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Treatment of locoregionally advanced (stage III and IV) head and neck cancer: The larynx and hypopharynx
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Apr 2012. | This topic last updated: Jan 24, 2012.

INTRODUCTION — Worldwide, there are approximately 130,000 new laryngeal cancer cases and 70,000 deaths annually [1]. In the United States, laryngeal cancer accounts for about 25 percent of the 52,000 cases of head and neck cancer diagnosed annually [2,3]. Glottic, supraglottic, and subglottic cancers represent approximately two-thirds, one-third, and two percent of laryngeal cancers, respectively. Hypopharyngeal cancer is less common than laryngeal cancer, with approximately one fourth as many cases.

Tumors of the glottic larynx commonly present with hoarseness and are diagnosed at an early stage. However, patients with supraglottic and subglottic laryngeal cancers, as well as hypopharyngeal cancers, usually present with advanced disease due to a paucity of symptoms, propensity for local extension (subglottis), and rich lymphatics resulting in a high incidence of lymph node metastases (supraglottis).

The management of locoregionally advanced laryngeal and hypopharyngeal cancer is presented here. The treatment of early stage laryngeal and hypopharyngeal cancers are discussed separately.

ANATOMY AND STAGING — The larynx is divided into three anatomic regions (figure 1A-B):

  • 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 lower boundary of the glottis to the lower margin of the cricoid cartilage

The hypopharynx lies beside and behind the larynx and extends to the esophageal inlet. It contains the paired pyriform sinuses, the posterior pharyngeal wall, and the postcricoid area (figure 2).

The tumor node metastases (TNM) staging system of the American Joint Committee on Cancer (AJCC) and the International Union for Cancer Control (UICC) is used to classify cancers of the larynx (table 1) and hypopharynx (table 2) [4]. For laryngeal cancers, staging of the primary tumor (T) is defined separately for supraglottic, glottic, and subglottic tumors. (See "Overview of the diagnosis and staging of head and neck cancer".)

OVERVIEW OF MANAGEMENT — All patients with advanced (stage III and IV) cancer of the larynx or hypopharynx should be seen prior to treatment by a multidisciplinary team with experience in the treatment of head and neck cancer. Selection of a treatment approach depends upon tumor extent and location, patient-specific factors (eg, age, performance status, comorbidity, psychosocial support), physician expertise, and the availability of rehabilitation services. Treatment-related toxicity associated with chemoradiotherapy and rehabilitation issues related to surgery must also be considered.

Functional organ preservation is widely recommended and generally utilizes a combination of chemotherapy plus radiation therapy (RT). However, advances in surgical techniques, such as laryngeal preservation surgery and minimally invasive surgery, offer alternative options for larynx preservation in carefully selected patients. These surgical approaches have not been directly compared to chemoradiotherapy [5]. (See 'Larynx preservation surgery' below.)

Although functional organ sparing approaches permit larynx preservation in patients with locoregionally advanced cancer of the larynx and hypopharynx, they do not provide a survival advantage over total laryngectomy. When feasible, most patients should be offered the option of organ preservation because of the importance of the larynx to speech and swallowing (table 3) [6].

In addition, patients should be counseled about smoking cessation; ongoing tobacco use during radiotherapy has been associated with reduced survival in patients with locally advanced head and neck cancer [7,8].

COMBINED MODALITY THERAPY — Induction chemotherapy was given as a neoadjuvant prior to definitive RT in the initial clinical trials. Subsequent trials have used chemotherapy given at the same time as RT (concurrent chemoradiotherapy), and induction chemotherapy has been combined with concurrent chemoradiotherapy in sequential therapy regimens.

Chemoradiotherapy and induction chemotherapy have replaced total laryngectomy plus postoperative RT as functional organ preserving alternatives in the treatment of potentially operable, locally advanced cancer of the larynx and hypopharynx for most good performance status patients. Chemoradiotherapy and induction chemotherapy approaches require that the patient be able to withstand the prolonged course of treatment and associated toxicities and participate in rehabilitation from the radiation [9].

Chemoradiotherapy and induction chemotherapy are also used to provide definitive treatment for patients who are inoperable because of extensive locoregional disease.

