Overview of Larynx Cancer

Symptoms, diagnosis, and treatment of cancer of the larynx.

Larynx Cancer

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor (08/2018)

The larynx is a short passageway shaped like a triangle that is just below the pharynx in the neck. The pharynx is a hollow tube about five inches long that starts behind the nose and goes down to the neck to become part of the esophagus. Food passes through the pharynx on the way to the esophagus. Air passes through the pharynx and then the larynx on the way to the windpipe (trachea) and into the lungs. The larynx has a small piece of tissue over it called the epiglottis to keep food from going into it or the air passages. Cancer of the pharynx is discussed under Throat Cancer.

The larynx contains the vocal cords, which vibrate to make sound when air is directed against them. The sound echoes through the pharynx, mouth and nose to make a persons voice. The muscles in the pharynx, face, tongue and lips help people form words with sounds to make them understandable.

There are three main parts of the larynx: the glottis (the middle part of the larynx where the vocal cords are), the supraglottis (the tissue above the glottis) and the subglottis (the tissue below the glottis). The subglottis connects to the trachea, which takes air to the lungs. Spread of cancer to lymph nodes in the neck has a different pattern for each of these sites.

The majority of laryngeal cancers are related to smoking and/or alcohol abuse. Heavy smoking and a low intake of vegetables and fruits increase the risk of laryngeal cancer 19-fold over that observed in non-smoking individuals who have a good intake of vegetables and fruits.[1] The increase in human life expectancy has led to a higher proportion of elderly patients with laryngeal cancer. Patients over the age of 70 with laryngeal cancer are more often women. Compared to younger patients, laryngeal cancer in elderly patients is associated with less tobacco and alcohol use, a predominance of glottic location and a higher incidence of other diseases. In a significant number of patients, cancer occurs without known risk factors.

Signs & Symptoms of Laryngeal Cancer

Symptoms of laryngeal cancer include a persistent sore throat, pain when swallowing, change in voice, hoarseness in the voice, pain in the ear or a lump in the neck.

Tests Used for Diagnosis of Laryngeal Cancer

The larynx can be observed with a lighted mirror but is usually examined with a laryngoscope, which is a lighted tube. Laryngeal cancer is diagnosed by taking a small piece of tissue (biopsy) from the suspected cancer through a laryngoscope. This tissue is evaluated under the microscope to determine if cancer is present. A laryngoscope is used to visualize the mouth, throat, larynx and upper esophagus. A thorough examination is necessary, even if the primary cancer is obvious, because approximately six percent of cases involve a second primary cancer. The incidence of new cancers in patients with laryngeal cancer is not linked to the site, size, staging or grade of differentiation of the index cancer.

Accurate determination of lymph node involvement is a prerequisite for individualized therapy in patients with cancer of the larynx. Clinical palpation (physician technique of feeling the suspect area by hand) of the neck is not very accurate and the role of imaging techniques such as ultrasound, ultrasound-guided fine needle aspiration, cytology, color Doppler ultrasound, computed tomography, magnetic resonance imaging (MRI) and positron emission tomography (PET) is being evaluated in order to improve upon the results of clinical investigation alone. The accuracy of computed tomography scanning and magnetic resonance imaging appears to be superior to palpation or ultrasound. Ultrasound-guided fine needle aspiration cytology can also improve the accuracy of diagnosis of lymph node spread.

The size and extent of spread of cancer (stage) at the time of diagnosis predicts outcome. Early stage cancers of the larynx may be treated effectively with surgery and/or radiation therapy while more advanced stages with spread to lymph nodes in the neck are often treated together with other head and neck cancers on clinical trials. The goal of therapy is to eradicate the cancer while preserving speech. Surgery and/or radiation therapy is highly effective in the treatment of early Stage I-II laryngeal cancers with minimal to moderate effects on speech. However, 30 to 50 percent or more of patients present with advanced local, regional and/or metastatic disease requiring multi-modality treatment. Despite aggressive therapy, only 30 to 50 percent of patients with advanced laryngeal cancer live three years or more.

It is important for patients to be treated in medical centers that treat many patients with laryngeal cancer. Patients with laryngeal cancer require a careful evaluation and a multidisciplinary team approach, which includes a head and neck surgeon, a radiation oncologist, a medical oncologist, a pathologist, a dentist and social services personnel to determine the optimal management strategy.

