Laryngeal Cancer

  • Dana-Farber/Brigham and Women's Cancer Care

    Laryngeal cancer forms in tissues of the larynx, the area of the throat that is used for breathing, swallowing, and talking. Most laryngeal cancers are squamous cell carcinomas, which begin in cells lining the larynx. Learn about laryngeal cancer and find information on how we support and care for people with laryngeal cancer before, during, and after treatment.

Treatment 

The Head and Neck Oncology Program is dedicated exclusively to treating patients with head and neck cancers, which include cancers of the throat, larynx, nose, sinuses, and mouth.

Our specialists evaluate and treat all types and stages, from early lesions to the rarest and most challenging cases.  We also specialize in the treatment of all forms and stages of salivary gland and thyroid cancer.

As a patient, you will be seen by highly experienced clinicians from numerous specialties, including head and neck surgery, medical and radiation oncology, dentistry, oral surgery, reconstructive surgery, nutrition services, social work, speech, voice, and swallowing therapy.

Beginning with the initial consultation, your team of specialists will work with you to create a comprehensive treatment plan tailored to your type of cancer, as well as your lifestyle and personal needs, to achieve the best possible outcome.

Providers meet regularly to discuss new developments in clinical and basic research. The close relationships between world-class researchers and medical clinicians ensure that the latest research findings are translated into new, effective treatment approaches as quickly as possible.

Learn more about treatment and support for patients with head and neck cancers 

Our clinicians are experts in treating all types of head and neck cancers, including: 

  • Hypopharyngeal cancer
  • Laryngeal cancer
  • Nasopharyngeal cancer
  • Oral cancer
  • Oral cavity cancer
  • Oropharyngeal cancer
  • Paranasal sinus and nasal cavity cancer
  • Pharyngeal cancer
  • Laryngeal cancer
  • Lip cancer
  • Ear and Temporal Bone cancer
  • Skull Base cancer
  • Head and Neck Sarcomas
  • Mandible and jaw cancer
  • Adult craniopharyngioma
  • Unknown primary cancer
  • Merkel cell carcinoma
  • Head and Neck Melanoma
  • Salivary gland cancer
  • Parotid gland cancer
  • Acinic cell cancer
  • Adenoidcystic carcinoma
  • Mucoepidermoid cancer
  • Adenocarcinoma cancer
  • Papillary thyroid cancer
  • Follicular thyroid cancer
  • Anaplastic thyroid cancer
  • Medullary thyroid cancer
  • Hurthle cell cancer

Contact us 

New patients 

If you have never been seen before at Dana-Farber/Brigham and Women’s Cancer Center, please call 877-442-3324 or use this online form to make an appointment.

For all other inquiries, please call 617-632-3090

Referring physicians: 617-632-6869

Fax: 617-632-4448

Mailing address
Head and Neck Oncology Center
Dana-Farber Cancer Institute
450 Brookline Ave.
Boston, MA 02115-5450

Information for: Patients | Healthcare Professionals

General Information About Laryngeal Cancer

Laryngeal cancer is a disease in which malignant (cancer) cells form in the tissues of the larynx.

The larynx (voice box) is located just below the pharynx (throat) in the neck. The larynx contains the vocal cords, which vibrate and make sound when air is directed against them. The sound echoes through the pharynx, mouth, and nose to make a person's voice.

Most laryngeal cancers form in squamous cells, the thin, flat cells lining the inside of the larynx.

There are three main parts of the larynx:

  • Supraglottis: The upper part of the larynx above the vocal cords, including the epiglottis.
  • Glottis: The middle part of the larynx where the vocal cords are located.
  • Subglottis: The lower part of the larynx between the vocal cords and the trachea (windpipe).

Use of tobacco products and drinking too much alcohol can affect the risk of developing laryngeal cancer.

Possible signs of laryngeal cancer include a sore throat and ear pain.

These and other symptoms may be caused by laryngeal cancer or by other conditions. A doctor should be consulted if any of the following problems occur:

  • A sore throat or cough that does not go away.
  • Trouble or pain when swallowing.
  • Ear pain.
  • A lump in the neck or throat.
  • A change or hoarseness in the voice.

Tests that examine the throat and neck are used to help detect (find), diagnose, and stage laryngeal cancer.

The following tests and procedures may be used:

  • Physical exam of the throat and neck: An examination in which the doctor feels for swollen lymph nodes in the neck and looks down the throat with a small, long-handled mirror to check for abnormal areas.
  • Laryngoscopy: A procedure in which the doctor examines the larynx (voice box) with a mirror or with a laryngoscope (a thin, lighted tube).
  • Endoscopy: A procedure to look at organs and tissues inside the body to check for abnormal areas. An endoscope (a thin, lighted tube) is inserted through an incision (cut) in the skin or opening in the body, such as the mouth. Tissue samples and lymph nodes may be taken for biopsy.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope to check for signs of cancer.
  • Barium swallow: A series of x-rays of the esophagus and stomach. The patient drinks a liquid that contains barium (a silver-white metallic compound). The liquid coats the esophagus and stomach, and x-rays are taken. This procedure is also called an upper GI series.

Certain factors affect prognosis (chance of recovery) and treatment options.

Prognosis (chance of recovery) depends on the following:

  • The stage of the disease.
  • The location and size of the tumor.
  • The grade of the tumor.
  • The patient's age, gender, and general health, including whether the patient is anemic.

Treatment options depend on the following:

  • The stage of the disease.
  • The location and size of the tumor.
  • Keeping the patient's ability to talk, eat, and breathe as normal as possible.
  • Whether the cancer has come back (recurred).

Smoking tobacco and drinking alcohol decrease the effectiveness of treatment for laryngeal cancer. Patients with laryngeal cancer who continue to smoke and drink are less likely to be cured and more likely to develop a second tumor. After treatment for laryngeal cancer, frequent and careful follow-up is important.

Stages of Laryngeal Cancer

After laryngeal cancer has been diagnosed, tests are done to find out if cancer cells have spread within the larynx or to other parts of the body.

The process used to find out if cancer has spread within the larynx or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage of the disease in order to plan treatment. The results of some of the tests used to diagnoselaryngeal cancer are often also used to stage the disease.

There are three ways that cancer spreads in the body.

