INTRODUCTION — The management of early laryngeal cancer is presented here. The treatment of locoregionally advanced laryngeal cancer is discussed separately, as is the management of metastatic disease:
●(See "Treatment of metastatic and recurrent head and neck cancer".)
EPIDEMIOLOGY AND RISK FACTORS — Worldwide, there are over 180,000 cases of laryngeal cancer and approximately 100,000 deaths annually [1]. In the United States, there are approximately 12,500 cases and 3800 deaths due to laryngeal cancer annually [2].
Laryngeal cancer is diagnosed predominantly in men, which, at least in part, reflects the effects of tobacco and alcohol use. (See "Epidemiology and risk factors for head and neck cancer".)
STAGING AND ANATOMY — The tumor, node, metastasis (TNM) staging system of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) is used to stage cancers of the larynx (table 1) [3]. (See "Overview of the diagnosis and staging of head and neck cancer".)
The larynx is divided into three anatomic regions: the supraglottis, glottis, and subglottis (figure 1A-B). Glottic, supraglottic, and subglottic cancers represent approximately two-thirds, one-third, and 2 percent of laryngeal cancers, respectively, in the United States and Europe [4,5]. This division is incorporated into staging the primary tumor:
●Supraglottis – Suprahyoid epiglottis, infrahyoid epiglottis, aryepiglottic folds (laryngeal aspect), arytenoids, and ventricular bands (false cords)
●Glottis – True vocal cords, including anterior and posterior commissures
●Subglottis – Subglottis, extending from the lower boundary of the glottis to the lower margin of the cricoid cartilage
By definition, patients with early laryngeal cancer have stage I or II tumors with no evidence of thyroid cartilage invasion or lymph node involvement (figure 2). The regional distribution of lymph node drainage varies by the primary anatomic location of the laryngeal tumor. These site-specific patterns of lymph node drainage and their influence on elective nodal treatment options are discussed below:
●(See 'Supraglottic regional lymph nodes' below.)
●(See 'Glottic regional lymph nodes' below.)
●(See 'Subglottic regional lymph nodes' below.)
Pretreatment evaluation with indirect, flexible, or rigid laryngoscopy is essential for both primary tumor staging and determining the three vital laryngeal functions: occlusion of the airway during the pharyngeal phase of swallowing, maintenance of airway patency via active abduction, and voice production. If indicated, such pretreatment evaluation, particularly in larger tumors, may also include videostroboscopy (to evaluate the mucosal wave of the true vocal cord) and/or a modified barium swallow (to assess laryngeal sensation, swallowing impairment, and risk for aspiration). (See "Overview of the diagnosis and staging of head and neck cancer", section on 'Diagnosis and staging evaluation'.)
GOALS OF THERAPY — Patients with early laryngeal cancer are treated with curative intent using local therapeutic modalities to optimize locoregional control and survival. In addition, patients should be treated with the goal of preserving laryngeal function, including swallowing ability, airway protection, and voice quality [6,7]. Optimal treatment maximizes both laryngeal functional outcomes and survival.
For all patients with early stage laryngeal cancer, estimated five-year disease-specific survival rates are high based on observational studies (>90 and 80 percent for stage I and II disease, respectively) [8].
For specific sites of disease, five-year overall survival rates are most favorable for glottic cancers (80 to 91 percent) but are less favorable for supraglottic cancers (55 to 75 percent) and subglottic cancers (50 to 86 percent) [9-13].
INITIAL SITE-SPECIFIC MANAGEMENT — The management of early stage laryngeal cancer is primarily based on the anatomic location of the tumor (glottic, supraglottic, or subglottic). Various other factors that influence selection of initial treatment include the following [7]:
●Tumor size, extent, and location
●Laryngeal function
●Patient age and comorbidities
●Pulmonary and swallowing function
●Available rehabilitation resources
●Clinician expertise and experience
●Patient logistic issues (eg, professional voice user), comorbidities, and treatment preferences
The site-specific management of glottic, supraglottic, and subglottic laryngeal cancers is discussed below. Unique administration details and the potential risks and toxicities of the various treatment modalities available for patients with early stage laryngeal cancer are discussed below. (See 'Treatment modalities' below.)
Glottic cancer — Most true vocal cord cancers occur on the anterior two-thirds of the vocal cords (vibratory vocal cords), with some also developing on the anterior commissure [14]. Persistent hoarseness, which is frequently the presenting complaint, tends to occur relatively early in the course of the disease and causes glottic cancers to be discovered at an earlier stage than other head and neck cancers. If disease is more advanced, symptoms may include dyspnea, dysphagia, referred otalgia, sore throat, chronic cough, hemoptysis, and stridor.
Surgery or radiation therapy for primary glottic tumors — For patients with early stage glottic cancer, standard treatment is a larynx-preserving approach with either transoral laser microsurgery (TLM) or radiation therapy (RT), as both approaches offer similar oncologic efficacy and survival outcomes. Evaluating pretreatment function and predicting posttreatment function after either surgery or RT are crucial to the choice of therapy.
