Lung cancer

Basic facts and ICD classification

Lung cancer is the uncontrolled growth of abnormal cells in one or both of the lungs, causing lump (tumour) growth and disrupting the normal functioning of the organ.

The ICD-10 classifies these cancers under rubric C34 as malignant neoplasms of the bronchus and lung. For the purpose of reporting, routine statistics for the lung and bronchus are often pooled with those of the trachea (C33).

This EUphact only covers tumours that originate in the lung. Malignant neoplasms that affect the lungs, but do not originate in the cells of the bronchus or lung are not covered within the scope of this EUphact.

Microscopic subtypes and smoking habits

Cancers that originate from lung cells can be divided into two groups, small cell lung cancers (SCLC) and non-small cell lung cancers (NSCLC), according to their microscopic characteristics. NSCLC's include squamous cell carcinoma (SQC), large-cell carcinoma (LCC) and adenocarcinoma (AD). Tobacco smoking causes all types of lung cancer, but predominantly increases the incidence of SQC. The incidence of this subtype is therefore more sensitive to the history of smoking in any given population.

The AD subtype dominates among non-smokers. It therefore appears to be more common among European women who took up the smoking habit considerably later than men.

The relative frequency of the different subtypes is therefore strongly influenced by the prevalence, duration and intensity of tobacco smoking in the population. For men, the typical distribution by subtype is 15% SCLC, 23% AD and 41% SQC. For women, it is 13% SCLC, 40 % AD and 23 SQC.

Lung cancer is one of most common cancers in the EU

Lung cancer is the third most commonly occurring form of cancer in the EU (after colorectal and breast cancer and excluding non-melanoma-skin cancers), accounting for almost 260,000 newly diagnosed cases in 2004 (Boyle & Ferlay, 2005).

EU Member States, regions and populations differ significantly in lung cancer incidence and mortality. These variations reflect differences in the development of the tobacco epidemic, as described in the EUphact Smoking.

Lung cancer incidence has peaked among men, but continues to rise among women

Southern (Italy, Greece) and Eastern and Central European (Hungary, Czech Republic) men currently have the highest incidence rates of lung cancer within the EU. Most of these countries are in stage three of the tobacco epidemic. The majority of Northern (Sweden, Finland) and Western (France, Netherlands, Germany) European countries show stable or declining incidence rates for men. These countries are in stage four of the tobacco epidemic. In general, the incidence of lung cancer is higher among European men than European women.

In recent decades, the incidence of lung cancer has been rising among women in almost all EU countries. Women in Northern and Western Europe (Denmark, UK) have the highest incidence of lung cancer for females in the EU. Hungary also has a high lung cancer incidence among women. Southern European countries (Malta, Cyprus, and Portugal), where women traditionally rarely smoked, show the lowest incidence rates for women. As smoking is currently very prevalent among younger women, an increase of the female lung cancer rates can be expected.

See also Incidence of trachea, bronchus and lung cancer in the EU-27.

Other factors determining trends in lung cancer incidence

Age

Lung cancer is rarely diagnosed before the age of forty and its incidence peaks between the ages of 75 and 85. There is a strong birth-cohort effect. This means that the smoking behaviour of today's adolescents will determine long-term developments in lung cancer occurrence and mortality in all EU countries (Tyczynski et al., 2003).

Socio-economic status

In many EU countries the incidence of smoking and lung cancer is significantly higher in lower socio-economic groups (Huisman et al., 2005a; Mackenbach et al., 2004). Exposure to smoking at an earlier age, as well as lower rates of successful cessation contribute to the higher risk of lung cancer in this segment of the population (Kunst et al., 2004).

Histopathologic type

Most lung cancers are microscopically SQC, SCLC or AD subtypes. The rates for squamous and small cell carcinoma in males are generally declining, while adenocarcinoma rates are on the rise in virtually all countries. In female populations across Europe, the incidence rates for all three types of lung cancer are rising, but most rapidly for AD. The reasons are not clear, but two hypotheses, both linked to the consumption of modern, low-tar, filter cigarettes, deserve some attention. Firstly that the consumption of filtered, milder cigarettes is linked to an increase in the number and depth of puffs taken. This practice exposes the peripheral lung regions, where adenocarcinoma generally occurs, to higher concentration of carcinogens (Devesa et al., 2005 ). Secondly that the risk of adenocarcinoma could have been increased by the different chemical composition of modern cigarettes that contain less PAHs and more nitrosamines, both carcinogens that may cause different types of lung tumours.

Male lung cancer mortality in the EU

Lung cancer is the most common cause of death from cancer in the EU, accounting for 20% of all cancer deaths. Most lung cancer deaths still occur in men.

