Lung cancer: Everything you need to know
What is lung cancer?
Lung cancer represents the main cause of death from cancer. It mainly affects men but is increasing significantly among women. Active and passive smoking is revealed to be the main risk factor.
Also known as bronchopulmonary cancer or bronchial cancer, lung cancer mainly develops from the cells of the bronchial wall and from bronchioles (tubes for transporting air outside of the lungs). In more rare cases, it is possible that cancer develops within the alveoli (small sacs where gaseous exchanges take place in the blood) or even the pleura (membrane that surrounds the lung).
There are different types of lung cancer:
- non-small cell lung cancers (NSCLC) which represents 85% of lung cancer cases. Among those, we find:
- adenocarcinomas (around 45%);
- squamous cell carcinomas (around 25%);
- large cell carcinomas (around 10%);
- and other forms, a lot less frequently (carcinoid tumours...)
- small cell lung cancers (SCLC), neuroendocrines, which represents 15% of lung cancer cases.
Is lung cancer common?
Lung cancer is the leading cause of death from cancer in the UK and in the world.
In the UK, it is the 3rd most common cancer, after breast cancer and prostate cancer. It is the 2nd most common cancer for men and women.
It is estimated that 47 000 new cases of lung cancer are diagnosed every year and 25 100 deaths.
Three quarters of lung cancer cases are diagnosed at an advanced stage. The average age to be diagnosed is 67 years old for men and 65 years old for women.
1 in 13 men and 1 in 15 women will be diagnosed with lung cancer in their lifetime but this gap tends to decrease due to the increase of smoking in women.
Life expectancy at 5 years is estimated at 21% and at 10 years after diagnosis, it is estimated at 10%.
Symptoms and complications of lung cancer
At an early stage of the disease, it is possible to notice no symptoms or that symptoms seem normal for a smoker or a former smoker.
However, at an advanced stage, different respiratory symptoms can be noticed and require a consultation with a GP:
- a persistent cough which tends to get worse, without an obvious cause;
- shortness of breath and respiratory difficulties;
- thoracic pain which gets worse with the cough;
- coughing up sputum (phlegm) containing blood (hemoptysis);
- hoarseness of the voice which does not go away;
- wheezing during respiration;
- repeated pulmonary infections (bronchitis, pneumonia...).
Other more general symptoms may appear depending on the extent of the tumour (presence of metastases or not):
- abnormal fatigue (asthenia);
- difficulty swallowing (dysphagia);
- sudden loss of appetite and rapid weight loss;
- an edema (swelling) of the face and neck;
- prolonged fever and headaches;
- bone pain...
Causes and risk factors of lung cancer
There are 2 main risk factors responsible in the development of lung cancer:
- tobacco smoking (active or passive): responsible for more than 70% of lung cancer cases.
In fact, smoking a cigarette contains more than 7000 chemicals, of which 60 are recognised as cancer-causing (polycyclic aromatic hydrocarbons, nitrosamines, benzene, formaldehyde, radioactive compounds such as polonium...). These chemicals are carcinogenic through many mechanisms such as DNA-binding that cause mutations, oxidative stress, inflammation or even epigenetic modifications (changes in gene expression without altering DNA).
It is considered that the risk of lung cancer increases both according to the quantity of tobacco smoked and the length of time smoking.
occupational and environmental exposure to toxic chemicals.
Asbestos, in particular, multiplies the risk of lung cancer by 5 in a non-smoking patient and by 50 in a smoking patient.
Numerous chemical elements (cobalt, chrome, cadmium, arsenic, nickel, silica, radon...), exposure to ionising rays, polycyclic aromatic hydrocarbons and exhaust fumes from diesel engines are also involved in the development of lung cancer.
Finally, chronic respiratory diseases (BPCO, emphysema, tuberculosis...), inhaled cannabis and the consumption of beta carotene, long-term and at a high dose (as is shown in the study lead by Françoise Clavel-Chapelon from the INSERM - Gustave Roussy Institute), by smokers or people exposed to asbestos, significantly increases the risk of developing lung cancer.
Lung cancer diagnosis
Systematic diagnostic examinations
Clinical exam: a GP appointment with the patient is carried out in order to research risk factors (tobacco smoking, exposure to toxins...) and a gradual change in general health.
