INVITED REVIEW ARTICLE


https://doi.org/10.5005/jp-journals-10001-1523
International Journal of Head and Neck Surgery
Volume 13 | Issue 1 | Year 2022

A Review on Early Glottic Cancer


Kanav Pradeep Kumar1, Mohsin Ahmed Abdul Nabi Shaikh2, Ankur Kirankumar Walli3, Rajan Kannan4, Sultan Ahmed Pradhan5

1-5Department of Surgical Oncology, Prince Aly Khan Hospital, Mumbai, Maharashtra, India

Corresponding Author: Kanav Pradeep Kumar, Department of Surgical Oncology, Prince Aly Khan Hospital, Mumbai, Maharashtra, India, Phone: +91 9819693213, e-mail: Kanav.k92@gmail.com

ABSTRACT

Early glottic cancers (Tis, T1a, T1b, T2) involve one or both cords. They may have some supraglottic or sub glottic extension, and the cords maybe either freely mobile or at the most have impaired mobility. For in situ cancer, microlaryngoscopic excision either with cold steel or CO2 laser is the treatment of choice. In T1 glottic cancers, the treatment trends have swung towards laser excision away from both radiation therapy and open partial laryngectomy. In T2 glottic cancers, radiation therapy is the mainstay of treatment in majority of the cases.

How to cite this article: Kumar KP, Shaikh MAAN, Walli AK, et al. A Review on Early Glottic Cancer. Int J Head Neck Surg 2022;13(1):41-46.

Source of support: Nil

Conflict of interest: None

Keywords: Chemoradiation, Early glottic cancer, Laryngeal cancer, Open partial laryngectomy, Radiation therapy, Transoral laser microsurgery

INTRODUCTION

About two-thirds of laryngeal cancers arise in the glottic area, the majority of which are diagnosed early, partly due to larynx anatomy, specifically its encasement in cartilage with sparse lymphatics and partly due to early onset of symptoms including hoarseness.1

Early glottic cancers (Tis, T1a, T1b, T2) involve one or both vocal cords. They may have some supraglottic or subglottic extension, and the cords maybe either freely mobile or at most have impaired mobility. All in all, these are confined to the endolarynx with no paraglottic or pre-epiglottic space involvement, with an intact laryngeal framework.

SURGICAL ANATOMY & PATTERNS OF SPREAD

The glottis consists of the right and left true vocal cords uniting anteriorly to form the anterior commissure. The vocal cord is membranous in its anterior two-thirds, consisting of the vocalis muscle and the overlying epithelium; the posterior one-third is cartilaginous and comprises of the vocal process of the arytenoids.

The glottis extends inferiorly for 5 mm, where it continues as the subglottis. Lymphatics of the true vocal cord are sparse. They drain into the prelaryngeal nodes, paratracheal nodes, and the deep cervical nodes along the inferior thyroid artery.

Reinke’s space is the submucosal space between the mucosa of the glottis and the underlying vocalis muscle. It allows the mucosa to slide over the underlying tissues producing fluent speech. Very early glottic cancers are superficial and rarely penetrate the deeper tissues, thus mucosal stripping can be done with minimal alteration in the quality of voice.

Paraglottic space is a potential paired space between the mucosa of the larynx and the thyroid cartilage (Fig. 1). The paraglottic space contains the thyroarytenoid muscle; infiltration of this space causes fixity of the cord by involvement of this muscle. Inferolaterally this space is continuous with the gap between the thyroid and cricoid cartilage, permitting the tumor an easy exit route to extralaryngeal spread.

Fig. 1: Schematic representation of a coronal section through the larynx and trachea. The paraglottic space is denoted in gray. H, hyoid bone; T, thyroid cartilage; C, cricoid cartilage.

Most glottic cancers arise from the free margin of the anterior two-thirds of the vocal cord. Initially glottic cancers tend to spread horizontally towards the anterior commissure. Vertical spread occurs in the later stages. Spread superiorly is uncommon because of the barrier at a plane passing through the ventricle.

