Malignant Tumors of the Larynx Treatment & Management

Treatment of patients with laryngeal carcinoma is complex because of the crucial functions of this anatomic area. If possible, the goal of treatment is to remove the tumor and prevent recurrence while maintaining laryngeal function.

To discuss the treatment options for laryngeal cancer, one must differentiate early (I-II) and advanced (III-IV) stage disease. Subsite location of the primary tumor, glottic, supraglottic or subglottic is also an important consideration when selecting therapy. Early-stage laryngeal carcinomas (stage I-II) are ideally treated with voice-saving surgery. Advanced-stage laryngeal carcinomas (stage III) are usually treated with concurrent chemo-radiation therapy for organ preservation. On the other hand, advanced laryngeal cancer (stage IV) is usually treated with total laryngectomy, reconstruction, and adjuvant postoperative chemoradiation therapy.

For carcinoma in situ or early-stage invasive glottic or supraglottic cancer, endoscopic surgical removal or radiation therapy are both equally effective with similar functional outcomes. The treatment modality depends on the patient’s wishes and compliance and the surgeon's and the institution's preferences and experience. A more complete discussion of surgical options is presented in Surgical Therapy.

Remarkable progress has been made in the past 20 years in the management of laryngeal cancer. Where total laryngectomy held a central role in the treatment of advanced laryngeal tumors, organ preservation strategies using chemotherapy and radiation therapy protocols have now become the standard of care. Landmark studies such as The Veteran Affairs Laryngeal Cancer Study Group in 1991 and the RTOG 91-11 intergroup trial helped establish the basis of laryngeal preservation therapies using chemotherapy (cisplatinum and fluorouracil) and radiation therapy protocols.^[3] Support for chemotherapy as part of a multimodality approach has been strengthened by many subsequent clinical trials with a slight benefit of concurrent chemoradiation protocols.

Current recommendations of the NCCN Practice Guidelines in Oncology for achieving laryngeal preservation in cases of locally advanced laryngeal cancer are concurrent radiation therapy and cisplatin 100mg/m² on days 1, 22, and 43.^[4] Radiation therapy alone can be considered for patients who are medically unfit to undergo chemotherapy. Good evidence exists that radiation efficacy is improved with accelerated and hyperfractionated treatment schemes. Concurrent chemoradiotherapy protocols are associated with significant acute and late toxicities. Some patients remain with dysfunctional swallowing and life-threatening aspiration episodes that require salvage laryngectomy.

Although the pendulum has swung toward larynx preservation protocols, laryngectomy is the best initial therapeutic option in certain situations. Primary surgical treatment should be considered in patients with high volume disease, patients with T4a tumors, or patients with anticipated poor functional outcome (eg. poor voice, intractable aspiration).

Significant early and late toxicities associated with concurrent chemoradiation protocols led to recent interest in targeted therapies such as monoclonal antibodies (eg, cetuximab). Cetuximab is presently used in many organ preservation protocols for laryngeal cancer following a landmark multicenter trial. Many other targeted therapies are under investigation.

In summary, therapy is predicated on histology type, grade, tumor stage, and overall health of the patient. Treatment must be individualized to consider each patient and his or her social circumstances.

Although laryngeal preservation strategies using chemoradiation have taken a central role in the treatment of advanced laryngeal cancer, late toxicities have led us to rethink the paradigm of laryngeal cancer treatment. The refinement of laryngeal surgeries and the sophistication of endolaryngeal laser techniques offer a wide array of laryngeal preservation options that should be carefully considered by the multidisciplinary team. As described in the previous section, total laryngectomy must be considered in cases of bulky or advanced disease, clear cartilage invasion, and failures of larynx-sparing strategies. The description of the surgical technique of partial and total laryngectomy is beyond the scope of this article.

Transoral laser microsurgery

Popularized and legitimized by Steiner and Ambrosch, transoral laser microsurgery is ideal for the treatment of early-intermediate glottic and supraglottic cancer. It is performed under suspension micro-laryngoscopy with a CO₂ laser. Adequate instrumentation and surgeon's experience are paramount.

The tumor is transected and removed piecemeal (which allows for precise tumor removal by margin visualization). The tumor must be well exposed through the laryngoscope.

This treatment has the same indications and contraindications as open partial laryngectomies. A functional cricoarytenoid unit must be preserved.

Survival and laryngeal preservation is comparable to other conventional treatments and results in excellent functional outcomes.

Open partial laryngectomy (cricohyoidopexy [CHP] and cricohyoidoepiglottopexy [CHEP])

Data from one study support previous reports of the efficacy of open horizon partial laryngectomy techniques. These techniques are a form of “voice conservation” procedures available for management of laryngeal cancer.^[5] Open partial laryngectomy is useful for cancer involving the anterior commissure with or without spread onto the pediole of the epiglottis and is a sound option for more advanced tumors (T3 or early T4).