The doctor will examine the patient, hit the thorax and examine lung and heart sounds with the help of a stethoscope, palpate the neck and the area above the clavicles to look for swollen lymph nodes, palpate the abdomen in order to assess the size of the liver, to measure blood pressure and pulse or even calculate BMI (Body Mass Index).
Biological exam: using a blood test, an estimate of kidney function is made before performing the injected CT. An assessment for hemostasis, with measurement of the prothrombin time (PT), activated partial thromboplastin time (aPTT), platelet dosage can eventually be required to facilitate further support (for histological sampling).
Chest x-ray: carried out from the front and profile, the aim of this exam is to reveal the presence of abnormalities within the lungs, using an X-ray machine. However, the x-ray does not allow you to identify whether the an is benign or malignant. It can also be normal even though lung cancer is present (particularly for small tumours).
Chest CT or computerised tomography (CT): requiring the injection of a contrast agent (often iodine) in the absence of contraindications (kidney failure). This exam allows you to perform a series of images of the lung in horizontal slices. It makes it possible to locate or not the presence of an abnormality, as well as its size and location. However, the scanner gives no information on the type of cancer cells.
Bronchial Fibroscopy with Biopsy: The biopsy is often performed during a bronchial fibroscopy. The latter consists in introducing a thin and flexible tube, connected to a light and a micro-camera, which, introduced by a nostril, allows you to observe the interior of the trachea and bronchi.
An anatomopathological and/or cytological examination is carried out on early tumours through a biopsy. This exam confirms the diagnosis of lung cancer and is done by a medical specialist with the naked eye then with a microscope. It makes it possible to precisely understand the type of cancer (small cells or non-small cells), to look for molecular changes in some cases (EGFR gene mutation or and, it is performed after surgery, to estimate the stage of cancer.
When the biopsy is not performed by fibroscopy, the medical team can take a sample of the tumour or pleural fluid through the chest wall under local anaesthetic, or a sample of the lymph nodes. The tissue sample may also be carried out during a surgical scan, requiring a short hospitalisation.
Record assessment examinations
Injection scan or MRI: routine in case of non-small cell lung cancers (NSCLC), it allows for the creation of precise images of the brain as well as looking for the presence of injury or brain metastases.
Positron Emission Tomography (PET, PET-CT, PET Scan, or Petscan): A painless examination that allows whole body images to be taken in slices after injection of a tracer into the blood (low-level radioactive product). This tracer has the unique feature of binding to cancer cells and therefore enables research of injuries or extra-cerebral metastases.
Abdominal scan (or CT): performed at the same time as the thoracic scan (or CT), it allows for the exploration of the liver and adrenal glands.
This classification is required for choosing the treatment strategy.
- T= Size of the tumour:
- TX: Unknown primary tumour or tumour proven by the presence of malignant cells in broncho-pulmonary secretions but not visible on radiological and endoscopic exams.
- TO: Absence of identifiable tumour.
- • Tis: Tumour (carcinoma) in situ (highly localized cancer).
• T1: Tumour 3 cm or less in its largest dimensions, surrounded by lung or visceral pleura (membrane that surrounds the lung), without evidence of more upstream invasion of the lobar bronchi to bronchoscopy (i.e. not in the stem bronchi):
• T1a(mi): minimally invasive adenocarcinoma;
• T1a: ≤ 1 cm;
• T1b: > 1 cm and ≤ 2 cm;
• T1c: > 2 cm and ≤ 3 cm.
• T2: Tumour greater than 3 cm but 5 cm or less, or with one of the following elements:
• invasion of a strain bronchus regardless of its distance from the carina (division of the trachea into two left and right stem bronchi), but
• without invasion of the carina;
• invasion of the visceral pleura;
• existence of atelectasis (pulmonary alveolar collapse or retraction) or obstructive pneumonia
o T2a: > 3 cm but ≤ 4 cm;
o T2b: > 4 cm but ≤ 5 cm.
• T3: Tumour greater than 5 cm and 7 cm or less or associated with one or more distinct tumor nodule(s) and in the same lobe, or directly invasive:
- chest wall (including vertebral tumours);
- the phrenic nerve;
- parietal pleura or parietal pericardium.
• T4: A tumour larger than 7 cm or associated with a separate or directly invading pulmonary nodule(s): mediastinum, heart or large vessels, trachea or carina, diaphragm, recurrent nerve, esophagus or vertebral body.
