What is Non–Small Cell Lung Cancer?
Each year, about 230,000 people in the United States are diagnosed with lung cancer, and roughly 135,000 people die from it. The number of lung cancer-related deaths has even surpassed the total number of deaths from prostate, breast, brain, and colorectal cancer combined. Lung cancer is now the leading cause of cancer deaths in men and the second most common cause in women. However, thanks to anti-smoking campaigns and fewer people using tobacco, these numbers are starting to decrease.
Lung cancers are classified based on a system established by the World Health Organization in 2015. This system uses methods such as immunohistochemistry and light microscopy to better understand the type of lung cancer and guide appropriate treatment options.
A category of lung cancer, known as non-small cell lung cancer (NSCLC), encompasses several different types of lung cancers. The most notable ones include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Adenocarcinoma is the most common type of lung cancer and makes up about half of all lung cancer cases. Once upon a time, squamous cell carcinoma used to be the most commonly diagnosed type of lung cancer, which usually starts at the beginning of the tracheobronchial tree (the part that connects the windpipe to the lungs). But now, it’s found more often at the edges of the lungs.
Large cell carcinoma is another type of NSCLC and is typically diagnosed when other types of lung cancer have been ruled out. It’s difficult to classify further due to its poor differentiation – meaning it doesn’t look much like the lung cells from which it originated. Nevertheless, in about 90% of cases, the tumor shows characteristics of squamous, glandular, or neuroendocrine differentiation. NSCLC also includes other subsets of lung cancer, such as adenosquamous carcinoma, sarcomatoid carcinoma, and non-small cell neuroendocrine tumors. These categories cover a wide range of lung cancer types, each with its unique set of characteristics.
What Causes Non–Small Cell Lung Cancer?
The cause of NSCLC, a type of lung cancer, can be divided into two categories: things you can avoid and things you can’t. Breathing in tobacco smoke is the most well-known preventable risk factor for NSCLC. Other reasons lung cancer can develop include drinking alcohol, being exposed to secondhand smoke, asbestos, radon, arsenic, chromium, nickel, being in a place with lots of ionizing radiation, and coming into contact with substances called polycyclic aromatic hydrocarbons. Plus, the treatments used to fight other types of cancer, like breast cancer and Hodgkin lymphoma, can sometimes lead to lung cancer.
If you have a condition called pulmonary fibrosis, your chances of getting lung cancer are about seven times higher. Research shows this is true even if you don’t smoke. People living with HIV also have a higher chance of getting lung cancer compared to those who do not have HIV, regardless of whether they smoke or take medications for HIV.
Risk Factors and Frequency for Non–Small Cell Lung Cancer
Tobacco use is the cause of about 90% of all lung cancer cases. If a person has 40 years of smoking history, they are twenty times more likely to develop lung cancer than someone who doesn’t smoke. People who smoke and are also exposed to things like asbestos have an even higher risk.
One type of lung cancer, called adenocarcinoma, is believed to have been caused by the invention of filter-cigarettes in the 1960s, although this hasn’t been proven.
- Lung cancer is the top cause of cancer death in men and the second most common in women worldwide.
- The occurrence of lung cancer greatly varies between different groups of people depending on how prevalent tobacco use is in their countries.
- If smoking rates increase or decrease in a population, so does the incidence of lung cancer.
- For example, the lung cancer death rate in the United States is estimated to drop by 79% from 2015 to 2065 due to fewer people smoking and the effects of anti-smoking campaigns.
Signs and Symptoms of Non–Small Cell Lung Cancer
Non-small cell lung cancer has two main types of effects: those inside the chest (intrathoracic) and those outside the chest (extrathoracic). Intrathoracic effects such as persistent cough, coughing up blood, chest pain, shortness of breath, or voice changes can be observed during medical history taking and physical check-ups.
A subtype of non-small cell lung cancer, called squamous cell carcinoma, can cause a condition known as Pancoast syndrome. This syndrome can result in shoulder pain that might extend into the arm, back of the shoulder blade, or fingers. Additionally, it can cause Horner syndrome, muscle wasting in the hand, or destruction of bone.
At the first doctor’s visit, about one in five non-small cell lung cancer patients may already have cancer spread to their bones. These cases can often be detected during the physical examination. The type of non-small cell lung cancer most likely to spread to the brain is known as adenocarcinoma. Symptoms of brain metastasis can include headaches, vomiting, vision problems, seizures, or specific neurological deficits.
