Squamous Cell Lung Cancer

Squamous cell lung cancer, also called squamous cell carcinoma of the lung, accounts for about 30% of all lung cancers. This type of lung cancer tends to be found in the middle of the lungs.

There are numerous treatment options available to people diagnosed with squamous cell lung cancer, and doctors are working hard to develop and improve these treatments.

Squamous cell lung cancer brochureTo help you understand and share this information, click here to download and print a booklet that summarizes the detailed information in the following sections.

This website can help you:

  • Learn about squamous cell lung cancer
  • Understand the treatment options available for squamous cell lung cancer
  • Consider whether participating in a clinical trial might be right for you
  • Understand how to manage the side effects associated with lung cancer treatment

What is squamous cell lung cancer?

Squamous cell lung cancer, or squamous cell carcinoma of the lung, is one type of non-small cell lung cancer (NSCLC). It is also called epidermoid carcinoma. This type of lung cancer begins in the squamous cells—thin, flat cells that look like fish scales when seen under a microscope. They line the inside of the airways in the lungs.1,2

Squamous cell lung cancer

Squamous cells are also found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the lining of the digestive tract.2 Only squamous cell carcinoma that begins in the lungs is considered lung cancer.

Squamous cell lung tumors usually occur in the central part of the lung or in one of the main airways (left or right bronchus). The tumor’s location is responsible for symptoms such as cough, trouble breathing, chest pain, and blood in the sputum. If the tumor grows to a large size, a chest X-ray or computed tomography (CT or CAT ) scan may detect a cavity in the lung. A cavity is a gas- or fluid-filled space within a tumor mass or nodule and is a classic sign of squamous cell lung cancer. Squamous cell lung cancer can spread to multiple sites, including the brain, spine and other bones, adrenal glands, and liver.3,4,5

About 30% of all lung cancers are classified as squamous cell lung cancer. It is more strongly associated with smoking than any other type of non-small cell lung cancer. Other risk factors for squamous cell lung cancer include age, family history, and exposure to secondhand smoke, mineral and metal dust, asbestos, or radon.3,4

Diagnosing squamous cell lung cancer

This type of lung cancer may be diagnosed in many different ways. In addition, doctors have come up with very specific modes of categorizing lung cancer to help treat them better. Understanding the ways that doctors categorize lung cancers may help you understand your diagnosis.

How Is Squamous Cell Lung Cancer Diagnosed?

Many different tests are used to diagnose lung cancer and determine whether it has spread to other parts of the body. Some can also help to decide which treatments might work best. The steps and tests used in diagnosing squamous cell lung cancer include:

  • Imaging tests
  • Laboratory tests
  • Biopsies

Not all of these will be used for every person. The approaches used for an individual will depend on your medical history and condition, symptoms, location of the nodule(s), and other test results.

Read the Diagnosing Lung Cancer section to learn more about the different steps and tests for making a lung cancer diagnosis.

Stages of Lung Cancer

Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting other parts of the body. Doctors use diagnostic tests to determine the cancer’s stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to recommend a treatment plan. Although lung cancer is treatable at any stage, only certain stages of lung cancer can be cured. 

The Lung Cancer Staging section provides more information about this way of understanding squamous cell lung cancer.

Biomarker Profile

Lung cancer describes many different types of cancer that start in the lung or related structures. There are two different ways of describing what kind of lung cancer a person has:

  • Histology—what the cells look like under a microscope. Squamous cell lung cancer is a histological subtype of non-small cell lung cancer. Other subtypes of non-small cell lung cancer include adenocarcinoma, large cell carcinoma, and some rarer types. Small cell lung cancer (SCLC) is the other major type of lung cancer
  • Biomarker profile (also called molecular profile, genetic profile, or signature profile)—the mutations, or characteristics, as well as any other unique biomarkers, found in a person’s cancer that allowed the cancer to grow

A person’s lung cancer may or may not have one of the many known mutations. For example, two patients may be treated with two different therapies because of their own cancer’s specific mutation or lack of a mutation.

Researchers are making progress in understanding mutations in squamous cell lung cancer. While no targeted therapies are approved yet for use in squamous cell lung cancer, several are being studied in clinical trials, so knowing your cancer’s biomarker profile may provide more treatment options.6,7

The decision to test for mutations should be made together by you and your oncologist.

Here are the mutations that have been identified for squamous cell lung cancer at this time.6,7

Biomarker profile of squamous cell lung cancer

More information about mutations, and how and when testing for them is performed, can be found here (see “What is a mutation?,” “How is biomarker testing performed?,” and “Who should have their tumor tested and when?”).