2. N=Regional lymphadenopathy (nodes for lymh nodes in English):
• Nx: Unknown locoregional invasion.
• N0: Lack of metastasis in regional lymph nodes.
• N1: Homolateral and/or hilar homolateral peribronchial lymph node metastases including direct extension.
• N2: Metastasis in homolateral mediastinal lymph nodes or sub-carinary lymph nodes.
• N3: Controlateral mediastinal lymph node metastases or scalenic or hilar controlateral, homo- or controlateral supraclavicular glandular metastases.
3. M = Metastases:
• M0: No remote metastasis.
• M1: Existence of metastases:
M1a: Separated tumor nodule(s) in a contralateral lobe, or pleural nodules or malignant pleurisy or malignant pericarditis;
M1b: A single extrathoracic metastasis in a single organ;
M1c: Several extrathoracic metastases in one or more organs.
Stages of lung cancer
The TNM classification makes it possible to differentiate several stages of lung cancer
- Localised cancer (stages I and II):
- Localised cancer (stage III):
- Metastatic cancer (stage IV) :
On the occasion of a multidisciplinary consultation meeting (RCP), a pre-therapeutic assessment is established. It identifies comorbidities and assesses the feasibility of different treatment options. It includes an assessment of:
• Patient performance score (performance status or PS):
• Body Mass Index (BMI), equal to weight (kg) divided by height squared (m2), and investigating any weight loss in the previous 3 months;
• smoking, as well as encouragement and support for smoking cessation.
Lung cancer treatments
The management of cancer treatment is different depending on the type of function (NSCLC or SCLC) and stage of cancer development (stages I, II, III or IV).
The different treatment options are:
• surgery, if possible;
• targeted therapies;
• symptomatic treatments (which is called "best supportive care").
Non-small cell lung cancers (NSCLC)
Operable cancer (stages I and II): Surgery is the standard treatment. It involves removing part or all (rarely) of the lung where the tumour is located, as well as the surrounding lymph nodes (hilar and mediastinal lymph node curage). In some cases, conventional chemotherapy is performed before (called neoadjuvant chemotherapy) and/or after surgery (if the tumor is ≥ 4 cm or if there is lymph node invasion).
Localised cancer of the chest but inoperable (stages 1 and 2): Stereotactic radiotherapy is the preferred technique which allows irradiation of very small volumes in high doses. In some cases, conformational radiotherapy, which destroys cancer cells using radiation and preserves healthy tissue as much as possible, may be offered alone or combined with chemotherapy. Chemotherapy alone may also be considered. Finally, in certain situations, a thermo-ablation (destruction of the tumour by cold or heat) is carried out.
Locally advanced unresectable cancer (stage 3): Treatment involves conventional chemotherapy combined with radiotherapy. In case of contraindication in the combination of the two, each of these techniques, alone, may be considered. In addition, during detection by immunohistochemistry (IHC) of a proportion > 1% of the ligand-1 protein of programmed cell death (PD-L1), which allows tumours to escape the immune system, the immunotherapy by durvalumab (Imfinzi®) is used in consolidation treatment for 1 year.
Metastatic Cancer (stage 4): Surgery is not offered as a primary treatment for metastatic lung cancers. Their management is based solely on drug approaches or radiotherapy.
The type of treatment will then depend on the type of NSCLC: non epidermoids (mostly adenocarcinomas) or epidermoids.
In non-epidermal histology, the search for oncogenic damage forms the initial step, with the need for EGFR genotyping as a minimum, and the identification of ALK, ROS1 and BRAF rearrangements.
In case of oncogenic damages, different targeted treatments can be used as a first line of treatment:
- osimertinib, afatinib, gefitinib, erlotinib if EGFR mutation;
- alectinib, brigatinib, ceritinib if ALK translocation;
- crizotinib if ROS1 translocation;
- dabrafenib + trametinib (as a second line of treatment) if BRAF V600 mutation.
In the absence of oncogenic changes, the key biomarker is PD-L1, expressed by tumour cells. The choice of treatment will then depend on:
• expression level of PD-L1 (≥ 50%);
• Patient status (performance score PS 0-1, 0-2, or 3-4);
• patient’s age ≥ or < 70.
