The different types of lung cancer

In the U.S. lung cancer possesses one of the highest cancer incidence rates (only behind skin cancer, breast cancer (in women), and prostate cancer (in men), as well as the highest cancer fatality rate. Lung cancer is broadly classified into two main types based on the appearance of the cancer cells under the microscope (percent of lung cancer cases in parentheses):

• Non-Small Cell Lung Cancer (NSCLC) (85-90%):
• Adenocarcinoma (40%): This type begins in the cells that line the alveoli and produce mucus and other substances. It is the most common type of lung cancer in both smokers and non-smokers.
• Squamous Cell Carcinoma (25-30%): This type starts in the flat cells that line the inside of the airways in the lungs. It is often linked to a history of smoking.
• Large Cell Carcinoma (10-15%): This type can appear in any part of the lung and tends to grow and spread quickly, making it harder to treat
• Small Cell Lung Cancer (SCLC) (10-15%):
• Small Cell Carcinoma (Oat Cell Cancer): This type tends to spread quickly and is usually caused by smoking. It often starts in the bronchi near the center of the chest.
• Combined Small Cell Carcinoma: This type includes both small cell carcinoma and non-small cell carcinoma components.

Lung cancer often doesn't cause noticeable symptoms in its early stages. When symptoms do appear, they can be varied and easily mistaken for other conditions. Some common symptoms include:

• Persistent Cough: A cough that doesn't go away or gets worse over time.
• Changes in Cough: Coughing up blood (even small amounts) or rust-colored sputum (phlegm).
• Chest Pain: Pain that may worsen with deep breathing, coughing, or laughing.
• Shortness of Breath: Feeling winded easily, even with minimal exertion.
• Wheezing: A whistling sound when breathing, often a sign of airway obstruction.
• Hoarseness: Changes in voice or a raspy sound that persists.
• Recurrent Respiratory Infections: Frequent bouts of bronchitis or pneumonia.
• Unexplained Weight Loss: Significant weight loss without dieting or increased exercise.
• Loss of Appetite: Decreased desire to eat, feeling full quickly.
• Fatigue: Persistent tiredness and lack of energy.

Lung cancer is diagnosed through a combination of clinical evaluations, imaging studies, and biopsy procedures. The first imaging test done to look for any masses or abnormal areas in the lungs is the chest X-ray (see Figure 1). CT scans can then be ordered to provide more detailed images of the lungs and can help detect smaller lesions or tumors that may not be visible on a chest X-ray. Finally, MRI is used in specific cases, such as to look for spread to the brain or spinal cord.

The needle biopsy is a second diagnostic method. A needle inserted through the chest wall is used to obtain a sample of tissue from the possibly cancerous region. Alternatively, transbronchial biopsy threads a fiberoptic bronchoscope through the main airways of the lung to take a tissue sample. 

Finally, molecular testing has become more popular in which genomic DNA from a biopsy sample or from DNA circulating in the blood (liquid biopsy) is sequenced. In this manner, specific genetic mutations can be identified in the tumor which can influence diagnosis and treatment options  (e.g. EGFR, ALK, PD-L1).

Smoking is the most significant risk factor, accounting for about 85% of lung cancers. Risk increases with the number of cigarettes smoked daily and the number of years a person has smoked. Non-smokers exposed to secondhand smoke also have an increased risk. Additional risk factors include long-term exposure to air pollution, especially particulate matter, genetics, and age.

The prognosis for lung cancer varies significantly depending on the type, stage at diagnosis, and several other factors. Here’s an overview of the prognosis for the different types of lung cancer:

• Non-Small Cell Lung Cancer (NSCLC)
• Adenocarcinoma: Generally, adenocarcinoma has a better prognosis than other types of NSCLC, especially if detected early. The 5-year survival rate for localized adenocarcinoma can be around 60%, but it drops significantly if the cancer has spread.
• Squamous Cell Carcinoma: Similar to adenocarcinoma, the prognosis is better if caught early. The 5-year survival rate for localized squamous cell carcinoma is also around 60%, decreasing with advanced stages.
• Large Cell Carcinoma: This type tends to grow and spread quickly, leading to a generally poorer prognosis compared to adenocarcinoma and squamous cell carcinoma. The 5-year survival rate for localized large cell carcinoma is approximately 40-50%.
• Small Cell Lung Cancer (SCLC)
• SCLC is more aggressive and tends to spread quickly, often diagnosed at a more advanced stage. The overall 5-year survival rate for SCLC is about 7%. For limited-stage SCLC (confined to one lung and nearby lymph nodes), the 5-year survival rate is around 20-30%. For extensive-stage SCLC (spread to other parts of the body), the 5-year survival rate drops to about 2-3%.

Treatments continue to improve for all types of lung cancer. The first priority is to remove the lung cancer, especially before it metastasizes. The treatment options have expanded to include the following:

• Surgery: Lobectomy (removal of a lobe), pneumonectomy (removal of an entire lung), segmentectomy or wedge resection (removal of part of a lobe).
• Radiation Therapy: External beam radiation therapy (EBRT), stereotactic body radiation therapy (SBRT).
• Chemotherapy: post- or pre-surgery.
• Targeted Therapy: EGFR inhibitors (e.g., erlotinib, gefitinib), ALK inhibitors (e.g., crizotinib, alectinib), and other targeted agents for tumors with specific genetic mutations (e.g., EGFR, ALK, ROS1).
• Immunotherapy: PD-1 inhibitors (e.g., pembrolizumab, nivolumab), PD-L1 inhibitors (e.g., atezolizumab), particularly if the tumor expresses PD-L1.
• Combination Therapy: Combining chemotherapy, targeted therapy, and/or immunotherapy based on the cancer's genetic profile and stage.

Recently, new targeted therapies and immunotherapies (QH) have demonstrated improved efficacy as we make slow by steady progress. They will be the subject of future posts.

Figure 1. A chest X-ray showing a tumor in the lung marked by arrow (Wikipedia).