The three ways that cancer spreads in the body are:

  • Through tissue. Cancer invades the surrounding normal tissue.
  • Through the lymph system. Cancer invades the lymph system and travels through the lymph vessels to other places in the body.
  • Through the blood. Cancer invades the veins and capillaries and travels through the blood to other places in the body.

When cancer cells break away from the primary (original) tumor and travel through the lymph or blood to other places in the body, another (secondary) tumor may form. This process is called metastasis. The secondary (metastatic) tumor is the same type of cancer as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer.

The following stages are used for laryngeal cancer:

Stage 0 (Carcinoma in Situ)

In stage 0, abnormalcells are found in the lining of the larynx. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Stage I

In stage I, cancer has formed. Stage I laryngeal cancer depends on where cancer is found in the larynx:

  • Supraglottis: Cancer is in one area of the supraglottis only and the vocal cords can move normally.
  • Glottis: Cancer is in one or both vocal cords and the vocal cords can move normally.
  • Subglottis: Cancer is in the subglottis only.

Stage II

In stage II, cancer is in the larynx only. Stage II laryngeal cancer depends on where cancer is found in the larynx:

  • Supraglottis: Cancer is in more than one area of the supraglottis or surrounding tissues.
  • Glottis: Cancer has spread to the supraglottis and/or the subglottis and/or the vocal cords do not move normally.
  • Subglottis: Cancer has spread to one or both vocal cords, which may not move normally.
Tumor size compared to everyday objects; shows various measurements of a tumor compared to a pea, peanut, walnut, and lime  
Pea, peanut, walnut, and lime show tumor sizes.

Stage III

Stage III laryngeal cancer depends on whether cancer has spread from the supraglottis, glottis, or subglottis.

In stage III cancer of the supraglottis:

  • cancer is in the larynx only and the vocal cords do not move normally, and/or cancer is in tissues next to the larynx; cancer may have spread to one lymph node on the same side of the neck as the original tumor and the lymph node is smaller than 3 centimeters; or
  • cancer is in one area of the supraglottis only and in one lymph node on the same side of the neck as the original tumor; the lymph node is smaller than 3 centimeters and the vocal cords can move normally; or
  • cancer is in more than one area of the supraglottis or surrounding tissues and in one lymph node on the same side of the neck as the original tumor; the lymph node is smaller than 3 centimeters and/or the vocal cords do not move normally.

In stage III cancer of the glottis:

  • cancer is in the larynx only and the vocal cords do not move normally, and/or cancer is in tissues next to the larynx; cancer may have spread to one lymph node on the same side of the neck as the original tumor and the lymph node is smaller than 3 centimeters; or
  • cancer is in one or both vocal cords and in one lymph node on the same side of the neck as the original tumor; the lymph node is smaller than 3 centimeters and the vocal cords can move normally; or
  • cancer has spread to the supraglottis and/or the subglottis and/or the vocal cords do not move normally. The cancer has also spread to one lymph node on the same side of the neck as the original tumor and the lymph node is smaller than 3 centimeters.

In stage III cancer of the subglottis:

  • cancer is in the larynx only and the vocal cords do not move normally; cancer may have spread to one lymph node on the same side of the neck as the original tumor and the lymph node is smaller than 3 centimeters; or
  • cancer is in the subglottis only and in one lymph node on the same side of the neck as the original tumor; the lymph node is smaller than 3 centimeters; or
  • cancer has spread to one or both vocal cords, which may not move normally, and to one lymph node on the same side of the neck as the original tumor; the lymph node is smaller than 3 centimeters.

Stage IV

Stage IV is divided into stage IVA, stage IVB, and stage IVC. Each substage is the same for cancer in the supraglottis, glottis, or subglottis.

  • In stage IVA:
    • cancer has spread through the thyroidcartilage and/or has spread to tissues beyond the larynx such as the neck, trachea, thyroid, or esophagus, and may have spread to one lymph node on the same side of the neck as the original tumor; the lymph node is smaller than 3 centimeters; or
    • cancer has spread to one or more lymph nodes anywhere in the neck and the lymph nodes are smaller than 6 centimeters; cancer may have spread to tissues beyond the larynx, such as the neck, trachea, thyroid, or esophagus. Vocal cords may not move normally.
     
  • In stage IVB:
    • cancer has spread to the space in front of the spinal column and surrounds the carotid artery, or has spread to parts of the chest and may have spread to one or more lymph nodes anywhere in the neck (the lymph nodes may be any size); or
    • cancer has spread to a lymph node that is larger than 6 centimeters and may have spread as far as the space in front of the spinal column, around the carotid artery or to parts of the chest. Vocal cords may not move normally.
     
  • In stage IVC, cancer has spread beyond the larynx to other parts of the body.

Recurrent Laryngeal Cancer

Recurrentlaryngeal cancer is cancer that has recurred (come back) after it has been treated. The cancer is most likely to come back in the first 2 to 3 years. It may come back in the larynx or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with laryngeal cancer.

Different types of treatment are available for patients with laryngeal cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Three types of standard treatment are used:

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Radiation therapy may work better in patients who have stopped smoking before beginning treatment. External radiation therapy to the thyroid or the pituitary gland may change the way the thyroid gland works. The doctor may test the thyroid gland before and after therapy to make sure it is working properly.

Surgery

Surgery (removing the cancer in an operation) is a common treatment for all stages of laryngeal cancer. The following surgical procedures may be used:

  • Cordectomy: Surgery to remove the vocal cords only.
  • Supraglottic laryngectomy: Surgery to remove the supraglottis only.
  • Hemilaryngectomy: Surgery to remove half of the larynx (voice box). A hemilaryngectomy saves the voice.
  • Partial laryngectomy: Surgery to remove part of the larynx (voice box). A partial laryngectomy helps keep the patient's ability to talk.
  • Total laryngectomy: Surgery to remove the whole larynx. During this operation, a hole is made in the front of the neck to allow the patient to breathe. This is called a tracheostomy.
  • Thyroidectomy: The removal of all or part of the thyroid gland.
  • Laser surgery: A surgical procedure that uses a laser beam (a narrow beam of intense light) as a knife to make bloodless cuts in tissue or to remove a surface lesion such as a tumor.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may be given chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the spinal column, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Chemoprevention

Chemoprevention is the use of drugs, vitamins, or other substances to reduce the risk of developing cancer or to reduce the risk cancer will recur (come back). The drug isotretinoin is being studied to prevent the development of a second cancer in patients who have had cancer of the head or neck.

