LUNG CANCER OVERVIEW
Lung cancer is the most common cause of cancer death in the world, with estimated total deaths of 1.18 million by GLOBOCAN of the International Agency for Research on Cancer (IARC). In the United States, there will be an estimated 222,000 new diagnoses and 157,000 deaths in 2010. Lung cancer is a lethal disease, with only 6% of all new cases surviving 5 years in the United States. The average 5-year survival rate in Europe is 10% and is 8.9% in developing countries. Lung cancer causes more deaths than the four next most common cancers combined (colorectal, breast, prostate, and pancreas). These numbers are staggering, especially because it was a rare disease in the early 1900s.
Cigarette smoking has been identiﬁed as the single most common etiologic agent and is estimated to cause 85% to 90% of all cases. Radon is reported to cause 10% of lung cancers. Other etiologic agents are of less frequency and are primarily occupational exposures (e.g., arsenic, asbestos, chromium, nickel, coal, tar). For a complete list of carcinogens to humans, refer to the IARC (http://monographs.iarc.fr). Secondhand smoke increases the risk of lung cancer by 30% or a relative risk of 1.3 versus a never smoker with no secondhand exposure. Lung cancer risk increases with age. Less than 5% of lung cancer occurs before the age of 40 years, and the average age at diagnosis in the United States is 68 years. Family history (genetics) is a risk factor and responsible for a two- to threefold relative risk increase if lung cancer has been diagnosed in a ﬁrst-degree relative, especially if he or she was at a younger age at diagnosis. The genetic predisposition of lung cancer is a subject of intense research, but to date, a lung cancer gene has not been identiﬁed. The gene 15q 24-25 encompasses the nicotinic acetylcholine receptor gene that has a role in nicotine addiction and has been associated with lung cancer risk, but it is currently uncertain if this gene is directly related to lung cancer, independent of nicotine use.
Overwhelming evidence suggests that cigarette smoking is the major cause of lung cancer. The lung cancer epidemic in Western countries parallels the incidence of smoking but lags by about 20 to 30 years. The relative risk among smokers compared with people who have never smoked is 10 to 15 times higher and is dependent on the age of onset of smoking, dose, and duration (pack-years). Stopping smoking has been shown to decrease the relative risk, but the risk does not return to that of someone who has never smoked unless one quits at an early age. Tobacco smoking increases the risk of all major histologic cell types, but the strongest association is with small cell and squamous cell and less strongly with adenocarcinoma. The most common histology in a never smoker is adenocarcinoma.
The frequency of lung cancer in women has risen dramatically in most Western countries over the past 4 to 5 decades. Globally, it is still a male-predominant disease (male : female ratio, 2-3 : 1). However, in the United States, women constitute 45% of all new lung cancer diagnoses. Lung cancer has surpassed breast cancer as the most common cause of cancer death, which occurred in the United States in the mid 1980s. Currently, 72,000 women die of lung cancer versus 40,000 deaths from breast cancer per year. Although there has been some controversy, recent studies have not shown a difference in risk between men and women who have smoked a similar amount. There is no clear evidence of ethnic differences in susceptibility to this disease.
The signs and symptoms of lung cancer are myriad, but the most common are new cough, dyspnea, hemoptysis, chest pain, or weight loss. Paraneoplastic symptoms of lung cancer are discussed later. Symptomatic lung cancer usually results in an abnormal chest radiograph. Approximately 15% to 20% of lung cancers are asymptomatic when they are detected by an incidental chest radiograph or computed tomography scan done for other reasons. Methods of diagnosis include sputum cytology, thoracentesis if pleural ﬂuid is present, bronchoscopy, transthoracic needle aspiration, or needle aspiration and biopsy of distant metastatic sites. In some cases, the diagnosis is made at the time of surgical resection.
The World Health Organization histologic classiﬁcation of lung tumors is the generally accepted standard. Lung cancer is classiﬁed as small cell and non–small cell. Non–small cell lung cancer includes squamous cell, adenocarcinoma, large cell, adenosquamous carcinoma, and sarcomatoid carcinoma. Small cell histology generally has the fastest growth rate, but tumor doubling times can vary tremendously within the same cell type. The slowest growing types have been bronchioloalveolar carcinoma (subtype of adenocarcinoma) and superﬁcial squamous carcinoma (in situ), but again, the variability in growth rate can be enormous.