Lung Squamous Cell Carcinoma Metastatic

Metastatic squamous cell carcinoma of the lung is an advanced form of cancer that has spread beyond the lungs to other parts of the body, presenting significant challenges for patients and requiring specialized treatment approaches.

Table of contents

• What Is Metastatic Lung Squamous Cell Carcinoma
• Where It Develops and Spreads
• Causes and Risk Factors
• Signs and Symptoms
• Diagnosis and Testing
• Stages of the Disease
• Treatment Options
• Prognosis and Survival

What Is Metastatic Lung Squamous Cell Carcinoma

Squamous cell carcinoma of the lung is a type of non-small cell lung cancer (NSCLC), which refers to a group of lung cancers that differ from small cell lung cancer in how the cells look under a microscope and how they respond to treatment^[1]. When this cancer becomes metastatic, it means the abnormal cells have spread beyond the lungs to other parts of the body^[5].

Squamous cell carcinoma accounts for approximately 25 to 30 percent of all lung cancer cases and is the second most common type of non-small cell lung cancer after adenocarcinoma^[4][8]. Among all types of NSCLC, squamous cell carcinoma has the strongest connection to smoking^[1].

In metastatic disease, cancer cells spread through the constant flow of blood and lymph through the lungs. These fluids can carry cancer cells to nearby areas or to distant organs throughout the body^[5].

Where It Develops and Spreads

• Lungs
• Bronchi
• Lymph nodes
• Liver
• Bones
• Adrenal glands
• Brain

Squamous cell lung tumors typically start in the central part of the lung or in the main airways, such as the left or right bronchus (the large air passages that branch from the windpipe into the lungs)^[1][4]. These cancers develop from thin, flat cells called squamous cells that line the airways, much like the lining of a pipe. These cells provide a barrier between the air in the lungs and the lung tissue itself^[4].

When squamous cell carcinoma spreads beyond the lungs, the cancer cells can reach several parts of the body. Common sites where this cancer metastasizes include the lymph nodes around and between the lungs, the liver, bones, adrenal glands, and brain^[5]. In some cases, squamous cell lung cancer can also spread to the gastrointestinal system^[7].

Because these tumors often develop in the central parts of the lungs, they may cause symptoms at an earlier stage compared to tumors located on the outer edges of the lungs^[5][8].

Causes and Risk Factors

Smoking cigarettes is by far the leading cause of squamous cell carcinoma of the lung. Approximately 80 percent of lung cancer cases in men and 90 percent of cases in women are linked to smoking^[1][6]. In fact, squamous cell carcinoma is more strongly associated with smoking than any other type of non-small cell lung cancer^[1][6]. It is very uncommon to find squamous cell carcinoma in people who have never smoked^[4].

Smoking-related lung cancer development is a multistep process. Before the cancer becomes invasive, the lung tissue may undergo several changes including abnormal growth patterns and cellular changes^[12].

Beyond smoking, several other factors increase the risk of developing squamous cell carcinoma of the lung. These include increasing age, which is the most important risk factor for most cancers^[12]. Family history of lung cancer also plays a role in raising risk^[1].

Exposure to secondhand smoke significantly increases risk for people who do not smoke themselves^[1][5]. Occupational exposure to certain substances is another important risk factor. These cancer-causing substances include asbestos, arsenic, chromium, beryllium, nickel, uranium, vinyl chloride, coal products, mustard gas, and diesel exhaust^[1][5][12].

Exposure to radon (a colorless, odorless radioactive gas that forms in the ground and can seep into buildings) is the second leading cause of lung cancer overall^[5]. Radiation exposure from radiation therapy to the breast or chest also increases lung cancer risk^[12].

Signs and Symptoms

Many people with squamous cell carcinoma do not experience symptoms in the early stages of the disease^[4]. However, as the cancer progresses, squamous cell carcinoma can cause symptoms to appear earlier than other types of lung cancer. This is because these tumors often develop in the central airways where they can cause noticeable problems^[4].

Common symptoms of squamous cell lung cancer include a persistent cough that does not go away. Coughing up blood is another symptom that may appear at an earlier stage with this type of cancer compared to others^[4][5].

People with this condition often experience shortness of breath and chest pain. The voice may become hoarse, and recurring chest infections such as bronchitis or pneumonia may develop^[1][4]. Wheezing is another respiratory symptom that can occur^[1].

Beyond respiratory symptoms, squamous cell lung cancer can cause general symptoms throughout the body. These include unexplained weight loss, loss of appetite, and persistent fatigue^[1][4]. When the cancer has spread to bones, bone pain may develop^[4].

Diagnosis and Testing

The diagnosis of lung squamous cell carcinoma typically begins when symptoms prompt concern or during screening for people at high risk. After a clinical examination, computed tomography (CT) imaging is frequently used as an initial test to evaluate the lungs, provided the tumor is large enough to be detected^[1].

A chest X-ray may be the first imaging test performed if symptoms are present^[20]. Additional imaging tests help determine the extent of disease and may include magnetic resonance imaging (MRI), CT scans, and positron emission tomography (PET) scans^[20].

