Supraglottic Cancer Treatment & Management

Radiation therapy

Cancers of the supraglottis commonly manifest in patients who are debilitated from years of smoking and drinking. Because of the high surgical risk in some of these patients, radiation therapy can be a better option than surgery. Treatment options involving radiotherapy are numerous, as protocols differ in dose, extent, and fractionation.

Comparing results of supraglottic laryngectomy with those of radiotherapy is difficult because some series of patients treated with radiotherapy alone include those with lesions that were anatomically unsuitable for conservative laryngeal surgery. In addition, patients treated with radiotherapy tend to be those whose medical conditions contraindicate surgical modalities. Both of these factors seem to bias a comparison against radiation therapy. Remember, however, that patients in whom radiation therapy fails have the option of surgical salvage, which increases overall survival rate for patients treated with definitive radiation therapy.

Primary radiotherapy is accepted as appropriate treatment for early-stage disease.^[11] Current recommendations for the use of radiation therapy in advanced disease, however, advocate the addition of platinum agents, particularly cisplatin, to radiation therapy when nonsurgical treatment is chosen.

Adjuvant radiation therapy has become highly recommended in patients whose tumor pathology suggests a high risk for recurrence, such as those with high-grade tumors or extracapsular spread. Postlaryngectomy patients are more commonly undergoing radiotherapy even without these risk factors, because of the propensity of supraglottic cancers for occult metastasis.

Role of chemotherapy

In the early 1990s, a landmark trial conducted by the Department of Veterans Affairs demonstrated that, in some patients, induction chemotherapy followed by radiation therapy allowed for preservation of the larynx while maintaining the same survival rates achieved with surgery followed by adjuvant radiation therapy.^[12] The regimen used in this trial, cisplatin plus 5-FU followed by radiation therapy, has been used by many as an alternative to laryngectomy in patients with advanced disease. Single agent cisplatin given concurrently with radiation therapy has since been shown to be more effective and better tolerated and is currently considered the standard when nonsurgical definitive treatment is chosen.^{[11, 13]} Cisplatin has been shown to enhance the effects of radiation on tumor cells, which is a likely explanation for the superiority of concurrent administration versus sequential administration.

Trials that compare larynx preservation regimens consisting of chemoradiation with those with radiation therapy alone have shown that chemotherapy adds the additional benefit of reducing the rate of distant metastasis. Currently ongoing trials are examining the usefulness of adjuvant chemotherapy regimens, as well as the use of some of the newer biologic agents in patients with various stages of this disease.

Various combinations of cytotoxic chemotherapy have been used for palliation of disease. SCC of the larynx often responds to chemotherapy in this setting, although it has not been shown to be effective in cure.

Decisions regarding proper management of primary supraglottic carcinoma remain controversial despite advances in radiotherapy and surgical procedures. Of the common treatment modalities, none have shown an advantage in overall survival.

The goal of treatment for supraglottic cancer is cure of disease, with preservation of speech, when possible. Treatment options include surgery, radiation therapy, chemotherapy, or a combination thereof. The selection of treatment modality relies on many factors: tumor size, clinical stage, the patient's overall medical condition, the philosophy and experience of the physician, and the patient's choice.

Early and moderately advanced lesions are usually managed with supraglottic laryngectomy or radiotherapy. Advanced lesions are usually managed with total laryngectomy, preoperative or postoperative radiotherapy, and, possibly, chemotherapy, since combined-modality therapy produces better results than a single modality alone.

The propensity of supraglottic lesions to spread to the cervical nodes should be kept in mind when treatment options for this disease are considered.

Supraglottic laryngectomy versus total laryngectomy

The traditional treatment for squamous cell carcinoma (SCC) of the larynx is laryngectomy. The classic supraglottic laryngectomy extends through the vallecula superiorly, the aryepiglottic folds posteriorly, the apex of the ventricle inferiorly, and the thyroid cartilage anteriorly. Included in the resection are the hyoid bone, epiglottis, superior half of the thyroid cartilage, aryepiglottic folds, and the false folds to the arytenoids. Occasionally, one or both arytenoid cartilages are removed. If surgery is selected as the primary treatment of supraglottic carcinoma, many believe that transcervical partial laryngectomy is the surgical therapy of choice for T1 and T2 lesions, while lesions that are more extensive (eg, T3, T4) demand total laryngectomy. Transcervical supraglottic laryngectomy, however, can be performed on T3 lesions, provided no true vocal fold involvement exists.

Contraindications for transcervical supraglottic laryngectomy include tumors that extend to the interarytenoid space, postcricoid mucosa, and true vocal folds. Additionally, tumors that cause cord fixation are a contraindication for supraglottic laryngectomy. Because aspiration is an issue in patients after supraglottic laryngectomy, patients with poor pulmonary function would be more appropriately treated with total laryngectomy or transoral supraglottic laryngectomy.

Laser surgery

The carbon dioxide laser is useful because of its hemostatic effects and precise tissue ablation. Consequently, the carbon dioxide laser has become an option for addressing T1 and T2 lesions transorally to avoid transcervical supraglottic laryngectomy.^{[14, 15, 16]}

Carbon dioxide laser surgery is performed with a spreadable laryngoscope. The laser is used as a cutting instrument and not used to vaporize tumor. Small tumors of the epiglottis and aryepiglottic folds are excised with a 1-cm margin as an excisional biopsy. In large tumors of the suprahyoid epiglottis, vertical division of the epiglottis facilitates resection. An incision is then made, guided by the valleculae, until the hyoid bone is reached and exposed. The incision continues caudal from the hyoid toward the thyrohyoid membrane until the upper border of the thyroid cartilage is reached. The entire preepiglottic space is then removed along the inner surface of the lamina of the thyroid cartilage toward the anterior commissure of the vocal fold. False cord tumors are excised similarly. Resection includes the preepiglottic space if the infrahyoid epiglottis is invaded and the preepiglottic space and paraglottic space if the false cords are involved.