Cellular Classification

Most laryngeal cancers begin in cells known as squamous cells and may be preceded by various pre-cancerous changes to the larynx.

The term “leukoplakia” is a descriptive term meaning that an unusual looking white patch of tissue can be observed during an examination and cannot be rubbed off. Cells from this unusual tissue are collected and examined under a microscope to determine their origin. “Leukoplakia” can be caused by a heaped up surface layer of normal cells (hyperkeratosis); an actual early invasive cancer; or may represent only a fungal infection or other benign oral disease.

Dysplasia is a term used to describe changes in the surface layer of the larynx that are not yet cancerous but that may develop into cancer if not treated. Often, severe dysplasia of the larynx is treated in the same way as Stage 0 laryngeal cancer.

Staging

Staging is the process of identifying how extensive the cancer is. Accurately identifying the stage of a cancer helps determine what treatments will be most effective.

Stage 0 or Carcinoma in Situ: The cancer is not invasive and present only in the superficial layer of the epithelium (surface layer) of the mucosa.

Stage I: The cancer is limited to a single area and has not spread to lymph nodes in the area.

Supraglottis: The cancer is only in one area of the supraglottis and the vocal cords are normal.

Glottis: The cancer is in the vocal cords and the vocal cords can move normally.

Subglottis: The cancer has not spread outside the subglottis.

Stage II: The cancer is only in the larynx and has not spread to lymph nodes in the area.

Supraglottis: The cancer is in more than one area of the supraglottis, but the vocal cords can move normally.

Glottis: The cancer has spread to the supraglottis or the subglottis or both and the vocal cords may or may not be able to move normally.

Subglottis: The cancer has spread to the vocal cords, which may or may not be able to move normally.

Stage III cancer is one of the following:

  • the cancer has not spread outside of the larynx, but the vocal cords cannot move normally or
  • the cancer has spread to tissues next to the larynx or
  • the cancer has spread to one lymph node on the same side of the neck as the cancer, and the lymph node measures no more than 3 centimeters (just over an inch).

Stage IV cancer is one of the following:

  • the cancer has spread to tissues around the larynx, such as the pharynx or the tissues in the neck; the lymph nodes may or may not contain cancer or
  • the cancer has spread to more than one lymph node on the same side of the neck as the cancer or
  • the cancer has spread to lymph nodes on one or both sides of the neck or
  • the cancer has spread to any lymph node that measures more than 6 centimeters (over two inches).

Metastatic cancer is cancer that has spread to other parts of the body.

Recurrent cancer is cancer that has failed to respond to initial treatment or has recurred after a remission.

Treatment of Laryngeal Cancer

Early stage cancer of the larynx is treated with surgery or radiation. More advanced stages and recurrent cancers often require a combination of surgery, radiation and systemic treatment with chemotherapy or precision cancer medicines.

Patients with cancer of the larynx should be evaluated in a medical center that treats many patients with these cancers because effective treatment typically require a multidisciplinary team approach comprised of a head and neck surgeon, a radiation oncologist, a medical oncologist, a pathologist, a dentist, and social services personnel. Evaluation and treatment by an experienced team is essential for optimal treatment and support.

Stage 0 Larynx Cancer

There are three main parts of the larynx: the glottis (the middle part of the larynx where the vocal cords are located), the supraglottis (the tissue above the glottis) and the subglottis (the tissue below the glottis). The subglottis connects to the trachea, which takes air to the lungs.

Stage 0 (also called carcinoma in situ) is non-invasive cancer limited to the cells that line the larynx, and has not spread to lymph nodes in the area or to distant sites.

Supraglottis: The cancer is only in one area of the supraglottis and the vocal cords are normal.

Glottis: The cancer is in the vocal cords and the vocal cords can move normally.

Subglottis: The cancer has not spread outside the subglottis.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage 0 cancer of the larynx. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Surgery

Carcinoma in situ (stage 0) and severe dysplasia (precancer) of the glottis may be treated by surgical stripping of the vocal cords or endoscopic laser surgery. There is a trend toward the exclusive use of laser surgery for this stage of larynx cancer as described below.