To confirm the diagnosis, doctors need to examine tissue or cells from the tumor. A biopsy is a procedure to remove a sample of tissue for testing in a laboratory^[20]. This can be done through several methods including bronchoscopy, where a thin, bendable tube with a camera is inserted through the mouth or nose into the lungs to collect samples^[20].

Sputum (the mucus coughed up from the lungs) can sometimes be examined under a microscope to look for cancer cells, a test called sputum cytology^[20]. Histological analysis (the study of tissue structure) and immunohistochemistry (special staining techniques) are performed on biopsy samples to characterize the tumor and confirm the specific type of cancer^[1].

For patients with advanced disease, testing may be done to look for specific gene changes in cancer cells. These results help doctors determine whether targeted therapy might be an appropriate treatment option^[13].

Stages of the Disease

Doctors classify squamous cell carcinoma into stages based on the size and location of the tumor, whether it has spread to nearby lymph nodes, and whether it has spread to distant parts of the body. The staging system helps guide treatment decisions^[8].

Stage 0, also called carcinoma in situ, means the cancer is found only in the top lining of the lung and has not spread outside the lung^[4][8].

In Stage I (with subdivisions IA and IB), the cancer has not spread to the lymph nodes or other parts of the body. The difference between the subdivisions is based on the size of the tumor and whether it has reached the lung lining^[4][8].

Stage II (subdivisions IIA and IIB) indicates the cancer is larger than Stage I and has begun to spread to nearby lymph nodes or tissues, but not to distant organs. The subdivisions differ based on tumor size, location, and lymph node involvement^[4][8].

Stage III (subdivisions IIIA, IIIB, and IIIC) means the cancer may be difficult to remove with surgery. The subdivisions are based on tumor size, location, and extent of spread^[4][8].

Stage IV is metastatic disease, meaning the cancer has spread to other areas of the body outside the lungs^[4][8]. Stage IV is further divided into Stage 4A and Stage 4B, with Stage 4B indicating more widespread metastasis^[19].

Treatment Options

Treatment for squamous cell carcinoma of the lung varies depending on the stage of cancer, overall health, and whether the cancer has spread to other parts of the body. Treatment typically consists of a combination of different approaches^[1].

For patients with disease that can be surgically removed, surgery may offer a chance for cure. Surgery alone or surgery followed by chemotherapy (treatment with cancer-killing drugs) may be used for earlier-stage disease^[1].

Radiation therapy can achieve local control in many patients whose disease cannot be removed with surgery, though cure is seen in relatively few patients with this approach alone^[1]. For patients with locally advanced disease that cannot be removed surgically, radiation therapy combined with chemotherapy may lead to long-term survival^[1].

For metastatic squamous cell carcinoma, treatment options have expanded significantly. Immunotherapy uses medications that help the body’s immune system fight cancer cells. One approach combines an immune checkpoint inhibitor called cemiplimab with platinum-based chemotherapy^[13].

Another treatment strategy involves giving two cycles of platinum-based chemotherapy along with two immunotherapy drugs (nivolumab and ipilimumab), followed by maintenance treatment with these immunotherapy medications^[13].

The choice between immunotherapy alone or combined with chemotherapy often depends on the level of a marker called PD-L1 in the tumor. Patients with very high PD-L1 levels (50 percent or greater) typically respond well to immunotherapy alone, while those with lower levels may benefit from adding chemotherapy^[13].

Targeted therapy medications that work against specific gene changes may be options for some patients, particularly those with Stage 4B disease who test positive for certain genetic markers^[19].

Palliative care focuses on improving quality of life by managing symptoms and may include treatments to relieve chest pain, address shortness of breath, remove blockages from airways, reduce fluid buildup in the lungs, or treat fluid around the heart^[19].

Clinical trials testing new treatments may also be available and represent an important option for some patients^[20].

Prognosis and Survival

The outlook for patients with metastatic squamous cell carcinoma varies based on multiple factors including the extent of disease spread, overall health, and response to treatment. Patients with advanced metastatic disease may achieve improved survival and symptom relief with chemotherapy, targeted medications, immunotherapy, and other supportive measures^[1].

The average survival time for squamous cell carcinoma of the lung is approximately one year, though some patients live longer with medical treatment^[6]. Treatment advances, particularly with immunotherapy combinations, have shown promising results. In one major clinical trial, more than 27 percent of patients treated with a combination of immunotherapy and limited chemotherapy were alive at three years^[13].

Overall survival rates for lung cancer vary markedly depending on the stage at diagnosis. The five-year relative survival rate for patients diagnosed with distant-stage disease is 9 percent^[12]. However, these statistics represent averages across many patients and may not predict individual outcomes.

Several factors influence prognosis beyond just the stage of disease. These include the patient’s overall health, ability to perform daily activities, specific characteristics of the tumor, and how well the cancer responds to treatment. Advances in treatment options continue to improve outcomes for many patients with metastatic squamous cell carcinoma^[10].