| Summary of Recommended Strategies for Treatment of the Primary Site for Larynx Preservation |
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Organ-Preservation Strategy |
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| Type of Cancer |
Recommended |
Other Options |
Basis for Recommendation |
Quality of Evidence |
| T1 cancer of the glottis: T1—tumor limited to the vocal cord(s) (may involve anterior or posterior commissure) with normal mobility T1a—tumor limited to one vocal cord T1b—tumor involves both vocal cords |
Endoscopic resection (selected patients) OR radiation therapy |
Open organ-preservation surgery |
High local control rates and quality of voice after endoscopic resection compared with radiation therapy; possible cost savings; ability to reserve radiation for possible second primary cancers of the upper aerodigestive tract; however, not suitable for all patients |
Comparison of outcomes from case series/ prospective single-arm studies |
| T2 cancer of the glottis, favorable*: T2—tumor extends to supraglottis and/or subglottis, or with impaired vocal cord mobility |
Open organ-preservation surgery OR radiation therapy |
Endoscopic resection (selected patients) |
Open organ-preservation surgery is associated with highest local control rates; however, leads to permanent hoarseness; local control rates after radiation therapy are also high, and functional outcomes may be better |
Comparison of outcomes from case series/prospective single-arm studies |
| T2 cancer of the glottis, unfavorable* |
Open organ-preservation surgery OR concurrent chemoradiation therapy (selected patients with node-positive disease) |
Radiation therapy Endoscopic resection (selected patients) |
Higher local control rates after surgery compared with radiation therapy alone; quality of voice after therapy of less concern if vocal cord function is irreversibly compromised by tumor invasion; endoscopic surgery requires careful patient selection For patients with T2 N+ disease, evidence from randomized trials supports concurrent chemoradiation therapy as an organ-preservation option |
Comparison of outcomes from case series/ prospective single-arm studies; randomized controlled clinical trials comparing concurrent chemoradiation therapy, and/or induction chemotherapy followed by radiation, and/or radiation therapy alone, and/or surgery followed by radiation |
| T1-T2 cancer of the supraglottis, favorable*: 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, medial wall of pyriform sinus) without fixation of the larynx |
Open organ-preservation surgery OR radiation therapy |
Endoscopic resection (selected patients) |
Open organ-preservation surgery associated with highest local control rates; however, requires temporary tracheostomy and may lead to increased risk of aspiration after therapy; local control rates after radiation therapy are also high, and functional outcomes may be better |
Comparison of outcomes from case series/ prospective single-arm studies |
| T2 cancer of the supraglottis, unfavorable* |
Open organ-preservation surgery OR concurrent chemoradiation therapy (selected patients with node-positive disease) |
Radiation therapy Endoscopic resection (selected patients) |
Open organ-preservation surgery is more likely to yield higher local control rates than radiation therapy; for patients with T2 N+ disease, evidence from randomized trials supports concurrent chemoradiation therapy as an organ-preservation option |
Comparison of outcomes from case series/ prospective single-arm studies; randomized controlled clinical trials comparing concurrent chemoradiation therapy, and/or induction chemotherapy followed by radiation, and/or radiation therapy alone, and/or surgery followed by radiation |
| T3-T4 cancers of the glottis or supraglottis: T3 glottis—tumor limited to the larynx with vocal cord fixation, and/or invades paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex) T3 supraglottis—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 glottis or supraglottis—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 glottis or supraglottis—tumor invades prevertebral space, encases carotid artery, or invades mediastinal structures |
Concurrent chemoradiation therapy OR open organ-preservation surgery (in highly selected patients) |
Radiation therapy |
Highest rate of larynx preservation is associated with concurrent chemoradiation therapy compared with other radiation-based approaches, at the cost of higher acute toxicities but without more long-term difficulties in speech and swallowing; when salvage total laryngectomy incorporated, no difference in overall survival; organ preservation surgery is an option in highly selected patients (e.g., there are patients with T3 supraglottic cancers that have minimal or moderate pre-epiglottic invasion and are candidates for organ preserving surgery) |
Randomized controlled clinical trials comparing concurrent chemoradiation therapy, and/or induction chemotherapy followed by radiation, and/or radiation therapy alone; and/or surgery followed by radiation; comparison of outcomes from case series/prospective single-arm studies |
*A favorable T2 glottic lesion is defined as a superficial tumor, on radiographic imaging, with normal cord mobility. An unfavorable T2 glottic lesion is defined as a deeply invasive tumor on radiographic imaging, with or without subglottic extension, with impaired cord mobility (indicating deeper invasion). A favorable supraglottic lesion is defined as a T1 or T2 tumor with superficial invasion on radiographic imaging and preserved cord mobility, and/or tumor of the aryepiglottic fold with minimal involvement of the medial wall of the pyriform sinus. More locally advanced and invasive T2 supraglottic lesions are considered unfavorable.
