Lung Cancer
Epidemiology
Causes of Death in the U.S.
#1 Cardiovascular disease
#2 Cancer Lung cancer (28% of cancer deaths) is the most common cause of death in both men and women.
#3 Cerebrovascular disease
Cancer as Cause of Death Most people with lung CA die from it. Only pancreatic and esophageal CA are more lethal than lung (but they are less common).
- Cancer Mortality:
- Men: Lung > Prostate > Colorectal
- Women: Lung > Breast > Colorectal
- Cancer Incidence:
- Men: Prostate (43%) > Lung (13%) > Colorectal
- Women: Breast (30%) > Lung (13%) > Colorectal
Trends in Lung Cancer Mortality
Overall, reached a plateau in 1980s and is declining. Mortality among women is still rising.
Most important link between lung CA incidence and mortality is tobacco use. 25% of people over 18yo smoke. There is a 20 year lag time b/w decline in smoking and decline in lung CA incidence or mortality.
Women are smoking less, but the decline in women smoking lagged behind the decline in men smoking.
Lung CA is unique in that it is almost entirely preventable without cigarettes, it would be a rare disease.
Risk Factors
(1) Smoking correlation b/w number of cigs/day and death from lung CA. Women smokers have 1.2-1.7xÝ risk compared to men who smoke the same amount (related to women having more gastrin releasing peptide receptor and it being more easily inducible by tobacco). Quitting smoking lowers risk of lung cancer after 15-20yrs, but never to baseline.
Ý risk. Causes 2-3% of lung cancers.
Other CAs associated with tobacco head and neck, esophagus, stomach, pancreas, kidney, bladder, cervix.
(2) Occupational Carcinogens arsenic, asbestos, chloromethyl ether, chromium, nickel, polycyclic hydrocarbons, radon, vinyl chloride, others.
- Radon rocky areas. A factor in miners, but household exposure shows contradictory data. Has a synergistic effect with smoking and other risk factors.
- Asbestos better known for causing mesothelomas, but causes twice as many lung CA as mesotheliomas.
(3) Air pollution in urban areas 10% of lung CA
(4) Nutrition and CA
Eating a large amount of fruits and veggies daily Þ 30-40%ß risk. Mechanism unknown.
Vit A and E deficiency linked to higher rates of lung CA.
Vitamin supplements do not decrease risk.
(5) Family history not a strong factor. Autosomal co-dominant for cases under 50yo causes 5% of lung CA.
(6) Oncogenes not well understood in lung CA.
Diagnosis
often have microscopic metastastes before diagnosis
Presentation cough, hemoptysis, hoarseness, dyspnea. May have Sx of metastatic disease (bone pain, etc).
Radiology mass on CT or CXR.
- Evaluate mass with bronchoscopy (proximal lesions) or CT-guided biopsy (distal lesions).
- Distinguish b/w small cell (25-40%) and non-small cell. Staging system and therapy differ.
Staging:
- Non-small cell
- Stage I: small tumor, negative nodes, Stage II: hilar nodes, Stage III: locally advanced (mediastinal nodes), Stage IV: metastatic disease
- Small cell
Limited: confined to one hemithorax, Extensive
Screening
no impact on long term survival, but study was flawed (may be a false negative).
CT more sensitive, will probably be recommended as a routine screening tool for smokers.
Treatment
Non-small cell 60% present with stage III/IV (most are 6-8 year old at diagnosis). Px is poor. Surgery, Chemo, Radiation.
Small cell need chemo, otherwise will metastasize.
- Limited chemo and radiotherapy. 25-45% cure rate.
- Extensive chemo. Median survival 3-4months. Few are cured, tends to become chemo-resistant.
Pathology
Normal Bronchial Epithelium pseudostratified columnar epithelium with cilia and goblet cells. The site of carcinoma. Other kinds of cancer occur in other parts of lung (Example: sarcoma in muscle)
(1) Primary Epithelial Carcinomas
aggressive neuroendocrine tumor. Accounts for 20% of common lung neoplasms. Frequently metastasizes. Histology smaller blue cells
Squamous Cell Carcinoma. Histology intercellular junctions, keratin pearls
Adenocarcinoma. Histology gland formation, demonstration of mucosubstance within cells
Large Cell Carcinoma. Histology cant tell on LM. On EM, >90% would be glandular or squamous. <10% would be truly undifferentiated. However, can only use LM to classify.
Adenosquamous Carcinoma. Histology squamous and adeno components
Carcinoid neuroendocrine tumor, not very aggressive. 1% of all lung tumors. Not related to smoking. Good Px.
Bronchial Gland Carcinoma, Others
(2) Primary Mesenchymal Tumors
Mesothelioma
(3) Metastatic CA to Lung
Conclusions
Lung cancer is the most important cause of cancer deaths in the US.
Most people who develop lung cancer die of their disease.
Most non-small lung cancers are 6-8 years old at the time of diagnosis.
In most cases microscopic metastatic disease has occurred prior to diagnosis.
92% of lung cancer is due to tobacco.
Rates of cigarette consumption are declining in the US.
After a 20 year lag time, lung cancer rates are declining as well (principally in men).
An overall drop in cancer mortality in the US is in part due to falling lung cancer mortality.
Asbestos is an important carcinogen, though most of the exposure took place more than 30 years ago.
Asbestos exposure causes many (2x) more cases of lung cancer than mesothelioma.
Radon is clearly a cause of lung cancer in miners; the significance of residential radon exposure remains unclear.
A genetic predisposition to lung cancer probably does exist, but it is difficult to separate from smoking habits and second hand smoke exposure.
A genetic predisposition to lung cancer may cause 5% of lung cancers and may be particularly important for those who develop lung cancer at age < 50.
There is a link between nutritional deficiency of vitamins A and E with increased rates of lung cancer.
Individuals with diets high in fruits and vegetables have lower rates of lung cancer.
Vitamin supplements do not appear to reduce the incidence of lung cancer in smokers.
The biochemical and genetic pathways that lead to lung cancer development are currently being defined.
Terms such as oncogenes, tumor suppressor genes, apoptosis, point mutation, gene amplification, GF, and GFR should be understood.
Opportunities to use this information therapeutically are forthcoming.
The treatment for early stage non-small cell lung cancer is primarily surgical.
Treatment for metastatic non-small cell lung cancer include chemotherapy vs. supportive care.
Recent studies affirm the effectiveness of chemotherapy prior to surgery or radiation for stage III disease.
Chemotherapy is the mainstay of treatment for small cell lung cancer.
For limited stage disease, chemotherapy is combined with radiotherapy.
The prognosis is improving with newer treatment approaches.
Lung cancer is unique among the major disease entities that cause mortality in adults in the US.
Unlike heart disease, strokes, and most types of cancer, lung cancer is almost entirely preventable.
In the case of lung cancer, if cigarettes did not exist, it would be a rare disease.