For patients with superficial midcord lesions who choose surgery, our surgical experts offer transoral surgery with TLM, as this minimally invasive surgical approach minimizes vocal cord resection and also offers good voice quality outcomes. For patients with glottic laryngeal tumors that require more extensive resection, we typically offer RT rather than surgery (with either TLM or open partial laryngectomy). As an example, tumors that deeply invade the vocalis muscle treated with resection may also require postoperative RT due to positive margins or other high-risk pathologic features, so initial therapy with RT may be preferred in this situation. With this approach, the estimated five-year overall survival rate is approximately 90 percent [9,13,15]. (See "Adjuvant radiation therapy or chemoradiation in the management of head and neck cancer".)
Both RT and transoral surgical approaches offer reasonable opportunities for voice preservation in early stage glottic tumors. Patients should be offered a risk-benefit discussion regarding the ability of the chosen therapy to achieve long-term vocal preservation. (See 'Vocal outcomes for radiation therapy versus surgery' below.)
In patients with early stage glottic cancer, both RT and surgery offer high locoregional control and overall survival; if posttreatment functionality is predicted to be equal, then either approach is reasonable [15-17]. For example, in a landmark trial, 269 patients with T1-2N0 laryngeal cancers were randomly assigned to receive either surgery (ie, open partial laryngectomy) or RT [16]. Five-year overall survival rates were similar between the two groups (100 versus 92 percent for stage I tumors and 97 versus 89 percent for stage II tumors, respectively). Although this trial used a less contemporary open surgical intervention, similar results were noted in later studies with less invasive surgical techniques. As an example, in a subsequent randomized trial of 60 patients with T1aN0 glottic cancer treated with either TLM or RT, two-year local recurrence rates were 10 and 12 percent, respectively, and survival rates were similar [15]. Several subsequent meta-analyses evaluating TLM versus RT have had mixed results, with some demonstrating similar locoregional control [18-21] and others reporting improved overall survival rates or laryngeal preservation with TLM relative to RT [18-20].
Vocal outcomes for radiation therapy versus surgery — Both RT and transoral surgery offer reasonable opportunities for voice preservation; however, since data are controversial regarding which treatment modality is superior, patients should be offered a risk-benefit discussion regarding long-term vocal preservation with either approach.
Voice quality is an important clinical outcome. The main factor in determining postoperative voice quality is the vibratory characteristics of the vocal cord segments uninvolved by the tumor. Any technique used should try to minimize the impact on these structures. In general, voice quality after surgical excision will vary with the extent of vocal cord resection and the amount of pliable vocal cord tissue that can be preserved [22,23]. Likewise, voice quality with RT is impacted by the extent of the radiated volume.
Data are controversial regarding which treatment modality offers superior voice outcomes in glottic tumors [15,16,18-20,24-28]. Observational studies and one randomized trial reported improved vocal quality with RT over surgery, including better outcomes for hoarseness, voice perturbation, jitter and shimmer, and maximum phonation time [15,19,20]. In addition, a randomized trial reported increased breathiness and glottal gap (which may promote aspiration) with surgery [15]. In contrast, other observational studies, including two meta-analyses, favored transoral surgical approaches over RT, including improved rates of laryngeal preservation with surgery and worsened voice acoustics with RT [18,19,27]. Other observational studies suggest equivalent outcomes between the two treatment modalities, including Voice Handicap Index (VHI) and patient perception of voice quality [20,26-28].
Transoral surgery may be preferred in select cases where vocal cord resection can be minimized. For example, superficial midcord lesions where the tumor involves only the membranous true cord can be easily treated with TLM using a limited subepithelial or subligamental resection approach. Voice quality after laser excision of such selected early lesions is usually excellent and comparable to that achieved with RT [29-32].
The choice of initial therapy for vocal preservation also impacts options for treatment in the event of a recurrence. For example, treatment with transoral surgery preserves the option of future RT to treat residual tumor or recurrence postoperatively. Surgery in a previously irradiated field may have a higher risk of complications. (See 'Management of recurrent disease' below.)
Ultimately, treatment choice may also be institution dependent and involve patient logistical issues (eg, professional voice users), comorbidities, and treatment preferences. The treating surgeon or radiation oncologist should have experience treating these tumors and should offer the patient an informed risk-benefit discussion regarding the ability of the chosen therapy to achieve durable laryngeal preservation.
Glottic regional lymph nodes — For patients with early stage glottic cancer and clinically negative neck nodes, we offer expectant management with observation of the neck rather than elective treatment with either RT or neck dissection. The glottic larynx possesses minimal lymphatic drainage, and nodal involvement is rare. Therefore, elective treatment of the neck with either surgery or RT is not indicated, as it does not impact survival outcomes and is associated with a risk of increased toxicities. (See 'Potential surgical complications' below and 'Risks and toxicities of radiation therapy' below.)