The importance of lung cancer as a cause of death has consistently grown throughout the twentieth century. In the early 1900s it was a rare disease causing fewer than 10 deaths in 100,000 men annually. By the 1950s, the lung cancer death rate has risen six-fold to 60 per 100,000 men. By the 1980s, the death rate was over 100 per 100,000 men. It peaked in the 1990s and has been declining since in most EU countries, particularly among younger age groups. An especially rapid decline in male mortality rates has been observed in countries with a history of high risk, such as Belgium, the Netherlands, Luxembourg, Italy and the UK (Bray et al., 2004).

In Eastern and Central Europe, the lung cancer mortality trends are similar, although less favourable. In most countries a decline in male mortality has been recorded in the 1990s. Exceptions are Hungary, where no decrease in mortality has been observed, but the increase rate has slowed down, and Poland where a plateau has been reached (Tyczynski et al., 2004 ).

Female lung cancer mortality in the EU

Female lung cancer mortality, although still appreciably lower than in the male population, rose by 17% from 1990-2000 in the EU-25. This increase was especially alarming among women younger than 55 years, where it increased more than 38%. The highest rises were observed in countries of Northern, Western, Central and Eastern Europe (Denmark, Germany Hungary, Poland). Only in the UK, Latvia and Lithuania has female lung cancer mortality been decreasing in the past decade.

In countries such as Belgium, Denmark, Sweden and the Netherlands, the smoking prevalence has fallen in recent years. Consequently, in these countries a deceleration of increasing lung cancer mortality trends for women, as seen in the UK, may be expected in the future. In France, Spain and Austria, where smoking prevalence in women has increased in the 1990s, a further rise in female lung cancer mortality in the coming decade is likely (Levi et al., 2004).

Lung cancer mortality associated with educational level

Among women the association between lung cancer mortality rates and educational level varies more between regions. In general, inequalities among women are smaller than among men in all age groups. In the Southern European poulations a lower educational level is even associated with a lower lung cancer mortality (Eurothine, 2007). See also: EUphocus Health inequalities.

See also:

Mortality (SDR) from trachea, bronchus and lung cancer in the EU-27, in 2002

Mortality (SDR) from trachea, bronchus and lung cancer for men and women of all ages, in the EU-27, in 2002 (interactive)

Mortality (SDR) from trachea, bronchus and lung cancer for men in the EU-25

Mortality (SDR) from trachea, bronchus and lung cancer for women in the EU-25

Lung cancer kills fast

Lung cancer has a very poor prognosis. The chance of survival depends on stage at presentation. Unfortunately, it is often diagnosed at a very late stage and the treatment options are limited. On average, 15% of those affected survive a 5-year period.

Differences in lung cancer survival

The 5-year survival for NSCLC is about 15% and for SCLC only 5% (Janssen-Heijnen & Coebergh, 2003). Lung cancer survival varies more than two-fold across Europe (but within a range of 10%), as uncovered by the EUROCARE study (Coleman et al., 2003a). The highest 5-year survival rates were found in Austria, France, and Spain at around 11-13% for men and 11-16% for women. Poland, Denmark and the Czech Republic had the lowest survival rates. These differences can partly be explained by differences in cancer type prevalence, stage at the time of detection, or access to optimal treatment (Coleman et al., 2003a). See also Age-standardised relative survival (%) for lung cancer.

High societal cost of lung cancer

Lung cancer treatment is costly. The total cost comprises the costs of hospitalisation and treatment, as well as the production losses due to the morbidity and mortality caused by the lung cancer.

One study from 2001 estimates the average costs of treating a patient with SCLC at €17,000 (European Lung White Book, 2003). Hospitalisation accounts for almost 50% of the costs of care, and chemotherapy for 13%.

The most controversial issues in the discussion about the cost-effectivenes of interventions are palliative chemotherapy, and screening for lung cancer. For more information about screening, see the chapter Interventions.

Smoking is the most important risk factor for lung cancer

Approximately 90% of lung cancers are smoking-related. However, not all smokers develop lung cancer. There is a clear dose-response relationship between the number of cigarettes smoked per day, the duration of the smoking habit and the risk of lung cancer. A lifetime smoker has a 20-40 times greater risk of developing lung cancer than a non-smoker (Tyczynski et al., 2003).

The impact of environmental factors

Passive exposure to tobacco smoke or environmental tobacco smoke (ETS), increases the risk of lung cancer by 15-25% (Tyczynski et al., 2003).

Occupational exposure to substances such as asbestos, radon, tar, soot and metals, such as arsenic, cadmium and nickel, and to ionising radiation is known to increase the risk of lung cancer. The effects of asbestos, radon and arsenic on lung cancer development are synergistic with smoking. In general, the contribution of environmental factors, except for cigarette smoke, to the risk of lung cancer is small.

