The goals of treatment of early glottic cancer are eradication of tumor and preservation of function, including phonatory and swallowing function. Many case series suggest that transoral laser microsurgery, open surgical procedures, and radiation have comparable rates of local control, ultimate local control after salvage therapy, laryngeal preservation, and survival, although there may be differences in cost and voice outcomes. Tumor factors, patient factors, and physician and patient preferences should dictate the choice of therapy.
Laryngeal cancers account for almost one fourth of the approximately 45,000 head and neck malignancies diagnosed in 2007 in the United States , making laryngeal cancer one of the most common sites for head and neck cancer. Of these, approximately one half affect the true vocal folds .
Because patients who have cancers affecting their true vocal fords often present with persistent hoarseness, most are identified in the early stages: T1 or T2 . In contrast, supraglottic and subglottic cancers usually do not produce early signs or symptoms; therefore, affected patients usually present with more advanced stage disease. Furthermore, unlike supraglottic and subglottic cancers, lymphatics are sparse in the glottis and metastases rarely occur in the early course of glottic cancers.
Therefore, the treatment of early glottic carcinoma is a topic of great importance and relevance. Although there is significant retrospective and uncontrolled prospective evidence that surgery or primary radiation is a good treatment option, there are no definitive, prospective, randomized controlled trials comparing the different modalities . There is considerable debate on treatment of early glottic cancers with regard to local control, laryngeal preservation rate, survival, functional outcome, and salvage options for treatment failures. Regardless, given the indispensable role of the larynx in speech and communication, maintaining voice is a critical aspect in the treatment of early-stage disease. In fact, the American Society of Clinical Oncology recommends that patients who have T1 or T2 disease should initially be managed with laryngeal-preserving modalities . This article reviews these management options for early glottic cancers.
Staging
Vocal fold mobility and subsite involvement are the primary determinants of glottic cancer staging. Squamous cell carcinoma of the larynx is defined by the American Joint Committee on Cancer (AJCC) as follows:
Tis: Carcinoma in situ
T1a: Tumor is limited to one vocal cord with normal vocal fold mobility, including anterior or posterior commissure involvement.
T1b: Tumor involves both vocal cords with normal vocal fold mobility, including anterior or posterior commissure involvement.
T2: Tumor extends to the supraglottis or subglottis or demonstrates impaired vocal cord mobility.
T3: Tumor is limited to the larynx with vocal fold fixation, invades the paraglottic space, or demonstrates minor thyroid cartilage invasion.
T4a: Tumor invades through the thyroid cartilage or invades tissues beyond the larynx.
T4b: Tumor invades the prevertebral space, encases the carotid artery, or invades mediastinal structures.
Tis, T1, and T2 are classified under AJCC stage groupings 0, I, and II, respectively. Early-stage glottic cancers are defined as stage 0, I, or II disease, although the authors specifically address T1 and T2 disease. By definition, early-stage glottic cancers lack regional lymph node involvement or distant metastasis.
Also evident from the classification is that early-stage glottic cancers represent a diverse group of clinical disease. Early glottic cancers encompass tumors ranging from small, superficial, distinct tumors to large, diffuse, infiltrative tumors affecting one or both vocal folds. Importantly, the surgical management of these nuances is classified and standardized by the European Laryngological Society (ELS) Working Committee as follows:
Type I: Subepithelial cordectomy—resection of the epithelium
Type II: Subligamental cordectomy—resection of the epithelium, Reinke’s space, and vocal ligament
Type III: Transmuscular cordectomy—resection through the vocalis muscle
Type IV: Total cordectomy (type IV)—resection of the cord up to the anterior commissure
Type Va: Extended cordectomy—resection up to the contralateral vocal fold and the anterior commissure
Type Vb: Extended cordectomy—resection includes the arytenoids
Type Vc: Extended cordectomy—resection encompasses the subglottis
Type Vd: Extended cordectomy—resection includes the ventricle
Type VI: Cordectomy—anterior commissurectomy with bilateral anterior cordectomy
Thus, the type of resection required to eradicate the cancer may be more accurately described by the ELS types, which provide a framework in characterizing the lesions. This becomes important, particularly in publications, so that outcomes and staging can be compared more directly.
Preoperative management
Regardless of the treatment course, tissue diagnosis is mandatory to diagnose a vocal fold lesion as carcinoma. The differential diagnosis for vocal fold lesions is diverse and includes benign and malignant lesions. The methods of tissue diagnosis include an office-based brush cytologic specimen obtained through a flexible endoscope or a cup biopsy with rigid endoscopy under general anesthesia. In approximately 15% to 20% of cases, a diagnostic biopsy can be diagnostic and curative . A careful examination of the lesion should be undertaken, along with documentation of its extent. In particular, anterior commissure involvement should be noted, because this can be a difficult area to treat with surgery or radiotherapy.