In observational studies, early stage glottic cancers had a low incidence of occult lymph node involvement (less than 5 percent) [6,33]. Additionally, one observational study suggested similar rates of locoregional nodal disease control between observation and neck dissection in patients with glottic tumors without clinical evidence of nodal disease (94 versus 98 percent) [34].
Supraglottic cancer — Supraglottic cancers, which constitute approximately one-third of laryngeal cancers, are aggressive tumors. Patients with supraglottic cancers often present with advanced disease, since hoarseness is not an early symptom and the supraglottis is rich in lymphatics (in contrast to those with cancers of the glottic larynx). Patients may present with signs of airway obstruction (stridor or dyspnea on exertion), dysphagia, pain, and/or metastatic lymphadenopathy [5]. The management of advanced disease is discussed separately. (See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx".)
Surgery or radiation therapy for primary supraglottic tumors — For patients with early stage supraglottic laryngeal cancer, we offer initial therapy with either RT or surgical resection. However, unlike glottic cancer, recurrences can be more difficult to salvage due to concomitant tumor progression within the neck. Treatment planning for the primary tumor must take into account the possibility of nodal disease and the added complexity of addressing the nodal basins. (See 'Supraglottic regional lymph nodes' below.)
In patients with early stage supraglottic cancer, both RT and surgery are effective in achieving local control (approximately 90 percent for stage I and 80 percent for stage II) and maintaining vocal cord mobility [10,35]. Despite excellent local control, the five-year overall survival rate is lower, at approximately 55 to 75 percent, primarily due to the increased risk of locoregional recurrence and distant metastasis in those with supraglottic cancers [10,11,36,37].
For patients who choose RT, we offer intensity-modulated radiation therapy (IMRT) with daily image guidance (ie, image-guided radiation therapy [IGRT]). RT techniques and efficacy are discussed separately. (See 'Radiation therapy techniques' below and "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Hypofractionation'.)
For patients with small early stage supraglottic tumors and good vocal cord mobility who choose surgery, we offer minimally invasive surgical resection with TLM rather than open supraglottic laryngectomy. TLM has similar rates of survival and laryngeal preservation but better functional outcomes and less postoperative morbidity compared with open partial laryngectomy in these patients [38,39]. Patients receiving surgery to the primary tumor should also undergo treatment of the neck lymph nodes. (See 'Supraglottic regional lymph nodes' below.)
Minimally invasive transoral surgery is an option for those with tumors involving the suprahyoid epiglottis, aryepiglottic fold, and superior rim of the epiglottis, and those with limited involvement of the false vocal cords; this approach may also be offered to select patients with tumors involving the infrahyoid epiglottis (figure 1A-B). Preoperative assessment of swallowing and pulmonary reserve is recommended to predict functional recovery (ie, safe swallowing) and reduce the risk of complications from aspiration. Regardless of the surgical approach, surgery aims to achieve negative resection margins [40]. The use of these surgical modalities is discussed separately. (See 'Larynx-preserving techniques' below.)
For patients who are not candidates for minimally invasive transoral surgery, we offer open surgery with either supraglottic laryngectomy (eg, for those with larger T2 lesions) or supracricoid laryngectomy (eg, for those with impaired vocal cord mobility), or RT on an altered fractionation schedule.
Modern surgical and RT techniques have not been directly compared in a randomized trial, and supporting evidence largely comes from indirect comparisons of observational studies [24,37,41-43]. A Surveillance, Epidemiology, and End Results (SEER) database analysis of approximately 2600 patients with early stage supraglottic tumors suggested improved five-year disease-specific survival for those treated with larynx-preserving surgery and neck dissection compared with RT (86 versus 68 percent for T1 tumors, 86 versus 60 percent for T2 tumors when neck dissection was also employed), although selection bias may have influenced these results [43]. Similarly, a randomized trial of open laryngectomy versus less contemporary RT techniques reported similar survival but higher rates of locoregional relapse with RT for laryngeal cancer, although data specific to supraglottic tumors are not available [16]. While there may be a small local control advantage for surgery, some patients may require postoperative RT and thus be at increased risk for toxicity due to the addition of more treatment modalities. The potential for this scenario often leads clinicians to use RT-based therapy, illustrating the selection bias seen in many series. Trials evaluating different RT techniques are discussed separately. (See "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Hypofractionation'.)
Supraglottic regional lymph nodes — Occult and bilateral neck lymph node metastases are frequent among patients with a clinically negative neck, as the supraglottis is a midline structure with rich bilateral lymphatic drainage [3,44-47]. Accordingly, for patients with early stage supraglottic cancer (T1 or T2 disease) treated with either primary RT or surgery, bilateral elective neck treatment of the upper, middle, and lower internal jugular nodes (levels IIA, III, and IV) is indicated, typically with the same modality used to treat the primary tumor (figure 2) [6]. The estimated relapse rate in those not receiving elective neck therapy is over 12 percent [43,48].
Patients receiving RT to the primary tumor should also receive elective neck RT directed at the associated bilateral neck draining lymph node basins. In observational studies, this approach is associated with similar rates of nodal relapse and survival compared with those treated with partial laryngectomy followed by neck RT [49].