The transoral use of the carbon dioxide laser has made it possible to avoid some of the complications that have traditionally excluded patients with pulmonary comorbidities from undergoing supraglottic laryngectomy. Studies have shown a rapid return of swallowing function and the virtual elimination of the need for tracheostomy when a supraglottic laryngectomy is performed transorally with a carbon dioxide laser.

A recent Phase II study conducted by the Southwest Oncology Group (SWOG) confirmed the relative safety and efficacy of this procedure when used in conjunction with postoperative radiation therapy in patients with Stage I, II, and III disease.^[17] Cabanillas et al performed a study that showed similar benefits when transoral laser supraglottic laryngectomy was compared with a traditional transcervical approach in patients with T1 or T2 supraglottic tumors.^[18] Assessment of the oncologic results of numerous series indicates that both the survival and local recurrence rates associated with transoral laser resection are comparable with those seen in patients who undergo traditional transcervical partial laryngectomy.

These results combined with those of other studies demonstrate that supraglottic laryngectomy can be a reasonable option not only in the typical patient but also in patients with pulmonary comorbidities.

Elective neck dissection

Long-term survival for patients with SCC of the supraglottic larynx is most dependent on the successful management of neck disease.^{[19, 20]} This is partially due to occult metastasis found on neck dissection in patients with supraglottic carcinoma is more common than in the other laryngeal subsites. Occult metastases are present approximately 16% of the time in patients with T1/T2 tumors and have been reported to be present as much as 62% of the time in patients with T3/T4 tumors. Because of this, bilateral neck dissections are performed when treating patients with advanced disease. Many institutions perform bilateral neck dissections on patients with any nodal stage;^[21] however, recent evidence suggests that a less extensive neck dissection may be adequate in patients with N0 disease.^[22]

Complications of treatment for supraglottic carcinoma largely depend on the therapeutic modality selected to treat the disease. For example, complications of radiotherapy include xerostomia, dysphagia, hoarseness, excessively thick mucous secretions, chondronecrosis of the larynx, transverse myelitis, and laryngeal edema with airway obstruction.

Patients who undergo supraglottic laryngectomy have a high incidence of aspiration, approximately 40-70%. Postoperative alteration of swallowing function is caused by disruption of the superior laryngeal nerves. Because of the high incidence of postoperative aspiration, some patients with poor pulmonary function are better served by nonsurgical therapy, total laryngectomy, or transoral supraglottic laryngectomy.

The transoral use of the carbon dioxide laser can reduce the incidence of aspiration because this technique does not involve disruption of the superior laryngeal nerves and, therefore, has a less deleterious effect on swallowing function. This makes supraglottic laryngectomy an option for some patients who have not been considered candidates for surgery in the past. Remember, however, that patients undergoing laser surgery may have an increased risk for bleeding and vestibular stenosis.

An additional complication seen in surgical patients, especially those with prior radiation therapy, is fistulous tract formation. The incidence of pharyngocutaneous fistula is also greatly reduced by using transoral laser surgery instead of transcervical resection.

The survival and prognosis of patients with laryngeal cancer has been shown to differ based on subsite. Supraglottic cancers have a worse prognosis than glottic cancers and are also more likely to be high-grade cancers. Supraglottic cancers have few initial symptoms; thus, they are often discovered later than cancers of the glottis and subglottis. Later presentation leads to a greater likelihood that the cancer has spread outside of the capsule or spread to regional lymph nodes. The presence of extracapsular spread and regional lymph node metastases are the 2 most significant negative prognostic indicators in supraglottic cancer.^[23] Tumors with extracapsular spread and regional metastases indicate a lower survival rate and a higher recurrence rate. High-grade tumors are also a factor associated with decreased survival.

Five-year overall survival for supraglottic cancers in general is reported to be between 40-50%. When broken down by cancer stage, the 5-year overall survival can vary significantly—from up to 82% in stage I disease to 45% or lower for stage IV disease. Recent analysis of the SEER database, however, has shown that the 5-year overall survival for patients with laryngeal cancer has decreased over the past 20 years.^[24] This decrease in survival corresponds with a change in treatment patterns in the 1990s that saw an increase in nonsurgical treatment of laryngeal cancer.^[25] Although the reasons for this decline in survival are unknown, a change in treatment patterns likely played some role;^[26] the treatment selection for patients with laryngeal cancer must be considered carefully, and, in patients with supraglottic SCC, the more aggressive behavior of the disease in comparison with glottic cancer should be kept in mind.

The diagnosis and treatment of supraglottic cancer has progressed greatly over the past 150 years. Surgical procedures, such as the supraglottic laryngectomy and laser excision, have allowed surgeons to remove tumors with less morbidity. Radiotherapists have developed better protocols and techniques to administer radiation to more precise anatomical fields. Chemotherapy is being used to protect laryngeal function through organ sparing protocols.

In the future, further refinements in diagnostic and therapeutic techniques will allow physicians to better treat patients with laryngeal cancers. Positron emission tomography (PET) scans may help diagnose lesions earlier and more accurately assess recurrence. Working with improved vectors and a better knowledge of the molecular biology of cancer may afford patients better treatment with fewer adverse effects using gene therapy.