Laser Surgery: A laser beam can be used instead of a scalpel to remove stage 0 cancers or severe dysplasia of the larynx.A retrospective review of 12 cases of carcinoma in situ of the glottis treated with laser surgery showed a 100 percent preservation rate of the larynx.[1] Initial control rate with laser surgery was 75 percent but with repeat treatment the ultimate control rate was 100 percent. In a study of 19 patients from Italy, the three-year control rate following laser surgery for carcinoma in situ was 100 percent.[2] Based on these and other studies, recommended treatment for cancer in situ is laser removal of the cancer in combination with a meticulous follow-up for early recognition of local recurrence.

Radiation Therapy

Until the advent of laser surgery, radiation therapy was frequently used in the initial treatment of carcinoma in situ of the larynx. A Canadian study reported a five-year control rate of 98 percent in 67 patients with carcinoma in situ treated with radiation therapy.[3] Twenty-one of these patients had failed surgical stripping. Despite the effectiveness of radiotherapy in treating carcinoma in situ, most guidelines suggest that laser surgery be used first.[4]

For more information, go to Radiation Therapy for Head & Neck Cancer.

Strategies to Improve Treatment

The progress that has been made in the treatment of early cancer of the larynx has resulted from early diagnosis, improved surgical and radiation therapy techniques, as well as participation in clinical studies. Future progress in the treatment of early cancer of the throat will result from patients and doctors continuing to participate in appropriate studies. Areas of active exploration to improve the treatment of cancer of the larynx include the following:

Photodynamic Therapy: The concept behind photodynamic therapy is that light from a laser, enhanced by photosensitizing agents (agents that make cells sensitive to light), can kill cancer cells without damage to normal cells. The basic technique is over 50 years old, but the past five years have seen the development of reliable, portable lasers and better photosensitizing agents, making the technique quick, effective and relatively free from side-effects. For some patients with head and neck cancer, functional outcomes with photodynamic therapy may be improved over that observed with surgery and radiation therapy.

In one study, complete responses were observed in eight of 10 patients with superficial laryngeal cancers treated with photodynamic therapy.[5] In another study, phototherapy was used successfully to treat leukoplakia.[6]

Cryosurgery: Cryoablation (freezing) is being increasingly used to treat a variety of cancers including laryngeal cancer. In one study, the combination of laser and cryotherapy was used to treat early-stage laryngeal cancer.[7]

Stage I Larynx Cancer

There are three main parts of the larynx: the glottis (the middle part of the larynx where the vocal cords are), the supraglottis (the tissue above the glottis) and the subglottis (the tissue below the glottis). The subglottis connects to the trachea, which takes air to the lungs.

Stage I cancer of the larynx is limited to one area and has not spread to lymph nodes in the area or to distant sites.

Supraglottis: The cancer is only in one area of the supraglottis and the vocal cords are normal.

Glottis: The cancer is in the vocal cords and the vocal cords can move normally.

Subglottis: The cancer has not spread outside the subglottis.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage I cancer of the larynx. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Treatment Overview

Treatment depends on where the cancer is found in the larynx. American Society of Clinical Oncology guidelines state that all patients with stage I-II laryngeal cancer should be treated with the intent of preserving the larynx.[1] Treatment may involve partial laryngectomy (removal of part of the larynx), radiation therapy, or laser surgery (use of laser beams to remove areas of cancer). Partial laryngectomies lead to the highest local control rates (lowest risk of cancer recurrence in the area of the larynx) reported so far; radiation therapy is believed to preserve the voice the best; and laser surgery requires relatively little time and expense, produces few adverse health effects, and has been linked with good local control rates and excellent treatment options in case of local failure. All specialists dealing with the treatment of early laryngeal cancer should be able to offer these different treatment modalities to their patients and to deal specifically with each patient’s individual needs and preferences.

Cancer of the Supraglottis

Radiation Therapy: Stage I cancer of the supraglottis can be treated with surgery or radiation therapy. When radiation therapy is used, surgery is reserved for the treatment of cancer recurrence. Most studies suggest that radiation therapy is associated with better preservation of vocal function than surgery. In one study, radiation therapy (with surgery after recurrence) resulted in local cancer control in 92 percent of patients with stage I supraglottic cancer, and regional lymph node control in 91 percent.[2] Five-year survival was 83 percent. These results suggest that radiation therapy is effective treatment for stage I cancer of the larynx in the supraglottic region.