Patients receiving surgery to the primary tumor should also be treated with either staging neck dissection (performed concurrently with resection of the primary tumor) or postoperative elective neck RT. Transoral laser surgery may be combined with postoperative elective neck RT, with high rates of locoregional control and survival (88 percent at three years), and good functional outcome in a majority of patients (90 percent) [50].
Subglottic cancer — Primary subglottic tumors are uncommon [12]. These tumors are usually asymptomatic until locally advanced and tend to present at later stages [51]. (See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx".)
However, small early stage subglottic tumors can occasionally present with hoarseness, dyspnea, or stridor. Direct extralaryngeal extension and cartilage invasion are common clinical findings [52]. Subglottic cancers have high rates of local recurrence and poor survival when compared with supraglottic and glottic cancers and require an aggressive treatment approach [52-54]. (See 'Epidemiology and risk factors' above.)
Radiation therapy for primary subglottic tumors — For patients with early stage subglottic tumors, we offer initial IMRT with daily image guidance (ie, IGRT), rather than initial laryngectomy, as this approach offers the best chance for laryngeal preservation and does not compromise long-term survival [55]. With this approach, estimated five-year disease-free and overall survival rates are 71 and 86 percent for stage I disease and 42 and 50 percent for stage II disease [12]. Patients with recurrent disease after initial RT are typically treated with salvage laryngectomy. (See 'Management of recurrent disease' below.)
Some experts may offer initial surgery with either a total or extended partial laryngectomy as an alternative to RT. Thyroidectomy (which includes pretracheal nodal dissection) and bilateral paratracheal nodal dissection are also performed in addition to laryngectomy. However, patients who choose surgery as initial therapy may eventually require adjuvant RT or chemoradiation due to the presence of high-risk features or positive surgical margins on postoperative pathology. Those who do not receive adjuvant RT are at risk for locoregional and stomal recurrences [56].
Because early stage subglottic tumors are rare (approximately 10 to 12 percent of all subglottic tumors) [55], data comparing RT with surgery mainly come from observational studies [51,54,55,57]. As an example, one observational study of those with early stage subglottic disease treated with RT suggested a local control rate of approximately 65 percent (15 of 23 patients), and many who developed recurrent disease after RT were able to receive salvage surgery [54].
Subglottic regional lymph nodes — Primary subglottic tumors drain to the prelaryngeal (Delphian) and pretracheal nodes, to the paratracheal and inferior jugular nodes, and in some cases, to the mediastinal nodes (figure 2) [58-61]. Patients receiving RT to the primary tumor should also receive elective nodal RT to its associated draining lymph node basins, including the upper, middle, and lower internal jugular nodes (levels IIA, III, and IV) and the anterior compartment nodes (level VI). Patients receiving surgery to the primary tumor should also be treated with pretracheal and bilateral paratracheal nodal dissection, with or without postoperative neck RT [51]. In one observational study, paratracheal nodal dissection was associated with a decrease in paratracheal recurrences in patients with subglottic tumors treated with surgical resection [62]. (See 'Adjuvant radiation therapy' below.)
TREATMENT MODALITIES — The most common treatment modalities for early stage laryngeal cancer are radiation therapy (RT) and larynx-preserving surgery (eg, transoral surgery and open partial laryngectomy). Both approaches can cure a high proportion of patients and offer good functional outcomes. However, each treatment modality has unique administration details and differs in its potential risks and toxicities.
The approach to locoregional therapy for specific sites of laryngeal cancer is discussed separately. (See 'Initial site-specific management' above.)
Radiation therapy
Radiation therapy techniques — Patients with early stage laryngeal cancer receiving RT are treated with standard three-dimensional conformal radiation therapy (3D-CRT) techniques, including intensity-modulated radiation therapy (IMRT) [63]. IMRT is the standard of care in the United States for supraglottic cancer. Additionally, IMRT can be enhanced with pretreatment imaging on a daily basis, a technique known as image-guided radiation therapy (IGRT). Both techniques accurately deliver radiation to the planned target tumor volume while minimizing toxicity to the uninvolved portions of the larynx and adjacent structures. Adjacent structures include the pharyngeal constrictors, oral mucosa, submandibular and parotid salivary glands, mandible, esophagus, carotid arteries, and spinal cord. Further details regarding 3D-CRT and IMRT techniques are discussed separately. (See "General principles of radiation therapy for head and neck cancer", section on 'Three-dimensional conformal RT'.)
RT for glottic cancer can be delivered using IGRT with standard RT techniques that include opposed lateral fields covering the larynx, with wedging of the beams to reduce dose heterogeneity. An anterior field or oblique fields can also be added to reduce dose inhomogeneity outside of the treatment volume or, if disease is lateralized to one cord, to reduce the RT dose to the contralateral cord. There is also interest in using IGRT or IMRT with smaller fields and sparing of the contralateral uninvolved vocal cord and carotid arteries, with the goals of reducing stroke risk and preserving tissue in case reirradiation is required for a second primary tumor [64,65]. However, these techniques are not considered standard [66-68].
