If an individual is suspected to have lung cancer based on signs and symptoms, detailed investigations are required to establish the diagnosis and stage the disease, which in turn helps in selecting an appropriate treatment option.
Following are some commonly used investigations for lung cancer:
- Sputum Cytology: In this test, a sputum sample is collected and examined under a microscope for the presence of cancer cells. This test can help in the diagnosis of cancer in the major airway of the lung like squamous cell carcinoma and small cell carcinoma.
The test is recommended to be performed on at least 3 sputum samples collected on 3 successive days. The test is safe and can help in early diagnosis of the disease.
- Bronchoscopy: Bronchoscopy is a diagnostic technique which uses a bronchoscope – a long, flexible, slender tube usually equipped with a camera, a light source, and some special instruments for biopsy or surgery.
The bronchoscope is passed through the nose or mouth into the trachea and bronchi. A real-time image of the interior of the airways is produced on a computer screen by the bronchoscope. This enables the doctors to directly observe the lining of the trachea and bronchi to determine the abnormalities.
Biopsy samples are generally collected from abnormal areas during the examination. Fluorescent light can also be used with bronchoscopy (fluorescence bronchoscopy), which can help in the detection of some early-stage cancerouschanges (pre-cancerous lesions) in the airway. This technique can also be utilized for delivering certain treatments for early-stage disease (for example, photodynamic therapy) or palliative treatments for advanced stage disease (for example, stent placement).
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- Endobronchial Ultrasound (EBUS): In this technique, an ultrasound device (transducer) is used along with an endoscope – a long, flexible, slender tube usually equipped with a camera, a light source, and some special instruments for biopsy or surgery. The endoscope is passed through the nose or mouth into the trachea and bronchi.
Very high-frequency sound waves are directed towards the tissue to be examined. The sound waves are reflected off the internal structures depending on their ability to reflect these waves and collected by a detector to produce a real-time image of the internal tissues on a computer screen.
This test helps the doctor to closely examine the lymph nodes and other structures in the space between the lungs (mediastinum) for any abnormality. This test can sometimes be used to guide a biopsy needle to take biopsy samples from the affected areas/enlarged lymph nodes observed during the test.
- Endoscopic (Esophageal) Ultrasound (EUS): This technique is very much similar to EBUS except that the endoscope is passed into the esophagus instead of the bronchi. Sometimes, it may be useful to approach those areas that are not possible with EBUS.
- Thoracoscopy: In this technique, an instrument similar to an endoscope is inserted into the space between the lungs and the chest wall through an incision made on the side of the chest wall.
This test helps in the diagnosis of cancer on the outer surface of the lungs and the pleural membranes. Biopsy samples can be collected from these areas and from affected lymph nodes diagnosed during the procedure. This can be used as a part of surgical treatment for early-stage lung cancers and the procedure is known as video-assisted thoracic surgery (VATS).
- Mediastinoscopy and Mediastinotomy: These techniques are used to collect tissue samples from the lymph nodes along the trachea and bronchi in the mediastinum.
In mediastinoscopy, an instrument similar to an endoscope is inserted into the space between the lungs via a cut in front of the neck. Mediastinotomy is more extensive than mediastinoscopy and provides access to more lymph nodes.
- Imaging Tests: These tests are generally employed after the establishment of the pathological diagnosis. They help to diagnose the extent of locoregional invasion and spread of disease to the distant organs.
Alternatively, these tests are employed after treatment to evaluate the treatment efficacy and to detect any signs of disease progression/recurrence.
Computed Tomography (CT) Scan: In this technique, detailed cross-sectional images of body organs are generated using x-rays, with or without a contrast medium.
It can help diagnose the spread of disease to nearby/distant lymph nodes and other organs, and may also be used to guide a biopsy needle into the affected area.
Positron Emission Tomography (PET) Scan: This technique uses a radioactive substance (fluorodeoxyglucose [FDG], etc) that is given via intravenous injection prior to the procedure. Cancer cells absorb larger amounts of the radioactive substance than normal cells.
The areas of higher radioactivity indicate cancerous tissue on the PET scan. Thus, this technique can diagnose unsuspected spread of disease to distant body parts. It is usually combined with a CT scan (PET/CT).
Magnetic resonance imaging (MRI) scan: This technique provides detailed images of tissues inside the body using radio waves, a strong magnetic field, and gadolinium contrast. It can accurately diagnose the extent of invasion and spread of disease to nearby/distant body parts.
Bone Scan: In this test, a radioactive material is injected into the vein of the patient, which gets accumulated in the areas of bones affected by the disease, which are then detected with the help of radioactivity detectors. In this way, it may help to detect the spread of cancer to bones.
Chest X-Ray: It can reveal any major abnormality in the lungs or the airway. However, this is relatively less-sensitive imaging technique for the diagnosis of lung cancer.
- Thoracentesis: This technique is generally utilized in case of accumulation of fluid between the pleural membranes (pleural effusion). This can result from lung cancer extending up to these membranes or due to other conditions such as heart failure or infections, etc.
The accumulated fluid sample is collected with the help of a needle inserted between the ribs and up to the pleural cavity. The collected sample is then examined under a microscope for the presence of cancer cells.
- Laboratory Tests for Biopsy Samples: Biopsy samples contain a small number of cells or a tiny piece of tissue, collected from the affected area or lymph node with the help of the biopsy instrument.
When subjected to various laboratory tests, these samples provide information about the type of cancer, the presence of specific defective genes or proteins, etc. The detected defects may then be targeted with a targeted therapy. Following are the techniques used for evaluation of biopsy samples for lung cancer treatment:
Immunohistochemical testing: In this, a very thin portion of the biopsy sample is first attached to a microscope glass slide. The sample is then treated with a specific antibody which gets attached to a protein specific to certain types of cancer cells.
Some reagents are then added to the treated sample that causes the bound antibody to changes its color. The change in color of the antibody-protein complex can be observed under the microscope.
Fluorescent in situ hybridization (FISH): In this technique, a fluorescent RNA probe is used which binds to a specific gene (a specific sequence of DNA) in the sample.
The presence of genetic alterations can be confirmed with the help of fluorescent microscopy.
With the development of targeted drugs to treat the different type of NSCLC, the role of molecular testing becomes crucial for the selection of the appropriate lung cancer treatment option.
Following are some tests recommended before starting a targeted or immune therapy for NSCLC: epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangements, ROS1 rearrangements, programmed cell death ligand 1 (PD-L1) testing, etc.
10. Lung/Pulmonary Function Tests: Lung volume measurements are generally performed with the help of spirometer – an instrument that measures air flow during inspiration and expiration.
These tests help in estimating the functional capability of the lungs so that the physician/surgeon can estimate how much part of the lung can be safely resected.