What are the larynx-preservation treatment options for limited stage (T1, T2) primary site disease that do not compromise survival? What are the considerations in selecting treatment options in this setting?
Evidence base. There are no randomized studies in which radiation therapy was compared with conservation surgery with respect to local control or survival for patients with limited-stage laryngeal cancer. Similarly, there are no randomized controlled data on comparison of functional outcomes, specifically the quality of voice and swallowing ability, after surgery or radiation therapy for patients with this stage of disease.
The recommendations to address these questions are based on evidence from prospective and retrospective cohort studies. The recommendations for T2 N+ disease are based on data from randomized controlled trials of chemoradiotherapy therapy (with either induction or concurrent chemotherapy compared with radiation therapy alone or surgery followed by adjuvant radiation therapy). The outcomes assessed included overall survival, disease-free survival, rates of laryngeal preservation, local-regional control, toxicity of therapy, and cost.
Limited-stage disease represents a spectrum. Treatment selection can be challenging, as the evidence base for most decisions is derived from nonrandomized studies and various factors need to be considered when choosing therapy. Selected examples for glottic cancer are illustrative. If voice outcome is predicted to be good after endoscopic laser resection for a T1 glottic cancer (e.g., a superficial tumor located in the middle third of the cord, especially on its free edge), then use of this modality is more efficient and thus preferred. However, lesions that are indistinct, especially those arising in the context of widespread, abnormal-appearing mucosa, are more suitable for radiation therapy than for surgery. Radiation therapy is preferred by many clinicians for treatment of T2 glottic carcinoma characterized as superficial on radiographic imaging, with preserved cord mobility, as local control rates are high and anticipated functional outcomes are good. But some investigators have noted compromised survival after the failure of radiation therapy inT2glottic carcinoma indicating the importance of obtaining initial local control. As such, supracricoid partial laryngectomy with cricohyoidoepliglottopexy remains a reasonable alternative for patients with a T2 glottic carcinoma who after pretreatment counseling would be willing to sacrifice voice quality in an effort to improve local control. Induction chemotherapy has been investigated as treatment for patients with limited-stage laryngeal cancer. However, insufficient data are currently available to recommend such an approach outside the context of a clinical trial.
Recommendations
- All patients with T1-T2 laryngeal cancer should be treated, at least initially, with intent to preserve the larynx.
- T1-T2 laryngeal cancer can be treated with radiation or larynx-preservation surgery with similar survival outcomes. Selection of treatment depends on patient factors, local expertise, and the availability of appropriate support and rehabilitative services. Every effort should be made to avoid combining surgery with radiation therapy because functional outcomes may be compromised by combined-modality therapy; single-modality treatment is effective for limited-stage, invasive cancer of the larynx.
- Surgical excision of the primary tumor with intent to preserve the larynx should be undertaken with the aim of achieving tumor-free margins; so-called narrow-margin excision followed by postoperative radiation therapy is not an acceptable treatment approach.
- Local tumor recurrence after radiation therapy may be amenable to salvage by organ-preservation surgery, but total laryngectomy will be necessary for a substantial proportion of patients, especially those with index T2 tumors.
- Concurrent chemoradiotherapy therapy may be used for larynx preservation for selected patients with stage III, T2 N+ cancers when total laryngectomy is the only surgical option, when the functional outcome after larynx-preservation surgery is expected to be unsatisfactory, or when surgical expertise in such procedures is not available.
- Limited-stage laryngeal cancer constitutes a wide spectrum of disease. The clinician must exercise judgment when recommending treatment in this category. For a given patient, factors that may influence the selection of treatment modality include extent and volume of tumor; involvement of the anterior commissure; lymph node metastasis; the patient's age, occupation, preference, and compliance; availability of expertise in radiation therapy or surgery; and history of a malignant lesion in the head and neck.
What are the larynx-preservation treatment options for advanced stage (T3, T4) primary site disease that do not compromise survival? What are the considerations in selecting among them?
Evidence base. The recommendations to address these questions are based on evidence from randomized controlled trials of different radiation fractionation schedules, chemoradiotherapy therapy (either induction or concurrent) compared with radiation therapy alone or surgery followed by adjuvant radiation therapy, on meta-analysis or other secondary analysis of data from randomized clinical trials, and on prospective and retrospective cohort studies. The outcomes evaluated included overall survival, disease-free survival, rates of laryngeal preservation, local-regional control, toxicity of therapy, and cost.