RT for supraglottic or subglottic cancers is typically delivered using IMRT with daily IGRT to both the primary tumor and elective nodes. (See "General principles of radiation therapy for head and neck cancer", section on 'Image-guided RT'.)
Treatment interruptions should be avoided while patients are receiving RT, as prolonged overall treatment time is associated with worse clinical outcomes [69]. Such interruptions can be minimized with appropriate supportive care. (See "Management and prevention of complications during initial treatment of head and neck cancer".)
Further information regarding RT techniques, doses, and schedules is discussed separately. (See "General principles of radiation therapy for head and neck cancer" and "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations".)
Altered fractionation schedules — Patients with early stage laryngeal cancer should be treated using altered fractionation schedules rather than standard fractionation schedules, with the selected schedule based on the site and stage. Hypofractionation uses higher daily RT doses per fraction with fewer total fractions, whereas accelerated fractionation uses the same or a slightly reduced dose per fraction with more fractions delivered either per day or per week [70]. Hyperfractionation employs lower doses per fraction with more fractions delivered per day.
●Glottic – Early stage glottic squamous cell carcinoma is commonly treated with altered fractionation schedules.
•T1 disease – For patients with T1 glottic cancer, our approach is to use hypofractionation, which has demonstrated an improvement in local control, with a similar toxicity profile relative to standard fractionation [71,72].
•T2 disease – Patients with T2 glottic cancer with normal vocal cord mobility are often treated with altered fractionation (eg, accelerated fractionation or hyperfractionation) without chemotherapy, which may improve local control [73-75].
●Supraglottic and subglottic – There are limited data evaluating altered fractionation schedules in patients with supraglottic cancers. The RT schedule is chosen at the discretion of the radiation oncologist. T1-2N0 supraglottic cancers are well treated with single-modality RT, and our experts prefer an accelerated fractionation schedule.
Further details regarding the various approaches and data for alternative RT fractionation schedules are discussed separately. (See "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Paradigms of dose and fractionation modification'.)
As described in more detail separately, accelerated RT and hyperfractionation have been compared with standard fractionation schedules in randomized trials of patients with laryngeal cancer (Danish Head and Neck Cancer Group [DAHANCA] 6 and 7, and RTOG 9512, respectively). In patients with glottic cancer, accelerated RT improved local control rates relative to standard schedules, and hyperfractionation trended towards improved local control, although the results were not statistically significant [73-75]. However, a majority of the patients evaluated in these studies had advanced-stage disease (approximately three-quarters with node-positive disease in the DAHANCA trial and one-half with impaired cord mobility suggesting higher stage [ie, T3] disease in RTOG 9512), neither study showed a difference in overall survival, and both demonstrated higher rates of acute toxicity, such as mucositis. (See "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Hyperfractionation' and "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Accelerated fractionation RT'.)
Definitive chemoradiation — RT is typically delivered as a single-agent modality, without concurrent chemotherapy, in patients with early stage laryngeal cancer. Only highly selected patients with T2 cancers (eg, bulky invasive T2 cancers, especially glottic or supraglottic cancers, with impaired cord mobility) may be appropriate for concurrent chemoradiation, although there are limited data to support this approach. More commonly, larger T2 cancers are treated with altered fractionation RT alone [74]. (See 'Altered fractionation schedules' above.)
Chemotherapy alone, without RT, does not have a role in the management of early stage laryngeal cancer outside of a clinical trial setting.
The approach to combined modality therapy with RT and chemotherapy in locoregionally advanced laryngeal cancer is discussed separately. (See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx", section on 'Combined modality therapy'.)
Risks and toxicities of radiation therapy — Early toxicities associated with RT include radiation dermatitis, mucositis, (increased) hoarseness, and swallowing difficulties. Odynophagia and dysphagia commonly develop during the course of RT, but these acute toxicities are mild (grade ≤2) and typically resolve within two to eight weeks of treatment completion. (See "Management and prevention of complications during initial treatment of head and neck cancer".)
Patients with early stage laryngeal cancer are less likely to have prolonged acute, subacute, and permanent toxicity than patients with advanced laryngeal cancer, who require larger RT volumes and concurrent chemotherapy [76]. It is also uncommon for those treated with RT to require permanent feeding tubes [24]. However, long-term toxicities can occasionally occur, including prolonged edema of the larynx, soft tissue necrosis leading to chondritis, and laryngeal or pharyngeal stenosis [10,77]. (See "Management of late complications of head and neck cancer and its treatment".)
The impact of RT on postoperative voice quality is discussed separately. (See 'Glottic cancer' above.)
Surgery — Minimally invasive larynx-preserving surgical techniques are preferred over open techniques when possible. Various techniques are described as follows. Anesthesia for head and neck surgery is discussed separately. (See "Anesthesia for head and neck surgery".)