Once breached, the tumor becomes a glotto-supraglottic tumour with a high tendency to erode the thyroid cartilage. Inferior spread towards the subglottis is more common. This spread is limited by the conus elasticus, which is a barrier between the glottis and subglottis. This membrane is weakest at points where the neurovascular bundles enter or exit the larynx. The extent of subglottic spread is vital if planning an open partial laryngectomy (OPL). The critical cut-off level is limited to the upper border of the cricoid cartilage, which lies 10 mm below the glottis anteriorly, and 5 mm posteriorly. Contiguous spread eventually leads to invasion of the laryngeal framework, strap muscles and the thyroid gland.

The anterior commissure is usually involved by the contiguous spread of cancers of the membranous vocal cord; rarely cancers may arise at the anterior commissure de novo. The anterior commissure is directly attached to the thyroid cartilage by the Broyle’s tendon without intervening inner perichondrium. Lesions at the anterior commissure can invade the thyroid cartilage early in the course of the disease because of the absence of the inner perichondrium at this site. Secondly, spread along the Broyle’s tendon may involve the base of the epiglottis superiorly. Inferiorly the attachment of the tough conus elasticus to the superior border of the cricoid cartilage forces the subglottic spread from the anterior commissure out into the extra laryngeal soft tissues. T4 lesions of the anterior commissure maybe erroneously staged as T1 because the vocal cords are mobile.

CLINICAL PRESENTATION

Indirect laryngoscopy. Physical examination of the larynx has been revolutionized with the use of Hopkins 70° or 90° rigid telescope with a endoscopic video camera or with the use of flexible fibreoptic nasopharyngolaryngoscope, both of which are office procedures. Mobility of the cords is noted. Distinction must be made between impaired cord mobility, fixity of the cord (with a mobile arytenoid), and fixity of the hemilarynx (fixity of cord and arytenoid) as the latter two are T3 lesions. This is important in the treatment planning.

Video laryngoscopy under anesthesia using a 0° telescope (supplemented with 30°, 70°, and 120° telescopes as needed), is extremely useful to determine the subsites involved by the tumor. This may be performed with the aid of an intubating laryngoscope, which is used to retract the base tongue anteriorly, thus exposing the endolarynx and hypopharynx to the telescope. It may be performed in some situations (e.g., subglottic involvement) with the aid of suspension laryngoscope. The 0° and 30° telescopes are useful in determining the disease extent at the anterior commissure and subglottis. The 70° telescope is used to inspect the anterior commissure or ventricle for disease extension. The 120° telescope may be used to view the under surface of the vocal cord.

Direct laryngoscopy by Jackson or Negus Laryngoscope helps assess the extent of the lesion accurately for treatment planning by forcibly lifting the larynx off the posterior pharyngeal mucosa.

Suspension laryngoscopy may be performed at the time of the direct laryngoscopy/rigid endoscopy under anesthesia if transoral laser microsurgery (TLM) is being contemplated. This will confirm the adequacy of exposure, which is a prerequisite for transoral resections of the larynx. A suction tip can be used to assess the suppleness of the paraglottis and the mobility of the arytenoids.

STAGING

Early glottic cancers comprise of:

Tis Carcinoma in situ
T1 Tumor limited to the vocal cord(s) (may involve anterior and posterior commissure) with normal mobility
T1a Tumor limited to one vocal cord
T1b Tumor involves both vocal cords
T2 Tumor extends to supraglottis and/or subglottis, and/or with impaired cord mobility

MANAGEMENT

Radiation or surgery as the sole treatment has been the mainstay of treatment of early glottic cancers. In recent years TLM has made a niche for itself in the management of early glottic cancer, replacing the need for OPL to a large extent and considerably reducing the need for radiation therapy.2 All three modalities have an important role in the management of early glottic cancer, at most times as a single modality treatment.

OPTIONS

Factors influencing treatment decisions.

T STAGE

This is the most important factor in selecting the modality of treatment.3-5 Studies have shown that TLM, radiation therapy and open surgery have equivalent local control rates for T1 glottic cancers, (Table 1) although there is probably a better long-term larynx preservation rate with TLM.6,7

Table 1: Local control rates in T1 glottic cancer: TLM vs OPL vs RT
Overall AC free AC involved
TLM
Steiner et al (2004)8
92% 95% 86%
VPL
Brumund, Laccourreye et al (2005)5
91% 96% 74%
RT, 6 mV
Tong et al (2012)9
91% 95% 86%

For T2 cancers, radiation therapy probably has better local control rates.3,10 For advanced T2 cancers (impaired cord mobility or bulky disease), chemoradiation maybe chosen instead of radiation therapy only if surgery is not being performed.3,11,12

INVOLVEMENT OF ANTERIOR COMMISSURE

Involvement of the anterior commissure poses several problems.