The routine use of CT in early glottic cancer is probably unnecessary in T1 lesions, can be considered in T2 lesions, and should be performed in cases involving the anterior commissure. Dullerud and colleagues reported that CT did not change the classification of T1 and T2 glottic tumors and concluded that imaging is required in advanced laryngeal cancers or cancers with anterior commissure involvement. In another study, CT scans resulted in changing T classification, mostly upstaging, in 21% of patients who had glottic cancers . Most upstaging occurred because of subclinical involvement of the thyroid cartilage, supraglottic and subglottic extension, and soft tissue extension. Fifty-four percent of patients who had T1 disease had no abnormal findings on the scans, whereas only 20% of patients who had T2 carcinoma had negative scans. Thus, the utility of scans in T1 disease is questionable unless there are other clinical indications.
If surgery is then pursued after obtaining tissue diagnosis, further meticulous resection is required for surgical margins and depth of invasion. Alternatively, if radiation is pursued as definitive therapy, surgery is reserved for salvage therapy.
Preoperative management
Regardless of the treatment course, tissue diagnosis is mandatory to diagnose a vocal fold lesion as carcinoma. The differential diagnosis for vocal fold lesions is diverse and includes benign and malignant lesions. The methods of tissue diagnosis include an office-based brush cytologic specimen obtained through a flexible endoscope or a cup biopsy with rigid endoscopy under general anesthesia. In approximately 15% to 20% of cases, a diagnostic biopsy can be diagnostic and curative . A careful examination of the lesion should be undertaken, along with documentation of its extent. In particular, anterior commissure involvement should be noted, because this can be a difficult area to treat with surgery or radiotherapy.
The routine use of CT in early glottic cancer is probably unnecessary in T1 lesions, can be considered in T2 lesions, and should be performed in cases involving the anterior commissure. Dullerud and colleagues reported that CT did not change the classification of T1 and T2 glottic tumors and concluded that imaging is required in advanced laryngeal cancers or cancers with anterior commissure involvement. In another study, CT scans resulted in changing T classification, mostly upstaging, in 21% of patients who had glottic cancers . Most upstaging occurred because of subclinical involvement of the thyroid cartilage, supraglottic and subglottic extension, and soft tissue extension. Fifty-four percent of patients who had T1 disease had no abnormal findings on the scans, whereas only 20% of patients who had T2 carcinoma had negative scans. Thus, the utility of scans in T1 disease is questionable unless there are other clinical indications.
If surgery is then pursued after obtaining tissue diagnosis, further meticulous resection is required for surgical margins and depth of invasion. Alternatively, if radiation is pursued as definitive therapy, surgery is reserved for salvage therapy.
Surgery
Surgery for early glottic cancer has evolved from partial laryngectomies by means of external approaches to transoral endoscopic laser resections. Open procedures honor established principles of en bloc resection. In fact, laser excision has provided a paradigm shift in the treatment of early glottic cancer. The approach and extent of resection depend on location, size of the primary tumor, stage, and patient and physician factors. The subsequent severity of functional deficit after surgical treatment, including phonatory function and swallowing, depends on the volume of tissue resected and the resulting defect.
Transoral laser microsurgery
Steiner’s landmark report in 1993 exhorted the use of laser microsurgery for laryngeal carcinoma. Since then, transoral laser microsurgery has become an established time-efficient treatment option for early laryngeal cancer. Laser excision often uses a piecemeal technique compared with the standard en bloc resection. This is possible because of the magnification and lighting afforded by the use of a microscope and the specific characteristic tissue properties when dissected with the carbon dioxide (CO 2 ) laser.
An integral aspect of this procedure is close follow-up to detect persistent or recurrent disease on a timely basis. Based on final pathologic findings, re-excision can be accomplished and further therapy, including further laser excisions, can be considered. In a study by Jackel and colleagues , approximately 30% of patients who had T1 to T4 laryngeal cancer and underwent transoral laser surgery required revision laser surgery. Even though almost a third of patients required another procedure, these investigators state that the ease of revision laser surgery makes the event “unproblematic” . Furthermore, most of these patients, despite pathologic reports of inadequate margins, had no residual cancer on the repeat resection specimen. If patients had residual disease on revision laser surgery, their locoregional control and laryngeal preservation rates were significantly worse but their length of survival was unaffected. Nevertheless, most patients were cleared of their disease, and only 0.7% of patients who had laryngeal cancer had persistent cancer after revision laser surgery.
Transoral laser excision is comparable to other surgical methods and radiation in terms of local control and laryngeal preservation for early glottic cancer. Several studies have reported local control rates for T1 and T2 disease in the range of 77% to 92% and 66% to 88%, respectively . Ultimate local control after salvage therapy is approximately 97% to 98%, with a laryngeal preservation rate of 90% to 99%. The 5-year disease-specific survival rate is reported to be 90% to 98%.
Laser resection provides more therapeutic options for management of persistent or recurrent disease. Patients can be salvaged with revision laser surgery, radiation therapy, conservation laryngeal surgery, or total laryngectomy. After laser resection for early glottic lesions, tracheostomy is almost always unnecessary and diet is expeditiously advanced. There is minimal pain involved with the procedure. Additional advantages of laser surgery are short treatment time and short hospital stays .