Gender, age, socio-economic status, genetics

Lung cancer is rarely diagnosed in those under 40 years, but incidence rises steeply thereafter, peaking between ages 75-84.The male/female ratio for lung cancer incidence, which was very high, has changed considerably in the past decades. Female rates are approaching male rates in some countries, as a result of the increase in smoking prevalence among women several decades ago.

The risk of lung cancer is associated with deprivation, including poverty and low educational levels, as is smoking.

Genetic factors may predispose to the development of lung cancer. It is well-documented that first-degree relatives of lung cancer patients have an increased risk of developing lung cancer. Recently, a major susceptibility locus influencing lung cancer risk has been identified (Bailey-Wilson et al., 2004).

Primary prevention consists mainly of refraining from smoking

Refraining from smoking is the most effective prevention of lung cancer. Details about the individual and collective interventions for preventing and/or quitting smoking are given in the EUphacts Tobacco smoking and Smoking policies.

Smoking cessation

Quitting smoking will substantially reduce the risk of lung cancer in long-term smokers. The proportion of the risk of lung cancer avoided by quitting smoking before age 40 ranges between 80 and 90%. Quitting before the age of 50 leads to avoiding approximately 60-70% of the excess risk of lung cancer (Crispo et al., 2004). This implies that ex-smokers remain at higher risk than those who never smoked.

Ultimately, only the success of efforts to prevent youth from starting to smoke tobacco will determine the future of the lung cancer epidemic in the EU..

Protective factors

Observational studies have provided consistent evidence for a protective role of cruciferous vegetables, such as broccoli and cabbage, against lung cancer. These vegetables are rich in isothyocyanates, to which the protective effect is attributed. The protective effect seems to depend on interaction with genes that regulate the elimination of isothyocyanates from the body (Brennan et al., 2005).

The evidence for chemoprotective effects of vitamin A and its analogues, retinoids, in lung cancer development is inconclusive. The majority of trials could not prove any chemoprotective effects for lung cancer.

Secondary prevention is controversial

Screening or early detection of lung cancer via conventional procedures, such as chest radiography and sputum examination does not lead to reduction in mortality from lung cancer. Newer screening options, such as low-dose spiral CT, are more effective in detecting small, asymptomatic lesions that have good survival rates when surgically resected (Bach et al., 2003). The I-ELCAP study (Henschke et al., 2006) reports an estimated 10-year survival rate of 88% among patients with an early stage lung cancer detected on spiral CT, who then underwent further diagnostic procedure and surgical treatment.

The available research however remains inconclusive about the potential benefits of spiral CT screening in terms of reduction of the lung cancer mortality and the cost-effectiveness of the intervention. Moreover, surgical resection of the lung is a very invasive procedure that not all patients can undergo. The risk of overdiagnosis and over-treatment are of high concern and have not been addressed appropriately as yet. More evidence is needed to convincingly answer the question whether spiral CT screening is a viable intervention for reducing the lung cancer mortality, and whether it may become a regular screening procedure for population at risk, as mammography did.

Treatment options are scarce and survival rates low

In spite of advances in diagnosis of lung cancer, most patients are still diagnosed at an advanced stage and curative treatment is rarely possible.The three therapy options for lung cancer are: surgery, radiation and chemotherapy. The choice of therapy depends on several factors, such as the histopathologic type, the stage of the disease and the patient’s condition.

Cancer survival

Disease-specific mortality

Life expectancy

Healthy life expectancy

Smoking

Smoking policies

Health Inequalities

Children's Health and the Environment

Eurostat Statistical Office of the European Communities

HFA-DB WHO Health for all database

EUCAN IARC database for cancer incidence, mortality and prevalence data in the EU

CAMON Comprehensive Cancer Monitoring Programme in Europe

Cancer Mondial access to information on the occurrence of cancer worldwide

Health_EU Portal, cancer

ECL European Cancer Leagues

ENCR European Network of Cancer Registries

ENHIS European Environment and Health Information System

ERS European Respiratory Society

ELF European Lung Foundation

IARC International Agency for Research on Cancer

IASLC International Association for the Study of Lung Cancer

EUROCHIP European Cancer Health Indicator Project

Incidence of lung cancer for men and women of all ages, in the EU-27, in 2002

Mortality (ASR) from lung cancer for men and women of all ages, in the EU-27, in 2002

Age-standardised relative survival for lung cancer five years after diagnosis, for men, women and total diagnosed 1990-1994, in Iceland, Norway, Switserland and the EU-27

Mortality (ASR) from lung cancer for men and women of all ages, in the EU-27, in 2002 (interactive)

Mortality (SDR) from lung cancer for men of all ages, in the EU-25 (1998-2002)

Mortality (SDR) from lung cancer for women of all ages, in the EU-25 (1998-2002)

Incidence of trachea, bronchus and lung cancer (ICD-10 code C33-C34) per 100,000 for men and women of all ages, in the EU-27, in 2002 (GLOBOCAN, 2007)