Larynx-preserving techniques — Minimally invasive larynx-preserving surgical techniques to treat patients with early laryngeal cancer include transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). These surgical techniques should be undertaken only when the surgeon is confident that tumor-free margins can be obtained. Often, these techniques can be performed on an ambulatory basis, and patients are discharged home after recovery from anesthesia.
For patients with early stage laryngeal cancer who choose surgery as initial therapy and are candidates for minimally invasive transoral surgical approaches, we offer TLM, rather than open partial laryngectomy, due to the comparable efficacy, decreased morbidity, and improved preservation of laryngeal function. Those who are not candidates for transoral surgical approaches are typically treated with open partial laryngectomy. In contrast, total laryngectomy is rarely indicated for stage I and stage II laryngeal cancer and should be reserved for salvage when no other meaningful option exists.
There are limited high-quality observational data comparing TORS with TLM in patients with early stage laryngeal cancer [24]. Although we do not use TORS in this setting, other experts with TORS experience may offer this technique to select patients. Further randomized trials are needed to directly evaluate the risks and benefits of TORS in patients with early stage laryngeal cancer.
●Transoral laser microsurgery – TLM is a minimally invasive technique that combines suspension laryngoscopy with an operating microscope, microsurgical instruments, and a carbon dioxide laser. The tumor is transected, revealing the depth of invasion and allowing visualization of tumor margins, and is removed piecemeal through the laryngoscope. At least one mobile arytenoid complex must be preserved so that function of the larynx is maintained.
A carbon dioxide laser is a cutting instrument that allows for retrieval of a specimen for margin analysis. It is typically used with TLM because its frequency of light is absorbed by water, thus minimizing tissue damage. However, because water is the target, the carbon dioxide laser is indiscriminate and the lamina propria is also damaged. The potassium titanyl phosphate (KTP) laser has also been used as an alternative to carbon dioxide for carcinoma in situ or small T1 cancers, as it preserves the lamina propria [78]. However, because KTP lasers vaporize the specimen, margin analysis is not possible for bulkier T1 or T2 cancers. Precise tumor excision is obtained with a KTP laser because microsurgical visualization of the cancer and peripheral normal tissue is superior due to enhanced hemostasis and minimal carbonized normal tissue obscuring the margin. The KTP laser may be reserved for glottic carcinoma in situ or small T1 cancers, as it spares the lamina propria, which never regenerates, promoting better voice quality, while the carbon dioxide laser is a better cutting tool for larger glottic and supraglottic tumors.
For patients with early stage laryngeal cancer in whom complete resection can be achieved, transoral laser surgery is preferred over open partial laryngectomy, as observational studies suggest comparable efficacy with decreased morbidity and improved preservation of laryngeal function with transoral laser surgery [17,79-81]. Further details on the use of TLM in patients with advanced laryngeal cancer are discussed separately. (See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx", section on 'Larynx preservation surgery'.)
●Transoral robotic surgery – TORS is another minimally invasive transoral surgical approach for patients with early stage disease. Although we do not offer TORS in this setting, other experts with TORS experience may offer this technique to carefully selected patients with adequate visualization of tumor using robotic retractors.
TORS has comparable local control outcomes and a decreased risk of morbidity and surgical complications relative to other more invasive open surgical techniques [17,82-85]. (See 'Potential surgical complications' below.)
Laryngectomy — Total laryngectomy is only rarely indicated for stage I and stage II laryngeal cancer and should be reserved for salvage when no other meaningful option exists. Although total laryngectomy is a straightforward surgical procedure that can eradicate tumor confined to the cartilaginous boundaries of the larynx, loss of natural voice and the stigma, lifestyle, and voice restrictions of a permanent stoma make it a procedure that patients fear. Although different options for voice rehabilitation exist, many patients express dissatisfaction with the results; social isolation, job loss, and depression are common sequelae [86,87]. (See "Health-related quality of life in head and neck cancer" and "Alaryngeal speech rehabilitation".)
Adjuvant radiation therapy — Occasionally, early stage laryngeal cancers will be resected but then will be found on postoperative pathology to have microscopically positive resection margins or lymphovascular or perineural invasion or will be upstaged to stage III/IV (eg, positive nodes, larger primary tumor, and/or deep cartilage invasion) [88]. In these settings, postoperative RT is indicated, although in some cases, secondary surgical clearance of a margin may allow for observation rather than RT. In some settings (eg, nodal extracapsular extension and/or grossly positive margins), adjuvant chemoradiation is indicated. (See "Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx" and "Adjuvant radiation therapy or chemoradiation in the management of head and neck cancer".)
Potential surgical complications — Potential acute complications of surgery include postoperative pain, bleeding, dysphagia or odynophagia, and postoperative infections. Many of these complications are less frequent and more limited in duration with transoral surgical approaches compared with open laryngectomy [89]. Certain transoral surgical techniques, particularly for supraglottic tumors, also require patients to have good swallowing and pulmonary reserve. Accordingly, careful preoperative evaluation is necessary to avoid certain treatment-related complications, such as aspiration pneumonia. In one systematic review, the event rate of aspiration in patients with early stage supraglottic tumors receiving larynx-preserving surgery was estimated to be approximately 4 percent [24]. (See 'Supraglottic cancer' above.)