Therefore, if PD-L1 ≥ 50% and the performance score (PS) is 0-1, immunotherapy with pembrolizumab (Keytruda®) in monotherapy is used in first line treatment. If the tumour progresses, platinum salt chemotherapy is performed.
Regardless of the expression rate of PD-L1 and if the PS is 0-2, the combination of pembrolizumab immunotherapy with pegmetriexed and platinum salt chemotherapy is traditionally used.
In patients with altered general condition, with PS ≥ 2, chemotherapy alone, based on carboplatin, often combined with pemetrexed, is the standard treatment. Finally, in the absence of immunotherapy treatment and contraindication, targeted therapy with bevacizumab can be added to chemotherapy, such as carboplatin + paclitaxel or cisplatin + gemcitabine.
If there is a progression of the tumor with a PS between 3 and 4, physicians use palliative care.
In squamous cell histology, the search for oncogenetic changes are not relevant, except for non-smoking or light smoking patients (< 15 packs-year). PD-L1 remains a key biomarker to guide treatment:
• if PD-L1 is ≥ 50%: pembrolizumab immunotherapy is used as monotherapy;
• If not, chemotherapy remains a standard treatment.
It can be noted that permetrexed and bevacizumab are not indicated for non-squamous NSCLC.
Small cell lung cancers (SCLC)
At an early stage, radiotherapy and chemotherapy are used in combination:
At an early stage, radiotherapy and concomitant chemotherapy are used:
• Chemotherapy is the most common: based on platinum salt (cisplatin or carboplatin) combined with etoposide.
• A complete response will be followed by prophylactic cranial radiotherapy.
However, the majority of patients are diagnosed at a metastatic stage (Stage IV). In this situation, immunotherapy by atezolizumab or durvalumab, combined with chemotherapy containing platinum and etoposide salts, is used.
Living with lung cancer
A close medical follow-up is required for several years in patients receiving treatment for lung cancer, to monitor early complications (such as febrile aplasia during chemotherapy) or potential late complications (such as peripheral neuropathies related to cisplatin) and prevent the onset of progressive cancer flare-up.
This follow-up is carried out by a multidisciplinary team composed among others of the general practitioner, a pulmonologist, an oncologist, a radiologist, a surgeon, a nutritionist or even a psychologist.
It is usually based on consultations and the completion of chest x-rays every 3 months for 2 years, then every 6 months for 3 years. CT scans and other additional exams are also performed every 6 months for 2 years, then every year for 3 years.
A healthy lifestyle
First of all, it is best to stop smoking permanently because the continuation of smoking after treatment increases the risk of treatment complications and increases the risk of secondary cancer.
In order to best combat the development of cancer and the side effects of treatments, it is also important to keep a varied and sufficient diet. It is particularly important to favour foods with anti-inflammatory properties and rich in antioxidants: fruits and vegetables, olive oil, fatty fish, nuts...
Finally, staying active and engaging in appropriate physical activity which is regular and moderate and is important for both physical and moral well-being. Indeed, walking, gardening or even cycling can fight against fatigue after treatments.
Communicating, sharing your doubts and fears about the disease (appearance of new side effects, questions about a new treatment) with your doctor, but also with those around you, is important. It is also beneficial to turn to speech groups, patient associations living with the same disease. You can also joing online patient communities such as Carenity’s Lung Cancer Forum. If necessary, psychological support (psychologist, psychiatrist...) may be considered.
If difficulties occur in daily life, it is possible to ask for help at home to carry out the daily tasks (getting up, washing, food, domestic activities, administrative tasks, organising family life, etc.).
A return to professional work
A work stoppage, the duration of which depends on the type of treatment and possible post-operative complications, may be prescribed by their doctor. In addition, suitable return-to-work adjustments can be planned, with the implementation of a part-time regimen over a short period or an adaptation of the workplace for example. Finally, after a stay of more than 30 days, a pre-work visit to the occupational doctor is compulsory.
In conclusion, lung cancer is the leading cause of death from cancer and the third most common cancer of all genders. Its diagnosis is usually late, in advanced stages, and the main risk factor involved is smoking. There are different treatment approaches (chemotherapy, radiotherapy, targeted therapies, etc.) and the choice of treatment depends mainly on the type of cancer (non small-cell lung cancers NSCLC in 85% of cases and small-cell lung cancers SCLC in 15% of cases).