Glottic Cancer

Frequency

According to data released by the American Cancer Society, approximately 10,000 new cases of laryngeal carcinoma are diagnosed each year in the United States and 3,900 deaths occur yearly as a result of this disease. ^[3] These cases account for 0.9% of cancers from all sites and 0.8% of all cancer deaths.

Laryngeal cancer affects men 4 times more frequently than women in the United States. In other countries, men are affected up to 10 times more frequently than women. The male-to-female ratio is higher for glottic tumors than for supraglottic tumors. This ratio has decreased in recent years, which is thought to be because of an increased incidence in women, rather than a decreased incidence in men. This trend follows that of lung cancer. The increased incidence of both of these malignancies is thought to be due to increased smoking in females.

Laryngeal cancer makes up 1-2% of all malignancies worldwide. The incidence of the disease varies greatly from country to country. Spain has one of the highest rates in the world, with an incidence approaching 20 cases per 100,000 persons in some regions. Poland, France, and Italy also have high rates of the disease.

Tobacco use is the most important and most preventable risk factor for the development of squamous cell carcinoma of the larynx. Smoking tobacco is believed to be a direct cause of up to 95% of glottic and supraglottic carcinomas. Alcohol is an independent risk factor for the development of laryngeal malignancy, increasing the risk up to 5 times in nonsmokers. More importantly, alcohol has been implicated as a synergistic cofactor when combined with tobacco use. The synergistic risk for smokers who drink is estimated to be 100 times that of individuals who do not smoke or drink.

Diet may play a role in both the development and prevention of laryngeal malignancies. A diet deficient in fruits and vegetables can increase the risk of development of laryngeal cancer, while a diet rich in these foods may be preventative. Occupational exposures such as diesel fumes, sulfuric acid, coal dust, and machining fluids have been associated with laryngeal malignancy. A link between human papillomavirus and laryngeal cancer has been investigated, but a firm causal relationship has not been established.

Squamous cell cancer is the most common type of glottic tumor and tends to arise in the anterior portion of the glottis, usually on the free margin of the vocal fold. These tumors spread horizontally along the cord margin toward the anterior commissure. The glottis is quite resistant to spread of malignancy because of a number of anatomic barriers; therefore, disease is confined within the larynx for a relatively long period. Although later-stage disease can cross the midline, the anterior commissure tendon initially prevents spread to the opposite cord. Invasion of the underlying thyroarytenoid muscle eventually occurs, resulting in cord fixation. The invasion may extend through the conus elasticus into the subglottic region.

Early stage disease rarely metastasizes to lymph nodes; however, when vocal fold fixation or subglottic extension occurs, spread to the paratracheal and cervical nodes is common. Further extension of the tumor into the laryngeal cartilage occurs at points of weakness, ie, anteriorly through the cricothyroid membrane into the lower border of the ala and posteriorly through the cricothyroid space into the strap muscles and deep surface of the thyroid gland. Tumor can also spread along the floor of the ventricle and may be deflected superiorly, resulting in supraglottic extension.

Persistent hoarseness is the usual presenting symptom of glottic carcinoma. Small vocal cord lesions can result in significant hoarseness, and patients with hoarseness often present at early stages. Glottic tumors can also cause hemoptysis and airway compromise if the tumors are large. Dysphagia and aspiration do not generally occur until later in the course of disease when the tumor is much larger, unless it initially involves the posterior commissure. Odynophagia or ipsilateral otalgia may or may not be present at presentation.

A complete head and neck examination is recommended for all patients who are suspected of having laryngeal cancer. The head and neck examination includes thorough examination of the structures of the skin, scalp, ears, nose, oral cavity, and neck. Examination of the larynx in most people can be accomplished with a laryngeal mirror, which provides an excellent panoramic view of the larynx, oropharynx, and hypopharynx. A flexible endoscope or rigid telescope can be used to examine the larynx, and an attached camera provides still photograph or videotape documentation. A stroboscopic examination is helpful to examine and document vocal cord dysfunction and any mucosal wave abnormalities. Examination of the neck is essential, with palpation for adenopathy, mobility of the laryngotracheal complex, and direct tumor extension.