- Intrathoracic effects such as persistent cough, coughing up blood, chest pain, shortness of breath, or voice changes
- Pancoast syndrome, which can cause shoulder pain, Horner syndrome, muscle wasting in the hand, or bone destruction
- Bone metastasis, observed in about 20 percent of non-small cell lung cancer patients at the first doctor’s visit
- Brain metastasis, specifically in adenocarcinoma, with symptoms such as headaches, vomiting, vision problems, seizures, or specific neurological deficits
Testing for Non–Small Cell Lung Cancer
If the doctor suspects that you have non-small cell lung cancer (NSCLC), they will first do a physical exam and then order blood tests, namely a complete blood count (CBC) and a complete metabolic panel (CMP). These tests help the doctor see if the cancer has caused any blood or electrolyte issues. For example, levels of calcium or an enzyme called alkaline phosphatase may be high if the cancer has spread to the bones.
The doctor will also order imaging tests, starting with a chest X-ray, to get a better look at your lungs. Since the signs of NSCLC can often be unclear, a chest X-ray alone may not be enough to make a diagnosis. So, if lung cancer is suspected, the doctor will likely order a computed tomography (CT) scan. A CT scan uses X-rays to make a detailed picture of your body and can show more details about the possible cancer seen on the chest X-ray.
At some point, the doctor will need to take a sample of tissue from your lung, a procedure called a tissue biopsy. Looking at this tissue under the microscope can confirm the diagnosis of NSCLC.
Once a diagnosis of NSCLC is confirmed, the doctor will order more tests to find out if the cancer has spread to other parts of the body. This usually includes a CT scan of your chest and upper belly to see if the cancer has spread to your adrenal glands, which are small, hormone-making organs located on top of your kidneys. A positron emission tomography (PET) scan might also be used to get a better idea of the extent and stage of the disease.
Finally, the doctor might order a magnetic resonance imaging (MRI) scan of your brain to check if the cancer has spread there. This is an important part of fully understanding how far the disease has progressed.
Treatment Options for Non–Small Cell Lung Cancer
The treatment plan for patients with non-small cell lung cancer (NSCLC) can vary. It depends on many factors including patient’s overall health and existing medical conditions, the level or stage of the cancer, and the specific characteristics of the cancer itself. Patients who have stage I, II, or III NSCLC are usually treated with the goal of curing the disease. The treatment might include surgery to remove the cancer, chemotherapy (drugs to kill cancer cells), radiation therapy (using high-energy waves to kill cancer cells), or a combination of these treatments.
When the disease is at a more advanced stage, like stage IV, or if the initial treatment doesn’t work and the disease comes back, then drugs that target the whole body (systemic therapy) are used. This is often the case when the cancer has spread to other parts of the body (distant metastases).
Surgery to remove a lobe of the lung, known as a lobectomy, is generally the first choice for treating early-stage NSCLC. After surgery, the removed tissue is examined to determine the extent of the disease (pathologic staging). Depending on these results, the patient may just be closely monitored (if at stage IA), or may receive chemotherapy (if at stage IB or II/III).
If after surgery, the doctors find evidence of remaining cancer cells (positive margins), the patient might need further radiation therapy or a second surgery, followed by chemotherapy. In cases where patients are not deemed suitable for surgery, treatment would focus on a very precise form of radiation therapy, known as stereotactic body radiation therapy (SBRT) or just radiation therapy (RT).
If the disease has already spread locally at the time of diagnosis (clinical stage III), then a team of different specialists including radiation oncologists, medical oncologists, and thoracic surgeons, will work together to determine the best combined approach to treat the disease.
For advanced stage NSCLC (stage IV), the cancer tissue can be tested to determine if it has specific genetic mutations that can be targeted with specialized drugs. For instance, if the cancer cells produce an excess of a protein called epidermal growth factor receptor (EGFR), then drugs that block the action of this protein might be used. Similarly, the presence of certain other mutations may open up the use of specific targeted drugs.
In cases where no specific genetic mutation is found or known, the amount of a protein called programmed cell death ligand 1 (PD-L1) will be measured. If the levels of this protein are high (greater than 50 percent), then specific immunotherapy drugs, such as pembrolizumab or atezolizumab may be used. These drugs can also be used alone, without chemotherapy.
Lastly, it’s important that patients are continuously monitored to see if they might be candidates for clinical trials. These are studies of new treatments, which can sometimes provide access to the latest advances in cancer therapy.
What else can Non–Small Cell Lung Cancer be?