Surgery: Surgery (partial removal of the larynx) is effective primary treatment of cancer of the supraglottis with results comparable to radiation therapy.[3]

Cancer of the Glottis (Vocal Cords)

Radiation Therapy: Prior to the development of laser surgery, radiation therapy was the standard treatment for glottic cancer. Radiation therapy produces excellent results, but these results do not appear to be superior to laser surgery. The overall control rates for patients with stage I and II glottic cancer is approximately 90 percent following radiation therapy.[4]

Surgery: Surgical stripping was also a common treatment of stage I glottic cancer before the development of laser surgery, but this approach is generally no longer used. Surgical treatment was associated with a 95 percent preservation rate of the larynx, which is approximately the same as for laser surgery.[5]

Laser Surgery: Several studies suggest that laser surgery offers an effective approach to the treatment of stage I glottic cancer. In an Italian study involving 117 patients with T1a glottic cancer (cancer limited to one vocal cord) and 22 patients with T1b glottic cancer (cancer in both vocal cords), laser surgery resulted in a local control rate of 90 percent and no cancer deaths.[6] In another study, laser surgery for treatment of stage 0 and stage I larynx cancer was initially successful in 86 of 98 patients.[7] Eight of 12 recurrences were treated successfully with repeat laser surgery and 4 with laryngectomy.

Cancer of the Subglottis

Cancer of the subglottis represents less than two percent of all cases of laryngeal cancer and most of these patients have advanced disease. Thus, data on treatment is sparse and limited to a few patients in each study. Stage I cancer in the subglottis is typically treated with radiation therapy. In some cases, a hemilaryngectomy (removal of one side of the larynx) may be necessary when radiation therapy is not successful. In a study from Canada, radiation therapy controlled local disease in seven of 11 patients with stage I subglottic cancer with successful additional treatment with surgery in the case of radiation failures.[8]

Treatment of the Neck

Cancers of the larynx may spread into the lymph nodes of the neck. The question of whether to treat the lymph nodes of patients with stage I larynx cancer is controversial. If recurrence were inevitable, preventive treatment, consisting of surgical removal of the lymph nodes or radiation therapy, would be best approach. However, for stage I patients this would mean treating a large number of patients who would not relapse. This is an important decision since there are side effects of radiation therapy or surgical removal of lymph nodes. The current consensus of opinion is that preventive treatment of the neck may not be indicated for stage I cancer of the larynx, but may be appropriate for stage II and III cancer without clinical lymph node involvement. However, there may be specific locations of stage I cancer of the larynx where the potential for undetected spread to lymph nodes would be high and preventive treatment desirable.[9][10]

Strategies to Improve Treatment

The progress that has been made in the treatment of early cancer of the larynx has resulted from early diagnosis, improved surgical and radiation therapy techniques, as well as participation in clinical studies. Future progress in the treatment of early cancer of the larynx will result from patients and doctors continuing to participate in appropriate studies. Areas of active exploration to improve the treatment of cancer of the larynx include the following:

Improved Radiation Therapy Techniques: Three-dimensional conformal radiation therapy and intensity modulated radiotherapy (IMRT) are relatively new promising techniques which could increase the dose of radiation to cancers without increasing toxicity. There are relatively few reports of these new techniques for treatment of stage I laryngeal cancer. For more information, go to Radiation Therapy for Head & Neck Cancer.

Cryotherapy: Cryotherapy (freezing) is being evaluated for the treatment of a variety of cancers. Recently, researchers from the Cleveland Clinic have reported that laser surgery performed in conjunction with cryotherapy resulted in excellent primary site control with improved voice quality.[11]

Photodynamic Therapy: The concept behind photodynamic therapy is that light from a laser, enhanced by photosensitizing agents, can kill cancer cells without damage to normal cells. The basic technique is over 50 years old but the past 5 years have seen the development of reliable, portable lasers and better photosensitizing agents, making the technique quick, effective and relatively free from side-effects. For patients with head and neck cancer, functional outcomes with photodynamic therapy are probably better than surgery or radiation therapy but there is inadequate long-term survival data.In one study 10 patients with recurrent early-stage laryngeal cancer were treated with photodynamic therapy, with local control in eight. This therapy was successful in preserving the larynx.