While chemoradiotherapy and induction chemotherapy usually maintain laryngeal function in patients with resectable disease, they are associated with considerable toxicity that in rare cases may compromise the patient’s ability to protect the airway and thus may not achieve the goal of functional larynx preservation. Thus, organ function-preserving approaches are not appropriate for all patients with locoregionally advanced cancer of the larynx and hypopharynx:

  • Elderly patients and those with a poor performance status may not be suitable candidates for this treatment because of the toxicity associated with chemotherapy and chemoradiotherapy. Definitive radiation therapy alone or total laryngectomy followed by postoperative RT may be preferable in this setting. (See 'Elderly and poor performance status patients' below.)
  • Patients with destruction of both vocal cords may not recover vocal or airway protective function with larynx-preservation approaches and may function better after total laryngectomy, when feasible, rather than induction chemotherapy and/or chemoradiotherapy. (See 'Total laryngectomy' below.)
  • The optimal treatment for tumors with limited cartilage invasion (stage T4a) is controversial (table 1). Significant cartilage destruction prior to treatment may be an indication for initial laryngectomy, because cartilage destruction limits the probability of adequate response and functional recovery with larynx-preserving approaches and increases the probability of radiation-induced necrosis [10,11].

    However, the presence of cartilage invasion alone does not necessarily preclude an organ sparing approach [12-15]. When the findings are unclear, an attempt at functional larynx preservation may be undertaken with surgery as salvage if needed.

Feasibility of functional organ preservation — The feasibility of functional organ preservation using induction chemotherapy prior to definitive RT was established by the Department of Veterans Affairs (VA) Laryngeal Cancer Study Group larynx trial. Similar results were seen in a European cooperative group trial that included patients with cancers of the hypopharynx as well as the larynx.

  • In the VA trial, 332 patients with stage III or IV laryngeal cancer were randomly assigned to either three cycles of induction chemotherapy with cisplatin and 5-fluorouracil (PF) followed by definitive RT or primary surgery (typically total laryngectomy) followed by postoperative RT [10]. Patients without at least a partial response and those with any evidence of disease progression during or after induction chemotherapy were treated with surgery and postoperative radiation therapy (RT).

    At a median follow-up of 33 months, the two-year survival rate was equal in both treatment groups (68 percent), and the larynx was successfully preserved in 64 percent of patients treated with induction chemotherapy [10]. A subsequent reported that the three-year survival rates were 53 and 56 percent for chemotherapy plus RT and surgery plus RT, respectively [16].
  • In the European trial, 194 patients with stage II through IV squamous cell carcinoma of the pyriform sinus or aryepiglottic fold were randomly assigned to receive induction chemotherapy with PF followed by definitive RT or surgery (total laryngectomy with partial pharyngectomy) followed by postoperative RT [17,18]. Patients who failed to achieve a complete response to induction chemotherapy underwent salvage surgery and postoperative RT. At a median follow-up of 10 years, similar five-year progression-free and overall survival rates were observed with induction chemotherapy compared with surgery (32 versus 26 percent and 38 versus 33 percent, respectively).

Following the demonstration of benefit with induction chemotherapy followed by RT, various subsequent trials evaluated the concurrent administration of chemotherapy with radiation therapy (concurrent chemoradiotherapy) and induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy). (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy".)

Concurrent chemoradiotherapy — The most extensive data on the role of different approaches in patients with stage III or IV laryngeal cancer come from the intergroup Radiation Therapy Oncology Group (RTOG) 91-11 trial [19]. In this trial, 547 patients were randomly assigned to one of three groups:

  • Induction chemotherapy, using cisplatin (100 mg/m2 on day 1) plus 5-fluorouracil (1000 mg/m2/day by continuous intravenous infusion for five days), for three cycles followed by definitive RT
  • Definitive RT, with concurrent cisplatin (100 mg/m2 on days 1, 22, and 43)
  • Definitive RT alone

Definitive RT in all three groups was given in 35 fractions of 2 Gy, for a total dose of 70 Gy.

At a median follow-up of 6.9 years, five-year locoregional disease control was significantly better with concurrent therapy compared with induction chemotherapy or RT alone (69 versus 55 and 51 percent, respectively). Laryngectomy-free survival was significantly better with either concurrent chemoradiotherapy or induction chemotherapy compared to RT alone (47 and 45 versus 34 percent). Overall survival was similar for all three arms (55, 59, and 54 percent, respectively) [20]. However, only 10 percent of the patients on this trial had T4 primary site presentations.