More chronic complications include tracheopharyngeal and laryngocutaneous fistulas, tracheostomy or feeding tube dependence, long-term fibrosis, dysphagia, and psychosocial distress [17,24]. However, many of these chronic toxicities occur less frequently with minimally invasive transoral surgical approaches compared with open laryngectomy [17,85,89]. For example, transoral laser surgery has been associated with improved swallowing outcomes, shorter hospital stays, decreased postoperative morbidity, and decreased postoperative dependence on tracheostomy and feeding tubes relative to open laryngectomy [17,38,39,90,91]. Furthermore, transoral laser surgery may eliminate the need for emergency tracheostomy in patients who present with obstructing lesions [17].
Potential complications related to anesthesia and the impact of transoral surgical approaches on postoperative voice quality in patients with early stage laryngeal tumors are discussed separately. (See "Anesthesia for head and neck surgery" and 'Vocal outcomes for radiation therapy versus surgery' above.)
MANAGEMENT OF RECURRENT DISEASE — While the prognosis for early stage laryngeal cancer treated with curative intent is excellent overall, some patients may develop locoregionally recurrent disease. Examples of prognostic factors for disease recurrence include T2 disease, subglottic extension, anterior commissure involvement, impaired vocal cord mobility, and high tumor volume [92-96].
Local recurrence following radiation therapy (RT) is typically treated with surgical salvage [97]. Although some patients can be salvaged with larynx-preserving procedures, total laryngectomy is necessary in more than one-half of cases [97-99]. For a minority of patients with laryngeal cancer who are not candidates for or decline further resection, reirradiation is a less preferred option and may be associated with rates of late grade 3 to 4 toxicity of 10 to 20 percent [100]. (See "Treatment of locally recurrent squamous cell carcinoma of the head and neck", section on 'Salvage surgery' and "Reirradiation for locally recurrent head and neck cancer".)
Local recurrence following initial surgery can either be treated with further surgical salvage or definitive RT. Further information regarding these treatment approaches for locally recurrent laryngeal cancer is discussed separately. (See "Treatment of locally recurrent squamous cell carcinoma of the head and neck".)
The use of systemic therapy in patients with metastatic disease is discussed separately. (See "Treatment of metastatic and recurrent head and neck cancer".)
POSTTREATMENT SURVEILLANCE — Regular posttreatment follow-up is an essential part of the care of patients after potentially curative treatment of laryngeal cancer. Patients should be educated about possible signs and symptoms of tumor recurrence, including hoarseness, pain, dysphagia, bleeding, dyspnea/stridor, and enlarged lymph nodes. The specific details and schedules for such surveillance are discussed separately. (See "Posttreatment surveillance of squamous cell carcinoma of the head and neck".)
In general, the intensity of follow-up is greatest in the first two to four years, since approximately 80 to 90 percent of all recurrences after curative-intent treatment will occur during this period. Continued follow-up beyond five years is generally suggested, for second primary malignancies, particularly in patients with a significant smoking history. Patients who smoke should be counseled about smoking cessation and options to help quit smoking. Chest imaging for lung cancer screening may also be indicated for patients with a smoking history. (See "Overview of smoking cessation management in adults" and "Screening for lung cancer".)
Supportive care in the posttreatment period is warranted, including assessment of late treatment-related toxicities as well as voice, swallowing, and physical rehabilitation. This is discussed separately:
●(See "Overview of approach to long-term survivors of head and neck cancer".)
●(See "Management of late complications of head and neck cancer and its treatment".)
●(See "Speech and swallowing rehabilitation of the patient with head and neck cancer".)
●(See "Physical rehabilitation for cancer survivors".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Head and neck cancer".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Laryngeal cancer (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Goals of therapy – Patients with early (stage I and II) laryngeal cancer (table 1) are treated with curative intent using therapies that optimize locoregional control, survival, and laryngeal function (eg, swallowing ability, airway protection, and voice quality). (See 'Goals of therapy' above.)
●Treatment modalities – The most common treatment modalities are radiation therapy (RT) and larynx-preserving surgery (eg, transoral surgery and open partial laryngectomy). Both approaches offer good survival and functional outcomes, but each has unique administration details and differs in its potential toxicities and complications. (See 'Treatment modalities' above and 'Risks and toxicities of radiation therapy' above and 'Potential surgical complications' above.)
●Voice preservation – Both RT and transoral surgical approaches offer reasonable opportunities for voice preservation in patients with early stage laryngeal cancer. Patients should be offered a risk-benefit discussion regarding long-term vocal preservation with either approach. (See 'Vocal outcomes for radiation therapy versus surgery' above.)