An advantage to photodynamic therapy is that it can usually be given to outpatients under local anesthetic. Patients receive intravenous temoporfin (an agent that makes cells sensitive to light), followed four days later by brief laser illumination of the cancer site. Sensitivity to light takes two to three weeks to resolve, during which time patients must avoid bright light. About 10 percent of some 1000 patients treated worldwide had photosensitivity reactions, which generally involved mild redness. Post-treatment pain may require treatment with opiate pain medications.

Chemoprevention of Second Cancers

Second primary cancers occur in 10 to 30 percent of head and neck cancer patients. A primary cancer is a new cancer, rather than a recurrence of a previous cancer. Chemoprevention (the use of drugs, vitamins, or other agents to reduce the risk of cancer) offers an attractive approach to combat this threat.  In the last 10 to 15 years several chemoprevention studies with vitamin A, retinoids or agents working through other mechanisms (such as antioxidants) have been launched.  Large chemoprevention trials are being carried out in the US and in Europe but no definitive study has yet been published.  End-points of these studies are second tumors, local/regional recurrence, distant metastasis and long-term survival rates.

Stage II Larynx Cancer

There are three main parts of the larynx: the glottis (the middle part of the larynx where the vocal cords are), the supraglottis (the tissue above the glottis), and the subglottis (the tissue below the glottis). The subglottis connects to the trachea, which takes air to the lungs.

Stage II cancer is only in the larynx and has not spread to lymph nodes in the area or to distant sites.

Supraglottis: The cancer is in more than one area of the supraglottis, but the vocal cords can move normally.

Glottis: The cancer has spread to the supraglottis or the subglottis or both and the vocal cords may or may not be able to move normally.

Subglottis: The cancer has spread to the vocal cords, which may or may not be able to move normally.

A variety of factors ultimately influence a patient’s decision to receive treatment of cancer. The purpose of receiving cancer treatment may be to improve symptoms through local control of the cancer, increase a patient’s chance of cure, or prolong a patient’s survival. The potential benefits of receiving cancer treatment must be carefully balanced with the potential risks of receiving cancer treatment.

The following is a general overview of the treatment of stage II cancer of the larynx. Circumstances unique to your situation and prognostic factors of your cancer may ultimately influence how these general treatment principles are applied. The information on this Web site is intended to help educate you about your treatment options and to facilitate a mutual or shared decision-making process with your treating cancer physician.

Most new treatments are developed in clinical trials. Clinical trials are studies that evaluate the effectiveness of new drugs or treatment strategies. The development of more effective cancer treatments requires that new and innovative therapies be evaluated with cancer patients. Participation in a clinical trial may offer access to better treatments and advance the existing knowledge about treatment of this cancer. Clinical trials are available for most stages of cancer. Patients who are interested in participating in a clinical trial should discuss the risks and benefits of clinical trials with their physician. To ensure that you are receiving the optimal treatment of your cancer, it is important to stay informed and follow the cancer news in order to learn about new treatments and the results of clinical trials.

Treatment Overview

Treatment depends on where the cancer is found in the larynx. American Society of Clinical Oncology guidelines state that all patients with stage I-II laryngeal cancer should be treated with the intent of preserving the larynx.[1] Partial laryngectomies lead to the highest local control rates (lowest risk of cancer recurrence in the area of the larynx) reported so far; radiation therapy is believed to be better for voice preservation; and laser surgery requires relatively little time and expense, produces few adverse health effects, and has been linked with good local control rates and excellent treatment options in case of local failure. All specialists dealing with the treatment of early laryngeal cancer should be able to offer these different treatment modalities to their patients and to deal specifically with each patient’s individual needs and preferences.

Cancer of the Supraglottis

Surgery for Supraglottic Cancer: Researchers from Spain have reported a five-year local control rate of 80 percent for patients with stage II supraglottic cancer treated with surgery, with a larynx preservation rate of 87 percent.[2]

Laser Surgery for Supraglottic Cancer: Laser surgery involves use of a directed laser beam, rather than a scalpel, to perform the operation. Reports indicate better functional outcome with laser surgery than with open surgical procedures, with shorter hospital duration, fewer adverse health effects, and equivalent survival rates.