Open partial laryngectomy involves resection of the vocal fold, thyroid cartilage, and paraglottic space, as well as impaction of the cricoid and hyoid bone for larynx reconstruction. The surgeon must preserve at least 1 functional cricoarytenoid unit for speech and swallowing. This procedure can be performed with (CHEP) or without (CHP) epiglottis preservation, depending on glottic or supraglottic involvement.

Contraindications include cartilage invasion, bilateral vocal fold fixation, interarytenoid involvement, significant tongue base involvement, transglottic lesion, or poor performance status.

Cure and organ preservation rates are comparable with chemoradiation. Decreased voice quality may result, but adequate swallowing can be achieved with rehabilitation.

When a patient is considering surgery, ascertaining that medical care is optimized is essential. Nutrition should be stable. Pain must be controlled. A trip to the dentist is essential to be sure the dentition is free of active infection. Tobacco and alcohol are best avoided.

Patients with severe lung disease may not be candidates for larynx-sparing surgery. Similarly, patients with compromised heart and renal disease may not be candidates for chemotherapy.

The patient who has had prior irradiation to the head and neck area represents a special problem. Re-irradiation can be undertaken, sometimes with good results, but the risk of severe complications is increased.

This chapter does not allow for an in-depth discussion of operative technique. The author would refer the interested reader to an atlas where the various techniques are depicted.

Under most circumstances, endoscopic resections are carried out with a tracheotomy. Many patients can be discharged on the day of the procedure. Extensive supraglottic resections do cause dysphagia and potentiate aspiration, so these patients require hospitalization and swallowing therapy.

Open partial laryngeal resections are almost always accompanied by a temporary tracheotomy. Most patients are decannulated prior to or soon after discharge. The vocal result is generally reflective of the extent of surgery. Most patients have a dysphonic but serviceable voice.

Following total laryngectomy, the authors recommend immediate insertion of a tracheoesophageal stent to accommodate a voice prosthesis. These patients can be speaking about 3 weeks after surgery. See the image below.

Recovery from laryngeal surgery is reflective of the structures removed, the extent of the resection, and the patient's underlying cardio-pulmonary health. The patient who undergoes resection for a small tumor can be predicted to have excellent functional recovery with good voice. Treatment of advanced cancer always results in compromise of some quality of life and functional capabilities.

Follow-up care is necessary because second primary cancers, recurrences, and late metastases are all strong possibilities. In the course of a lifetime, one third of patients with head and neck cancer may develop another cancer.

The assistance of speech therapists, occupational therapists, and physical therapists with experience in swallowing or secretion control should also be considered.

The complications and consequences of surgery, radiation therapy, and chemotherapy are well known. However, in the larynx, unique or at least unusual complications must be considered. These are listed as follows:

• Loss of upper body strength after laryngectomy
• Psychosocial trauma from surgery and/or radiation therapy^[6]
• Limited mobility of the neck
• Daily stoma care
• Vocal cord–powered voice loss in some procedures
• Aspiration pneumonia, in some procedures
• Radiation-induced neoplasms of the neck
• Osteoradionecrosis
• Chondroradionecrosis
• Chronic pain
• Breathing difficulties
• Stoma infections
• Potential stoma malignancies

Outcomes in malignant tumor of the larynx are measured by relative survival rates. Data from Surveillance, Epidemiology and End Results Program shows that the 5-year relative survival rates of laryngeal cancer by stage at diagnosis, 1989-1996 is as follows:

• All stages - 65%
• Local - 81%
• Regional - 51%
• Distant - 41%

Keep in mind that the outcome for laryngeal carcinoma depends on the initial staging. In general, early-stage disease is treated with single modality therapy, either surgery or radiation therapy. The outcomes in early disease are quite good, approaching over 90% 5-year survival rates with either modality of treatment.

Advanced disease (stage III-IV) is generally treated with multimodality therapy, concurrent chemoradiation therapy and surgery. The 5-year survival rates vary depending on the treatment modality. The 5-year survival rate after concurrent chemoradiation therapy is 54% with preservation of 88% of the larynx at 2 years. The 5-year survival after endoscopic laser laryngeal surgery is 55%.

Quality of life is emerging as an outcome measure in the treatment of laryngeal carcinoma. New data are showing the functional outcomes and quality of life after different treatment modalities.^[7]

Functional preservation of the larynx remains a challenging goal in the treatment of malignant laryngeal tumors. Organ-sparing chemoradiation protocols have become the standard of care for advanced laryngeal cancer. Although these strategies were proven effective in preserving the larynx, the may not necessarily preserve the function. Improving surgical techniques such as endolaryngeal lasers, sophistication of radiation techniques such as IMRT, and the development of novel targeting agents such as cetuximab will surely change the landscape of current trends in laryngeal cancer treatment. Novel work in tumor angiogenesis and immunotherapy also holds promise. In the near future, individualizing treatment through optimal patient selection and biomarker analysis will be an interesting challenge.