Recommendations
- Organ-preservation surgery, concurrent chemoradiotherapy therapy, and radiation therapy alone, all with further surgery reserved for salvage, offer potential for larynx preservation without compromising survival. Anticipated success rates for larynx preservation, associated toxicities, and suitability for a given patient will vary among these approaches. Selection of a treatment option will depend on patient factors, local expertise, and the availability of appropriate support and rehabilitation services.
- All patients should be evaluated regarding their suitability for a larynx-preservation approach, and they should be apprised of these treatment options. No larynx-preservation approach offers a survival advantage compared with total laryngectomy and appropriate adjuvant treatment.
- A minority of patients with T3-T4 primary site disease will be suitable for specialized organ-preservation procedures, such as a supracricoid partial laryngectomy. The addition of postoperative radiation therapy will compromise anticipated functional outcomes. Induction chemotherapy before organ-preservation surgery is not recommended outside of a clinical trial.
- Concurrent chemoradiotherapy therapy offers a significantly higher chance of larynx preservation than does radiation therapy alone or induction chemotherapy followed by radiation, albeit at the cost of higher acute in-field toxicities.
- The best available evidence supports the use of cisplatin as the drug of choice in this setting.
- There is insufficient evidence to indicate that survival or larynx-preservation outcomes are improved by the addition of induction chemotherapy before concurrent treatment or the use of concurrent chemotherapy with altered fractionated radiation therapy in this setting.
- For patients who desire larynx-preservation therapy but are not candidates for organ-preservation surgery or chemoradiotherapy therapy, radiation therapy alone is an appropriate treatment. With this last approach, survival is similar to that associated with chemoradiotherapy therapy when salvage surgery is incorporated, but the likelihood of larynx preservation is lower.
What is the appropriate treatment of the regional cervical nodes in patients with laryngeal cancer who are treated with an organ-preservation approach?
Evidence base. There are no randomized studies that address treatment of the neck for limited-stage disease in the primary site. The randomized studies of more advanced primary disease do not focus on treatment of the neck as a primary end point.
The recommendations to address this question are based on evidence from derivative analyses of randomized controlled trials of chemoradiotherapy (either induction or concurrent) compared with radiation therapy alone or surgery followed by adjuvant radiation therapy, a randomized trial comparing the different types of neck dissection, and on prospective and retrospective cohort studies. With respect to adjuvant therapy, evidence was drawn from randomized controlled trials of radiation therapy compared with concurrent chemoradiotherapy. The outcomes assessed included overall survival, disease-free survival, local-regional control, and toxicity of therapy.
Recommendations
- Most patients with T1-T2 lesions of the glottis and clinically negative cervical nodes (N0) do not require routine elective treatment of the neck.
- Patients with advanced lesions of the glottis and all patients with supraglottic lesions should have elective treatment of the neck, even if clinically N0.
- Patients with clinically involved regional cervical nodes (N1) who are treated with definitive radiation therapy or chemoradiotherapy therapy and who have a complete clinical response do not require elective neck dissection. Neck dissection should be performed for patients who do not have a complete clinical response to radiation therapy.
- Surgical treatment of the neck is recommended for patients with N2 or N3 disease who are treated with definitive radiation therapy or chemoradiotherapy therapy, regardless of response. Some surgeons and patients are reluctant to risk the morbidity of neck dissection, given the prospect of a negative pathologic diagnosis in most cases, but there is no standard imaging approach in this setting that has been validated to significantly improve on this decision-making process. Salvage surgery for recurrent disease in the neck is rarely successful if subsequently required in this setting. These two points should be discussed with all patients who have an apparent complete clinical response to radiation therapy or chemoradiotherapy therapy and choose to be followed up with expectant observation.
- Patients with clinically involved cervical nodes who are treated with surgery for the primary lesion should have neck dissection. If there are poor-risk features, adjuvant concurrent chemoradiotherapy therapy is indicated.
Are there methods for prospectively selecting patients with laryngeal cancer to increase the likelihood of successful larynx preservation?
Evidence base. The recommendations addressing this question are based on evidence from prospective and retrospective cohort studies of clinical, radiographic, and/or pathologic parameters associated with clinical outcomes and on derivative analyses of a randomized controlled trial. The outcomes assessed included overall survival, disease-free survival, local-regional control, and rates of laryngeal preservation.
Recommendations
- There are no validated markers that consistently predict outcomes of larynx-preservation therapy. However, patients with tumor penetration through cartilage into soft tissues are considered poor candidates for a larynx-preservation approach. Primary surgery, usually total laryngectomy, is commonly recommended in this setting.
- Selection of therapy for an individual patient requires assessment by a multidisciplinary team, as well as consideration of patient comorbidity, psychosocial situation and preferences, and local therapeutic expertise.
- Continued cigarette smoking appears to be associated with a worse outcome after radiation therapy. Patients should be encouraged to abstain from smoking after diagnosis and throughout treatment.
