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At the level of the bifurcation, the epithelium lining the bronchi is particularly susceptible to injury and the bifurcation itself favours the deposition of carcinogens (tobacco smoke, paint, pollution, etc.).
The initial irritation that follows results in the growth of mucus-secreting cells, as an attempt at defence, but over time these cells are replaced by stratified squamous cells and their evolution invariably entails the disorganisation of the bronchial mucosa, with the emergence of more or less evident atypia (metaplasia).
If the entire thickness of the mucosa is affected by this disruption, one speaks of ‘carcinoma in situ’, the first stage of the tumour proper, which then overflows from the bronchial mucosa and invades the surrounding parenchyma.
This stage (from initial inflammation to extramucosal development) lasts 10-20 years and the agents that cause it are all substances recognised as carcinogenic: first of all tobacco smoke, then asbestos, aromatic hydrocarbons, nickel, chromium, paints and all environmental and occupational pollutants.
Lung cancer is the first cause of death from cancer in males over 35 years of age, and the second in females aged 35-75, with a gradual increase over the years for the latter, so that, if things do not change, it will also become the first cause of death from cancer for women over time.
The mortality line parallels that of incidence, since the 5-year survival of a lung cancer patient is no more than 15%, taking into account that 70% of patients already have lymph node or distant metastases at the time of diagnosis.
When lung cancer begins to grow locally and invade the body, objectively evident signs and symptoms experienced by the patient arise, which differ depending on the mode of expansion of the tumour mass, and can be listed as follows:
Due to central (endobronchial) growth:
Due to regional lymph node involvement or distant metastases:
Unfortunately, by the time the symptoms are evident and the tumour can be documented radiologically, the patient has already been attacked with the formation of regional or distant metastases, as revealed by the autopsies of patients who died after an excision deemed ‘curative’ of a lung cancer: on autopsy, tumour cells are very often found even at a distance from the site of the primary tumour, in many cases at the level of the abdominal cavity.
The problem of diagnosis is complex, but essentially boils down to the finding of a suspected lung image by means of a chest X-ray, which, while requiring further investigation in a symptomatic or high-risk patient, may create difficulties in the case of an asymptomatic individual whose X-ray has been taken for other reasons: his or her family history, personal history, age, smoking habit, exposure to environmental or occupational carcinogens, exposure to infectious diseases that could cause the formation of a pulmonary nodule, general health condition, surgical risk, and psychological situation must be considered.
If all this leads to further investigation, the first step is a biopsy with anatomo-pathological analysis, combined with cytological analysis of the sputum
Standard X-ray or CT scan is the most important imaging.
It is essential to have old X-rays of the patient (if they exist), since the stability of the nodule over time is a very important factor of probable benignity.
Another favourable element is the presence of large calcifications within the nodule, especially if they take on a concentric appearance, bearing in mind, however, that cancer can develop in the vicinity of calcifications, so that the increase in volume in a short time assumes an unfavourable prognostic character.
Cytological diagnosis is the least invasive means of diagnosis, with a sensitivity of 60%-70% for central lesions but unfortunately much less for small peripheral lesions.
While obtaining sputum is not difficult, the reliability of this examination is unfortunately not absolute, so that more invasive sampling is often resorted to, either by biopsy through bronchoscopy or through the chest wall: in this case, if the lesion is visible directly in the bronchus the diagnostic sensitivity is 95%, while for peripheral lesions it again drops to around 60%-70%.
Lung cancer staging is indispensable for determining the prognosis and choosing the most effective therapy.
A meticulous anamnesis and an accurate physical examination must be accompanied by laboratory tests (essential blood count, liver function, serum calcium dosage) and, of course, by an accurate radiological study using traditional radiology, CT and MRI.
The most commonly used classification is the TNM method, whereby the tumour (T), lymph nodes (N) and any metastases (M) are given an abbreviation.
Tx – positive cytology but tumour not detectable;
T1S – carcinoma in situ;
T3 – diameter ³ 3 cm with extension to visceral pleura or chest wall or arising less than 2 cm from tracheal carina
T4 – invasion of heart, great vessels, oesophagus, trachea, vertebrae, pleura.
N1 – peribronchial or ipsilateral hilar lymph nodes affected;
N2 – mediastinal lymph nodes affected;
N3 – mediastinal or contralateral hilar lymph nodes affected; any supraclavicular lymph node affected.
Therapy is essentially based on surgical removal of the tumour, combined with radiotherapy to control the local situation.
The use of chemotherapy, another fundamental cornerstone in the fight against cancer, is controversial in the case of the lung, since studies have produced discordant results.
From the available data, however, it appears that the combination of radiotherapy plus chemotherapy prolongs patient survival.
The most important form of prevention is to deter smoking habits, especially in young people: the problem is not only medical but also social, economic and political, and if we do not want to cause the deaths of around 34,000 Italians each year, drastic decisions must be taken that affect not inconsiderable economic aspects.
It is almost impossible to avoid passive smoking altogether, but the bans imposed in public places and workplaces, especially in the presence of children, must be enforced at all times.
It is unfortunately disheartening to see young mothers pushing a pushchair with their small child while quietly smoking a cigarette!
Finally, lifestyle also matters: exercise and a healthy diet (lots of fruit and vegetables) are fundamental cornerstones in the prevention of many diseases, including cancer.
For some time now, screening by means of a spiral CT scan (a special computed tomography system, in which the couch moves continuously in synchrony with the apparatus, thus managing to obtain much sharper and ‘still’ images despite respiratory and cardiac movements) has been proposed, but the results are still under discussion, since the effectiveness of screening in terms of reducing mortality has not been unequivocal: published studies have reported a significant increase in lung cancer diagnoses thanks to this test, not always associated, however, with consistent decreases in mortality.
For example, an Italian study from 2009 showed no benefit on overall mortality, while the results of the largest American study (NSLT: National Screening Lung Trial = 53,000 current or former smokers) published in 2011 showed that screening subjects for three years with spiral CT compared to conventional x-ray screening resulted in a 20% reduction in lung cancer-specific mortality, but only a 6.9% reduction in overall mortality.
The IEO (European Institute of Oncology) study also produced results that point in the same direction, adding the identification of certain molecular markers (micro-RNA) that could increase the potential of screening.
At present, the indication is to subject not the entire population to a spiral CT scan but only a selected category of subjects: males, over 50 years old, current or former smokers.
Finally, it is essential to remember one fact: cessation of cigarette smoking is the best possible prevention and abstinence from smoking for seven years achieves the same decrease in mortality as is achieved by screening with spiral CT.
Until people are convinced that smoking is the worst enemy of their health, lung cancer (along with many other cancers) will continue to kill mercilessly.
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