Radiosensitizers

Radiosensitizers are drugs that make tumor cells more sensitive to radiation therapy. Combining radiation therapy with radiosensitizers may kill more tumor cells.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's clinical trials database.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

A link to a list of current clinical trials is included for each treatment section. For some types or stages of cancer, there may not be any trials listed. Check with your doctor for clinical trials that are not listed here but may be right for you.

Stage I Laryngeal Cancer

Treatment of stage I laryngeal cancer depends on where cancer is found in the larynx.

If cancer is in the supraglottis, treatment may include the following:

  • Radiation therapy.
  • Supraglottic laryngectomy.

If cancer is in the glottis, treatment may include the following:

  • Radiation therapy.
  • Cordectomy.
  • Partial laryngectomy, hemilaryngectomy, or total laryngectomy.
  • Laser surgery.

If cancer is in the subglottis, treatment may include the following:

  • Radiation therapy with or without surgery.
  • Surgery alone.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I laryngeal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage II Laryngeal Cancer

Treatment of stage II laryngeal cancer depends on where cancer is found in the larynx.

If cancer is in the supraglottis, treatment may include the following:

  • Radiation therapy.
  • Supraglottic laryngectomy or total laryngectomy with or without radiation therapy.
  • A clinical trial of radiation therapy.
  • A clinical trial of chemoprevention.

If cancer is in the glottis, treatment may include the following:

  • Radiation therapy.
  • Partial laryngectomy, hemilaryngectomy, or total laryngectomy.
  • Laser surgery.
  • A clinical trial of radiation therapy.
  • A clinical trial of chemoprevention.

If cancer is in the subglottis, treatment may include the following:

  • Radiation therapy with or without surgery.
  • Surgery alone.
  • A clinical trial of radiation therapy.
  • A clinical trial of chemoprevention.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II laryngeal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage III Laryngeal Cancer

Treatment of stage III laryngeal cancer depends on where cancer is found in the larynx.

If cancer is in the supraglottis or glottis, treatment may include the following:

  • Surgery with or without radiation therapy.
  • Radiation therapy with or without surgery.
  • A clinical trial of radiation therapy.
  • A clinical trial of chemotherapy combined with radiation therapy, with or without laryngectomy.
  • A clinical trial of radiosensitizers.
  • A clinical trial of chemoprevention.

If cancer is in the subglottis, treatment may include the following:

  • Laryngectomy plus total thyroidectomy and removal of lymph nodes in the throat, usually followed by radiation therapy.
  • Radiation therapy with or without surgery.
  • A clinical trial of radiation therapy.
  • A clinical trial of chemotherapy.
  • A clinical trial of radiosensitizers.
  • A clinical trial of chemoprevention.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III laryngeal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Stage IV Laryngeal Cancer

Treatment of stage IV laryngeal cancer depends on where cancer is found in the larynx.

If cancer is in the supraglottis or glottis, treatment may include the following:

  • Total laryngectomy with radiation therapy.
  • Radiation therapy with or without surgery.
  • A clinical trial of radiation therapy.
  • A clinical trial of chemotherapy combined with radiation therapy, with or without laryngectomy.
  • A clinical trial of chemotherapy.
  • A clinical trial of radiosensitizers.
  • A clinical trial of chemoprevention.

If cancer is in the subglottis, treatment may include the following:

  • Laryngectomy plus total thyroidectomy and removal of lymph nodes in the throat, usually with radiation therapy.
  • Radiation therapy.
  • A clinical trial of radiation therapy.
  • A clinical trial of chemotherapy combined with radiation therapy.
  • A clinical trial of chemotherapy.
  • A clinical trial of radiosensitizers.
  • A clinical trial of chemoprevention.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV laryngeal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Laryngeal Cancer

Treatment of recurrentlaryngeal cancer may include the following:

  • Surgery with or without radiation therapy.
  • Radiation therapy.
  • Chemotherapy.
  • A clinical trial of chemotherapy as palliative therapy to relieve symptoms caused by the cancer and improve quality of life.

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent laryngeal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. General information about clinical trials is available from the NCI Web site.

To Learn More About Laryngeal Cancer

For more information from the National Cancer Institute about laryngeal cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on August 19, 2009.


Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of laryngeal cancer. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.

Information about the following is included in this summary:

  • Prognostic factors.
  • Cellular classification.
  • Staging.
  • Treatment options by cancer stage and type.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

General Information

Note: Estimated new cases and deaths from laryngeal cancer in the United States in 2009:[1]

  • New cases: 12,290.
  • Deaths: 3,660.

The larynx is divided into three anatomical regions. The supraglottic larynx includes the epiglottis, false vocal cords, ventricles, aryepiglottic folds, and arytenoids. The glottis includes the true vocal cords and the anterior and posterior commissures. The subglottic region begins about 1 cm below the true vocal cords and extends to the lower border of the cricoid cartilage or the first tracheal ring.

The supraglottic area is rich in lymphatic drainage. After penetrating the pre-epiglottic space and thyrohyoid membrane, lymphatic drainage is initially to the jugulodigastric and midjugular nodes. About 25% to 50% of patients present with involved lymph nodes. The precise figure depends on the T stage. The true vocal cords are devoid of lymphatics. As a result, vocal cord cancer confined to the true cords rarely, if ever, presents with involved lymph nodes. Extension above or below the cords may, however, lead to lymph node involvement. Primary subglottic cancers, which are quite rare, drain through the cricothyroid and cricotracheal membranes to the pretracheal, paratracheal, and inferior jugular nodes, and occasionally to mediastinal nodes.[2]

A clear association has been made between smoking, excess alcohol ingestion, and the development of squamous cell cancers of the upper aerodigestive tract.[3] For smokers, the risk of the development of laryngeal cancer decreases after the cessation of smoking but remains elevated even years later when compared to that of nonsmokers.[4] If a patient who has had a single cancer continues to smoke and drink alcoholic beverages, the likelihood of a cure for the initial cancer, by any modality, is diminished, and the risk of second tumor is enhanced. (Refer to the PDQ summary on Smoking Cessation and Continued Risk in Cancer Patients for more information.) Second primary tumors, often in the aerodigestive tract, have been reported in as many as 25% of patients whose initial lesion is controlled. A study has shown that daily treatment of these patients with moderate doses of isotretinoin (i.e., 13-cis-retinoic acid) for 1 year can significantly reduce the incidence of second tumors.[5] No survival advantage has yet been demonstrated, however, in part because of recurrence and death from the primary malignancy.