Researchers from Italy treated 61 patients with stage II supraglottic laryngeal cancer with laser surgery.[3]Local control was achieved in 63 percent of patients with stage II disease and the ultimate laryngeal preservation rate was 94 percent.

Radiation Therapy for Supraglottic Cancer: In one study, treatment with radiation therapy alone (followed by surgery if radiation failed) produced local control in 81 percent of patients with stage II supraglottic cancer. Overall regional lymph node control was 88 percent and five-year survival was 78 percent. Serious health problems requiring surgery were seen in two percent of cases. These results confirm that radiation therapy is effective treatment for stage II cancer of the larynx in the supraglottic region. This treatment enables preservation of the larynx in most cases, with acceptable regional control and no loss of survival compared to adjuvant (post-surgery) radiation to the neck.

Cancer of the Glottis

The best therapy for treatment of stage II glottic cancer is controversial. This stage of disease can be treated with surgery, laser surgery or radiation therapy.

Surgery for Glottic Cancer: Researchers from the Washington University have reported a local control rate of 85 percent for patients receiving either surgery or high-dose radiation therapy for stage II glottic cancer.[4]

Laser Surgeryfor Glottic Cancer: According to the results of a study involving 45 patients with stage II glottic cancer, the recurrence rate after laser surgery was 29 percent.[5] Half of the patients who relapsed required a total laryngectomy and the other half were able to be treated by repeat laser therapy or radiotherapy.

In another study, 140 patients underwent laser surgery for previously untreated stage 0-II glottic cancer.[6]When laser surgery failed, patients were treated with several different procedures, including repeat laser surgery, partial or total laryngectomy and/or radiation therapy. The larynx was preserved in 96 percent of patients. By the end of the study, 14 patients had died, but only two of them had died of laryngeal cancer. Five-year survival was 93 percent.

In a third study, laser surgery was used to treat 285 patients with stage 0-II glottic cancers.[7] Over five years, less than two percent of study participants died of laryngeal cancer. Initial treatment resulted in local control in 86 percent of study subjects. The rate of larynx preservation was 94 percent.

Radiation Therapy for Glottic Cancer: A large study from Denmark reported that radiation therapy for stage II glottic cancer resulted in locoregional control in 67 percent of patients; 18 percent of patients eventually had a laryngectomy performed.[8] In another study, the 10-year locoregional control rate for stage II glottic cancer treated with radiation therapy was 89 percent.[9] This study was of interest in that 22 percent of patients developed a second primary cancer (a new cancer that was not a recurrence of the original cancer).

Although radiation preserves speech better than surgery there can still be significant speech problems, with reduced voice quality and greater than normal effort in voice production. Voice therapy during and after radiation therapy may result in better voice quality.

Cancer of the Subglottis

Cancer of the subglottis represents less than two percent of all cases of laryngeal cancer and most of these patients have advanced disease. Thus, data on treatment is limited to a few patients in each study. Stage II cancer in the subglottis is typically treated with radiation therapy. In some cases, a hemilaryngectomy (removal of one side of the larynx) may be necessary when radiation therapy is not successful. In a study from Canada, radiation therapy controlled local disease in 8 of 12 patients with stage II subglottic cancer with successful additional treatment with surgery in the case of radiation failures.[10]

Treatment of the Neck

Cancers of the supraglottis frequently spread into the lymph nodes of the neck. Cancer may be present in the lymph nodes even if the nodes feel normal during an exam.  Spread of glottic and subglottic cancers is less frequent. Prophylactic (preventive) treatment of lymph node areas in the neck is usually recommended for stage II supraglottic cancers. In many centers it is common to surgically remove lymph nodes or to administer radiation therapy to the neck. A review of data from one medical center suggested that surgical removal of lymph nodes from both sides of the neck (bilateral lymph node dissection) decreased the risk of neck recurrences from 20 percent to 8 percent in patients with stage II-IV supraglottic laryngeal cancer.[11]These authors also reported that bilateral neck dissection improved five-year survival from 72 percent to 83 percent. However, researchers from Spain reported similar results with unilateral (one-sided) and bilateral neck dissection.[12] This suggests that removal of lymph nodes on only one side of the neck may be sufficient to prevent lymph node recurrences.

