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What Patients Should Know in Decision Making

Written by Gregory T. Wolf, M.D.
Head and Neck Oncology Program; Department of Otolaryngology - Head and Neck Surgery

Cancers arising in the larynx (voice box) are devastating malignancies that account for roughly 200,000 deaths annually worldwide. Although this only represents 2-5% of all malignancies, these cancers have special importance because of their significant effects on voice, swallowing and quality of life. In the United States, it is estimated that over 12,000 new cases are diagnosed each year and that this incidence is increasing during a time that many other cancers are decreasing.

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Tobacco use is known to be the major predisposing factor for laryngeal cancer. However, alcohol use, nutritional deficiencies, genetic predisposition and viral factors may also play a role. The vast majority (85-90%) of cancers of the larynx are squamous cell carcinomas that arise from the covering of the vocal cords.

Common Symptoms of Laryngeal or Voice Box Cancer

Common symptoms are hoarseness, painful swallowing, earache or development of a mass in the neck. When diagnosed early, these cancers are readily curable. Modern treatment approaches have become increasingly complex, as sophisticated methods have been developed to try and preserve vocal function. Because of this, a variety of treatment options are available and selecting the optimal treatment has become a complex and often confusing process for patients. In making these decisions, patients and their families can benefit greatly from understanding how various cancer treatments will affect vocal function and quality of life and how cancer staging and tumor location influence treatment recommendations. This brief article will outline some of the essential considerations that impact treatment decision-making for patients with cancer of the larynx.

How Cancer Affects Vocal Function

As tumors grow they encroach on the airway and affect the muscles of the voice box. These muscles are vitally important in providing protection of the trachea (windpipe) during swallowing of solids, liquids and saliva. When interfered with, closure of the larynx is incomplete and can lead to severe coughing, choking or even chronic pneumonia. The structure of the voice box also provides rigid support for the trachea (windpipe) to facilitate respiration. Compromise of this function causes shortness of breath, noisy and labored breathing. Finally, the larynx is important in communication. The voice box consists of upper and lower components. The upper part is called the supraglottic larynx and consists of the epiglottis; false vocal cords and supporting muscles within the framework of the cartilaginous "box" called the thyroid cartilage. When cancers grow here, they interfere with swallowing and cause pain in the ear, but only affect the voice in a minor way, leading to "thick" speech, "hot potato" voice or change in timbre. The lower part of the voice box contains the true vocal cords and extends down to the top of the windpipe, the cricoid cartilage. Cancer in this region, termed the glottis, causes significant hoarseness as the primary symptom.

There are natural cartilage and fibrous barriers to spread of cancer within the larynx that are well understood by head and neck surgeons. These barriers prevent the spread and invasion of malignant cells so that cancer of the glottis (true vocal cords) tends to remain localized for long periods of time, often six to eight months, before they are discovered. Because there is a sparse lymphatic drainage system in this region, spread of cancer to adjacent lymph nodes in the neck is generally a late stage of malignant growth. In the supraglottic larynx (false vocal cords and epiglottis), however, the tissues are looser, lymphatics more abundant and spread to lymph nodes occurs early and often. Thus, most treatment approaches for cancer, even early ones arising in the supraglottic larynx, include treatment of the lymph nodes in the neck, while treatment of early vocal cord (glottic) cancer is focused on the primary tumor in the larynx.

Cancer Evaluation and Staging

The first step in decision-making for patients with cancer of the larynx is accurate diagnosis and staging. This requires adequate tissue biopsy and histologic interpretation by a pathologist. Generally, these cancers are not difficult to diagnose by the pathologist, but if the clinical presentation is unusual (i.e. cancer in a younger person or non-smoker), or if the appearance is not typical or the growth is too slow or too fast, a second interpretation or re-biopsy may be warranted.

Because most treatment decisions are based on the size and extent of the cancer, precise direct visualization of the cancer is required. This usually involves examination with an endoscope in the physician's office, which allows determination of vocal cord mobility and other dynamic features and also direct laryngoscopy with a microscope under anesthesia. The exact size, shape and depth of invasion can be better determined and a search for adjacent areas of pre-malignant or malignant change can be assessed in other areas such as the oral cavity, pharynx and esophagus. The larynx is connected with the back of the tongue and the lower swallowing passageways and so these areas must also be examined thoroughly.

Radiologic imaging studies such as computerized tomographic (CAT) scans and magnetic resonance imaging (MRI) are often used to examine the neck for cancer spread outside the larynx or involvement of lymph nodes. Chest x-ray and barium swallow x-rays of the esophagus are routinely obtained looking for cancer involving the lungs or the esophagus (swallowing passage). With modern approaches, newer imaging techniques such at PET scans are often used to assess for cancer spread elsewhere in the body. Using information derived from these assessments, the cancer is "staged", i.e. descriptive numbers are assigned that categorize the cancer's size and potential for curability.

The AJCC has established guidelines for staging of cancer of the larynx that assign a description for the tumor (T), the regional or neck lymph nodes (N) and presence of distant metastases (spread of cancer) (M). Cancer of the larynx is often grouped into early (Stage I), intermediate (Stage II) or advanced (Stages III & IV) disease groups. Early cancers are remarkably curable with five-year survival or "cure rates" of 80-95% compared to advanced stages that have five-year survival rates of 25-50%.

Important elements of prognosis that are not represented in such a staging system include a patient's general health, age, immune function, and co-morbidities such as weight loss, heart disease, hypertension or diabetes. Because these cancers usually occur in patients in the sixth or seventh decade of life, as many as 15-20% die of causes other than the cancer itself.

