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.

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 booklet was produced in February 2016, before the later approvals by the FDA of several additional drugs. Information about these recently approved drugs can be found in the Chemotherapy and Immunotherapy sections below.)

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.

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 carcinomaCancer that begins in the skin or in tissues that line or cover internal organs of the lung, is one type of non-small cell lung cancer (NSCLC)A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. It is also called epidermoid carcinomaCancer that begins in squamous cells. 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 tumorsAn abnormal mass of tissue that results when cells divide more than they should or do not die when they should usually occur in the central part of the lung or in one of the main airways (left or right bronchusOne of the large air passages that lead from the trachea (windpipe) to the lungs). The tumor’s location is responsible for symptoms such as cough, trouble breathing, chest pain, and blood in the sputumMucus and other matter brought up from the lungs by coughing. If the tumor grows to a large size, a chest X-rayA type of high-energy radiation that can go through the body and onto film, making pictures of areas inside the chest, which can be used to diagnose disease or computed tomography (CT or CAT ) scanA procedure that uses a computer linked to an X-ray machine to make a series of detailed pictures of areas inside the body may detect a cavityA hollow area or hole in the lung. A cavity is a gas- or fluid-filled space within a tumor mass or noduleA growth or lump that may be malignant (cancer) or benign 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 smokeSmoke that comes from the burning of a tobacco product and smoke that is exhaled by smokers, mineral and metal dust, asbestosA group of minerals that take the form of tiny fibers, or radonA radioactive gas that is released by uranium, a substance found in soil and rock.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, genomic 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 driver mutations that cause lung cancer. While researchers are making progress in understanding driver mutations in squamous cell lung cancer, there are no targeted therapies approved yet for its treatment. However, several are being studied in clinical trials, so knowing your cancer’s biomarker profile may provide more treatment options.

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

Below are the driver mutations that have been identified for squamous cell lung cancer at this time.6,7,8

Driver mutations in squamous cell lung cancer

More information about driver mutations, and how and when testing for them is performed, can be found here (see “What is a driver 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 healthcare 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 For Supporters & Advocates 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.  

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.9

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.10

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 lung cancer 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. An example of this is cisplatin in combination with gemcitabine.9

Another type of chemotherapy was recently approved by the FDA 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. While 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.11,12

Another drug, the kinase inhibitor afatinib (Gilotrif®), is FDA-approved for the treatment of patients with metastatic squamous cell lung cancer that has progressed after platinum-based chemotherapy.13

There are a number of other post-first-line therapy options for squamous cell lung cancer, such as chemotherapy with or without an angiogenesis inhibitor, or immunotherapy, such as nivolumab. 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, and 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 lung cancer. The high risk of bleeding is thought to be due to the central location of these tumors.15,16

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 FDA-approved for non-small cell lung cancer, but only one of them, ramucirumab (Cyramza®) is approved for treating squamous cell lung cancer. This drug is FDA-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. This drug is considered a VEGF Receptor 2 antibody.17

The other angiogenesis inhibitor, bevacizumab (Avastin®), is not an option for squamous cell lung cancer.15

Read more about how angiogenesis inhibitors work and common side effects, as well as questions to ask your healthcare 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 healthcare team 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 the team know if you have a history of an autoimmune disease. It is possible that immunotherapies 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. More are being studied for lung cancer at this time.

The three FDA-approved immunotherapy drugs are:

  • Nivolumab (Opdivo®)18: For patients with metastatic NSCLC whose cancer has progressed after platinum-based chemotherapy. Patients with EGFR or ALK mutations should have disease progess on FDA-approved therapy for those mutations before they are treated with this drug
  • Pembrolizumab (Keytruda)19:
    • ​For first-line treatment of patients with metastatic NSCLC whose tumors have high PD-L1 expression as determined by an FDA-approved test, with no EGFR or ALK mutations
    • For patients with metastatic NSCLC whose tumors express PD-L1 as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK mutations should have disease progession on FDA-approved therapy for those mutations before they are treated with this drug
    • For first-line treatment of patients with metastatic non-squamous NSCLC, irrespective of PD-L1 expression
  • Atezolizumab (Tecentriq®)20:  For patients with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK mutations  should have disease progression on FDA-approved therapy for those mutations before they are treated with this drug

Note: Platinum-based chemotheraies include carboplatin and cisplatin.

