eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery
Glottic Cancer: Treatment
Updated: Jan 2, 2009
Treatment
Medical Therapy
Radiation is the primary nonsurgical treatment for early-stage glottic tumors (ie, T1, T2). Although radiotherapy techniques and doses may vary, a standard course of radiation for glottic cancer usually consists of a total of 60-70 Gy administered in single daily fractions over 6 weeks. Advantages of radiotherapy include the avoidance of surgery and the subsequent hospitalization and a superior voice outcome. A useful voice is preserved in 80-95% of patients who were treated with radiation for an early glottic tumor. Of these patients, 80-90% are reported to have good-to-excellent voice quality.
Disadvantages to the use of radiation include long treatment course, adverse effects and potential complications associated with radiation, and difficulty in diagnosis of a recurrence or second tumor in the irradiated larynx. Radiation failures can be salvaged successfully with surgery; however, complication rates may be higher than with primary surgical procedures. Some patients who were initially candidates for conservative laryngeal surgery may no longer be candidates after unsuccessful radiation therapy and may require total laryngectomy.
In the early 1980s, chemotherapy regimens for the treatment of laryngeal carcinoma were introduced, and a correlation between chemosensitivity and radiosensitivity was identified. Induction chemotherapy became a way to identify those patients who were likely to have a good response to radiotherapy.
In 1991, the Veterans Administration Larynx Study Group published the results of a study in which patients with laryngeal cancer were assigned randomly to treatment with standard surgery and postoperative radiation or 2 cycles of induction chemotherapy.2 Patients in the chemotherapy arm who demonstrated less than a partial response or disease progression after 2 cycles of chemotherapy underwent surgery, and those who showed partial or complete response underwent an additional cycle of chemotherapy followed by irradiation. Long-term follow-up revealed no differences in survival rates between the 2 arms, and 31% of the total population were able to retain the larynx (66% of 4-y survivors).
More recently, data have emerged that indicate improved disease control with radiation and chemotherapy given simultaneously. Acute side effects are clearly greater, however.
To become more selective in the attack of tumors, and in response to the often substantial morbidity associated with combination therapy, the recent use of monoclonal antibodies that inhibit key aspects in tumor growth has proliferated. The potential advantage is a change in the type and severity of adverse events. For example, radiation therapy with cetuximab, a monoclonal antibody against the epidermal growth factor receptor, has been shown to be more effective than radiation alone. What has not been demonstrated is a direct comparison of cetuximab and radiation versus standard platinum-based chemotherapy and radiation. Until such a study demonstrates comparable efficacy with reduced side effects, the use of cetuximab and radiation should be reserved in patients with contraindications against standard chemotherapy.
Surgical Therapy
Endoscopic management of premalignant lesions and stage I and some stage II glottic carcinomas can be performed during direct laryngoscopy using an operative microscope. Lesions are excised with either microlaryngoscopic instruments or a carbon dioxide laser. These procedures are usually performed on an outpatient basis. The use of endoscopic techniques for more extensive lesions has been touted by German investigators and is currently being investigated in the United States. The use of this technique must take into account the skill of the operating surgeon, the ability of the larynx to be visualized, and the state of disease in the neck. If the patient can be treated without the use of adjuvant radiation therapy, endoscopic surgery may provide a reasonable alternative to total laryngectomy or combination chemotherapy and radiation. The key appears to be in proper patient selection.
Vertical partial laryngectomy is indicated in the treatment of tumors that arise on the true vocal cord with limited involvement of the anterior commissure. In this type of resection, most of the ipsilateral thyroid cartilage, the true vocal cord, and portions of the subglottic mucosa and false vocal cord are removed. Closing the strap muscles over the defect can create a pseudocord. All patients require a tracheotomy, which is generally left in place for 3-7 days postoperatively. In the case of anterior commissure involvement, a frontolateral partial laryngectomy may be considered. This procedure extends the resection to the contralateral cord, including the anterior commissure. Contraindications for both types of vertical partial laryngectomy include tumor involvement of the interarytenoid area, subglottic extension greater than 10 mm, and poor medical condition, especially significant pulmonary disease.