Although the laser offers many advantages, safe use of the CO 2 laser mandates special awareness, training, and skill of the surgeon and operating room team. Airway fire is a potential serious complication during laryngeal laser surgery that must be avoided at all costs. Other potential complications include infection, granulomas, emphysema, cutaneous fistula, bleeding, dyspnea or shortness of breath requiring temporary or permanent tracheotomy, and dysphagia or aspiration pneumonia. The incidence of these complications is relatively rare, occurring in only approximately 4% of patients .
Open surgical procedures
Open surgical procedures for early glottic cancers can be regarded as organ preservation procedures because they aim to preserve speech and swallowing without a permanent stoma. Historically, open procedures required a tracheotomy. These procedures have been refined, and meticulous surgery usually obviates the need for a permanent tracheotomy. Nevertheless, patients may require a temporary tracheostomy after open partial surgery. Swallowing can be variably affected for some period, leading to wavering degrees of aspiration. Hence, patients require adequate pulmonary reserve for conservational laryngeal surgical procedures.
Several open surgical laryngeal procedures are available for the treatment of early glottic cancers . Laryngofissure with cordectomy entails resection of a vocal fold through a thyrotomy. This procedure is indicated for midthird mobile vocal fold lesions. The vertical partial hemilaryngectomy, which includes removal of half of the larynx, can be successfully used for lesions without anterior commissure involvement. Other select T1 and T2 lesions, including cancers involving the anterior commissure, are treated with frontolateral hemilaryngectomy or supracricoid laryngectomy. Frontolateral partial laryngectomy removes a vocal fold, anterior commissure, anterior third of the contralateral vocal fold, and the overlying medial thyroid cartilage. Supracricoid laryngectomy preserves at least one cricoarytenoid unit and cricoid cartilage. Lesions involving the anterior commissure may involve anterior commissure procedures that remove the anterior portions of both vocal folds and the overlying cartilage.
For open surgical procedures in general, the local control rates range from 86% to 98% . The ultimate local control rates vary from 99% to 100% after salvage therapy, with a laryngeal preservation rate of 88% to 100%. A 5-year disease-specific survival rate of 92% to 97% is reported for T1 and T2 lesions.
The complications after open surgical procedures depend on the procedure performed. They include formation of adhesions, granulation tissue, or stenosis; infection; cutaneous fistula; bleeding; aspiration pneumonia; gastrostomy tube dependence; tracheotomy dependence; and death.
Radiation therapy
Radiotherapy has become one of the most frequently used modalities in the United States because it offers the benefits of no surgery and has good local control and survival rates. The energies most appropriate for radiotherapy are Cobalt 60 or 4- to 6-MV photons. The typical field for radiotherapy for early glottic cancers covers the area between the superior aspect of the thyroid notch, the inferior border of the cricoid cartilage, 1 cm deep to the skin, and the prevertebral fascia .
Overall, for T1 and T2 lesions, the local control rates are between 82% and 87%. The 5-year disease-specific survival rate has been reported as 96% . More specifically, the local control rate with radiation therapy for T1 disease is generally accepted to be approximately 90%, although there is considerable variability. Data from some of the larger studies suggest that the range is from 82% to 94% . Most failures are surgically salvaged with ultimate local control and laryngeal preservation rates of 90% to 96% and laryngeal preservation rates of 83% to 95%, respectively. The 5-year disease-specific survival rate is 95% to 98%. Local control rates for T2 disease are in the range of 61% to 80% . Ultimate local control after surgical salvage ranges from 80% to 91%, with a laryngeal preservation rate ranging from 60% to 82%. The 5-year cause-specific survival rate is 86% to 95%.
There is a direct correlation between the total dose and the control rate, with doses less than 65 Gy resulting in lower local control . The daily fraction size also seems to be important, with 5-year local control rates of 84% to 100%, 77%, and 44% when treated with 2.25 Gy or greater, 2 Gy, and less than 1.8 Gy, respectively . A prospective randomized study in Japan comparing 2.25 Gy with 2 Gy showed improved local control with the higher fraction size . Logically, the duration of therapy is also important, with a treatment time of greater than 40 days associated with a local control rate of 79% to 84% versus a control rate of 95% to 100% for therapy lasting less than 40 days .
In some studies, poor prognostic factors for radiation therapy include bulky tumors , anterior commissure involvement , vocal fold motion impairment , and a larger number of subsites involved .
Surgical salvage after radiation treatment for persistent or recurrent cancer is a viable option. Steiner and colleagues described successfully using transoral laser microsurgery to salvage radiation failures. Seventy-one percent of patients with early-stage recurrence were cured after laser surgery, with a 5-year disease-specific survival rate of 86%. Salvage surgery can also include conservational laryngeal surgery in certain cases or total laryngectomy . The rate of complications, including pharyngocutaneous fistula, after surgical salvage for radiation failures is related to the dose of radiation therapy and, overall, is considered to be higher.
Adverse events associated with radiation to the larynx result from early edema and mucositis and late fibrosis, xerostomia, and stenosis. Hoarseness is a common occurrence acutely and improves in most patients. Swallowing function may be altered from the fibrosis but usually also improves. Severe complications occur at a frequency between 1% and 2%, requiring a tracheotomy or total laryngectomy .
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