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 that the drugs can target the cancer cells.21

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 healthcare team, see the Treatment Options: Immunotherapy section of this website.

What 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.22 The following describe some, but by no means all, of the clinical trials available for people with squamous cell lung cancer.

Immunotherapy

Immune checkpoint inhibitors continue to be studied in clinical trials for all types and stages of lung cancer. Other types of immunotherapy that are currently being studied include therapeutic cancer vaccines and adoptive T cell transfer.22

Targeted Therapy

Drugs that target certain mutations in a tumor are called targeted therapies. As discussed earlier, a number of driver mutations have been found in squamous cell lung cancer. Currently, scientists 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. In those cases, ALK inhibitors or EGFR inhibitors may be a treatment option.23,24

Clinical trials studying targeted therapies for squamous cell lung cancer include22:

  • The Lung-MAP clinical trial, which is focused on patients with recurrent and stage 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 driver mutations that are frequently seen in squamous cell lung cancer, including PIK3CA, PTEN, and FGFR1 

Finding a Clinical Trial That Might Be Right for You

If you are considering participating in a clinical trial, start by asking your healthcare 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 For Supporters & Advocates 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 healthcare 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 healthcare team that a patient sees over the course of his or her care. Your healthcare team can describe your treatment options, the expected results of each option, and the possible side effects. You and your healthcare team can work together to develop a treatment plan.

Read more about what each member of your healthcare team does.