Supraglottic cancers typically present with sore throat, painful swallowing, referred ear pain, change in voice quality, or enlarged neck nodes. Early vocal cord cancers are usually detected because of hoarseness. By the time they are detected, cancers arising in the subglottic area commonly involve the vocal cords; thus, symptoms usually relate to contiguous spread.

The most important adverse prognostic factors for laryngeal cancers include increasing T stage and N stage. Other prognostic factors may include sex, age, performance status, and a variety of pathologic features of the tumor, including grade and depth of invasion.[6]

Prognosis for small laryngeal cancers that have not spread to lymph nodes is very good, with cure rates of 75% to 95% depending on the site, tumor bulk,[7] and degree of infiltration. Although most early lesions can be cured by either radiation therapy or surgery, radiation therapy may be reasonable to preserve the voice, leaving surgery for salvage. Patients with a preradiation hemoglobin level higher than 13 g/dL have higher local control and survival rates than patients who are anemic.[8] This observation is being evaluated in a randomized clinical trial.

Locally advanced lesions, especially those with large clinically involved lymph nodes, are poorly controlled with surgery, radiation therapy, or combined modality treatment. Distant metastases are also common, even if the primary tumor is controlled.

Intermediate lesions have intermediate prognoses, depending on site, T stage, N stage, and performance status. Therapy recommendations for patients with these lesions are based on a variety of complex anatomic, clinical, and social factors, which should be individualized and discussed in multidisciplinary consultation (surgery, radiation therapy, and dental and oral surgery) prior to prescribing therapy.

Patients treated for laryngeal cancers are at the highest risk of recurrence in the first 2 to 3 years. Recurrences after 5 years are rare and usually represent new primary malignancies. Close, regular follow-up is crucial to maximize the chance for salvage. Careful clinical examination and repetition of any abnormal staging study are included in follow-up, along with attention to any treatment-related toxic effect or complication.

References:

  1. American Cancer Society.: Cancer Facts and Figures 2009. Atlanta, Ga: American Cancer Society, 2009. Also available online. Last accessed January 6, 2010.

  2. Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis. Int J Radiat Oncol Biol Phys 13 (7): 963-8, 1987.  

  3. Spitz MR: Epidemiology and risk factors for head and neck cancer. Semin Oncol 21 (3): 281-8, 1994.  

  4. Bosetti C, Garavello W, Gallus S, et al.: Effects of smoking cessation on the risk of laryngeal cancer: an overview of published studies. Oral Oncol 42 (9): 866-72, 2006.  

  5. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.  

  6. Yilmaz T, Hoşal S, Gedikoglu G, et al.: Prognostic significance of depth of invasion in cancer of the larynx. Laryngoscope 108 (5): 764-8, 1998.  

  7. Reddy SP, Mohideen N, Marra S, et al.: Effect of tumor bulk on local control and survival of patients with T1 glottic cancer. Radiother Oncol 47 (2): 161-6, 1998.  

  8. Fein DA, Lee WR, Hanlon AL, et al.: Pretreatment hemoglobin level influences local control and survival of T1-T2 squamous cell carcinomas of the glottic larynx. J Clin Oncol 13 (8): 2077-83, 1995.  

Cellular Classification

The vast majority of laryngeal cancers are of squamous cell histology. Squamous cell subtypes include keratinizing and nonkeratinizing and well-differentiated to poorly differentiated grade. A variety of nonsquamous cell laryngeal cancers also occur.[1] These are not staged using the American Joint Cancer Committee staging system, and their management, which is not discussed here, can differ from that of squamous cell laryngeal cancers. In situ squamous cell carcinoma of the larynx is usually managed by a conservative surgical procedure such as mucosal stripping or superficial laser excision. Radiation therapy may also be appropriate treatment of selected patients with in situ carcinoma of the glottic larynx.[2]

References:

  1. Mendenhall WM, Riggs CE Jr, Cassisi NJ: Treatment of head and neck cancers. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 662-732.  

  2. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.  

Stage Information

The staging system is clinical and based on the best possible estimate of the extent of disease before treatment. The assessment of the primary tumor is based on inspection and palpation when possible and by both indirect mirror examination and direct endoscopy when necessary. The tumor must be confirmed histologically, and any other pathological data obtained on biopsy may be included. Head and neck magnetic resonance imaging or computed tomography should be done prior to therapy to supplement inspection and palpation.[1] Additional radiographic studies may be included. The appropriate nodal drainage areas in the neck are examined by careful palpation.

The American Joint Committee on Cancer (AJCC) has designated staging by TNM classification.[2]

TNM Definitions

Primary tumor (T)

  • TX: Primary tumor cannot be assessed
  • T0: No evidence of primary tumor
  • Tis: Carcinoma in situ 

Supraglottis

  • T1: Tumor limited to one subsite* of supraglottis with normal vocal cord mobility
  • T2: Tumor invades mucosa of more than one adjacent subsite* of supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, or medial wall of pyriform sinus) without fixation of the larynx
  • T3: Tumor limited to larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre-epiglottic tissues, paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex)
  • T4a: Tumor invades through the thyroid cartilage, and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of the neck including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
  • T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

    Subsites include the following:

    • Ventricular bands (false cords)
    • Arytenoids
    • Suprahyoid epiglottis
    • Infrahyoid epiglottis
    • Aryepiglottic folds (laryngeal aspect)
     

Supraglottis involves many individual subsites. Relapse-free survival may differ by subsite and by T and N groupings within stage.

Glottis

  • T1: Tumor limited to the vocal cord(s), which may involve anterior or posterior commissure, with normal mobility
    • T1a: Tumor limited to one vocal cord
    • T1b: Tumor involves both vocal cords
     
  • T2: Tumor extends to supraglottis and/or subglottis and/or with impaired vocal cord mobility
  • T3: Tumor limited to the larynx with vocal cord fixation and/or invades paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex)
  • T4a: Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck, including deep extrinsic muscle of the tongue, strap muscles, thyroid, or esophagus)
  • T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Glottic presentation may vary by volume of tumor, anatomic region involved, and the presence or absence of normal cord mobility. Relapse-free survival may differ by these and other factors in addition to T and N subgroupings within the stage.

