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Incidence and Mortality
Estimated new cases and deaths from laryngeal cancer in the United States in 2020:
The larynx is divided into the following three anatomical regions:
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 (tumor) 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.
A clear association has been made between smoking, excess alcohol ingestion, and the development of squamous cell cancers of the upper aerodigestive tract. For smokers, the risk of the development of laryngeal cancer decreases after the cessation of smoking but remains elevated even years later when compared with that of nonsmokers. 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. 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.
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 (regional lymph node) 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.
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, 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.
Locally advanced lesions are treated with combined modality treatment involving radiation and chemotherapy with or without surgery, the aim of which is laryngeal preservation in appropriately selected candidates. 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.
Follow-up and Survivorship
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. No survival advantage has been demonstrated, partially because of recurrence and death from the primary malignancy.
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.
The clear 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. 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.
The staging system for laryngeal cancer 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 fiberoptic laryngoscopy. Panendoscopy under anesthesia ensures careful clinical examination to determine clinical extent of local disease. The tumor must be confirmed histologically, and any other pathological data obtained on biopsy may be included. Head and neck magnetic resonance imaging, computed tomography, or positron emission tomography-computed tomography should be done before therapy to supplement inspection and palpation. Additional radiographic studies may be included. The appropriate nodal drainage areas in the neck should be examined by careful palpation.
Definitions of TNM
The American Joint Committee on Cancer (AJCC) has designated staging by TNM (tumor, node, metastasis) classification to define laryngeal cancer.
AJCC Prognostic Stage Groups
Surgery and/or Radiation Therapy
Surgery and radiation therapy have been the standards for treatment of laryngeal cancer; however, outcome data from randomized trials are limited. Studies have attempted to address the question of whether to use surgery or radiation, but the studies have been underpowered. Selection of primary surgery versus radiation therapy-based treatment should be made in a multidisciplinary setting with consideration of disease stage, comorbidities, and functional status, including voice and swallowing outcomes and lung capacity.
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 with concurrent chemotherapy for larynx preservation and total laryngectomy for bulky T4 disease or salvage.[2,3,4]
Evaluation of treatment outcome can be reported in various ways: locoregional control, disease-free survival, determinate survival, and overall survival (OS) 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.
A review of published clinical results of definitive 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]
Direct comparison of the results of radiation therapy versus endolaryngeal surgery (with or without laser) has not been made for patients with early-stage laryngeal cancer. The evidence is insufficient to show a clear difference in the results between treatment options regarding local control or OS. Retrospective data suggest that in comparison with surgery, radiation therapy might cause less perturbation of voice quality without a significant difference in patient perception.
Concurrent Chemoradiation Therapy
Concurrent chemoradiation therapy is a standard treatment option for patients with locally advanced (stage III and stage IV) laryngeal cancer.
Evidence (concurrent chemoradiation therapy):
(Refer to the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation for more information about oral toxicities.)
Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation Therapy
In a meta-analysis of five randomized trials, a total of 1,022 patients with locally advanced head and neck squamous cell cancer were randomly assigned to receive either neoadjuvant chemotherapy with TPF (docetaxel, cisplatin, and fluorouracil) followed by concurrent chemoradiation therapy or concurrent chemoradiation therapy alone. The analysis failed to show an OS (HR, 1.01; 95% confidence limits [CLs], 0.84, 1.21; P = .92) or PFS (HR, 0.91; 95% CLs, 0.75, 1.1; P = .32) advantage for neoadjuvant chemotherapy using the TPF regimen over concurrent chemoradiation therapy alone.[Level of evidence: 1iA]
Evidence (neoadjuvant chemotherapy followed by concurrent chemoradiation therapy):
Altered Fractionation Versus Standard Fractionation Radiation Therapy
Radiation therapy alone with altered fractionation may be used for patients with locally advanced laryngeal cancer who are not candidates for chemotherapy. Altered fractionation radiation therapy yields a higher locoregional control rate compared with standard fractionated radiation therapy for patients with stage III and stage IV head and neck cancer.
Evidence (altered fractionation vs. standard fractionation radiation therapy):
In a long-term analysis, the three investigational arms were compared with SFX.
An additional late effect from radiation therapy is hypothyroidism, which occurs in 30% to 40% of patients who have received external-beam radiation therapy to the entire thyroid gland. Thyroid function testing of patients is a consideration before therapy and as part of posttreatment follow-up.[16,17]
Prospective data of two randomized controlled trials reported the incidence of hypothyroidism.
For patients with well-lateralized oropharyngeal cancer, such as a T1 or T2 tonsil primary tumor with limited extension into the palate or tongue base and limited ipsilateral lymph node involvement without extracapsular extension, elective treatment to the ipsilateral lymph nodes results in only minimal risk of spread to the contralateral neck. For T3 and T4 tumors that are midline or approach the midline, bilateral nodal treatment is a consideration. In addition to the cervical lymph node chain, retropharyngeal lymph nodes can also be encompassed in the elective nodal treatment.
Surgery Followed by Postoperative Radiation Therapy (PORT) With or Without Chemotherapy for Patients With Locally Advanced Disease
New surgical techniques for resection and reconstruction that provide access and functional preservation have extended the surgical options for patients with stage III or stage IV laryngeal cancer. Specific surgical procedures and their modifications are not described here because of the wide variety of surgical approaches, the variety of opinions about the role of modified neck dissections, and the multiple reconstructive techniques that may give the same results. This group of patients is managed by head and neck surgeons who are skilled in the multiple procedures available and are actively and frequently involved in the care of these patients.