Treatment options for squamous cell lung cancer

Questions to discuss with your health care team when planning your treatment approach include:

  • What are my treatment options?
  • What treatment plan do you recommend for me?
  • What is our goal with these treatment(s)? To eliminate my cancer? To slow its growth? To treat symptoms?
  • How long will my treatment take?
  • When do I need to decide on my treatment plan?
  • What are the risks and potential side effects of the different treatment options?
  • Will my insurance cover these treatment options?

More helpful sets of questions and checklists can be found in the Support & Survivorship section.

There are a number of treatment options for squamous cell lung cancer. Which ones are used to treat a specific patient’s lung cancer will depend on the stage of the cancer and the patient’s overall health and preferences.  

Treatments options fall into two categories:

  • Those that are available for your doctor to prescribe, having been already approved by the FDA in the U.S. or other drug regulatory agencies in other countries
  • Those that are being studied in clinical trials

What Are Currently Approved Treatment Options?

Approved treatment options for squamous cell lung cancer include:

  • Surgery
  • Radiation therapy
  • Chemotherapy
  • Angiogenesis inhibitor
  • Immunotherapy

It is important to note that a patient’s age has never been useful in predicting whether that patient will benefit from treatment. A patient’s age should never be used as the only reason for deciding what treatment is best, especially for older patients who are otherwise physically fit and have no medical problems besides lung cancer.

Surgery

Lung cancer that is only in one lung and that has not spread to other organs is often treated with surgery, if the patient can tolerate it. Read more about different surgical options and what to expect after surgery in the Treatment Options: Surgery section.

Radiation Therapy

Radiation therapy is a type of cancer treatment that uses high-powered energy beams to kill cancer cells. Depending on the individual patient’s situation, radiation therapy may be used when trying to cure cancer, control cancer growth, or relieve symptoms caused by the tumor, such as pain.

Radiation therapy can be given as the main treatment in early-stage squamous cell lung cancer if surgery is not possible. In that case, it may be given either with or without chemotherapy. In some cases, radiation therapy is used before or after surgery.

Read more about radiation treatment, including how it works, how and when it is given, the different kinds, and common side effects in the Treatment Options: Radiation Therapy section.

Chemotherapy

Patients whose lung cancer has spread beyond the lung to local lymph nodes are often given chemotherapy and radiation therapy. As with other types of non-small cell lung cancer, patients with squamous cell carcinoma are often given two chemotherapy agents as first-line therapy. Which drugs are chosen will depend in part on the patient’s overall health and ability to tolerate different possible side effects.

Most often, the platinum-based drugs cisplatin or carboplatin are combined with another chemotherapy drug. Two combinations that have been shown to work particularly well in squamous cell lung cancer are:

  • Cisplatin and gemcitabine
  • Carboplatin and nab-paclitaxel (Abraxane®)8

Another type of chemotherapy was recently approved as first-line treatment of people with metastatic squamous cell lung cancer. The drug, necitumumab (PortrazzaTM), was approved to be used in combination with cisplatin and gemcitabine.9

Whereas squamous cell lung cancer has not been shown to have epidermal growth factor receptor (EGFR) mutations, this drug seems to work by blocking EGFR protein expression, which is seen in squamous cell lung cancer.10

Another drug, afatinib (Gilotrif®), is FDA-approved for the treatment of patients with metastatic squamous cell lung cancer that has progressed after platinum-based chemotherapy.11

There are a number of other post-first-line therapy options for squamous cell carcinoma, such as chemotherapy with or without an angiogenesis inhibitor, or immunotherapy, such as nivolumab.12,13 These are discussed in more detail below. Your doctor will help to select the best treatment based on your medical history. Read more about chemotherapy, including how it works, how and when it is given, possible side effects and how to manage them in the Treatment Options: Chemotherapy section.

Angiogenesis Inhibitors

As the body develops and grows, it makes new blood vessels to supply all of the cells with blood. This process is called angiogenesis. When the new blood vessels provide oxygen and nutrients to cancer cells, they help the cancer cells grow and spread.

Note: Bevacizumab is thought to have a different way of blocking VEGF from ramucirumab and is approved only in non-squamous cell lung cancer. It has been found to cause life-threatening and fatal bleeding in the lungs of patients with squamous cell carcinoma. The high risk of bleeding is thought to be due to the central location of these tumors.15

Angiogenesis inhibitors help stop or slow the growth or spread of tumors by stopping them from making new blood vessels. The tumors then die or stop growing because they cannot get the oxygen and nutrients they need. The inhibitors work by blocking the cancer cells’ vascular endothelial growth factor (VEGF) receptors.14

Currently, two angiogenesis inhibitors are approved for non-small cell lung cancer, but only one of them is approved for treating squamous cell lung cancer:

  • Ramucirumab (Cyramza®): Approved in combination with the chemotherapy docetaxel for the second-line treatment of patients with metastatic non-small cell lung cancer, including non-squamous and squamous histologies. Cyramza is considered a VEGF Receptor 2 antibody. The most common side effects are high blood pressure, diarrhea, fatigue, neutropenia, bleeding from the nose, and stomatitis/mucosal inflammation12
  • The other angiogenesis inhibitor, bevacizumab (Avastin®), is not an option for squamous cell lung cancer

Read more about how angiogenesis inhibitors work and common side effects, as well as questions to ask your health care team, in the Treatment Options: Angiogenesis Inhibitors section.

