Lung cancer is the leading cause of cancer death in the United States and around the world. Almost as many Americans die of lung cancer every year than die of prostate, breast, and colon cancer combined (Fig. 1).1 Siegel and colleagues1 reviewed recent cancer data and estimated a total of 239,320 new cases of lung cancer and 161,250 deaths from lung cancer in the United States in 2010.2 The statistics reflect data from 2007 and, therefore, likely underestimate the current lung cancer burden. Lung cancer has been the most common cancer worldwide since 1985, both in terms of incidence and mortality. Globally, lung cancer is the largest contributor to new cancer diagnoses (1,350,000 new cases and 12.4% of total new cancer cases) and to death from cancer (1,180,000 deaths and 17.6% of total cancer deaths). The 5-year survival rate in the United States for lung cancer is 15.6%, and although there has been some improvement in survival during the past few decades, the survival advances that have been realized in other common malignancies have yet to be achieved in lung cancer. There has been a large relative increase in the numbers of cases of lung cancer in developing countries. Approximately half (49.9%) of the cases now occur in developing countries whereas in 1980, 69% of cases were in developed countries. The estimated numbers of lung cancer cases worldwide has increased by 51% since 1985 (a 44% increase in men and a 76% increase in women). In the United States, cancer of the lung and bronchus ranks second in both genders, with an estimated 115,060 new cases in men (14% of all new cancers) and 106,070 in women (14% of all new cancers).1,2 The age-adjusted incidence rate of lung cancer is 62 per 100,000 men and women per year in the United States, with the incidence rate higher in men than in women (75.2 vs 52.3 per 100,000).3 Lung cancer in both genders tops the list on the number of estimated deaths yearly (85,600, or 28% of all cancer deaths for men, and 71,340, or 26% of all cancer deaths for women) (Fig. 2).
Lung cancer incidence in men in the United States has been decreasing since the early 1980s. The incidence and mortality rates for lung cancer tend to mirror one another because most patients diagnosed with lung cancer eventually die of it. Siegel and colleagues,1 in their review of cancer statistics in 2011, noted decreases in death rates from lung cancer in men by 2.0% per year from 1994 to 2006 (Fig. 3). In women, however, lung cancer death rates continued to increase by 0.3% per year from 1995 to 2005, but more recent data from 2003 to 2006 show a more encouraging trend with a start in decline of 0.9% per year (see Figs. 3 and and4).4). The lung cancer incidence among women has declined over the past decades, from 5.6% between 1975 and 1982, to 3.4% between 1982 and 1990, to 0.4% between 1991 and 2006, and more recently to −2.3% between 2006 and 2008 (see Fig. 4). Because of the change in lung cancer incidence in women, recent figures show that lung cancer death rates decreased in women for the first time, more than a decade after decreases in men.4 The lag in the decline of lung cancer rates in women compared with men has been attributed to the fact that cigarette smoking in women peaked two decades later than in men. Lung cancer mortality rates thus seem to be reaching a plateau, which is an encouraging change from the steep rise in the 1970s (see Fig. 3).
The Surveillance, Epidemiology and End Results (SEER) data from 2004 to 2008 reported the median age at diagnosis for cancer of the lung and bronchus as 71 years (Fig. 5). No cases were diagnosed in patients younger than 20 years (see Fig. 5).3 Approximately 0.2% of lung cancers was diagnosed in patients between age 20 and 34 years; 1.5% between 35 and 44 years; 8.8% between 45 and 54 years; 20.9% between 55 and 64 years; 31.1% between 65 and 74 years; 29% between 75 and 84 years; and 8.3% at 85 years and older.
Lung cancer arises from the cells of the respiratory epithelium and can be divided into two broad categories. Small cell lung cancer (SCLC) is a highly malignant tumor derived from cells exhibiting neuroendocrine characteristics and accounts for 15% of lung cancer cases. Non–small cell lung cancer (NSCLC), which accounts for the remaining 85% of cases, is further divided into 3 major pathologic subtypes: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Adenocarcinoma by itself accounts for 38.5% of all lung cancer cases, with squamous cell carcinoma accounting for 20% and large cell carcinoma accounting for 2.9%.3,5 In the past several decades, the incidence of adenocarcinoma has increased greatly, and adenocarcinoma has replaced squamous cell carcinoma as the most prevalent type of NSCLC. The 5-year total survival rate for lung cancer in the United States from 2001 to 2007 was 15.6%. Patients with localized disease at diagnosis have a 5-year survival rate of 52%; however, the more than 52% of patients with distant metastasis at diagnosis have a dismal 5-year survival rate of 3.6%, which begs for the need for better screening methods to detect early-stage cancers (Fig. 6). (See article elsewhere in this issue by Mithun.)
Lung cancer was the most commonly diagnosed cancer and the leading cause of cancer death in men in 2008 globally.2 For women, lung cancer was the fourth most commonly diagnosed cancer and the second leading cause of cancer death. Overall, lung cancer accounted for 13% or 1.6 million of total cancer cases and 18% or 1.4 million cancer-related deaths worldwide in 2008. Lung cancer incidence and mortality rates are highest in the United States and the developed countries. In contrast, lung cancer rates in underdeveloped geographic areas, including Central America and most of Africa, are lower, except the rates are slowly increasing (Fig. 7A). More developed countries have higher incidence and mortality rates from lung cancers in both genders than less developed countries (see Fig. 7B, C). The World Health Organization estimates that lung cancer deaths worldwide will continue to rise, largely as a result of an increase in global tobacco use, especially in Asia. Tobacco use is the principal risk factor for lung cancer, and a large proportion of all pulmonary carcinomas are attributable to the effects of cigarette smoking.6 Despite efforts to curb tobacco smoking, there are approximately 1.1 billion smokers worldwide, and if the current trends continue, that number would increase to 1.9 billion by 2025.7 As of 2008, 20.6% (46.0 million) of American adults smoke.8 Of these, 79.8% (36.7 million) smoke every day and 20.2% (9.3 million) smoke some days. During the past decade, there has been a 3.5% point decrease in the number of US adults who smoke (20.6% in 2008 and 24.1% in 1998).
Despite the availability of new diagnostic and genetic technologies, advancements in surgical techniques, and the development of new biologic treatments, the overall 5-year survival rate for lung cancer in the United States remains at a dismal 15.6%.9 The situation globally is even worse, with 5-year survival in Europe, China, and developing countries estimated at only 8.9%.
This introductory article to the current edition of Clinics in Chest Medicine dedicated to lung cancer focuses on modifiable risk factors, including tobacco smoking, occupational carcinogens, diet, and ionizing radiation. It also discusses briefly the molecular and genetic aspects of lung carcinogenesis.