Radiation therapy can also be administered to the lymph nodes of the neck to prevent recurrences. A study of 32 patients with stage II supraglottic cancer reported a local neck recurrence rate of only 3.3% following prophylactic radiation therapy to the neck.[13] These authors suggested that radiation therapy was as effective as surgery with fewer adverse health effects.

Strategies to Improve Treatment

The progress that has been made in the treatment of early cancer of the larynx has resulted from early diagnosis, improved surgical and radiation therapy techniques and doctor and patient participation in clinical studies. Future progress in the treatment of early cancer of the larynx will result from patients and doctors continuing to participate in appropriate studies. Areas of active exploration to improve the treatment of cancer of the larynx include the following:

Improved Radiation Therapy Techniques: Three-dimensional conformal radiation therapy and intensity modulated radiotherapy (IMRT) are relatively new promising techniques which could increase the dose of radiation to cancers without increasing toxicity. There are relatively few reports of these new techniques for treatment of stage II laryngeal cancer.

Chemoradiotherapy: Researchers from Japan have reported that administering chemotherapy and radiation therapy at the same time may improve local control of patients with stage II glottic cancer.[14] In this study of 20 patients the three-year survival with preservation of the larynx was 100%.

Cryotherapy: Cryotherapy (freezing) is being evaluated for the treatment of a variety of cancers. Recently, researchers from the Cleveland Clinic have reported that laser surgery performed in conjunction with cryotherapy resulted in excellent primary site control with improved voice quality.[15]

Photodynamic Therapy: The concept behind photodynamic therapy is that light from a laser, enhanced by photosensitizing agents, can kill cancer cells without damage to normal cells. The basic technique is over 50 years old but the past five years have seen the development of reliable, portable lasers and better photosensitizing agents, making the technique quick, effective and relatively free from side-effects. For patients with head and neck cancer, functional outcomes with photodynamic therapy are probably better than surgery or radiation therapy but there is inadequate long-term survival data.In one study 10 patients with recurrent early-stage laryngeal cancer were treated with photodynamic therapy, with local control in eight. This therapy was successful in preserving the larynx.

An advantage to photodynamic therapy is that it can usually be given to outpatients under local anesthetic. Patients receive intravenous temoporfin (an agent that makes cells sensitive to light), followed four days later by brief laser illumination of the cancer site. Sensitivity to light takes two to three weeks to resolve, during which time patients must avoid bright light. About 10 percent of some 1000 patients treated worldwide had photosensitivity reactions, which generally involved mild redness. Post-treatment pain may require treatment with opiate pain medications.

Chemoprevention of Second Cancers

Second primary cancers occur in 10 to 30 percent of head and neck cancer patients. A primary cancer is a new cancer, rather than a recurrence of a previous cancer. Chemoprevention (the use of drugs, vitamins, or other agents to reduce the risk of cancer) offers an attractive approach to combat this threat.  In the last 10 to 15 years several chemoprevention studies with vitamin A, retinoids or agents working through other mechanisms (such as antioxidants) have been launched. Large chemoprevention trials are being carried out in the US and in Europe but no definitive study has yet been published. End-points of these studies are second tumors, local/regional recurrence, distant metastasis and long-term survival.

Reference:

[1]Gallus S, Bosetti C, Franceschi S, et al. Laryngeal cancer in women: tobacco, alcohol, nutritional, and hormonal factors. Cancer Epidemiology Biomarkers Prevention 2003;12:514-517.

[1] De Mones E, Hans S, Hartl DM et al. Carbon dioxide laser transoral microsurgery for glottic carcinoma in situ. Annals Otolaryngol Chir Cervicofac 2002;119:21-30.

[2] Gallo A, de Vincentiis M, Manciocco V, et al. CO2 laser cordectomy for early-stage glottic carcinoma: a long-term follow-up of 156 cases. Laryngoscope 2002;112:370-374.

[3] Spayne JA, Worde P O’Sullivan B, et al. Carcinoma-in-situ of the glottic larynx: results with treatment with radiation therapy. International Journal of Radiation Oncology Physics 2001;49:1235-1238.