Total laryngectomy is the standard for treatment of advanced laryngeal cancer. Adequate treatment of tumors that have invaded beyond the confines of the larynx involves resection of the disease with a margin of normal extralaryngeal tissue. In this procedure, the entire larynx, hyoid bone, and overlying strap muscles are resected in an en bloc manner. If tumor is involved, the thyroid gland is removed with the larynx. Pharyngotomy incisions are made with a margin of approximately 1.5 cm of mucosa that is healthy in appearance. The inferior tracheal margin should also have at least 1.5 cm of mucosa that appears healthy. Pharyngeal closure is accomplished primarily or with flap augmentation. The margin status is intraoperatively confirmed with frozen section. Careful skin-mucosal approximation creates a permanent tracheal stoma.
With any head and neck malignancy, the elective treatment of cervical lymph nodes is generally recommended when the risk of occult nodal disease is at least 15-20%. For stage I and II glottic cancer, the risk of cervical lymph node metastasis is low, ranging from 1-8% in most series. Given this low rate of occult metastasis, elective neck treatment is usually not indicated in these patients. With later-stage disease, the risk for nodal disease increases to 20-30%. Elective treatment of the neck is recommended for late-stage disease (ie, T3, T4). The nodal groups at risk for laryngeal cancer include levels II, III, and IV, with rare involvement of levels I and V. The elective treatment of the neck in glottic cancer usually consists of selective removal of the nodes in levels II, III, and IV; however, radiotherapy is also a possible treatment option.
Most necks with clinical disease can be managed with an ipsilateral selective or modified radical neck dissection, depending on the extent of the disease. Consider bilateral neck dissection when managing glottic lesions that approach midline and when bilateral disease is clinically present in the neck.
Follow-up
Following surgery or radiation treatment, patients are monitored closely for healing and for the development of complications. Both the patient and family members often need significant assistance and reassurance as they adjust to the physical and functional changes that occur with treatment of this disease. After healing is complete and adjuvant treatment is completed, patients undergo a complete head and neck examination every 3 months. If the larynx remains, careful attention is directed to the larynx.
One of the most difficult areas of practice for the head and neck surgeon or radiation therapist is follow-up of the irradiated larynx. Postradiation edema makes the recognition of recurrence very difficult. The dilemma of whether to perform an examination under anesthesia with biopsy, imaging studies, or periodic clinical examination is perplexing. Each carries its own pros and cons.
Examination under anesthesia with biopsy is the criterion standard for proving recurrence. However, the risk of further swelling, chondronecrosis, and precipitation of a tracheostomy makes this a decision not to be entered into lightly (particularly because laryngeal reflux, candidiasis, and continued trauma from cigarette smoke may further complicate the clinical picture). Serial examination provides the clinician with a picture over time and carries the least morbidity from the actual procedure.
The role of CT scanning and MRI may provide an adjunct to clinical follow-up. Changes on CT scans and MRI after radiation are frequent and often difficult to differentiate between edema, infection, and recurrence. Like clinical examination, changes over time may provide the best use of these studies. The role of PET scanning is currently being defined. Sensitivity and specificity of PET alone are generally in the same range as CT or MRI and still leave the clinician to choose between biopsy and follow-up.
The emerging role of PET/CT is also under investigation. Preliminary data suggest that it may have enhanced sensitivity over CT scanning, MRI, or PET scan alone. The proper timing of the examination is still uncertain, with some reports suggesting that PET/CT can be performed 3-4 months following completion of radiation and others suggesting a year's wait. Rarely are the art of medicine and the necessity of judgment more critical than in the evaluation of the postirradiated larynx.
Two years after completion of treatment, follow-up examinations are decreased to every 4 months. Follow-up examinations scheduled at 6-month intervals can be started at 4 years after completion of treatment, and yearly examinations can be started at 5 years after completion of treatment. Yearly chest radiography and liver function testing are important screens for second primary tumors (eg, lung cancer) and distant metastases. If patients present with symptoms of depression and lethargy, screening for thyroid dysfunction is recommended.
Depression complicates head and neck cancer treatment in 20-40% of patients. Asking about symptoms of depression is important; many of the signs of depression can be confused with the rigors of treatment itself. Feelings of guilt, hopelessness, or suicidality should prompt the clinician to further investigate for the presence of depression. Many treatment options are available if the diagnosis is made. Treatment of depression can improve quality of life and likely improves survival as well.
