Squamous Cell Carcinoma of the Lungs

Squamous cell carcinoma (SCC) of the lung is one form of non-small cell lung cancer. Non-small cell lung cancers account for about 85% of lung cancers. Of these, roughly 30% are squamous cell carcinomas.

Squamous cell carcinoma begins in the tissues that line the air passages in the lungs. It is also known as epidermoid carcinoma. Most squamous cell carcinomas of the lungs are located centrally, usually in the larger bronchi that join the trachea to the lung.

This article discusses squamous cell carcinoma lung and its symptoms and causes, notably its association with smoking. It also presents information about diagnosis and treatment.

Squamous Cell Carcinoma Symptoms

Common signs and symptoms of squamous cell carcinoma of the lung are not unlike those of other lung cancers. Symptoms typically include:

• A persistent cough
• Shortness of breath
• Wheezing
• Coughing up blood 
• Fatigue
• Discomfort when swallowing
• Chest pain
• Fever
• Hoarseness
• Loss of appetite
• Unexplained weight loss of more than 5% over six to 12 months

But there's also a difference that distinguishes this form of cancer from others. Squamous cell carcinoma tends to cause symptoms earlier because it affects the larger airways of the lungs, as opposed to adenocarcinoma, which affects the edges.

This translates to higher rates of early detection, but 75% of cases are still only diagnosed after the cancer has spread.

Squamous cell carcinoma is the most common cause of Pancoast syndrome, also known as superior sulcus syndrome. Pancoast syndrome is caused by cancers that begin near the top of the lungs and invade nearby structures, such as nerves. Symptoms include:

• Shoulder pain that radiates down the inside of the arm
• Weakness or prickly sensations in the hands
• Flushing or sweating on one side of the face
• A droopy eyelid, called Horner’s syndrome

People with squamous cell carcinoma of the lung are also more likely to experience an elevated calcium level, or hypercalcemia, which can result in muscle weakness and cramps. Hypercalcemia is one of the symptoms of paraneoplastic syndrome and is caused by a tumor secreting a hormone-like substance that raises the calcium level in the blood.

Squamous Cell Carcinoma Causes

Squamous cell carcinomas are linked more strongly with smoking than other forms of non-small cell lung cancers and are more common in men than in women.

Research suggests that as many as 91% of squamous cell lung cancers are attributed to cigarettes and that the degree of risk is directly linked to the number of cigarettes smoked per day.

While squamous cell carcinomas are intrinsically linked to smoking, other causes can contribute. Among these, radon exposure in the home is the second leading cause of lung cancer. Occupational exposures to diesel fuel and other toxic fumes and gases are also important risk factors.

Genetics may also play a role, given that the risk is statistically increased in people who have other family members with lung cancer.

Diagnosing Squamous Cell Carcinoma

Squamous cell carcinoma of the lungs is often first suspected when abnormalities are seen on an X-ray. Further evaluation may include:

• Chest CT scan (a form of X-ray that produces cross-sectional images of the lungs)
• Sputum cytology (which tends to be effective given that cancer cells are more readily dislodged from the large airways)
• Bronchoscopy (a direct form of visualization in the lungs)
• PET scan (which is better able to detect current cancer activity)
• Endobronchial ultrasound (involving an ultrasound probe inserted into the windpipe)

Depending on the results, your healthcare provider may want to obtain a sample of tissue (lung biopsy) to confirm the diagnosis and will order further tests to check to see if your cancer has spread.

Disease Staging

If cancer is confirmed, your healthcare provider will next want to stage the malignancy. Squamous cell carcinoma of the lungs is broken down into four stages:

• Stage 1: the cancer is localized and has not spread to any lymph nodes
• Stage 2: the cancer has spread to lymph nodes or the lining of the lungs, or is in a certain area of the main bronchus
• Stage 3: the cancer has spread to tissue near the lungs
• Stage 4: the cancer has spread (metastasized) to another part of the body, the most common sites being the bones, brain, liver, or adrenal glands

Healthcare providers will also use a more complex means of staging called TNM staging. With this, they will look at the size of the tumor (represented by a T); the number and locations of nodes affected (N), and whether the tumor has metastasized (M).

Subtypes

Squamous cell lung cancers can be further divided into four subtypes based on how they look under a microscope and how they behave. The pathologist will then classify the cancer as either:

• Primitive
• Classical
• Secretory
• Basal

Survival rates vary significantly between the subtypes, with primitive carcinomas having the poorest outcomes overall. The subtypes are also important in that they help healthcare providers determine how the cancer will respond to drug treatment. Most subtypes respond to at least one of the commonly used chemotherapy drugs.

The only exception may be secretory squamous cell lung cancer. This subtype is less sensitive to commonly used drugs because it tends to be slow-growing. By and large, chemotherapy is most effective in targeting and destroying cancers with fast-dividing cells. 

Squamous Cell Carcinoma Treatment

Depending upon the stage of squamous cell carcinoma of the lungs, treatment may include:

• Surgery
• Chemotherapy
• Radiation therapy
• Targeted therapy
• Immunotherapy
• A combination of these treatments

Many clinical trials are in progress looking for new ways to treat this cancer and to help decide which treatments are most effective.

Oftentimes in the past, these different categories of treatment were used separately. For example, with metastatic squamous cell tumors, first-line therapy usually included either an immunotherapy drug or chemotherapy, but combination therapy may prove most beneficial.