Subglottis

  • T1: Tumor limited to the subglottis
  • T2: Tumor extends to vocal cord(s) with normal or impaired mobility
  • T3: Tumor limited to larynx with vocal cord fixation
  • T4a: Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck, including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus)
  • T4b: Tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures

Regional lymph nodes (N)

  • NX: Regional lymph nodes cannot be assessed
  • N0: No regional lymph node metastasis
  • N1: Metastasis in a single ipsilateral lymph node 3 cm or smaller in greatest dimension
  • N2: Metastasis in a single ipsilateral lymph node larger than 3 cm but 6 cm or smaller in greatest dimension, or in multiple ipsilateral lymph nodes 6 cm or smaller in greatest dimension, or in bilateral or contralateral lymph nodes 6 cm or smaller in greatest dimension
    • N2a: Metastasis in a single ipsilateral lymph node larger than 3 cm but 6 cm or smaller in greatest dimension
    • N2b: Metastasis in multiple ipsilateral lymph nodes 6 cm or smaller in greatest dimension
    • N2c: Metastasis in bilateral or contralateral lymph nodes 6 cm or smaller in greatest dimension
     
  • N3: Metastasis in a lymph node larger than 6 cm in greatest dimension

In clinical evaluation, the actual size of the nodal mass should be measured, and allowance should be made for intervening soft tissues. Most masses larger than 3 cm in diameter are not single nodes but confluent nodes or tumors in soft tissues of the neck. There are three stages of clinically positive nodes: N1, N2, and N3. The use of subgroups a, b, and c is not required but recommended. Midline nodes are considered homolateral nodes.

Distant metastasis (M)

  • MX: Distant metastasis cannot be assessed
  • M0: No distant metastasis
  • M1: Distant metastasis

AJCC Stage Groupings

Stage 0

  • Tis, N0, M0

Stage I

  • T1, N0, M0

Stage II

  • T2, N0, M0

Stage III

  • T3, N0, M0
  • T1, N1, M0
  • T2, N1, M0
  • T3, N1, M0

Stage IVA

  • T4a, N0, M0
  • T4a, N1, M0
  • T1, N2, M0
  • T2, N2, M0
  • T3, N2, M0
  • T4a, N2, M0

Stage IVB

  • T4b, any N, M0
  • Any T, N3, M0

Stage IVC

  • Any T, any N, M1

Evaluation of treatment outcome can be reported in various ways: locoregional control, disease-free survival, determinate survival, and overall survival at 2 to 5 years. Preservation of voice is an important parameter to evaluate. Outcome should be reported after initial surgery, initial radiation, planned combined treatment, or surgical salvage of radiation failures. Primary source material should be consulted to review these differences.

Because of clinical problems related to smoking and alcohol use in this population, many patients succumb to intercurrent illness rather than to the primary cancer.

Direct comparison of results of radiation versus surgery is complicated. Surgical studies can report outcome based on pathologic staging, whereas radiation studies must report on clinical staging, with the obvious problem of understaging in patients treated with radiation, particularly in the neck. In addition, radiation alone is often recommended for patients with poor performance status, which leads to less favorable results.

References:

  1. Thabet HM, Sessions DG, Gado MH, et al.: Comparison of clinical evaluation and computed tomographic diagnostic accuracy for tumors of the larynx and hypopharynx. Laryngoscope 106 (5 Pt 1): 589-94, 1996.  

  2. Larynx. In: American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002, pp 47-57.  

Treatment Option Overview

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

Small superficial cancers without laryngeal fixation or lymph node involvement are successfully treated by radiation therapy or surgery alone, including laser excision surgery. Radiation therapy may be selected to preserve the voice and to reserve surgery for salvaging failures. The radiation field and dose are determined by the location and size of the primary tumor. A variety of curative surgical procedures are also recommended for laryngeal cancers, some of which preserve vocal function. An appropriate surgical procedure must be considered for each patient, given the anatomic problem, performance status, and clinical expertise of the treatment team. Advanced laryngeal cancers are often treated by combining radiation and surgery.[1][2][3][4] A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible.[5][6] Because the cure rate for advanced lesions is low, clinical trials exploring chemotherapy, hyperfractionated radiation therapy,[7] radiation sensitizers, or particle-beam radiation therapy should be considered.[8][9] Although cure rates are not changed with chemoradiation administered in a neoadjuvant setting, organ preservation is increased.[10]

A multi-institutional trial randomized patients to induction cisplatin plus fluorouracil (5-FU) followed by radiation therapy, radiation therapy administered concurrently with cisplatin, or radiation therapy alone.[10] Concurrent radiation therapy plus cisplatin resulted in a statistically significantly higher percentage of patients with an intact larynx at 2 years (i.e., 88% vs. 75% and 70% for concurrent chemotherapy, induction chemotherapy, and radiation alone, respectively) and higher locoregional control (i.e., 78% vs. 61% and 56%, respectively) than the other two regimens. Both chemotherapy regimens had a lower incidence of distant metastases and better relapse-free survivals than radiation therapy alone, but they also had a higher rate of high-grade toxic effects. Overall survival rates were not significantly different between the different groups.[10][Level of evidence: 1iiC]

The risk of lymph node metastases in patients with stage I glottic cancer ranges from 0% to 2%, and for more advanced disease, such as stage II and stage III glottic, the incidence is only 10% and 15%, respectively. Thus, there is no need to treat glottic cancer cervical lymph nodes electively in patients with stage I tumors and small stage II tumors. Consideration should be given to using elective neck radiation for larger or supraglottic tumors.[11]

For patients with cancer of the subglottis, combined modality therapy is generally preferred though for the uncommon small lesions (i.e., stage I or stage II), radiation therapy alone may be used.

Patients who smoke during radiation therapy appear to have lower response rates and shorter survival durations than those who do not;[12] therefore, patients should be counseled to stop smoking before beginning radiation therapy.

Accumulating evidence has demonstrated a high incidence (i.e., >30%–40%) of hypothyroidism in patients who have received external-beam radiation to the entire thyroid gland or to the pituitary gland. Thyroid-junction testing of patients should be considered prior to therapy and as part of posttreatment follow-up.[13][14]

References:

  1. Silver CE, Ferlito A: Surgery for Cancer of the Larynx and Related Structures. 2nd ed. Philadelphia, Pa: Saunders, 1996.  

