Cancer that forms in tissues of the lung, most often in the cells that line the air passages is known as lung cancer. The two major types of lung cancer are small-cell lung cancer and non-small cell lung cancer. These types are diagnosed based on the biopsy results i.e. how the cells appear under a microscope.
What kind of cancer is the leading cause of cancer-related deaths worldwide?
Data collected from 1930 to 2000 A.D shows lung cancer to be the major cause of cancer-related deaths worldwide. After increasing awareness regarding the adverse effects of smoking, there has been a steady decline in the total number of lung cancer cases worldwide. In spite of the steady decline, lung cancer is still the leading cause of cancer worldwide in both males and females.
Lung cancer has the highest mortality and morbidity of cancer in the world.
What is the cause of lung cancer?
According to multiple research papers, the main established risk of lung cancer is cigarette smoking. Over 90% of lung cancers arise directly as a consequence of tobacco usage. The risk for lung cancer based on smoking can even be estimated based on the number of packs smoked and the total number of years. This equation is called as pack-years of smoking history and is equivalent to packs/day*years. People who have been exposed indirectly to second-hand smoke, also known as passive smokers, also are at higher risk of developing lung cancer.
Other less common but important risk factors for lung cancer are occupational exposure to asbestos or radon gas, air pollution, genetic predisposition, firewood stoves, etc.
Classification Of Lung Cancer
Classification of lung cancer is essential to determine the type of treatment required, the prognosis of the diagnosis, and the potential risk factors. There are various classification techniques for lung cancer based on their anatomic location, histology, and prognosis.
1. Anatomic Classification
Peripheral Lung cancer: Cancer that is located at the peripheral lining of the lung or near the pleura is peripheral lung cancer.
Central Lung cancer: Cancer that is located near or attached to the bronchial tubes is known as central lung cancer.
2. Histological Classification
Small Cell Lung Cancer:
Small cell lung cancer accounts for almost 15% of the lung cancer types and is mainly located near the bronchi. They are made of poorly differentiated small cells and are classically seen in male smokers. These cancers are the most common cause of superior vena cava syndrome due to their anatomic location. It also causes paraneoplastic syndrome as it is a neuroendocrine tumor. Due to its neuroendocrine nature, it can cause elevated levels of ACTH resulting in Cushing syndrome, elevated ADH causing SIADH, and antibodies against calcium channels in neurons causing muscle weakness. It has a high rate of malignancy and therefore a poor prognosis. Metastasis occurs early, especially in the brain. As this cancer type has often metastasized by the time of diagnosis, surgery is not usually an option thus making chemotherapy the mainstay of treatment. Of all the cancer types, Small cell lung cancer has the worst prognosis.
Non-small Cell Lung Cancer:
Traditionally, lung cancer was classified into two major types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). About 85 percent of all lung cancers are identified as non-small cell lung cancer. Management for Non-small cell lung cancer includes both surgery and chemotherapy depending upon the stage of lung cancer. Within this category, there are four types of lung cancer based on their histopathology.
a. Adenocarcinoma: It is the most common type of lung cancer worldwide, accounting for about 30-40% of lung cancer. It is chiefly made of glandular adenomatous cell type, hence it is called adenocarcinoma. It is often located in the periphery of the lung with pleural involvement. Although adenocarcinoma can be seen in smokers, it is the most common histological type seen in non-smokers, females, and young patients.
b. Squamous cell carcinoma: It accounts for 25-30% of lung cancer cases, is made of squamous cell type, and is often located centrally near the proximal bronchi similar to small cell lung cancer. As this cancer type can produce PTHrP, it can cause hypercalcemia which manifests in the form of kidney stones, bone & abdominal pain, and confusion. It has the best prognosis among all lung cancer types.
c. Large cell carcinoma: It accounts for only 15% of lung cancer types, and can be located either at the center or periphery. It is poorly differentiated lacking both squamous or glandular differentiation. It has a poor prognosis.
d. Bronchioalveolar carcinoma: Similar to adenocarcinoma, it is located peripherally and a common histological type in non-smokers. It is derived from either mucous secreting goblet cells or type II pneumocytes. It is sometimes confused with pneumonia on preliminary diagnosis due to its X-ray featuring lobar consolidation. It has a relatively good prognosis.
Symptoms and Signs of Lung Cancer
The signs and symptoms of lung cancer depend on the site, size, extent of invasion, and metastases. Cancer located in the peripheral zone is often asymptomatic. If symptoms are present, they include:
- Chest pain: This is a sign that the tumor has likely invaded the chest wall.
- Pleural effusion: Once the lung cancer has extended to the pleura, pleural effusion can develop resulting in difficulty breathing or shortness of breath.
- Hoarseness of voice can occur when the tumor invades or irritates the recurrent laryngeal nerve which innervates the vocal cords.
- Horner’s syndrome: Pinpoint pupils, drooping eyelids, and absent sweating in one side of the face can be present when the tumor invades the sympathetic trunk.
