Epidemiology
Incidence of Lung Cancer
Lung cancer is generally the top cause of cancer-related death globally and in the United States (US). In the US in 2023, lung cancer was responsible for an estimated 127,070 deaths. The Surveillance, Epidemiology and End Results (SEER) program estimates that 234,580 new cases of lung and bronchus cancer and 125,070 deaths due to lung cancer will occur in 2024. The overall incidence of lung cancer in the US between 2015-2019 was 56.3 cases per 100,000 population. Recent data specific for non-small cell lung cancer (NSCLC) is limited; data from the United States Cancer Statistics (USCS)and the SEER-18 databases show that, between 2010 and 2017, there were 1.28 million new diagnoses of non-small cell lung cancer (NSCLC) made in the US. In the same period, NSCLC incidence decreased from 46.4 per 100,000 to 40.9 per 100,000. The incidence of Stage I disease increased (from 10.8 to 13.2 per 100,000) while Stage IV disease decreased (from 21.7 to 19.6 per 100,000);…
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Incidence of Lung Cancer
Lung cancer is generally the top cause of cancer-related death globally and in the United States (US). In the US in 2023, lung cancer was responsible for an estimated 127,070 deaths. The Surveillance, Epidemiology and End Results (SEER) program estimates that 234,580 new cases of lung and bronchus cancer and 125,070 deaths due to lung cancer will occur in 2024. The overall incidence of lung cancer in the US between 2015-2019 was 56.3 cases per 100,000 population. Recent data specific for non-small cell lung cancer (NSCLC) is limited; data from the United States Cancer Statistics (USCS) and the SEER-18 databases show that, between 2010 and 2017, there were 1.28 million new diagnoses of non-small cell lung cancer (NSCLC) made in the US. In the same period, NSCLC incidence decreased from 46.4 per 100,000 to 40.9 per 100,000. The incidence of Stage I disease increased (from 10.8 to 13.2 per 100,000) while Stage IV disease decreased (from 21.7 to 19.6 per 100,000); incidence rates remained stable for other stages of NSCLC. These changes likely reflect a continuing decline in smoking prevalence (which contributes to a decrease in lung cancer development in the population) and improved lung cancer screening (which contributes to increased detection of early-stage lung cancer cases).
In contrast to incidence, the USCS and SEER-18 data revealed an increase in NSCLC prevalence from 2010 (175.3 per 100,000) to 2016 (198.3 per 100,000). Patients younger than 65 years of age showed an increase in prevalence (from 77.5 to 87.9 per 100,000), while patients 65 years of age and older exhibited a decrease in prevalence (825.1 to 812.4 per 100,000). The overall increase in prevalence is likely explained by improved screening and diagnostics (i.e., catching more cases) and by improved survival rates.
Lung cancer survival has remained stagnant in the last quarter of the 20th century; the 2-year relative survival of patients with NSCLC was the same in 1975-76 (25% for men and 32% for women) and 2003-4 (26% for men and 35% for women). The development of molecularly-targeted treatments and immunotherapy (see Treatment Options) in the last two decades led to significant improvements in the treatment of NSCLC, which was reflected in increased survival rates. In 2017-8, the 2-year relative survival of patients with NSCLC was 41% for men and 52% for women. By contrast, small-cell lung cancer (SCLC), which is still treated primarily by chemotherapy, did not see dramatic improvements in survival (Figure 1-1).
Risk Factors
Lung cancer in general, and NSCLC in particular, is associated with several well-established risk factors. The most impactful single risk factor is tobacco smoking; cigarettes contain over 70 known human carcinogens, and the risk of lung cancer increases with increased duration of smoking and quantity of cigarettes consumed. An analysis of eight cohort studies and 14 case-control studies from Japan revealed an increased relative risk (RR) of NSCLC in current smokers compared to never smokers. The risk also varied according to the NSCLC subtype. For squamous cell carcinoma (SqCC), the RR was 11.7 and 11.3 for men and women, respectively; for adenocarcinoma, the RR was 2.3 in men and 1.37 in women. Other studies have reported similar results; a study of the National Institutes of Health (NIH)-AARP cohort reported hazard ratios (HR) as high as 50 or more for current heavy smokers (>40 cigarettes per day). Furthermore, second-hand exposure to smoke in the workplace or household also increases the odds of lung cancer. In never smokers, the risk is increased by 16 to 27%, depending on the intensity and duration of smoking by coworkers or household members. The impact of smoking can easily be visualized by comparing a map of lung cancer mortality in the US compared to a map of adult smoking prevalence (Figure 1-2).
While tobacco smoking is by far the greatest individual risk factor for lung cancer, other environmental risk factors have also been identified, including radon gas exposure, air pollution and occupational hazards. Radon is a chemically inert noble gas, but it undergoes radioactive decay which may cause carcinogenesis in tissues exposed to the gas, such as the lung. The risk is highest for miners, but there is evidence that residential exposure also increases risk. A meta-analysis of eight epidemiological studies from the US and Scandinavia showed a RR of 1.14 for exposure to radon radiation at the dose of 150 Bq/m3, with a significant dose-response relationship. Ambient air pollution – in the form of fine particulate matter – is another established risk factor for lung cancer. This includes welding fumes and metallic particles from foundries, motor vehicles exhaust gases (e.g., nitrogen oxides) and industrial byproducts. The Adventist Health and Smog Study-2 (AHSMOG-2) found that for each 10 μg/m3 increase in the concentration of ambient fine particulate matter (≤2.5 μm in aerodynamic diameter), the adjusted HR for lung cancer was 1.43. Occupational exposure to lung carcinogens such as asbestos, arsenic, beryllium, cadmium, chromium, diesel fumes, nickel and silica, is also associated with increased lung cancer risk – in one estimate, up to 10% of lung cancer cases are caused by occupational carcinogens.
Importance of Early Detection and Treatment
Lung cancer, including NSCLC, is curable by surgical resection if it is locally confined. It is, thus, of paramount importance that the disease is detected and diagnosed as early as possible, ideally at Stage I. Lung cancer screening of individuals at high risk (primarily smokers) began in the 1950s and 1960s, as incidence rates were increasing and a link was established between tobacco smoking and the disease. In the early days, screening was done by chest X-ray (CXR) and sputum cytology, but this was not effective in reducing mortality. A major breakthrough occurred in the 1990s with the development of low-dose computed tomography (LDCT), which allows for rapid cross-sectional imaging at a lower radiation dose compared to conventional chest computed tomography (CT).
Two key trials led to a wider adoption of LDCT-based screening. Initial results from the Early Lung Cancer Action Program (ELCAP) showed that screening by LDCT significantly improved the probability of detecting early-stage lung cancer compared to CXR. The other milestone trial was the National Lung Screening Trial (NLST), which was the first prospective randomized controlled trial to show lung-cancer specific mortality reduction. Persons at high risk of lung cancer were randomized to receive three yearly screening sessions by either CXR or LDCT; compared to the CXR, screening with LDCT led to a 20% reduction in lung cancer mortality, and a 6.7% reduction in all-cause mortality.
As mentioned in the Epidemiology subsection, these advances in screening are likely responsible for the relative increase in Stage I diagnoses, and improvements in survival rates seen in the first decades of the 21st century.
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