  2. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.  

  3. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. Philadelphia, Pa: WB Saunders, 1999.  

  4. Mendenhall WM, Riggs CE Jr, Cassisi NJ: Treatment of head and neck cancers. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 662-732.  

  5. Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992.  

  6. Hansen O, Overgaard J, Hansen HS, et al.: Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation. Radiother Oncol 43 (1): 47-51, 1997.  

  7. Bourhis J, Wibault P, Lusinchi A, et al.: Status of accelerated fractionation radiotherapy in head and neck squamous cell carcinomas. Curr Opin Oncol 9 (3): 262-6, 1997.  

  8. Taylor SG 4th: Integration of chemotherapy into the combined modality therapy of head and neck squamous cancer. Int J Radiat Oncol Biol Phys 13 (5): 779-83, 1987.  

  9. Stupp R, Weichselbaum RR, Vokes EE: Combined modality therapy of head and neck cancer. Semin Oncol 21 (3): 349-58, 1994.  

  10. Forastiere AA, Goepfert H, Maor M, et al.: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349 (22): 2091-8, 2003.  

  11. Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis. Int J Radiat Oncol Biol Phys 13 (7): 963-8, 1987.  

  12. Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993.  

  13. Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995.  

  14. Constine LS: What else don't we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995.  

Stage I Laryngeal Cancer

Supraglottis

Standard treatment options:  

  1. External-beam radiation therapy alone.
  2. Supraglottic laryngectomy. Total laryngectomy may be reserved for patients unable to tolerate potential respiratory complications of surgery or the supraglottic laryngectomy. Radiation, however, should be preferred because of the good results, preservation of the voice, and the possibility of surgical salvage in patients whose disease recurs locally.[1]

Glottis

Standard treatment options:  

  1. Radiation therapy.[2][3][4][5]
  2. Cordectomy for very carefully selected patients with limited and superficial T1 lesions.[6][7]
  3. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic considerations.
  4. Laser excision.[6]

Subglottis

Standard treatment options:  

  • Lesions can be treated successfully by radiation therapy alone with preservation of normal voice. Surgery is reserved for failure of radiation therapy or for patients who cannot be easily assessed for radiation therapy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage I laryngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid carcinoma of the supraglottic larynx. Laryngoscope 85 (11 pt 1): 1808-15, 1975.  

  2. Mittal B, Rao DV, Marks JE, et al.: Role of radiation in the management of early vocal cord carcinoma. Int J Radiat Oncol Biol Phys 9 (7): 997-1002, 1983.  

  3. Wang CC: Factors influencing the success of radiation therapy for T2 and T3 glottic carcinomas. Importance of cord mobility and sex. Am J Clin Oncol 9 (6): 517-20, 1986.  

  4. Mendenhall WM, Amdur RJ, Morris CG, et al.: T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy. J Clin Oncol 19 (20): 4029-36, 2001.  

  5. Foote RL, Olsen KD, Kunselman SJ, et al.: Early-stage squamous cell carcinoma of the glottic larynx managed with radiation therapy. Mayo Clin Proc 67 (7): 629-36, 1992.  

  6. Steiner W: Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14 (2): 116-21, 1993 Mar-Apr.  

  7. Olsen KD, Thomas JV, DeSanto LW, et al.: Indications and results of cordectomy for early glottic carcinoma. Otolaryngol Head Neck Surg 108 (3): 277-82, 1993.  

Stage II Laryngeal Cancer

Supraglottis

Standard treatment options:  

  1. External-beam radiation therapy alone for the smaller lesions.[1][2]
  2. Supraglottic laryngectomy or total laryngectomy, depending on location of the lesion, clinical status of the patient, and expertise of the treatment team. Careful selection must be made to ensure adequate pulmonary and swallowing function postoperatively. Radiation should be preferred because of the good results, preservation of the voice, and the possibility of surgical salvage in patients whose disease recurs locally.[3]
  3. Postoperative radiation therapy is indicated for positive or close surgical margins.

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2][4]
  2. Isotretinoin (i.e., 13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[5]

Glottis

Standard treatment options:  

  1. Radiation therapy.[1][2][6][7][8]
  2. Partial or hemilaryngectomy or total laryngectomy, depending on anatomic considerations. Under certain circumstances, laser microsurgery may be appropriate.[9]

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2][4]
  2. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[5]

Subglottis

Standard treatment options:  

  • Lesions can be treated successfully by radiation therapy alone with preservation of normal voice.[1][2] Surgery is reserved for failure of radiation therapy or for patients in whom follow-up is likely to be difficult.

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2][4]
  2. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[5]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage II laryngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Mendenhall WM, Riggs CE Jr, Cassisi NJ: Treatment of head and neck cancers. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 662-732.  

  2. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.  

  3. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid carcinoma of the supraglottic larynx. Laryngoscope 85 (11 pt 1): 1808-15, 1975.  

  4. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for head and neck cancer. Int J Radiat Oncol Biol Phys 14 (4): 649-58, 1988.  

  5. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.  

  6. Mittal B, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53 (1): 151-61, 1984.  

  7. Medini E, Medini I, Lee CK, et al.: Curative radiotherapy for stage II-III squamous cell carcinoma of the glottic larynx. Am J Clin Oncol 21 (3): 302-5, 1998.  

  8. Mendenhall WM, Amdur RJ, Morris CG, et al.: T1-T2N0 squamous cell carcinoma of the glottic larynx treated with radiation therapy. J Clin Oncol 19 (20): 4029-36, 2001.  