- Pancoast tumor: If the tumor is located at the apex of the lung, it can compress the surrounding structures such as the brachiocephalic vein causing upper limb swelling, brachial plexus compression resulting in numbness and paraesthesias in the upper limb, subclavian artery causing absent pulses in one hand, recurrent laryngeal nerve compression causing hoarseness of voice, Horner’s syndrome, and phrenic nerve compression causing difficulty in breathing from diaphragm paralysis.
- SVC syndrome: When the tumor obstructs the Super Vena Cava, there appears a characteristic clinical presentation of facial swelling, arm swelling, and increased intracranial pressure resulting in headache, vomiting, confusion, and even coma if not managed in time.
Metastasis Of Lung Cancer
Lung cancer can metastasize to any location within the body but it most frequently metastasizes to the bone, liver, brain, and adrenal glands. When metastasis to bone occurs, it can present as a pathological fracture with minimal trauma, brain metastasis can present as headache, liver metastasis can present as jaundice, etc. Symptoms and signs vary depending upon the organ involved.
Diagnosis Of Lung Cancer
Diagnosis involves detailed patient history taking, physical examination, chest X-rays, CT scan, MRI, biopsy, etc. Definite diagnosis and grading are done via histopathological examination which is the gold standard for diagnosis. Tissue sample for biopsy can be obtained by sputum cytology which although cheap has low sensitivity, fiberoptic bronchoscopy, percutaneous fine-needle aspiration via CT guidance, thoracocentesis, thoracoscopy, lymph node biopsy, and mediastinoscopy.
Staging of Lung Cancer
Lung Cancer staging is important to determine both the prognosis and the treatment plan for the patient. It is done via TNM staging, where T stands for primary tumor size, N stands for lymph Nodes, and M stands for Metastasis. Based on these values, the staging is classified into stages I, II, III, and IV.
Management of Lung Cancer
Preoperative evaluation is essential prior to surgery to determine the location, resectability, risk of surgery, and therapeutic potential of surgery.
Resectability: Tumor can be totally encompassed by excision including stage I, Ⅱ, and Ⅲa.
Cardiopulmonary function: Pulmonary resection can be performed with acceptable perioperative risk.
- Lobectomy—currently the standard of care
Radiotherapy can be used in NSCLC at any stage. Indications for radiotherapy in different stages are:
Early lung cancer: The patient cannot tolerate the operation.
Resectable disease: It can be used as an adjuvant treatment to improve local control or preoperative treatment to improve radical resection.
Advanced and metastatic lung cancer: as palliative treatment to relieve pain.
Palliative chemotherapy: It is used in late lung cancer — may improve survival for patients with stage Ⅳ and improve outcomes for patients with locoregional disease.
Adjuvant chemotherapy: It is used after surgical resection or radiotherapy. It may improve the survival of patients undergoing resection.
Neoadjuvant chemotherapy: It is administered before local therapy with surgery or radiotherapy. It appears to be beneficial for locally advanced NSCLC.
Targeted molecular therapy:
EGFR mutations: reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors such as gefitinib, erlotinib, etc.
Anaplastic lymphoma kinase (ALK) rearrangement: Crizotinib, a mesenchymal-epithelial transition (MET)/ALK multi-targeted receptor tyrosine kinase inhibitor.
All lung tumors are not malignant, and some can be benign such as granulomas or hamartomas. Malignancy of tumors can only be definitely confirmed via a biopsy for histopathological analysis.
Lung Cancer has a poor prognosis without treatment but with early aggressive treatment employing surgical resection, chemotherapy, and targeted molecular therapy, the prognosis for lung cancer can be much better. In the past, being diagnosed with lung cancer was akin to a death sentence but with currently evolving treatment strategies, the life span can be significantly prolonged in diagnosed cases of lung cancer.
As the major risk factor for lung cancer is tobacco smoking, it goes without saying that the best preventive measure for lung cancer is smoking cessation. The number of pack-years of smoking has been found to directly correlate with the percentage of risk for lung cancer, therefore even current smokers can substantially reduce their risk of lung cancer by smoking cessation. Another important preventable risk factor especially in rural developing countries has been found to be using alternative sources of fuel instead of firewood for cooking purposes whereas in the urban areas, minimizing air pollution by using electric or solar energy sourcing vehicles can minimize the risk of lung cancer for the entire world.
Lung cancer is the leading cause of mortality worldwide in spite of being a relatively preventable condition. The incidence of lung cancer had increased exponentially in the late 20th century when advertisements for smoking used to be widely done and cigarettes would be sold without any health warning labels. But as reports of lung cancer in smokers became widely publicized, placement of hazardous effects of smoking became mandatory and likewise, the incidence of lung cancer started to decline from the early 21st century. This directly shows that public awareness can in itself minimize the incidence of lung cancer by preventing it from occurring in the first place. Prevention is always better than treatment.
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