Additional data supporting the role of concurrent chemotherapy come from the 2011 update of the Meta-Analysis of Chemotherapy on Head and Neck Cancer (MACH-NC) Collaborative Group, which conducted a comprehensive analysis by tumor site [21]. This analysis was based upon individual patient data for 3216 patients with laryngeal cancer. There was an overall benefit for the addition of chemotherapy to locoregional therapy (hazard ratio [HR] for death 0.87, 95% CI 0.80-0.96). Furthermore, this benefit with concomitant chemoradiotherapy (HR 0.80, 95% CI 0.71-0.90) was significantly better than with neoadjuvant chemotherapy or adjuvant chemotherapy, although this analysis did not examine PF or TPF induction specifically as has been the case for the analyses of 2009 and 2010. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Concurrent chemotherapy'.)

For the 2767 patients with hypopharyngeal cancer, a similar benefit in survival with chemotherapy was observed (HR 0.88, 95% CI 0.80-0.96). However, there was no statistically significant difference between those given concomitant chemoradiotherapy (HR 0.85) and those given neoadjuvant chemotherapy (HR 0.88), although the authors cautioned that the study may not have adequate power to detect a difference in this disease site.

Based upon these results, concurrent chemoradiotherapy is widely recommended for good performance status patients with resectable locally advanced (stage III and carefully selected stage IV) laryngeal and hypopharyngeal cancer, with a platinum-based chemotherapy regimen, such as cisplatin (100 mg/m2 every three weeks).

Induction chemotherapy — Induction chemotherapy followed by definitive RT is an alternative for the functional organ preservation treatment of locally advanced cancer of the larynx and hypopharynx. Although this approach may not be as effective as concurrent chemoradiotherapy in initial control of locoregional disease without salvage laryngectomy, induction therapy may decrease the incidence of distant metastases compared with concurrent chemoradiotherapy alone [10,19,22].

In earlier reports of the MACH-NC meta-analysis, there was no statistically significant survival benefit for induction chemotherapy in general versus definitive locoregional therapy alone, although there was a benefit for induction chemotherapy in the subset of trials using induction with cisplatin plus 5-fluorouracil (hazard ratio (HR) 0.88, 95% CI 0.79-0.97) [21,22]. Furthermore, the subsequent TAX 323 trial found that a three-drug combination that added a taxane to cisplatin plus 5-fluorouracil regimen significantly improved overall survival compared with cisplatin plus 5-fluorouracil alone, when both were followed by definitive RT [23]. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Induction chemotherapy'.)

The responsiveness of the tumor to induction therapy provides predictive and prognostic information that may be useful in deciding whether functional organ preservation is feasible or whether surgical resection is indicated or whether more intensive chemoradiotherapy might be given. Three or four cycles of docetaxel, cisplatin, and fluorouracil (TPF) chemotherapy are typically used for induction therapy [23,24].

Sequential chemoradiotherapy — Sequential therapy incorporates induction chemotherapy followed by concurrent chemoradiotherapy. In theory, sequential therapy combines the reduction in distant metastases afforded by induction chemotherapy with improvements in locoregional control achieved with concurrent chemoradiotherapy. The most extensive data on sequential chemoradiotherapy in squamous head and neck cancer come from the TAX 324 trial, which demonstrated improved effectiveness of induction with docetaxel, cisplatin, plus 5-fluorouracil (TPF) rather than cisplatin plus 5-fluorouracil alone, with both regimens followed by concurrent chemoradiotherapy using weekly carboplatin [24].

Sequential therapy has not been compared with concurrent chemoradiotherapy alone in adequately powered randomized trials. Patients who might benefit the most from sequential therapy are those with large primary tumors (T4) and/or advanced nodal presentations (large N2a, N2b, N2c, and N3) who are at high-risk for distant metastases. When a sequential therapy approach is chosen, we generally use TPF induction chemotherapy, followed by concurrent therapy with carboplatin, as used in the TAX 324 trial [24]. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Induction chemotherapy'.)

[10-15,25-27]

Experimental chemotherapy approaches — In two series, carefully selected patients with locally advanced laryngeal cancer (predominantly glottis cancers) were managed with observation only following a complete response to induction chemotherapy [28,29].

This approach resulted in long-term disease control in about 30 percent. This is lower than would be expected with an initial combined modality approach and may compromise the opportunity for cure.