Complications
During the course of radiotherapy, patients may experience a number of acute adverse effects, including mucositis, loss of taste, xerostomia, dysphagia, skin burns, and desquamation. Approximately 10% of patients who undergo radiation require gastrostomy feeding tubes for nutritional support. Patients who receive concomitant chemotherapy and radiation are much more likely to require a gastrostomy feeding tube. Some patients require unplanned breaks in therapy because of adverse effects, which can compromise treatment efficacy and cure rates.
Late complications associated with radiation therapy include permanent xerostomia, poor wound healing, soft tissue fibrosis, dental caries, chondritis, and rarely, osteoradionecrosis of the mandible. Persistent dysphagia, aspiration, and laryngeal edema are serious complications that occur most often in patients with advanced disease. Similar complications are observed in patients who undergo adjuvant radiation therapy following surgery and usually occur with a higher frequency.
Endoscopic procedures are less invasive and have fewer complications than more extensive laryngeal surgery. A tracheotomy is rarely required in patients who undergo endoscopic resections. Aspiration can occur postoperatively; however, aspiration is rare and depends on the extent of tissue resection and the location of the tumor.
Most patients who undergo a vertical partial laryngectomy undergo tracheotomy at the same time, but they are usually decannulated within the first month. Complications are generally dependent on the extent of surgical resection. Acute complications include wound infection, fistula formation, and glottic incompetence with aspiration. Granulation tissue formation can result in an inferior voice outcome. Endoscopic laser resection can remove granulation tissue effectively, and control of acid reflux may prevent recurrence. Postoperative laryngeal stenosis is very difficult to treat and may result in permanent tracheotomy.
Early complications following total laryngectomy include hematoma formation, wound infection, wound dehiscence, and pharyngocutaneous fistula. Development of a hematoma can cause a separation of the pharyngeal suture line and may require a return to the operating room for evacuation. Wound infections and dehiscence are treated with antibiotic coverage and local wound care, including daily packing. A persistent nonhealing wound dehiscence may require flap coverage for definitive management.
Pharyngocutaneous fistula is a relatively frequent complication following total laryngectomy. Multiple studies have examined predisposing factors for the development of pharyngocutaneous fistula. Although results are conflicting, poor nutritional status, previous radiation, positive surgical margins, concurrent medical disease, and intraoperative blood transfusion have been found to be associated with higher fistula rates. Management of a pharyngocutaneous fistula consists of restriction of oral intake, antibiotic coverage, and wound care, including packing. Surgical closure can be considered but is often unsuccessful.
The most common late complications following total laryngectomy are stomal stenosis, pharyngoesophageal stenosis and stricture, and hypothyroidism. A stomal button or standard tracheotomy tube can sometimes prevent stomal stenosis. Consider these devices, especially in patients who undergo postoperative radiation. Stenosis, stricture of the neopharynx, or tumor recurrence can cause late onset of dysphagia in a patient who has undergone total laryngectomy. Evaluate new dysphagia with endoscopy and biopsy to rule out tumor. Benign strictures can usually be dilated effectively. Hypothyroidism occurs in 50% of patients following total laryngectomy and in 65% of patients after combined therapy of radiation and surgery.
Potential complications following neck dissection include hematoma, wound infection and dehiscence, and chylous fistula. The first 3 complications are managed as discussed previously. A chylous fistula occurs when the thoracic duct on the left side of the neck or the major chylous drainage on the right is disrupted and not recognized at the time of the operation. In most cases, the fistula is recognized intraoperatively; however, a fistula is suspected postoperatively when drain output increases after a diet is started. Conservative management includes wound drainage, pressure dressings, and a low-fat diet. Occasionally, surgical exploration is required.
Carotid artery rupture is the most serious complication associated with neck dissection, and the outcome with this event can be fatal. Wound infection, flap dehiscence, and salivary fistula, especially in a previously irradiated neck, can result in carotid artery exposure. Coverage of the carotid with a pedicle or free vascularized flap may help prevent a catastrophic outcome. Cerebral edema, blindness, and occasionally, death can result following bilateral neck dissections, especially in radical dissections when both internal jugular veins are ligated.
More on Glottic Cancer |
| Overview: Glottic Cancer |
| Workup: Glottic Cancer |
 Treatment: Glottic Cancer |
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Further Reading
Keywords
glottic cancer, cancer, laryngeal carcinoma, laryngeal cancer, glottic tumors, squamous cell carcinoma, glottic cancer staging, glottis cancer, cancer of the glottis, head and neck cancer