●Initial site-specific management – The preferred therapy differs according to the location of disease (ie, supraglottic, glottic, or subglottic larynx (figure 1A-B)) (see 'Initial site-specific management' above):
●Glottic cancer – For patients with glottic cancer, we offer initial therapy to the primary tumor with either transoral surgery or RT, as both approaches offer similar efficacy and survival outcomes. (See 'Glottic cancer' above.)
•Surgery – For patients with superficial midcord lesions who choose surgery, we offer transoral laser microsurgery (TLM) to minimize vocal cord resection and maximize voice quality outcomes. For those who require more extensive resection, RT is preferred over open laryngectomy.
•Radiation therapy – For patients who choose RT, three-dimensional conformal radiation therapy (3D-CRT) with image-guided radiation therapy (IGRT) is standard; however, the use of intensity-modulated radiation therapy (IMRT) with smaller RT fields (to spare the contralateral uninvolved vocal cord and carotid arteries) is becoming more common. (See 'Radiation therapy techniques' above.)
•Glottic regional lymph nodes – For those with clinically negative neck nodes, elective treatment of the neck is not indicated, as nodal involvement is rare. (See 'Glottic regional lymph nodes' above.)
●Supraglottic cancer – For patients with supraglottic cancer, we offer initial therapy to the primary tumor with either RT or surgical resection. (See 'Supraglottic cancer' above.)
•Radiation therapy – For patients who choose RT, IMRT with IGRT is standard. (See 'Radiation therapy techniques' above.)
•Surgery – For select patients with good vocal cord mobility who choose surgery, we suggest minimally invasive transoral surgical approaches (with preoperative assessment of swallowing and pulmonary reserve) rather than open supraglottic laryngectomy (Grade 2C).
For those who are not candidates for minimally invasive transoral surgery (eg, those with larger T2 lesions and/or impaired vocal cord mobility), we offer either open supraglottic laryngectomy or altered fractionation RT.
•Supraglottic regional lymph nodes – For those with clinically negative neck nodes, we recommend bilateral elective neck treatment of the upper through lower internal jugular chain lymph nodes (levels IIA through IV) (figure 2) rather than observation (Grade 2C). Patients receiving RT to the primary tumor should also be treated with elective neck RT, whereas those receiving surgery to the primary tumor should also be treated with either staging neck dissection or postoperative elective neck RT. (See 'Supraglottic regional lymph nodes' above.)
●Subglottic cancer – For patients with subglottic cancer, we suggest initial RT to the primary tumor, rather than initial laryngectomy, to optimize laryngeal preservation (Grade 1C). IMRT with daily IGRT is the standard treatment approach. While some experts may offer initial surgery with laryngectomy, this is a morbid procedure, and a subset may ultimately require adjuvant RT or chemoradiation based on findings at surgery. (See 'Subglottic cancer' above and 'Radiation therapy techniques' above.)
•Subglottic regional lymph nodes – For those with clinically negative neck nodes, we recommend bilateral elective neck treatment of the upper through lower internal jugular chain lymph nodes (levels IIA through IV) and the anterior compartment nodes (level VI) (figure 2) rather than observation (Grade 2C). Patients receiving RT to the primary tumor should also be treated with elective nodal RT, whereas those receiving surgery to the primary tumor should also be treated with pretracheal and bilateral paratracheal nodal dissection, with or without postoperative neck RT. (See 'Subglottic regional lymph nodes' above.)
●Altered fractionation schedules for radiation therapy – For patients with glottic laryngeal cancer receiving RT, we offer an altered fractionation schedule, which improves local control and has a similar toxicity profile relative to standard fractionation. (See 'Altered fractionation schedules' above and "Definitive radiation therapy for head and neck cancer: Dose and fractionation considerations", section on 'Paradigms of dose and fractionation modification'.)
●Surgical approaches – For patients who are surgical candidates for minimally invasive transoral approaches, we suggest TLM, rather than open partial laryngectomy, due to the comparable efficacy, decreased morbidity, and improved functional preservation (Grade 2C). Those who are not candidates for transoral surgical approaches are treated with open partial laryngectomy. Total laryngectomy is rarely indicated for early stage laryngeal cancer and is typically reserved for salvage therapy. (See 'Surgery' above.)
●Indications for postoperative radiation therapy – We offer postoperative RT to patients treated with primary surgery with microscopically positive resection margins, lymphovascular or perineural invasion, deep cartilage invasion, or pathologically positive lymph nodes identified after neck dissection. We offer postoperative concurrent chemoradiation to those with grossly positive margins or extracapsular extension. (See 'Adjuvant radiation therapy' above.)
●Posttreatment surveillance – Regular posttreatment follow-up is an essential part of the care of patients after potentially curative treatment of laryngeal cancer. Local recurrence following RT is typically treated with surgical salvage, while local recurrence following initial surgery can either be treated with further surgical salvage or definitive RT. (See 'Posttreatment surveillance' above and "Treatment of locally recurrent squamous cell carcinoma of the head and neck".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Mitchell Machtay, MD, who contributed to an earlier version of this topic review.