  9. Steiner W: Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 14 (2): 116-21, 1993 Mar-Apr.  

Stage III Laryngeal Cancer

Supraglottis

Standard treatment options:  

  1. Surgery with or without postoperative radiation therapy, as evidenced in RTOG-7303, for example.[1][2][3][4][5][6]
  2. Definitive radiation therapy with surgery for salvage of radiation failures.[7]
  3. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease. Laryngectomy would be reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[8][9][10][11][12][13]

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[14][15]
  2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[16][17][18][19][20]

    A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil (5-FU), followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

  3. Isotretinoin (i.e., 13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Glottis

Standard treatment options:  

  1. Surgery with or without postoperative radiation therapy, as evidenced in RTOG-7303, for example.[1][2][3][4][5][6][23]
  2. Definitive radiation therapy with surgery for salvage of radiation failures.[7][24]
  3. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease. Laryngectomy would be reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[8][9][10][11][12][13]

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[14][15]
  2. Clinical trials exploring chemotherapy, radiosensitizers, or particle beam radiation therapy.[16][17][19][20]

    A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

  3. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Subglottis

Standard treatment options:  

  1. Laryngectomy plus isolated thyroidectomy and tracheoesophageal node dissection usually followed by postoperative radiation therapy.[1][2][3]
  2. Treatment by radiation therapy alone is indicated for patients who are not candidates for surgery. Patients should be closely followed, and surgical salvage should be planned for recurrences that are local or in the neck.

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[14][15]
  2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[16][17][19][20]

    A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

  3. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage III laryngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. Philadelphia, Pa: WB Saunders, 1999.  

  2. Mendenhall WM, Riggs CE Jr, Cassisi NJ: Treatment of head and neck cancers. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 662-732.  

  3. Arriagada R, Eschwege F, Cachin Y, et al.: The value of combining radiotherapy with surgery in the treatment of hypopharyngeal and laryngeal cancers. Cancer 51 (10): 1819-25, 1983.  

  4. Spaulding CA, Krochak RJ, Hahn SS, et al.: Radiotherapeutic management of cancer of the supraglottis. Cancer 57 (7): 1292-8, 1986.  

  5. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid carcinoma of the supraglottic larynx. Laryngoscope 85 (11 pt 1): 1808-15, 1975.  

  6. Tupchong L, Scott CB, Blitzer PH, et al.: Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. Int J Radiat Oncol Biol Phys 20 (1): 21-8, 1991.  

  7. MacKenzie RG, Franssen E, Balogh JM, et al.: Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: a comparison limited to patients eligible for surgery. Int J Radiat Oncol Biol Phys 47 (1): 65-71, 2000.  

  8. Spaulding MB, Fischer SG, Wolf GT: Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. J Clin Oncol 12 (8): 1592-9, 1994.  

  9. Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.  

  10. Adelstein DJ, Saxton JP, Lavertu P, et al.: A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck 19 (7): 567-75, 1997.  

  11. Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000.  

  12. Forastiere AA, Goepfert H, Maor M, et al.: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349 (22): 2091-8, 2003.  

  13. Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004.  

  14. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.  

  15. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for head and neck cancer. Int J Radiat Oncol Biol Phys 14 (4): 649-58, 1988.  

  16. Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 20 (2): 243-6, 1991.  

  17. Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer 67 (4): 915-21, 1991.  

  18. Wang CC, Suit HD, Blitzer PH: Twice-a-day radiation therapy for supraglottic carcinoma. Int J Radiat Oncol Biol Phys 12 (1): 3-7, 1986.  

  19. Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol 12 (12): 2648-53, 1994.  

  20. Adelstein DJ, Lavertu P, Saxton JP, et al.: Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 88 (4): 876-83, 2000.  

  21. Pignon JP, Bourhis J, Domenge C, et al.: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355 (9208): 949-55, 2000.  

  22. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.  

  23. Mittal B, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53 (1): 151-61, 1984.  

  24. Medini E, Medini I, Lee CK, et al.: Curative radiotherapy for stage II-III squamous cell carcinoma of the glottic larynx. Am J Clin Oncol 21 (3): 302-5, 1998.  

Stage IV Laryngeal Cancer

Supraglottis

Standard treatment options:  

  1. Total laryngectomy with postoperative radiation therapy, as evidenced in RTOG-7303, for example.[1][2][3][4][5][6][7]
  2. Definitive radiation therapy with surgery for salvage of radiation failures.[8]
  3. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease. Laryngectomy would be reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[9][10][11][12][13][14]

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2][15]
  2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[16][17][18][19][20]

    A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

  3. Isotretinoin (i.e., 13-cis-retinoic acid) daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Glottis

Standard treatment options:  

  1. Total laryngectomy with postoperative radiation therapy.[1][2][3][4][23]
  2. Definitive radiation therapy with surgery for salvage of radiation failures.[8]
  3. Chemotherapy administered concomitantly with radiation therapy can be considered for patients who would require total laryngectomy for control of disease. Laryngectomy would be reserved for patients with less than a 50% response to chemotherapy or who have persistent disease following radiation.[9][10][11][12][13][14]

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2][15]
  2. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[16][17][19][20]

    A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

  3. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Subglottis

Standard treatment options:  

  1. Laryngectomy plus total thyroidectomy and bilateral tracheoesophageal node dissection usually followed by postoperative radiation therapy.[1][2][3][4]
  2. Treatment by radiation therapy alone is indicated for patients who are not candidates for surgery.

Treatment options under clinical evaluation:  

  1. Hyperfractionated radiation therapy to improve tumor control rates and diminish late toxicity to normal tissue.[2][15]
  2. Simultaneous chemotherapy and hyperfractionated radiation therapy.[24]
  3. Clinical trials exploring chemotherapy, radiosensitizers, or particle-beam radiation therapy.[16][17][19][20]

    A meta-analysis of three trials of patients with locally advanced laryngeal carcinomas compared patients who received standard radical surgery plus radiation therapy with patients who received neoadjuvant cisplatin and fluorouracil, followed by radiation therapy alone in responders or radical surgery plus radiation therapy in nonresponders.[21] The meta-analysis demonstrated a nonsignificant trend in favor of the control group who received standard radical surgery plus radiation therapy with an absolute negative effect in the chemotherapy arm that reduced survival at 5 years by 6%. The possibility of a slightly decreased survival must be balanced by the retention of the larynx in those patients whose disease was controlled.

  4. Isotretinoin daily for 1 year to prevent development of second upper aerodigestive tract primary tumors.[22]

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with stage IV laryngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Mendenhall WM, Riggs CE Jr, Cassisi NJ: Treatment of head and neck cancers. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 662-732.  

  2. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.  

  3. Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. Philadelphia, Pa: WB Saunders, 1999.  

  4. Arriagada R, Eschwege F, Cachin Y, et al.: The value of combining radiotherapy with surgery in the treatment of hypopharyngeal and laryngeal cancers. Cancer 51 (10): 1819-25, 1983.  