Depending on pathological findings after primary surgery, PORT with or without chemotherapy is used in the adjuvant setting for the following histological findings:
The addition of chemotherapy to PORT for laryngeal cancer squamous cell carcinoma demonstrates a locoregional control and OS benefit compared with radiation therapy alone in patients who have high-risk pathological risk factors, extracapsular extension of a lymph node, or positive margins, based on a pooled analysis of the EORTC-22931 [NCT00002555] and RTOG-9501 [NCT00002670] studies.[20,21,22,23][Level of evidence: 1iiA]
For patients with intermediate pathological risk factors, the addition of cisplatin chemotherapy given concurrently with PORT is unclear. Intermediate pathologic risk factors include:
The addition of cetuximab with radiation therapy in the postoperative setting for these intermediate pathological risk factors is being tested in a randomized trial (RTOG-0920 [NCT00956007]).
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, the incidence is 10%, and for stage III glottic, the incidence is 15%. Thus, there is no need to treat glottic cancer cervical lymph nodes electively in patients with stage I tumors and small stage II tumors. Elective neck radiation is a consideration for T3 or T4 glottic tumors or T1 to T4 supraglottic tumors.
For patients with cancer of the subglottis, combined modality therapy is generally preferred for the uncommon small lesions (i.e., stage I or stage II); however, 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; therefore, patients should be counseled on smoking cessation before beginning radiation therapy.
Standard treatment options:
(Refer to the Treatment Option Overview for Laryngeal Cancer section of this summary for more information.)
Standard treatment options:
Selection of treatment should include an evaluation of voice function and quality after treatment. Endoscopic CO2 laser resections may also achieve similar results in terms of local control and function  compared with radiation therapy, although no randomized studies have been performed.
A meta-analysis of 22 consecutive case series to examine oncologic control demonstrated no clear differences between transoral CO2 laser excision and external beam radiation therapy (EBRT) in terms of local control (odds ratio [OR], 0.81; 95% confidence interval [CI], 0.51–1.3 and laryngectomy-free survival [OR, 0.84, 95% CI, 0.42–1.66]).
Conventional and hypofractionated regimens have been studied regarding radiation-dose fractionation for patients with early-stage larynx cancer. In a randomized study of patients with early-stage larynx cancer, patients were randomly assigned to standard fractionation in 2 Gy daily fractions compared with a hypofractionated regimen of 2.25 Gy daily; 82 patients were allocated to a conventional fractionation (CONV) arm (66 Gy/33 fractions for T1 and 70 Gy/35 fractions for T2), with 74 patients to the hypofractionation (HYPO) arm (63 Gy/28 fractions for T1 and 67.5 Gy/30 fractions for T2). The study was underpowered and closed early because of a lack of accrual, although no statistically significant differences were seen between treatment arms in terms of local progression-free survival (PFS).
Earlier single-institution reports support hypofractionated regimens using 2.25 Gy per fraction for early T1 and T2 larynx cancer with high local control rates.[Level of Evidence: 3iiDiv]
Current Clinical Trials
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
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. (Refer to the Treatment Option Overview for Laryngeal Cancer section of this summary for more information.)
Treatment options under clinical evaluation:
Treatment options under clinical evaluation:
Role of Neck Dissection in the Post Radiation Therapy Setting
In a prospective randomized trial, 564 head and neck cancer patients with N2 or N3 disease were randomly assigned to planned neck dissection versus surveillance with positron emission tomography/computed tomography (PET/CT). With a median follow-up of 36 months, PET/CT resulted in fewer neck dissections compared with the surgical arm (54 vs. 221), with a 2-year survival of 84.9% versus 81.5%, respectively. The hazard ratio (HR)death slightly favored PET/CT-guided surveillance and indicated noninferiority (upper boundary, 95% confidence interval for HR, <1.50; P = .004).[Level of evidence: 1iiA]
Treatment of recurrent and metastatic supraglottic, glottic, and subglottic cancer includes further surgery or clinical trials.[1,2,3]
Platinum-based chemotherapy is often used as first-line treatment for patients with recurrent or metastatic squamous cell carcinoma (SCC) of the head and neck.
Tumor EGFR gene copy number was not found to be a predictive biomarker for the efficacy of cetuximab plus platinum and fluorouracil as first-line therapy for patients with recurrent or metastatic SCC of the head and neck.[Level of evidence: 1iiA]
Pembrolizumab is a monoclonal antibody and an inhibitor of the programmed death (PD-1) pathway.
Nivolumab is a fully human immunoglobulin G4 (IgG4) anti–PD-1 monoclonal antibody.
Salvage after previous combined total laryngectomy and radiation therapy is poor.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Laryngeal Cancer
Updated statistics with estimated new cases and deaths for 2020 (cited American Cancer Society as reference 1).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult laryngeal cancer. It 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.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Laryngeal Cancer Treatment (Adult) are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this 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.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Laryngeal Cancer Treatment (Adult). Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/adult/laryngeal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389189]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
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Last Revised: 2020-01-23
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