Non-small cell lung carcinoma (NSCLC)

Clinical picture

Malignant growths in the lungs are what is commonly known as lung cancer or lung carcinoma. There are two types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC presents tumorous cells that are the same size or larger than normal lung cells. This is a relatively slow growing cancer type that does not spread as much as SCLC does, and therefore presents a better outlook.

The lungs are positioned on either side of the heart and consist of elastic sponge-like tissue. The right lung consists of three lobes, the left one of two. The lungs are enrobed in the pulmonary membrane. The lungs are the organs through which we breathe. The wind pipe splits into two branches known as the bronchi, and these in turn branch into the alveoli, where oxygen is passed on to the bloodstream.

Lung cancer is one of the most prevalent cancers in Belgium, being third for women and second for men, and most often found in patients over the age of 60.

There are three types of non-small cell lung cancers:

Adenocarcinoma: Adenocarcinoma is the most common form of non-small cell lung cancers. Of NSCLC, this is the tumour most often found in young adults, women and people who have never smoked. Lung adenocarcinoma usually begins in the outer regions of the lungs and can grow quite large before it is detected. Early symptoms are often subtle, with shortness of breath with activity and a general sense of ill health.

Squamous cell carcinoma of the lungs: Squamous cell carcinoma of the lung accounts for roughly 30% of non-small cell lung cancers. It usually starts in the bronchial tubes, centrally in the lungs, and is commonly found after people develop a persistent cough, cough up blood or develop recurrent respiratory infections (due to obstruction of the airways).

Large cell carcinoma of the lungs: Large cell lung cancers are less common, accounting for up to 10% of non-small cell lung cancers. They occur in the outer edges of the lungs and tend to grow rapidly.

NSCLC makes up around 80% of all lung cancer cases. Men are more likely to develop NSCLC than women. Patients who are diagnosed with stage I NSCLC show a survival rate of 62% over five years. For patients in stage IV this drops off to 2%.

Symptoms

NSCLC is often diagnosed fairly late, due to the fact that symptoms are hardly noticeable at the outset of the disease. Symptoms depend on location, size and spread of the tumour. In general, tumours in the upper part of the lungs will cause earlier symptoms than cancers that develop deeper inside the lungs.

Possible warning signs include:

a dry cough that won’t go away
being short of breath
difficulty in swallowing
vena cava superior syndrome: blockage of the vena cava, the main artery that carries blood from the head towards the heart
recurrent pneumonia
hoarseness

Other symptoms include:

unusual coughing
bronchitis
pain in the chest, shoulder and back area
coughing up phlegm, sometimes with blood in it
stridor: squeaking or hissing sounds caused by narrowing of the windpipe
fatigue or drowsiness
loss of appetite
weight loss for no apparent reason
frequent headaches

Cause

It is impossible to pinpoint the exact origin of small cell lung cancer, but there is a correlation between NSCLC and certain habits or environmental factors.

Smoking: In 86% of all cases, lung cancer occurs in people who smoke tobacco or have done so. ‘Passive smoking’ also raises the risk of cancer.
Air pollution: Around 8% of lung tumours is caused by air pollution, especially by fine dust and ultrafine dust.
COPD or asthma: people with COPD (e.g., emphysema) have frequent inflammations of the lungs that can lead to tissue damage. These damaged areas are often where malignant cells start to form.
Exposure to certain materials such as arsenic, asbestos, nickel or radon has been found to be carcinogenic.

About one quarter of all lung cancer patients have never smoked tobacco. This group of patients often have mutated tumours, which point to changes in the DNA. Patients with this type of cancer have a better outlook than patients who have smoked.

Diagnosis

Upon suspicion of possible lung cancer, a GP will refer a patient to a pulmonary specialist who will conduct further tests. These include lung X-rays, CT scans, FDG-PET scans, bronchoscopy, long function tests, lung biopsy, diagnostic thoracotomy or VATS. In a bronchoscopy, a flexible tube with a nano-camera is introduced into the windpipe via the nose or mouth. Diagnostic thoracotomy or VATS involves keyhole surgery during which a biopsy may take place.

As soon as a diagnosis of NSCLC has been reached, further tests determine the advancement stage of the cancer. These tests include: MRI scans, perfusion scans, endo-ultrasound of the oesophagus, mediastinoscopy, PET scans, thoracoscopy, bone scans, pleural puncture and abdominal ultrasound. Mediastinoscopy and thoracoscopy are forms of keyhole surgery under general anaesthetic. A pleural puncture involves draining and examining lung fluid from between the pulmonary membranes.

In order to come up with the best possible therapy, it is vital that the exact stage of advancement of the cancer is determined. For this, the TNM classification system is used. T stands for the state of the primary tumour, N denotes the amount of spreading to the lymph nodes and M stands for metastasis to other organs.

Stage 0: Restless cells in the lungs denote a preliminary stage to actual cancer.
Stage I:
- Ia: A tumour has developed that is smaller than 3 centimetres and has not grown into surrounding tissue.
- Ib: The tumour is between 3 to 7 centimetres and may have grown into surrounding tissue.
Stage II:
- IIa: The tumour is less than 3 centimetres across but malignant cells have been found in adjacent lymph nodes.
- IIb: The tumour measures between 3 and 7 centimetres and the cancer has spread to the adjacent lymph nodes. Stage IIb can also denote a tumour larger than 7 centimetres but without spreading to the lymph nodes
Stage III:
- IIIa: The tumour has grown into surrounding tissue and has also affected the lymph nodes.
- IIIb: The tumour has grown into surrounding tissue and cancerous cells have been detected in distant lymph nodes.
Stage IV: The cancer has spread to other organs in the body.

Treatment

Often, NSCLC is detected in a late stage, when metastasis has already occurred. Chemotherapy, radiotherapy, targeted therapy, immune therapy and endobronchial therapy are generally offered, sometimes in combination. NSCLC can, contrary to SCLC, often still be cured. Only when the disease has progressed into Stage III or IV, is full recovery no longer an option, and therapy shifts towards palliative care. For patients that are eligible, targeted therapy options include EGFR, VEGF, ALK, BRAF, MET, RET and kinase inhibitors.