  5. Spaulding CA, Krochak RJ, Hahn SS, et al.: Radiotherapeutic management of cancer of the supraglottis. Cancer 57 (7): 1292-8, 1986.  

  6. Ogura JH, Sessions DG, Spector GJ: Conservation surgery for epidermoid carcinoma of the supraglottic larynx. Laryngoscope 85 (11 pt 1): 1808-15, 1975.  

  7. Tupchong L, Scott CB, Blitzer PH, et al.: Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03. Int J Radiat Oncol Biol Phys 20 (1): 21-8, 1991.  

  8. MacKenzie RG, Franssen E, Balogh JM, et al.: Comparing treatment outcomes of radiotherapy and surgery in locally advanced carcinoma of the larynx: a comparison limited to patients eligible for surgery. Int J Radiat Oncol Biol Phys 47 (1): 65-71, 2000.  

  9. Spaulding MB, Fischer SG, Wolf GT: Tumor response, toxicity, and survival after neoadjuvant organ-preserving chemotherapy for advanced laryngeal carcinoma. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. J Clin Oncol 12 (8): 1592-9, 1994.  

  10. Merlano M, Benasso M, Corvò R, et al.: Five-year update of a randomized trial of alternating radiotherapy and chemotherapy compared with radiotherapy alone in treatment of unresectable squamous cell carcinoma of the head and neck. J Natl Cancer Inst 88 (9): 583-9, 1996.  

  11. Adelstein DJ, Saxton JP, Lavertu P, et al.: A phase III randomized trial comparing concurrent chemotherapy and radiotherapy with radiotherapy alone in resectable stage III and IV squamous cell head and neck cancer: preliminary results. Head Neck 19 (7): 567-75, 1997.  

  12. Jeremic B, Shibamoto Y, Milicic B, et al.: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. J Clin Oncol 18 (7): 1458-64, 2000.  

  13. Forastiere AA, Goepfert H, Maor M, et al.: Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 349 (22): 2091-8, 2003.  

  14. Bernier J, Domenge C, Ozsahin M, et al.: Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350 (19): 1945-52, 2004.  

  15. Parsons JT, Mendenhall WM, Cassisi NJ, et al.: Hyperfractionation for head and neck cancer. Int J Radiat Oncol Biol Phys 14 (4): 649-58, 1988.  

  16. Bachaud JM, David JM, Boussin G, et al.: Combined postoperative radiotherapy and weekly cisplatin infusion for locally advanced squamous cell carcinoma of the head and neck: preliminary report of a randomized trial. Int J Radiat Oncol Biol Phys 20 (2): 243-6, 1991.  

  17. Merlano M, Corvo R, Margarino G, et al.: Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck. The final report of a randomized trial. Cancer 67 (4): 915-21, 1991.  

  18. Wang CC, Suit HD, Blitzer PH: Twice-a-day radiation therapy for supraglottic carcinoma. Int J Radiat Oncol Biol Phys 12 (1): 3-7, 1986.  

  19. Browman GP, Cripps C, Hodson DI, et al.: Placebo-controlled randomized trial of infusional fluorouracil during standard radiotherapy in locally advanced head and neck cancer. J Clin Oncol 12 (12): 2648-53, 1994.  

  20. Adelstein DJ, Lavertu P, Saxton JP, et al.: Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck. Cancer 88 (4): 876-83, 2000.  

  21. Pignon JP, Bourhis J, Domenge C, et al.: Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data. MACH-NC Collaborative Group. Meta-Analysis of Chemotherapy on Head and Neck Cancer. Lancet 355 (9208): 949-55, 2000.  

  22. Hong WK, Lippman SM, Itri LM, et al.: Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 323 (12): 795-801, 1990.  

  23. Mittal B, Marks JE, Ogura JH: Transglottic carcinoma. Cancer 53 (1): 151-61, 1984.  

  24. Weissler MC, Melin S, Sailer SL, et al.: Simultaneous chemoradiation in the treatment of advanced head and neck cancer. Arch Otolaryngol Head Neck Surg 118 (8): 806-10, 1992.  

Recurrent Laryngeal Cancer

Treatment of recurrent supraglottic, glottic, and subglottic cancer includes further surgery or clinical trials.[1][2][3][4]

Standard treatment options:  

  • Salvage is possible for failures of surgery alone or of radiation therapy alone and further surgery [5] and/or radiation therapy should be attempted, as indicated. Selected patients may be candidates for partial laryngectomy after high-dose radiation therapy has failed.[6] Re-irradiation for laryngeal salvage following radiation therapy failure has resulted in long-term survival in a small number of patients; it may be considered for small recurrences after radiation therapy, especially in patients who refuse or are not candidates for laryngectomy.[7] A response of variable duration may be achieved after systemic chemotherapy.[8]

    Salvage after previous combined total laryngectomy and radiation therapy is poor.

Treatment options under clinical evaluation:  

  • Patients whose disease does not respond to combined radiation therapy and surgery probably are best treated by palliative chemotherapy in clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent laryngeal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Million RR, Cassisi NJ, eds.: Management of Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott, 1994.  

  2. Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.  

  3. Vikram B, Strong EW, Shah JP, et al.: Intraoperative radiotherapy in patients with recurrent head and neck cancer. Am J Surg 150 (4): 485-7, 1985.  

  4. Jacobs C, Lyman G, Velez-García E, et al.: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol 10 (2): 257-63, 1992.  

  5. Wong LY, Wei WI, Lam LK, et al.: Salvage of recurrent head and neck squamous cell carcinoma after primary curative surgery. Head Neck 25 (11): 953-9, 2003.  

  6. Lavey RS, Calcaterra TC: Partial laryngectomy for glottic cancer after high-dose radiotherapy. Am J Surg 162 (4): 341-4, 1991.  

  7. Wang CC, McIntyre J: Re-irradiation of laryngeal carcinoma--techniques and results. Int J Radiat Oncol Biol Phys 26 (5): 783-5, 1993.  

  8. Al-Sarraf M: Head and neck cancer: chemotherapy concepts. Semin Oncol 15 (1): 70-85, 1988.  

More Information

About PDQ  

Additional PDQ Summaries  

Important:  

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).


This information is provided by the National Cancer Institute.

This information was last updated on July 2, 2009.

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