The treatment goal for glottic cancer is cure of the disease. Secondary objectives include the preservation or reconstruction of voice and the ability to swallow without aspiration. Surgery, radiation, or multiple-modality treatment can accomplish the management of this disease. Chemotherapy is used as an induction agent in some treatment protocols. To determine the best treatment modality for management of glottic carcinoma in each patient, several factors must be considered, including tumor stage and characteristics, patient factors, and treatment facilities.

When planning treatment, one must evaluate tumor characteristics and determine the stage of the tumor. In general, poorly differentiated tumors tend to metastasize more readily than well-differentiated tumors, and exophytic tumors respond to radiation better than endophytic tumors. Patient factors such as occupation, mental status, and overall health must be used to guide treatment decisions. General medical condition is critical to the assessment process, particularly pulmonary function and performance status as described using either Karnofsky or Eastern Cooperative Oncology Group (ECOG) scoring systems.

Ideally, a treatment team consisting of members with expertise in oncologic laryngeal surgery, radiotherapy, and medical oncology should evaluate each patient. A multidisciplinary planning conference is also valuable in the management of any head and neck malignancy. When considering radiation therapy, adequate treatment facilities must be available within a reasonable distance. Support services for speech and swallowing therapy, dental oncology, and rehabilitation (ie, psychosocial, emotional, occupational, vocational) are also important to a comprehensive therapeutic team.

In general, early stage glottic cancers (ie, T1 and T2, see Staging) are managed with a single modality, such as radiation, endoscopic excision, or conservation laryngeal surgery. Moderately advanced lesions (ie, T3) are typically treated with a combination of radiation and chemotherapy. Some centers prefer induction chemotherapy to select patients who are thought less likely to respond to radiation. In responders, radiation delivered in combination with chemotherapy is typically used. Surgery, usually a total laryngectomy, is then used in patients who do not respond to chemotherapy.

Surgical options include conservation laryngeal surgery or total laryngectomy, depending on the extent of the disease. Some authors are advancing endoscopic laser surgery as an alternative to laryngectomy or chemoradiation in selected T3 glottic cancers. Invasive tumors (ie, T4 due to cartilage destruction) are usually managed with a total laryngectomy and appropriate neck dissections. Radiation therapy is typically performed postoperatively, and chemotherapy is given with radiation if certain pathologic features are evident, such as positive margins or extracapsular invasion in lymph nodes.

During development, the larynx begins as a slitlike groove in the pharyngeal floor. The epiglottis arises anteriorly from the ventral ends of the third and fourth branchial arches. The arytenoids form laterally from the sixth branchial arches, and the laryngeal cartilages develop from the ventral fourth and fifth arches. The supraglottic larynx arises from the buccopharyngeal analogue, and the glottic and subglottic portions develop from the tracheopulmonary analogue. The lymphatics of the supraglottic and glottic larynx (above the ventricle) drain superiorly, while the lymphatics of the areas below the ventricle drain inferiorly.

The rationale for bilateral neck dissections in a supraglottic laryngectomy is based on the midline development of the epiglottis and consequent bidirectional lymphatic flow. However, when neck dissection is indicated for a lesion limited to the true vocal cord, a unilateral dissection is usually adequate because each half of the larynx below the epiglottis develops independently.

The larynx is divided anatomically for staging purposes. The supraglottic larynx includes the epiglottis, aryepiglottic folds, arytenoids, and false cords. The true vocal cords and the anterior and posterior commissures comprise the glottis. The subglottis begins below the true vocal cords and involves the remaining portion of the larynx to the inferior border of the cricoid cartilage.

Offer treatment to all patients with the diagnosis of glottic malignancy. No absolute contraindications exist for the treatment of any patient with glottic cancer. When treatment is managed properly, survival rates are encouraging, even for very advanced cancers. Each treatment method has specific indications and contraindications, which are covered in the following sections.