Surgery

Lung cancer surgery may be possible for squamous cell carcinoma. With stage 1A squamous cell lung cancer, surgery alone may be curative. Surgery may also be considered for those with stage 1B, stage 2, and stage 3A lung cancer, usually combined with chemotherapy and radiation therapy.

Sometimes, a tumor may initially be inoperable but may be reduced in size with chemotherapy and/or radiation therapy so that surgery is then possible.

Chemotherapy

Chemotherapy may be used alone, in conjunction with radiation therapy, or before or after surgery for lung cancer. It may also be combined with immunotherapy, and this combination appears to have the most benefit on survival in those who have metastatic disease. In fact, the combination of the immunotherapy drug Keytruda (pembrolizumab) with chemotherapy may significantly prolong overall survival for people with metastatic squamous cell cancers of the lung.

Squamous cell carcinoma of the lungs responds somewhat differently to chemotherapy medications than other lung cancers, such as adenocarcinoma. The use of platinum-based drugs is more likely to achieve complete remission.

Common medications used initially for this type of cancer include:

• Platinol (cisplatin)
• Paraplatin (carboplatin)
• Eloxatin (oxalaplatin)
• Gemzar (gemcitabine)

For those who respond to treatment, continuous (maintenance treatment) with Tarceva (erlotinib) or Alimta (pemetrexed) may be used.

Radiation Therapy

Radiation therapy may be used to treat cancer or to control symptoms related to the spread of cancer. Radiation may be given externally, or internally (brachytherapy) in which radioactive material is delivered to a precise area of the lungs during a bronchoscopy.

Targeted Therapy

You may have heard about the use of targeted drugs to treat EGFR mutations in lung adenocarcinoma. EGFR, or epidermal growth factor receptor, is a protein involved in driving the growth of a cancer. Squamous cell carcinoma of the lungs may also be treated by targeting the EGFR pathway, but by using a different mechanism.

Instead of targeting EGFR mutations, anti-EGFR antibodies are a class of drugs used to bind to EGFR on the outside of cancer cells. When EGFR is thus bound, the signaling pathway which tells the cell to grow is halted.

Portrazza (necitumumab) may be used along with chemotherapy for advanced squamous cell cancers. Gilotrif (afatinib), another type of targeted therapy, is also used with chemotherapy, specifically in cases where a person is not eligible for immunotherapy. This type of treatment is most commonly prescribed for people with epidermal growth factor genetic aberrations.

Immunotherapy

Immunotherapy drugs were first approved for the treatment of lung cancer in 2015. Four immunotherapy drugs have now been approved for SCC of the lungs, including:

• Opdivo (nivolumab)
• Keytruda (pembrolizumab)
• Imfinzi (durvalumab)
• Tecentriq (atezolizumab)
• Imjudo (tremelimumab)

These treatments enhance the immune system's ability to fight off cancer cells.

To understand how these drugs work, it may help to think of your immune system as a car. The "brakes" are controlled by a protein called PD-1. Drugs like Opdivo in this analogy work to block PD-1 (the brakes) to allow the immune system to fight against the cancer without interference —in essence, taking the brakes off the car.

As noted above, for metastatic squamous cell carcinoma, the combination of Keytruda and chemotherapy greatly improved survival.

Squamous Cell Carcinoma Prognosis

Before answering the question “what is the prognosis of squamous cell lung cancer?” it is important to talk about what the numbers describing survival rate really mean. First of all, everyone is different.

Statistics tell us what the “average” course or survival is, but they don’t tell us anything about specific individuals. Many factors can affect the prognosis of squamous cell lung cancer including your age at diagnosis, your sex, the condition of your general health, and how you respond to treatments.

It is also helpful to keep in mind that statistics are based on information that is several years old. As new treatments become available, these numbers may not accurately reflect what your prognosis is today.

For example, the five-year survival rate for lung cancer is based on people who were diagnosed five years earlier. Since many significant treatments for SCC of the lung may have been approved after those individuals were diagnosed, statistics do not necessarily indicate how someone diagnosed today will do.

Five-year survival rates range from an average of 50% with stage 1 non-small cell lung cancer to only 2% to 4% by stage 4. Because most diagnoses are made in the later stages, the overall five-year survival rate is 18%.

It is important to note that many people treated for lung cancer live well in excess of five years and that advances in treatment are promising higher rates of sustained remission.

Coping

A diagnosis of squamous cell carcinoma of the lungs is frightening and you may feel very alone. This is the time to reach out and allow your friends and loved ones to support you. 

Take the time to learn about your cancer. Studies tell us that people who better understand their cancer not only feel more empowered, but that knowledge can sometimes make a difference in survival as well.

For example, not all oncologists may be familiar with the latest study showing significantly improved survival with metastatic disease for people initially treated with a combination of immunotherapy and chemotherapy.

Since general oncologists may not be abreast of fast-changing research, many lung cancer survivors recommend obtaining a second opinion from one of the larger National Cancer Institute-designated cancer centers.

See if you can find a support group for people with lung cancer in your community or connect with a lung cancer community online. Check out the lung cancer organizations such as LUNGevity, the American Lung Association Lung Force, and the Lung Cancer Alliance.

Most of all, be your own advocate for your cancer care. Squamous cell carcinoma of the lung treatments are changing rapidly, and many survivors are currently alive because they educated themselves and were an advocate for their care.

A Word From Verywell

Coping with lung cancer in a loved one can be a challenge. Ask about specific ways in which you can help, rather than saying "call me if you need me." Take a moment to learn more about living with lung cancer and how you can better support a loved one with cancer.