Many factors enter into decision-making when it comes to the treatment or laryngeal cancer. Perhaps more than any other type of cancer, a patient's wishes are a significant element in every decision because of the wide variety of treatments available, the differences in how each treatment affects voice, swallowing and quality of life and the similarities in cure rates among the various treatments. Many of the decisions are influenced by subtle variations in the size or location of the cancer such that patients should seek out the most knowledgeable head and neck oncologists to get information specific to their individual cancer.

A skilled practitioner experienced in the diagnosis and staging of these cancers can only provide such advice. These cancers are usually slow growing and so, if necessary, there is ample time for consultation with both surgical, radiation and medical oncologists. Usually the surgical oncologist will "stage" the cancer and outline various treatment options and often will consult the specialists in the other disciplines. Usually a "team" of oncologists that include surgeons, medical oncologists and radiation specialists will meet to jointly plan a treatment and make recommendations for the patient to consider. These discussions are frequently referred to as a "tumor board."

Management Alternatives

Early Disease:

Early cancer of the glottis (vocal cords) or supraglottis (false vocal cords) can be effectively treated with either surgery alone or radiation therapy. Most surgical procedures can spare major portions of the voice box and with modern techniques, reconstruction of the voice box can be accomplished with preservation of reasonable voice quality and swallowing. The past ten years have seen the introduction of laser resections for many of these cancers thereby avoiding external neck incisions. In general, cancers that are superficial or limited in extent are best treated with laser removal. Similar tumors are also easily cured with 6-7 weeks of radiation treatment. Many physicians feel that voice quality may be better following radiation compared to surgery, but side effects of permanent dry mouth and risks of some long-term swallowing problems are associated with radiation. Decision making as to treatment of choice also depends on availability of skilled surgeons or radiation therapists and the depth of invasion (extent) and the overall size (volume) of cancer.

Intermediate Disease:

For those cancers that are of intermediate size (T2, small T3), treatment decisions are more difficult. Deeply invasive cancers are best treated with surgical excision, often combined with modified or selective neck dissection (removal of lymph nodes). Most of these procedures can preserve some vocal function without permanent tracheostomy. More extensive surgical resections are associated with significant problems with voice and swallowing and radiation therapy or combinations of chemotherapy and radiation may be recommended. A recent advancement, pioneered in Europe, includes near total laryngectomy (supracricoid partial laryngectomy) which has achieved excellent results in young, properly selected patients. Superficial cancers or those of smaller volume can be effectively treated with radiation alone, but local recurrence rates are higher than with primary surgery. Overall cure rates are when subsequent surgical salvage of these radiation failures is successful. Unfortunately, many of the patients suffering recurrences after radiation must undergo total laryngectomy in order to be cured.

Advanced Disease:

Standard treatment for patients with advanced laryngeal cancer has historically consisted of total laryngectomy, often combined with modified neck dissection. When metastatic cancer is present in the lymphatics of the neck, surgery is combined with radiation therapy. Five-year cure rates vary from 40-60%. The major sequelae of total laryngectomy include loss of natural voice and problems associated with living with a permanent tracheal stoma (hole in the neck). Modern voice restoration techniques with tracheoesophageal puncture (Blom-Singer prosthesis) has significantly reduced loss of voice as a result of total laryngectomy since the majority of patients are able to speak with a naturally sounding, lung powered voice and fewer patients must rely on the artificial electrolarynx or esophageal speech.

Many patients and physicians will select primary radiation for treatment of advanced laryngeal cancers. When there is no clinical evidence of regional (neck) metastases, cure rates are acceptable even though local tumor control is not as good as with surgery. This is because of the possibility of successful surgical salvage of radiation failures. When clinical metastases have occurred, cure rates with radiation alone are not good and optimal treatment incorporates surgery followed by radiation.

One of the most exciting advances in the treatment of patients with advanced laryngeal cancer has been the introduction of chemotherapy as initial treatment. In pioneering work, the Veterans Affairs Laryngeal Cancer Study Group demonstrated that several cycles of initial chemotherapy combined with radiation can be as successful as total laryngectomy in curing patients with advanced cancer when the tumor responds to initial chemotherapy. For such patients, laryngeal function, voice, swallowing and quality of life are preserved. This approach has now been extended to patients with pharyngeal (throat) cancers that would normally also require total laryngectomy. More recent studies have shown the feasibility of using a single treatment of initial chemotherapy to determine which cancers will respond and then treating these patients with combined, simultaneous chemotherapy and radiation. Unfortunately, patients who have cancer, which is unresponsive to initial chemotherapy, must undergo total laryngectomy with its resultant side effects. Fortunately, cure rates are the same in both groups of treated patients. Typically, nearly 2/3 of patients will be able to avoid surgery with this new approach. Five-year cure rates for patients with advanced disease managed in this fashion are now in the range of 80% at the University of Michigan. There is increasing evidence that combined (concurrent) chemotherapy and radiation may be better treatment than radiation alone. These combined approaches have substantially increased toxicity and make subsequent surgery for cancer recurrences more difficult. Thus, using an initial chemotherapy treatment to select the right patients for combined chemoradiation and selecting the optimal patients for total laryngectomy represents the first real advance in cure rates for this disease and justifies the increased risk of toxicities from combined treatment.

None of the other treatment approaches have demonstrated improvements in survival rates compared to total laryngectomy. Therefore, all patients should be informed about the effects of total laryngectomy and the chances of subsequent total laryngectomy if either radiation or radiation and chemotherapy are offered as initial treatment. The selection of treatment therefore depends on a balance between side effects, experience of the treating physicians, cost and patient desire. Currently, larynx preservation techniques using chemotherapy and radiation can be offered as alternatives to total laryngectomy if the treatment team has experience with these special techniques or is participating in controlled clinical trials of these approaches.

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