When a person has a lung nodule visible on a chest x-ray and is experiencing symptoms within the chest, this could indicate Non-small Cell Lung Cancer (NSCLC). However, there are other potential causes for these symptoms and findings that the doctor would need to consider. These include:
- Different types of lung cancer (such as adenocarcinoma, squamous cell carcinoma, large cell carcinoma, small cell carcinoma)
- Cancer spread from other parts of the body like the breast, head/neck, skin (melanoma), colon, kidney, germ cell tumor, sarcoma
- Pulmonary carcinoid
- Lymphoma that started outside of lymph nodes
- Plasmacytoma or schwannoma
- Non-cancerous tumors such as fibroma, neurofibroma, lipoma, hamartoma, leiomyoma, angioma
- Blood-related conditions such as hematoma, dead lung tissue due to lack of blood supply (pulmonary infarct), abnormal connection between arteries and veins (arteriovenous malformation)
- Lung cysts that start from the bronchial tubes
- Inflammatory conditions such as sarcoidosis, rheumatoid nodules, granulomatosis with polyangiitis
- Infections causing granuloma (lump of infected tissue) such as histoplasmosis, coccidioidomycosis, tuberculosis, atypical mycobacteria, cryptococcus, blastomycosis
- Bacterial lung abscess
- Aspergillus infection
- Pseudotumor (false tumor)
- Mucoid impaction (blockage of the airways with mucus)
Doctors will use this information as a starting point to make the correct diagnosis.
What to expect with Non–Small Cell Lung Cancer
The outlook for people with non-small cell lung cancer (NSCLC), a common type of lung cancer, largely depends on the size and spread of the tumor, which is often summarized by doctors as “tumor, node, metastasis” or TNM staging. The patient’s overall health or other existing conditions also play a critical role.
Patients who are generally unwell or have other severe medical conditions tend to have a shorter survival duration. Having a poor appetite and losing weight can also indicate that the disease may take a more severe course.
The cancer’s spread to lymphatic vessels and hidden spread to lymph nodes can also negatively affect the disease’s outlook. However, patients with certain changes in their cancer cells (known as “actionable mutations”) usually have a better prognosis. For instance, certain mutations related to lung cancer in people who never smoked or women with a specific ethnic background usually results in a significantly better survival rate.
A PET scan, a type of imaging test, is also used to detect the presence of cancer. It has shown that a high metabolic activity, signifying rapid cancer growth, can indicate a poor prognosis in stages I-IV NSCLC.
Recurrence, or the cancer coming back after being completely removed by surgery, has been reported in about 41% of patients. Typically, the median time it takes for the cancer to come back is 11.5 months and the average survival duration after recurrence is 8.1 months. Factors such as overall health, how long the patient has been disease-free, the spread of cancer to distant parts of the body, and prior use of chemotherapy or radiation therapy can lead to shorter survival durations.
Possible Complications When Diagnosed with Non–Small Cell Lung Cancer
Complications of non-small cell lung cancer (NSCLC) depend on how far the cancer has spread locally and if it has spread to other parts of the body. Problems within the chest may arise, such as a condition called malignant pleural effusion. This condition can cause shortness of breath or difficulty breathing, depending on how advanced the disease is and if the patient has other health issues.
Non-small cell lung cancer is also the leading cause of a condition called superior vena cava syndrome, making up about 50% of all cases. This normally develops slowly and presents with symptoms like swelling of the face or neck, bulging neck veins, and swelling of the upper body. This happens because the flow of blood through the superior vena cava, a major vein in the body, is being blocked.
Common complications:
- Malignant pleural effusion (may cause shortness of breath or breathing difficulty)
- Superior vena cava syndrome (can cause facial or neck swelling, bulging neck veins, upper body swelling)
Preventing Non–Small Cell Lung Cancer
It’s necessary for patients to understand the importance of stopping smoking and steering clear of second-hand smoke. A strategy, known as the “5 A’s”, is recommended by the US Preventative Services Task Force to help doctors discuss quitting smoking. This strategy involves asking about a patient’s smoking habits, advising them to quit, checking if the patient is ready to quit, helping with the quitting process, and organizing follow-up discussions with the patient.
Treatment plans can consist of both behavior-changing practices and medications. Behavior-changing practices will include counseling to help change the smoking habit. Medicines to help with quitting can be in the form of nicotine gum, lozenges, or patches which all provide nicotine without the harmful effects of smoking. Alternatively, Bupropion and Varenicline are also available as prescription medicines to help people stop smoking.
