomas and adenocarcinomas. LCLC is, in effect, a "diagnosis of exclusion", in that the tumor cells lack light microscopic characteristics that would classify the neoplasm as a small-cell carcinoma, squamous-cell carcinoma, adenocarcinoma, or other more specific histologic type of lung cancer. LCLC is differentiated from small cell lung carcinoma (SCLC) primarily by the larger size of the anaplastic cells, a higher cytoplasmic-to-nuclear size ratio, and a lack of "salt-and-pepper" chromatin.Lung adenocarcinoma
Adenocarcinoma of the lungLung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
is currently the most common type of 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...
in "never smokers" (lifelong non-smokers). Adenocarcinomas account for approximately 40% of lung cancers. Historically, adenocarcinoma was more often seen peripherally in the lungs than small cell lung cancer and squamous cell lung cancer, both of which tended to be more often centrally located. Interestingly, however, recent studies suggest that the "ratio of centrally-to-peripherally occurring" lesions may be converging toward unity for both adenocarcinoma and squamous cell carcinoma.
Staging
The American Joint Committee on CancerAmerican 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....
(AJCC) and the International Union Against Cancer
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...
(UICC) recommend TNM staging, using a uniform scheme for non-small cell lung carcinoma, small-cell lung carcinoma and broncho-pulmonary carcinoid
Carcinoid
Carcinoid is a slow-growing type of neuroendocrine tumor, originating in the cells of the neuroendocrine system.In 2000, the World Health Organization redefined "carcinoid", but this new definition has not been accepted by all practitioners. This has led to some complexity in distinguishing...
tumors. AJCC has provided an accessible poster version of these copyrighted TNM descriptors to which readers are directed. Extensive presentation of prognostic data for both 6th and 7th edition individual TNM descriptors and overall groups is available.
Treatment
More than one kind of treatment is often used, depending on the stage of the cancer, the individual's overall health, age, response to chemotherapy, and other factors such as the likely side effects of the treatment.Early/non-metastatic NSCLC
NSCLCs are usually not very sensitive to chemotherapy and/or radiation, so surgery is the treatment of choice if diagnosed at an early stage, often with adjuvant (ancillary) chemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
involving cisplatin
Cisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
. Other treatment choices are chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, 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...
(radiotherapy), and targeted therapy
Targeted therapy
Targeted therapy is a type of medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with rapidly dividing cells...
.
New methods of giving radiation treatment allow doctors to be more accurate in treating lung cancers. This means less radiation affects nearby healthy tissues. New methods include Gamma knife, Cyberknife
Cyberknife
The CyberKnife is a frameless robotic radiosurgery system used for treating benign tumors, malignant tumors and other medical conditions. The system was invented by John R. Adler, a Stanford University Professor of Neurosurgery and Radiation Oncology, and Peter and Russell Schonberg of Schonberg...
and stereotactic radiosurgery
Radiosurgery
Radiosurgery is a medical procedure that allows non-invasive treatment of benign and malignant tumors. It is also known as stereotactic radiotherapy, when used to target lesions in the brain, and stereotactic body radiotherapy when used to target lesions in the body...
(SRS).
Other treatments are radiofrequency ablation
Radiofrequency ablation
Radio frequency ablation is a medical procedure where part of the electrical conduction system of the heart, tumor or other dysfunctional tissue is ablated using the heat generated from the high frequency alternating current to treat a medical disorder...
and chemoembolization
Chemoembolization
Chemoembolization is a procedure in which anticancer drugs are administered directly into a tumor through its feeding blood supply, with concurrent or subsequent blockage of the feeding vessel by occlusive agents that are injected through the delivery catheter...
.
Advanced/metastatic NSCLC
A wide variety of chemotherapiesChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
are used in advanced (metastatic) NSCLC.
Some patients with particular mutations in the EGFR
Epidermal growth factor receptor
The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...
gene respond to EGFR tyrosine kinase inhibitors such as gefitinib
Gefitinib
Gefitinib INN , trade name Iressa, is a drug used in the treatment of certain types of cancer, particularly those with mutated and overactive EGFR. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor in target cells...
.
There are many phase III clinical trials of new therapies for advanced NSCLC, including intedanib
Intedanib
Nintedanib is a small molecule inhibitor of vascular endothelial growth factor receptor , fibroblast growth factor receptor and platelet derived growth factor receptor being developed by Boehringer Ingelheim for use as an anti-vascular anti-cancer agent.-Mechanism of action:Nintedanib is an...
(BIBF 1120).
ALK mutations
About 7% of NSCLC have EML4-ALK translocations; these may benefit from ALK inhibitorALK inhibitor
ALK inhibitors are potential anti-cancer drugs that act on tumours with variations of anaplastic lymphoma kinase such as an EML4-ALK translocation.-EML4-ALK:About 7% of Non-small cell lung carcinomas have EML4-ALK translocations....
s which are in clinical trials. Crizotinib
Crizotinib
Crizotinib , is an ALK inhibitor, approved for treatment of some non-small cell lung carcinoma in the US, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children.- Mechanism of...
gained FDA approval in Aug 2011.