Definition

The lungs are air-filled organs which expand and collapse to conduct gas exchange essential for our survival. Non small-cell lung cancer (NSCLC) is a disease which consists of different types of malignant cells in the lung tissue. These cells are mutated to multiply rapidly and grow uncontrollably, thus forming cancerous tumours. In the most severe circumstances, these cancer cells can metastasize to different parts of the body by either the circulatory or lymphatic systems (Eldrige). There are around 1.8 million newly diagnosed lung cancer cases per year globally, which accounts for approximately 13% of all newly diagnosed cancer cases (Gridelli et al.).

Incidence And Demographics

Around 85% of all lung cancer cases are non-small cell lung carcinoma and it is one of the leading causes of mortality related to cancer (Gridelli et al.). Older adults,  between the ages of 55 to 74, are at higher risk for developing NSCLC, especially if they are current or past smokers (American Cancer Society, Lung Cancer Risk Factors). Regular screening for these demographics has been strongly recommended by the American Cancer Society to increase chances of early detection and to improve survival rates.

Types of NSCLC

Distinguishing between the different types of NSCLC can help inform clinicians of the best course of treatment. The 3 main types of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma (American Cancer Society, What Is Lung Cancer?).

• Adenocarcinoma is the most common type of NSCLC and it is characterized by cancerous tumours that start in the mucus-secreting cells of the lung alveoli. These mucous-secreting cells normally protect lung tissue from harmful particles, infection, and other damage.
• Squamous cell carcinoma is the 2nd most common type of NSCLC. It arises in the flat, thin squamous epithelial cells found in lining the various airways. Squamous cell carcinoma is usually found in the primary bronchi of the lungs and the central part of the lungs.
• Large cell carcinoma is a type of NSCLC that can start anywhere in the lung tissue and in various different large cells. It is less common than the other types, but is usually the one that grows and spreads the fastest, therefore it slightly resembles small cell lung cancer, an extremely aggressive form of lung cancer that will not be discussed in this chapter.
  

  

Causes And Risk Factors

Due to the complex nature of NSCLC, exact causes can be difficult to deduce, however there are factors that have been identified to contribute to its development.

Genetics

• Certain genetic mutations, especially those related to oncogenes and tumour suppressor genes, can increase the risk of developing NSCLC. These mutations may occur randomly during one’s lifetime, and are mainly caused by environmental interactions, rather than inheritance (Molina et al.). The most prominent acquired genetic mutations that increase the risk of NSCLC are p16 tumour suppressor gene, the KRAS oncogene, and TP53 tumour suppressor gene (American Cancer Society, Lung Cancer Risk Factors). In more rare cases, genetic mutations can be inherited from parents, such as genes involved in DNA repair mechanisms, cell proliferation, and apoptosis. An example of this would be mutations in the epidermal growth factor receptor (EGFR) gene (Molina et al.).
• A family history of non-small cell lung cancer can increase the risk of developing NSCLC for the patient, suggesting there is a genetic component involved as well (American Cancer Society, Lung Cancer Risk Factors).

Environmental risk factors

• Tobacco smoking is a well-known risk factor as it contains harmful carcinogenic substances that damage lung tissue. These harmful effects can contribute to cell abnormalities. Secondhand smoke exposure may also increase the risks of NSCLC. It has been reported that smoking is the cause of 80% of lung cancer deaths (American Cancer Society, Lung Cancer Risk Factors).
• Long-term air pollution has been linked to increased incidence rates of NSCLC in various urban and industrialized areas. Studies report that 11% of lung cancers in Europe are directly linked to air pollution (Molina et al.).
• Radon gas exposure, especially in mining labor, has been strongly linked to increased risk of developing NSCLC due to its radioactive properties. These radioactive properties can damage lung tissue and cause cell mutations (American Cancer Society, Lung Cancer Risk Factors).
• Asbestos and other carcinogens from the workplace can also increase the risk of developing NSCLC as these substances are known to be strongly linked to cancers (Molina et al.).

Clinical Symptoms Of NSCLC

Most NSCLC patients do not show many symptoms in early stages of the cancer, however symptoms may develop as the disease worsens. Symptoms of NSCLC can overlap with common flu-like symptoms, making it harder to catch. Some common ones are (National Cancer Institute):

• A persistent and/or worsening cough that does not go away with other treatments
• Chest pain, shortness of breath, pain when breathing hardly and coughing
• Blood in coughed-up phlegm
• Loss of stamina, appetite, and weight loss
• Local symptoms in areas where cancer may have metastasized

Diagnosis And Staging

Most NSCLC cases are found through lung cancer screening or accidentally, via tests for other conditions and symptoms. Additionally, cases are usually detected when the cancer is in an advanced stage, reducing treatment options. To diagnose NSCLC, physicians may order various tests, such as an X-ray, computerized tomography (CT) scan, positron emission tomography (PET) scan, sputum cytology, and tissue biopsy on abnormal lung masses (National Cancer Institute). Lung tissue biopsies can be performed through techniques such as a bronchoscopy or a mediastinoscopy to examine abnormal lung cells in the lab (National Cancer Institute). Once NSCLC is diagnosed, staging occurs based on the tumour, node, metastasis (TNM) system (Molina et al.). This categorizes the extent of the cancer based on tumour size and state, the spread to lymph nodes, and also the spread of cancer to other areas of the lung and body. Staging is important for determining the most suitable prognosis and treatment for the patient.

Video 1 Staging for Non-Small Cell Lung Cancer (You and Lung Cancer).

References

American Cancer Society. Lung Cancer Risk Factors. https://www.cancer.org/cancer/lung-cancer/causes-risks-prevention/risk-factors.html. Accessed 6 Dec. 2020.

American Cancer Society. Non-Small Cell Lung Cancer Staging. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-nsclc.html. Accessed 6 Dec. 2020.

American Cancer Society. What Is Lung Cancer? https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed 6 Dec. 2020.

Bee, JR. Common Sites of Lung Cancer Metastases. https://www.verywellhealth.com/where-does-lung-cancer-spread-2249368. Accessed 6 Dec. 2020.

Common Risk Factors for Lung Cancer. https://ib.bioninja.com.au/standard-level/topic-6-human-physiology/64-gas-exchange/lung-disorders.html. Accessed 6 Dec. 2020.

Gridelli, Cesare, et al. “Non-Small-Cell Lung Cancer.” Nature Reviews. Disease Primers, vol. 1, 21 2015, p. 15009. PubMed, doi:10.1038/nrdp.2015.9.

Molina, Julian R., et al. “Non-Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship.” Mayo Clinic Proceedings, vol. 83, no. 5, May 2008, pp. 584–94. PubMed, doi:10.4065/83.5.584.

National Cancer Institute. Non-Small Cell Lung Cancer Treatment (PDQ®)–Patient Version. 4 Dec. 2020, https://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq.

Roberts, Emily. Types of Non-Small Cell Lung Cancer. https://www.verywellhealth.com/non-small-cell-lung-cancer-2249281. Accessed 6 Dec. 2020.

You and Lung Cancer. Staging of Lung Cancer. 2017. YouTube, https://www.youtube.com/watch?v=6moQ47RsgYg.