Chemotherapy followed by observation is investigational and should be considered only in the context of a clinical trial.

SURGERY — Although chemoradiotherapy is now widely used in patients with locoregionally advanced disease, surgery retains a role in carefully selected patients as an alternative approach to functional organ preservation. Surgery is also important for the management of patients who are not candidates for chemoradiotherapy.

Larynx preservation surgery — Surgical approaches that preserve the larynx, used in combination with postoperative RT or chemoradiotherapy, may provide an alternative treatment option for patients with advanced disease due to neck node burden but with small T-stage primary lesions. In carefully selected cases, such approaches may provide effective local control while maintaining laryngeal function and avoiding a permanent tracheal stoma. Following detailed preoperative evaluation, partial laryngectomy or minimally invasive surgery may be considered.

Preoperative evaluation — Detailed preoperative assessment is critical for patient selection for larynx preservation surgery:

  • Preoperative laryngeal examination (typically flexible fiber optic examination and/or videostroboscopy), with careful attention to the mobility of the vocal cord and arytenoid cartilages, is critical. Fixation of the vocal cord is an important negative prognostic finding.
     
  • Imaging using CT or MRI can help assess the degree of invasion; however, these techniques are limited by low sensitivity [30-33]. Dynamic imaging, such as a modified barium swallow, is also important in evaluating laryngeal function.
  • Patient selection should consider the patient's ability to actively participate in speech and swallowing rehabilitation. Other treatment options should be considered in patients with significant impairments to rehabilitative potential and in those who will require postoperative radiation therapy (RT), since functional outcomes after laryngeal conservation surgery and postoperative RT might be significantly worse than after concurrent chemoradiotherapy.
  • Pulmonary reserve, assessed with pulmonary function tests and assessment of exercise tolerance, is an important indicator of how a patient will tolerate postoperative aspiration [31].
     
  • Intraoperative assessment, with visualization through a rigid endoscopic examination and palpation of the larynx, aids surgical planning by determining tumor extent and evaluating the uninvolved larynx.

Partial laryngectomy — Partial laryngectomy (partial horizontal supracricoid laryngectomy with cricohyoidopexy) may offer an alternative to concurrent chemoradiotherapy and total laryngectomy as primary treatment for advanced tumors [34-36]. Partial laryngectomy has also been used in carefully selected cases as salvage treatment for locally recurrent disease following RT [37].

In general, partial laryngectomy can be used in selected cases of T2 to T4 supraglottic and glottic tumors, with invasion of the anterior commissure, thyroid cartilage, pre-epiglottic space, paraglottic space, or subglottis [38-40]. The procedure involves resection of the entire thyroid cartilage, epiglottis, and pre-epiglottic and paraglottic spaces. Although a temporary tracheostomy is required because of acute impairment of swallowing and aspiration, permanent tracheostomy and/or gastrostomy are rarely required.

In case series operated on by experienced surgeons, partial laryngectomy has resulted in three-year actuarial survival rates of 70 to 85 percent and recurrence rates less than 6 percent for selected supraglottic and glottic tumors [34-36]. Total laryngectomy is required for local failure, positive margins, or aspiration. Laryngeal conservation surgery is combined with postoperative RT for locoregional control of T3 and T4 lesions [39,41-43]. It may also be preceded by induction chemotherapy [44,45]. (See 'Postoperative radiation therapy' below.)

Minimally invasive surgery — Minimally invasive surgery, including transoral laser surgery (TLS, also transoral laser microsurgery [TLM]) and the transoral robotic surgical system (TORS), with or without postoperative RT, is another effective laryngeal-preservation strategy, more commonly reserved for small, T1 and T2, tumors rather than for T3 or T4 lesions [46-49]. Postoperative hemorrhage is the most common complication (6 percent), and tracheostomy and gastrostomy dependence is uncommon [50,51]. TLS is discussed separately. (See "Treatment of early (stage I and II) head and neck cancer: The larynx".)

Low local recurrence rates and good larynx function have been reported for carefully selected, locally advanced cancers (stage III and IV) of the larynx (glottic and supraglottic) and hypopharynx, with five-year locoregional control rates of 69 to 76 percent, recurrence-free survival rates of 60 to 69 percent, and overall survival rates of 47 percent [47-49].