Immunotherapy

Immunotherapy aims to strengthen the natural ability of the patient’s immune system to fight cancer. Instead of targeting the person’s cancer cells directly, immunotherapy trains a person’s natural immune system to recognize cancer cells and selectively target and kill them. Some squamous cell carcinomas may grow and spread by avoiding the immune response that would otherwise help to keep cancer cells in check.

Note: It’s important to let your doctor or nurse know if you are experiencing any problems while on treatment, so they can sort out whether the problems are related to treatment or not. It is also important to let your doctor or nurse know if you have a history of an autoimmune disease. This is because nivolumab may make autoimmune diseases worse.

Currently, there are three immunotherapy drugs available outside clinical trials for people with non-small cell lung cancer, including squamous cell lung cancer. Many more are being studied for lung cancer at this time.

Nivolumab (Opdivo®),13 pembrolizumab (Keytruda®),16 and atezolizumab (Tecentriq®)17 are all FDA-approved for people who have metastatic non-small cell lung cancer.

Pembrolizumab is the only drug approved for both first-line and later treatment. Nivolumab and atezolizumab are only appoved for people whose disease has progressed during or after treatment with platinum-based chemotherapy.13,16,17

Note: Platinum-based chemotherapies include carboplatin and cisplatin.

Pembrolizumab’s approval also requires the following:

  • The patient’s tumors must express PD-L1
  • And, for patients with ALK-positive or EGFR-positive non-small cell lung cancer, their lung cancer should have progressed on an approved ALK or EGFR inhibitor before they are treated with pembrolizumab

These drugs belong to the type of immunotherapy called immune checkpoint inhibitors. The immune checkpoint inhibitors work by targeting and blocking the fail-safe mechanisms of the immune system. Their goal is to block the immune system from limiting itself, so they can target the cancer cells.10,16,18,19,20

For more about immunotherapy, including how the immune system works, other kinds of immunotherapy being studied, possible side effects and how to manage them, and questions to ask your health care team, see the Treatment Options: Immunotherapy section of this website.

What clinical research study (clinical trial) treatment options are available?

In addition to the approved treatments described above, there is a great deal of promising research going on now in clinical trials focused on people with squamous cell lung cancer.21 The following describe some, but by no means all, of the clinical trials available for people with squamous cell lung cancer.

Immunotherapy

Three main types of immunotherapy are currently being studied in people with non-small cell lung cancer:

  • Immune checkpoint inhibitors
  • Therapeutic cancer vaccines
  • Adoptive T cell transfer

Nivolumab and other immunotherapies continue to be studied in clinical trials for all types and stages of lung cancer. Immune checkpoint inhibitors, such as ipilimumab and nivolumab, are being investigated extensively.21 Other types of immunotherapy that are currently being studied include the therapeutic cancer vaccine TG1040 and adoptive T cell transfer.22

Targeted Cancer Therapy

Drugs that target certain mutations in a tumor are called targeted cancer therapies. As discussed earlier, a number of mutations have been found in squamous cell lung cancer. Currently, researchers are still working to develop drugs that target most of these mutations.

Note that anaplastic lymphoma kinase (ALK) rearrangements and epidermal growth factor receptor (EGFR) mutations, which are seen in adenocarcinoma, have not been seen in pure squamous cell lung cancer. Cases where they seem to occur in squamous cell lung cancer may be adenosquamous carcinoma or misdiagnosed solid adenocarcinoma.6,7 In those cases, ALK inhibitors or EGFR inhibitors may be a treatment option.