Updated January 4, 2018


References

  1. Non-Small Cell Lung Cancer Treatment (PDQ®): General Information About Non-Small Cell Lung Cancer. National Cancer Institute website. http://www.cancer.gov/types/lung/patient/non-small-cell-lung-treatment-pdq#section/all. Updated November 9, 2017. Accessed December 4, 2017.
  2. NCI Dictionary of Cancer Terms. National Cancer Institute website. http://www.cancer.gov/dictionary. Accessed December 4, 2017.
  3. Wistuba I, Brambilla E, Noguchi M. Chapter 17. Classic Anatomic Pathology and Lung Cancer. In: Pass HI, Ball D, Scagliotti GV, eds. IASLC Thoracic Oncology, Second Edition. Philadelphia, PA: Elsevier. 2018: 143-146.
  4. Squamous cell carcinoma of the lung. Harvard Health Publishing. https://www.health.harvard.edu/cancer/squamous-cell-carcinoma-of-the-lung. Posted November 2014. Accessed December 13, 2017.
  5. Gill  R, Matsusoka S, Hatabu H. Cavities in the Lung in Oncology Patients: Imaging Overview and and Differential Diagnosis. Applied Radiology website. https://appliedradiology.com/articles/cavities-in-the-lung-in-oncology-patients-imaging-overview-and-differential-diagnosis. Posted June 9, 2010. Accessed December 13, 2017.
  6. Cancer Genome Atlas Network. Comprehensive genomic characterization of squamous cell lung cancers. Nature. Sep 27 2012; 489(717): 519-525. https://www.nature.com/articles/nature11404. Accessed December 4, 2017.
  7. Paik P, Shen R, Won H, et al. Next generation sequencing of stage IV squamous cell lung cancers reveals an association of P13K aberrations and evidence of clonal heterogeneity in patients with brain metastases. Cancer Discovery. 2015 Jun;5(6):610-21. doi: 10.1158/2159-8290.CD-14-1129. http://www.ncbi.nlm.nih.gov/pubmed/25929848. Accessed December 4, 2017.
  8. Perez-Moreno P, Brambilla E, Thomas R, Soria JC. Squamous cell carcinoma of the lung: molecular subtypes and therapeutic opportunities. Clinical cancer research: an official journal of the American Association for Cancer Research. May 01 2012; 18(9): 2443-2451. http://clincancerres.aacrjournals.org/content/18/9/2443.long. Accessed December 4, 2017.
  9. Lung Cancer — Non-Small Cell Lung Cancer. Cancer.Net website. http://www.cancer.net/cancer-types/lung-cancer-non-small-cell/stages. Approved August 2017. Accessed December 4, 2017.
  10. When might radiation therapy be used? American Cancer Society website. https://www.cancer.org/cancer/non-small-cell-lung-cancer/treating/radiation-therapy.html. Revised May 16, 2016. Accessed December 13, 2017.
  11. PortrazzaTM (necitumumab) injection [package insert]. Eli Lilly and Company. Indianapolis, IN. http://pi.lilly.com/us/portrazza-uspi.pdf. Revised November 2015. Accessed December 4, 2017.
  12. 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. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/abstract. Accessed December 4, 2017.
  13. 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 November 2017. Accessed December 4, 2017.
  14. Angiogenesis Inhibitors. National Cancer Institute website. http://www.cancer.gov/cancertopics/factsheet/Therapy/angiogenesis-inhibitors. Reviewed October 7, 2011. Accessed December 4, 2017.
  15. Avastin® (bevacizumab) [package insert]. Genentech, Inc., South San Francisco, CA; November 2014. http://www.gene.com/download/pdf/avastin_prescribing.pdf. Revised December 2016. Accessed December 4, 2017.
  16. Reck M,  Barlesi F, et al. Predicting and managing the risk of pulmonary hemorrhage in patients with NSCLC treated with bevacizumab: a consensus report from a panel of experts. Annals of Oncology. 23: 1111-1120, 2012. https://www.ncbi.nlm.nih.gov/pmc/aticles/PMC3335247/pdf/mdr463.pdf. Posted November 4, 2011. Accessed December 13, 2017.
  17. Cyramza® (ramucirumab) [package insert]. Eli Lilly and Company, Indianapolis, IN; December 2014. http://pi.lilly.com/us/cyramza-pi.pdf. Revised March 2017. Accessed December 4, 2017.
  18. Opdivo® (nivolumab) injection [package insert]. Bristol-Myers Squibb Company. Princeton, NJ; March 2015. http://packageinserts.bms.com/pi/pi_opdivo.pdf. Revised October 2017. Accessed December 4, 2017.
  19. 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 November 2017. Accessed December 4, 2017.
  20. Tecentriq® (atezolizumab) injection (package insert]. Genentech, Inc., South San Francisco, CA, October 2016. https://www.gene.com/download/pdf/tecentriq_prescribing.pdf. Revised April 2017. Accessed December 4, 2017.
  21. Pardoll D. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12:252-264. doi: 10.1.1038/nrc3239. http://www.nature.com/nre/journal/v12/n4/full/nrc3239.html. Accessed December 4, 2017.
  22. Clinicaltrials.gov. US National Institutes of Health website. http://clinicaltrials.gov. Accessed December 13, 2017.
  23. Dragnev K, Gehr G. ALK-Rearranged Adenosquamous Lung Cancer Presenting as Squamous Cell Carcinoma: A Potential Challenge to Histologic Type Triaging of NSCLC Biopsies for Molecular Studies. Clinical Lung Cancer, May 2014. Volume 15 Issue 3, pages e37-e40. http://www.clinical-lung-cancer.com/article/S1525-7304(14)00022-9/fulltext. Accessed December 13, 2017.
  24. Powrózek T, Krawczyk P. EGFR mutations in patients with adenosquamous lung carcinoma. Asia Pac J Clin Oncol, 2014 Dec; 10(4): 340-5. doi: 10.111/ajco.12177. https://www.ncbi.nlm.nih.gov/pubmed/24575772. Posted February 27, 2014. Accessed December 13, 2017. 

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