Postoperative radiation therapy — Following larynx preservation surgery, postoperative RT with or without concurrent chemotherapy is indicated for all T3 and T4 tumors after surgical excision as well as for patients who have positive resection margins, lymphovascular or perineural invasion, or positive lymph nodes.

The concurrent administration of chemotherapy with postoperative RT is generally preferable to RT alone for high-risk patients, such as those with positive margins or lymph nodes with extracapsular extension. Postoperative RT or chemoradiotherapy should be initiated within six weeks of surgery. (See "Postoperative radiation therapy in the management of head and neck cancer".)

Total laryngectomy — Total laryngectomy may be more appropriate than chemoradiotherapy for some patients with advanced laryngeal and hypopharyngeal cancer [9,41,52,53]. In addition, total laryngectomy is frequently needed to treat recurrent disease following chemoradiotherapy.

  • The elderly and frail patient, as well as patients with poor compliance or functional status and those with poor psychosocial support, may have less difficulty with acceptance and care of a tracheal stoma than the rigors of prolonged treatment with induction chemotherapy and/or concurrent chemoradiotherapy and the associated toxicities. The lack of psychosocial support, however, may make postlaryngectomy communication a significant issue and/or barrier to appropriate care.
  • Patients with resectable tumors with destruction of both vocal cords may not recover vocal or airway protective function with larynx-preservation approaches and may function better after total laryngectomy.

Total laryngectomy confers protection from aspiration, often results in functionally easier swallowing, and provides the ability to create voice through the patient's mouth (via a tracheoesophageal prosthetic). The main stigma for patients is the presence of the tracheostomy. Postoperative radiation or chemoradiotherapy, however, is still required for most of these patients. (See "Alaryngeal speech rehabilitation".)

MANAGEMENT OF THE NECK — The management of the neck is complex. The risk of occult lymph node metastases or residual disease following treatment must be balanced against the potential complications of neck dissection and/or irradiation. Factors that should be considered include the site of the primary tumor, as well as the extent of disease, treatment modality used to treat the primary tumor, and response to therapy [54].

Patients treated with chemoradiotherapy — Observation is recommended for patients with N0 or N1 disease who attain a complete clinical response in the neck. Neck dissections are indicated for all patients with clinically residual nodal disease.

In patients with N2-3 disease, management of the neck following complete clinical response with induction chemotherapy and/or concurrent chemoradiotherapy is controversial, with some experts feeling that patients can be safely observed while others believe that a neck dissection is indicated for all of these patients.

The key criteria for selecting such patients for observation include the absence of any clinical or imaging evidence of residual disease, and the assessment that the patient will be reliable for careful follow-up. Many centers now are use the results of a combined computed tomography/positron emission tomography (CT/PET) scan 12 weeks following treatment completion to assess response; performance of neck dissection is then based on results of the CT/PET scan. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Management of the neck'.)

The role of selective versus comprehensive neck dissection is also controversial.

Patients managed with primary surgery — Prophylactic selective neck dissection, including levels II-IV, is recommended for patients with T3 and T4 tumors with clinically negative cervical nodes (N0) or early nodal disease (N1) (figure 3). Bilateral treatment is recommended for midline or bulky glottic lesions and for supraglottic, subglottic, and hypopharyngeal cancers. RT is an alternative treatment for patients with N0 or N1 lymph nodes, particularly if the primary site requires adjuvant RT.

When primary surgery is used to treat laryngeal or hypopharyngeal cancers with N2 or N3 disease, we suggest a modified or radical neck dissection if the nodes are invading the jugular vein, accessory nerve, or sternocleidomastoid muscle. If the nodes are mobile and tissue planes preserved, many head and neck surgeons will perform selective neck dissections, if feasible, in order to preserve contour and function.

All patients with pathologically confirmed lymph node involvement should undergo postoperative RT, with the addition of concurrent chemotherapy if adverse pathologic factors are present. (See "Postoperative radiation therapy in the management of head and neck cancer".)

ELDERLY AND POOR PERFORMANCE STATUS PATIENTS — Induction chemotherapy and concurrent chemotherapy are often avoided in the elderly and those with poor performance status since the use of chemotherapy may delay or prevent the delivery of a course of definitive RT. In this setting, definitive RT alone remains a treatment option for elderly patients and those with a poor performance status. This decreases the opportunity for functional organ preservation. However, it may not compromise survival, especially in laryngeal cancer. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Patient selection'.)