Clinical trials studying targeted cancer therapies for squamous cell carcinoma include21:

  • The Lung-MAP clinical trial, which is focused on patients with recurrent stage IIIB-IV squamous cell lung cancer. This first-of-its-kind clinical trial uses a targeted method to match patients with studies of a number of new treatments being researched. Lung-MAP treatments are being studied as second-line or later therapy. More information can be found at www.lung-map.org
  • New drugs targeting mutations that are frequently seen in squamous cell lung cancer, including PIK3CA, PTEN, FGFR1, DDR2, AKT1, CDK4, and CDK6

New Approaches to Existing Treatments

In addition to new treatments, doctors are also trying new approaches to existing treatments. Some examples include:

  • Chemotherapy agents given in combination with radiation therapy, surgery, immunotherapy, and targeted cancer therapy
  • The chemotherapy nab-paclitaxel (Abraxane®) given as maintenance therapy in patients with advanced squamous cell lung cancer to keep the cancer from coming back
  • Radiation therapy given in combination with chemotherapy and surgery. Doctors are also looking at which type of radiation therapy is best to use in squamous cell lung cancer. For example, there is a study comparing stereotactic body radiation therapy to proton therapy

Finding a Clinical Trial That Might Be Right for You

If you are considering participating in a clinical trial, start by asking your health care team whether there is one that might be a good match for you in your geographic area. In addition, there are several online and phone-based resources to help you find one that may be a good match. Read more about clinical trials and resources for finding one for you.

Managing symptoms and side effects

As already noted, lung cancer treatments can cause side effects. Some cancer therapy side effects are temporary, while others can be more long-term. When you start a new treatment, you should discuss with your doctor which potential side effects to expect, what can be done to manage them, and which side effects are serious and need to be reported immediately. Often, drugs can be prescribed to help reduce many of these side effects.  

In addition to the side effects of lung cancer treatment, lung cancer itself can result in a number of symptoms. Read more about the symptoms of lung cancer.

Tips for managing specific symptoms and side effects related to treatment can be found in the Support & Survivorship section of the website, along with other practical and supportive resources for patients/survivors and caregivers.

To help reduce the severity and duration of most side effects and alleviate the cancer’s symptoms, you may want to request palliative care, also called “supportive care” or “symptom management.” There is sometimes confusion about the difference between palliative care and hospice care. Hospice care is a form palliative care given only to patients whose life expectancy is six months or less. On the other hand, palliative care in general is an extra layer of support than can be initiated alongside other standard medical care. In fact, scientific evidence is starting to emerge that shows that palliative care may actually help patients live longer.

Read more about how palliative care can improve quality of life from the time of diagnosis.

Your health care team

There are a number of doctors and other medical professionals who diagnose and treat people with lung cancer. Together, they make up the comprehensive medical or health care team that a patient sees over the course of his or her care. Your health care team can describe your treatment options, the expected results of each option, and the possible side effects. You and your health care team can work together to develop a treatment plan.

Read more about what each member of your health care team does.

Updated November 2, 2016.


References

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  2. NCI Dictionary of Cancer Terms. National Cancer Institute website. http://www.cancer.gov/dictionary. Accessed February 22, 2016.
  3. Lung Cancer – Non-Small Cell: Symptoms and Signs. American Society of Clinical Oncology website. http://www.cancer.net/cancer-types/lung-cancer-non-small-cell/symptoms-and-signs. Accessed December 10, 2015.
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  9. PortrazzaTM (necitumumab) injection [package insert]. Eli Lilly and Company. Indianapolis, IN. http://pi.lilly.com/us/portrazza-uspi.pdf. Accessed December 10, 2015.
  10. Thatcher N, Hirsch FR, et al. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015;16(7):763-774.
  11. Gilotrif® (afatinib) tablets [package insert]. Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, 2013. http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Gilotrif/Gilotrif.pdf?DMW_FORMAT=pdf. Revised April 2016. Accessed October 26, 2016.
  12. Cyramza® (ramucirumab) [package insert]. Eli Lilly and Company, Indianapolis, IN; December 2014. http://pi.lilly.com/us/cyramza-pi.pdf. Revised April 2015. Accessed February 22, 2016.
  13. Opdivo® (nivolumab) injection [package insert]. Bristol-Myers Squibb Company. Princeton, NJ; March 2015. http://packageinserts.bms.com/pi/pi_opdivo.pdf. Revised January 2016. Accessed February 22, 2016
  14. Angiogenesis Inhibitors. National Cancer Institute website. http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors. Reviewed October 7, 2011. Accessed March 25, 2015.
  15. Avastin® (bevacizumab) [package insert]. Genentech, Inc., South San Francisco, CA; November 2014. http://www.gene.com/download/pdf/avastin_prescribing.pdf. Revised December 2015. Accessed February 22, 2016.
  16. Keytruda® (pembrolizumab) injection [package insert]. Merck & Co., Inc. Whitehouse Station, NJ; 2014. http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf. Revised October 2016. Accessed October 26, 2016.
  17. Tecentriq® (atezolizumab) injection (package insert]. Genentech, Inc., South San Francisco, CA, October 2016. https://www.gene.com/download/pdf/tecentriq_prescribing.pdf. Accessed October 25, 2016.
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  21. Clinicaltrials.gov. US National Institutes of Health website. http://clinicaltrials.gov. Accessed February 22, 2016.
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