A heterogeneous group of cancers of pulmonary origin
Known risk factors: first and foremost smoking; in addition work-related exposure agents in certain occupations
Particular groups at risk include middle-aged and older (over 45 years) smokers with e.g.
altered characteristics of usual cough, haemoptysis
recurrent respiratory infections
weight loss and impaired general condition.
Some lung cancers, however, develop in non-smokers or people who have smoked only a little.
Epidemiology
Globally, lung cancer causes more cancer deaths than any other disease.
The incidence is in correlation with the prevalence of smoking.
E.g. in Finland, the incidence in women has continuously increased as smoking among women has become more common.
On the other hand, age-adjusted incidence in men has declined as smoking among men has decreased; still, lung cancer is the third most common cancer in Finnish men, after prostate cancer and colorectal cancer.
Aetiology
Smoking
Smoking causes about 80-90% of cases of lung cancer.
It should be kept in mind, however, that in about 15% of cases the patient has no significant history of smoking. The pathogenesis of lung cancer in non-smokers is different.
The best known signaling pathway changes found in adenocarcinomas that occur particularly in non-smokers are EGFR mutations as well as ALK and ROS1 rearrangements.
Asbestos
A smoker significantly exposed to asbestos has an up to 50-fold risk of lung cancer compared with a non-exposed non-smoker.
Other
E.g. arsenic, chromium and nickel (occupational exposure)
Radiation (radon particularly in association with smoking)
Genetic predisposition
Histopathological subgroups
Non-small cell carcinomas - share of all lung cancers about 75%
Squamous cell carcinoma (30-40%); share is on the decline
Adenocarcinoma (50-60%); share is on the increase.
Several subtypes that differ from each other by their clinical behaviour and prognosis, e.g. tumours with lepidic growth and solid adenocarcinomas
Large cell anaplastic carcinoma (5%)
Small cell carcinoma - share of all lung cancers about 15-20%
Symptoms and findings
Symptoms are either caused by the primary tumour in the pulmonary area or by metastases, or they can be paraneoplastic. The most common symptoms include
cough or altered cough, haemoptysis
pains (thoracic or extrathoracic e.g. from bone metastases)
dyspnoea
hoarseness
loss of appetite, weight loss.
Findings in suspected lung cancer
An opacity in the lung on a chest x-ray with or without enlarged lymph nodes in the hilum and/or mediastinum (pictures 12)
Enlarged lymph nodes in the neck, clavicular fossae- and/or axillae
Findings related to metastases (brain, bones, lungs, liver, adrenals)
Dissemination
Dissemination within the thorax
To another lobe of the same lung, to the other lung
To hilar, mediastinal, clavicular or axillary lymph nodes
Direct invasion into the mediastinum, great vessels, chest wall, pericardium, pleura, vertebrae, ribs, or brachial plexus
Dissemination to extrathoracic organs
Brain, bones, liver and adrenals are the most common targets.
Small cell carcinoma is usually disseminated at the time of diagnosis. It typically spreads at an early stage to both local and extrathoracic sites. In limited-stage small cell carcinoma the pathological changes are confined to one side of the thorax only.
Chest x-ray is the most important examination at the early stage.
If on the basis of the chest x-ray findings and the symptoms there is a suspicion of lung cancer, the patient is referred for further investigations to a pulmonary medicine unit.
The most important further investigations include contrast-enhanced CT scan of the thorax and upper abdomen, and based on the results bronchoscopy and/or other methods to obtain histological specimens (biopsies from the primary tumour and/or metastases). In some cases, a PET scan may bring additional information for the assessment of the cancer's stage.
There are no serum tumour marker assays suitable for the diagnostics of lung cancer.
In a number of patients (individuals in poor health or with multiple diseases), invasive diagnostic investigations do not provide any additional treatment benefit; therefore, carrying out of such investigations should also be individually assessed (see below for possibilities of treatment).
Concerning differential diagnoses, the most important diseases and conditions include e.g. old scars in the lungs, changes caused by infections, and metastases caused by other malignancies.
The choice of therapy is based on the extent of the disease (TNM stage) and the cell type of the carcinoma (non-small cell with its different subtypes vs. small cell), in disseminated non-small cell lung cancer additionally on molecular biological markers (possible identified mutations, and if such mutation is not present, the PD-L1 expression level of the tumour).
The patient's general condition (WHO 0-4) and comorbidities also influence the treatment possibilities and the potentially achieved benefits.
The primary treatment for unspread non-small cell lung cancers is surgery Surgery for Early Stage Non-Small Cell Lung Cancer: resection of a pulmonary lobe or an entire lung. Radical surgery is possible in 20-25 % of these patients. Some of the patients who have undergone radical surgery will benefit from postoperative cytotoxic chemotherapy.
In disseminated disease (60%), in patients in good condition, when no treatable target mutations are found in the tumour, and depending on the expression level of PD-L1 of the tumour, a combination therapy of cytotoxic agents and an immunological drug, or immunological pharmacotherapy alone, is used Intensive research efforts are directed at immunotherapy in the treatment of lung cancer. Primarily in adenocarcinoma, in a small share (about 15%) of patients, an EGFR mutation or ALK or ROS1 rearrangement is expressed in the tumour, in which case the treatment consists of oral medication targeted on the molecular level (EGFR inhibitor, ALK/ROS1 inhibitor).
In some patients with disseminated non-small cell lung cancer the disease does not respond significantly to any of the currently known drug therapies. It is important to keep this in mind in order to avoid burdensome but futile treatment attempts.
The benefit from systematic follow-up concerning all lung cancer patients has not been verified. The follow-up is meaningful if active oncological treatment can be provided in the case of a possible recurrence. The aim of the follow-up is to identify recurrence or progress of the disease; it may also play a role in implementing good symptomatic treatment.
The most important parameters to be monitored
General clinical condition, charting of symptoms
Auscultation of the lungs, palpation of lymph node areas
Chest x-ray and, if needed, CT scan
General status, weight loss, pains
There is no evidence on the benefit or applicability of serum tumour markers in the follow-up.
Prognosis
Non-small cell lung cancers
Five-year survival rate for all patients is about 15%.
Five-year survival rate for those treated exclusively by radical surgery is 65%.
In disseminated cancers the survival rates vary depending on the subtype. On average, after 2 years about 25% of the patients are alive.
Small cell lung cancer
In localised disease the average survival is about 14-20 months and in disseminated disease about 7-12 months. Five-year survival rate is less than 3%.
Rossi A, Tay R, Chiramel J ym. Current and future therapeutic approaches for the treatment of small cell lung cancer. Expert Rev Anticancer Ther 2018;18(5):473-486. [PubMed]