[4] Kaanders JH, Hordijk GJ:Dutch Cooperative Head and Neck Oncology Group. Carcinoma of the larynx: the Dutch national guideline for diagnostics, treatment, supportive care and rehabilitation. Radiotherapy Oncology 2002;63:299-307.

[5] Schweitzer VG. PHOTOFRIN-mediated photodynamic therapy for treatment of early stage oral cavity and laryngeal malignancies. Lasers Surg Med 2001;29:305-313.

[6] Sieron A, Namyslowski G, Misiolek M, et al. Photodynamic therapy of premalignant lesions and local recurrence of laryngeal and hypopharyngeal cancers. Eur Arch Otophinolaryngol 2001;258:349-352.

[7] Knott PD, Milstein CF, Hicks DM, et al. Vocal outcomes after laser resection of early-stage glottic cancer with adjuvant cryotherapy. Arch Otolaryngol Head and Neck Surg 2006;132:1226-1230.

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[10] Chiu RJ, Myers EN, Johnson JT. Efficacy of routine bilateral neck dissection in the management of supraglottic cancer. Otolaryngol Head and Neck Surg 2004;131:485-488.

[11] Knott PD, Milstein CF, Hicks DM, et al. Vocal outcomes after laser resection of early-stage glottic cancer with adjuvant cryotherapy. Arch Otolaryngol Head Neck Surg 2006;132:1226-1230.

[1] American Society of Clinical Oncology. American Society of Clinical Oncology clinical practice guideline for the use of larynx-preservation strategies in the treatment of laryngeal cancer. Journal of clinical Oncology 2006;24:3693-3704.

[2] Laudadio P, Presutti L, Dall’Olio D, et al. Supraglottic laryngectomies: Long-term oncological and functional results. Acta Otolaryngol. 2006;126:640-649.

[3] Motta G, Esposito E, Testa D, et al. CO2 laser treatment of supraglottic cancer. Head Neck 2004;26:442-446.

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[5] Konig O, Bockmuhl U, Haake K, et al. Glottic laryngeal carcinoma. Tis, T1 and T2-long term results. HNO 2006;54:93-98.

[6] Pretti G, Nicolai P, Redaelli de Zinis LO, et al. Endoscopic CO2 laser excision for tis, T1, and T2 glottic carcinomas: cure rate and prognostic factors.Otolaryngol Head Neck Surg2000;123:124-31.

[7] Eckel HE, Thumfart W, Jungehulsing M, et al. Transoral laser surgery for early glottic carcinoma. European Arch Oto 2000;257:221-226.

[8] Jorgensen K, Godbaile C, Hansen O, et al. Cancer of the larynx-treatment results after primary radiotherapy with salvage surgery in a series of 1005 patients. Acta Oncol 2002;41:69-76.

[9] Franchin G, Minatel E, Gobitti C et al. Radiotherapy for patients with early-stage glottic carcinoma: univariate and multivariate analyses in a group of consecutive, unselected patients. Cancer 2003;98:765-772.

[10] Paisley S, Warde PR, O’Sullivan B, et al. Results of radiotherapy for primary subglottic squamous cell carcinoma. International Journal of Radiation Oncology Biology Physics 2002;52:1245-1250.

[11] Chiu RJ, Myers EN, Johnson JT. Efficacy of routine bilateral neck dissection in the management of supraglottic cancer. Otolaryngol Head and Neck Surg 2004;131:485-488.

[12] Rodrego JP, Cabanillas R, Franco V, et al. Efficacy of routine bilateral neck dissection in the management of N0 neck in T1-T2 unilateral supraglottic cancer. Head Neck 2006;28:534-539.

[13] Alpert TE, Marbidini-Gaffney S, Chung CT, et al. Radiotherapy for the clinically negative neck in supraglottic laryngeal cancer. Cancer Journal 2004;10:335-338

[14] Concurrent chemoradiotherapy with carboplatin and uracil-ftegafur in patients with stage two (T2 N0 M0) squamous cell carcinoma of the glottic larynx. Journal of Laryngeal Otol 2006;120:478-481.

[15] Knott PD, Milstein CF, Hicks DM, et al. Vocal outcomes after laser resection of early-stage glottic cancer with adjuvant cryotherapy. Arch Otolaryngol Head Neck Surg. 2006;132:1226-1230.

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