Total laryngectomy may also be an option. (See 'Total laryngectomy' above.)

COMPLICATIONS OF TREATMENT — Complications from treatment for advanced laryngeal and hypopharyngeal head and neck cancer include vocal, swallowing, and airway problems, loss of taste and smell, fistula, cranial nerve and spinal accessory nerve injuries, vascular injury and events, fibrosis, and hypothyroidism. These complications and their management are discussed separately. (See "Management of late complications of head and neck cancer and its treatment".)

POSTTREATMENT EVALUATION AND SURVEILLANCE — For patients treated with concurrent chemoradiation or sequential chemoradiotherapy, assessment to insure the absence of residual disease is critical. The clinical examination is critical in this evaluation. Imaging studies, particularly computed tomography (CT) and positron emission tomography (PET), augment this evaluation but can be difficult to interpret if they are performed too soon (prior to 12 weeks) after the completion of concurrent chemoradiotherapy [55]. (See "Overview of the diagnosis and staging of head and neck cancer".)

Regular posttreatment follow-up is an essential part of the care of patients after potentially curative treatment of head and neck cancer, both to detect recurrent disease and to diagnosis second malignancies that may develop. Patients should be educated about possible signs and symptoms of tumor recurrence, including hoarseness, pain, dysphagia, bleeding, and enlarged lymph nodes.

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 within this timeframe. Continued follow-up beyond five years is generally recommended because of the risk of late recurrence, second malignancy, and late complications. Posttreatment surveillance of head and neck cancer, including screening for treatment-related complications, is reviewed separately. (See "Posttreatment surveillance of head and neck cancer".)

Rehabilitation of voice and swallowing function following treatment are discussed separately. (See "Alaryngeal speech rehabilitation" and "Speech and swallowing rehabilitation of the patient with head and neck cancer".)

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SUMMARY AND RECOMMENDATIONS

  • Prior to treatment, all patients with advanced (stage III and IV) cancer of the larynx or hypopharynx should be seen by a multidisciplinary team with experience in the treatment of head and neck cancer. Selection of a treatment approach depends upon tumor extent and location, patient-specific factors (eg, age, performance status, comorbidity, psychosocial support), physician expertise, and the availability of rehabilitation services. (See 'Overview of management' above.)
  • For most good performance status patients with locally advanced (stage III or IV) laryngeal or hypopharyngeal cancer, we recommend a functional organ preservation strategy rather than surgical resection (Grade 1B). Organ-sparing approaches may permit larynx preservation but do not provide a survival advantage compared with total laryngectomy. (See 'Overview of management' above.)

  • Both concurrent chemoradiotherapy and sequential chemoradiotherapy are used as functional organ preservation techniques. Concurrent chemoradiotherapy may be preferable for patients with N0 and N1 presentations, while sequential therapy may offer advantages for patients with a relatively high risk of distant metastases (ie, more extensive lymph node disease). (See 'Combined modality therapy' above.)
  • Partial laryngectomy and minimally invasive surgery may be options for carefully selected patients, especially those with relatively small primary tumors combined with more extensive neck disease. Postoperative RT is generally required in these cases. (See 'Surgery' above and 'Postoperative radiation therapy' above.)

  • Patients who may not be candidates for an organ preservation approach include patients with resectable tumors that have destroyed both vocal cords, elderly patients for whom the toxicity associated with chemoradiotherapy is problematic, and those with extensive cartilage destruction from the primary tumor. (See 'Overview of management' above and 'Total laryngectomy' above and 'Elderly and poor performance status patients' above.)
  • Management of the neck is complex and depends upon disease extent, treatment modality used to treat the primary tumor, and response to therapy. (See 'Management of the neck' above.)
  • For patients who are not candidates for a functional organ preserving approach, total laryngectomy is a potential alternative. Definitive RT alone may be used as a functional organ preserving approach for laryngeal cancer patients who are not felt to be candidates for chemotherapy, although there is a higher risk of recurrence and thus a need for salvage laryngectomy. (See 'Total laryngectomy' above and 'Elderly and poor performance status patients' above.)
  • Adequate posttreatment surveillance and long-term follow-up are crucial to ensure adequate voice and swallowing rehabilitation and to monitor for disease recurrence or a second primary malignancy. (See "Posttreatment surveillance of head and neck cancer".)

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