Fig. 2: T2 glottic cancer involving the anterior commissure

Fig. 3: Anterior commissure growth with subglottic extension

TUMOR HISTOLOGY

Verrucous and nonsquamous histologies respond poorly to radiation and generally require TLM or open surgery. It is also believed that radiation therapy may lead to de-differentiation of verrucous cancers.19,20

OCCUPATION

Patients whose occupation has stringent demands on voice-quality, maybe better served with radiation, where there is a better preservation of timbre and shingle of the voice.17,21 TLM and OPL may result in a slightly breathy voice.

AGE

There are concerns in giving high doses of radiation to the very young; surgery is preferred over radiation therapy in young patients. There is a possibility of these patients developing a de-novo secondary primary cancer in the upper aerodigestive tract in subsequent years and they may be deprived of the use of adequate tumoricidal doses of radiotherapy to the same region should they need it. There is also a risk of developing a radiation-induced malignancy such as differentiated thyroid cancers.

COMORBIDITIES

Compromised hepatic and renal function may preclude the use of chemotherapy in combination with radiation (page 126, 24). Chronic pulmonary disease may render supracricoid partial laryngectomy nonfeasible.22,23

TREATING CLINICIAN’S PREFERENCE AND EXPERTISE

For surgery, access to centers with surgeons skilled in the various treatment modalities is necessary.

TIS

The gold standard for the assessment and treatment of carcinoma in situ (Fig. 4) is microlaryngoscopy and mucosal excision either with the CO2 laser or with cold steel instruments.

Fig. 4: Direct laryngoscopic view of a diffuse bilateral cord leukoplakia

In situ cancers have a tendency to progress to invasive carcinoma; hence, there is no question of a “wait and watch” policy in managing these lesions. They have to be treated.

A localized patch is excised into with minimal margins. If it is a diffuse lesion, then mucosal stripping is done. For a bilateral lesion going across the anterior commissure, staged excision is preferable in order to avoid web formation.

During the laser excision of these in situ carcinomas, thermal damage maybe minimized by injecting saline submucosally, a technique described by Zeitel.24

The specimen is subjected to histopathological examination. If there is no invasive component, then the excision is considered therapeutic. No further treatment is necessary in carcinoma in situ. Regular and long-term follow up is maintained and the patient is advised to quit smoking.

Multifocal and diffuse lesions have a tendency to recur and often repeated sessions of mucosal excisions are needed over several years. Subligamental excision may be worth undertaking in selected cases of recurring dysplastic lesions.25

Radiation therapy is best avoided in these noninfiltrative lesions unless the recurrences are very frequent, occur at short intervals and regular follow-up is not possible or if the exposure is inadequate on suspension laryngoscopy.

T1 GLOTTIC CANCER

Transoral laser microsurgery is the preferred treatment modality for T1 glottic cancers, wherever the facilities and expertise are available.

TLM is the treatment of choice for a T1 mid-cord cancer (Fig. 5).

Fig. 5: T1 midcord glottic cancer

A patient presenting with a mid cord growth can be taken up for definitive surgery of complete excision with clear margins (2-3 mm) if malignancy is suspected. Alternatively, a punch biopsy can be taken with definitive surgery being performed after confirmation of the diagnosis. Only an excisional biopsy without clear margins should not be done. Should the histopathology report show malignancy, during the definitive resection the post biopsy edema would lead to a lot more tissue being excised than necessary leading to a poor voice quality. While in cases without post biopsy edema, the epicenter of the lesion maybe missed by the surgeon performing the definitive resection.

For lesions that extend onto the anterior commissure, TLM may still be the best option, if exposure is adequate but will significantly affect the quality of life. If the demands of voice quality are high then radiotherapy should be the preferred treatment in lesions involving the anterior commissure.

Laser resection can be repeated as necessary for recurrences or a second primary. This is a very big advantage of TLM over radiotherapy. Satisfactory exposure on suspension laryngoscopy is the most important criteria in case selection.

Radiotherapy is still the most widely used treatment modality for T1 glottic cancers, especially where the facilities and expertise for laser microsurgery are unavailable. The radiation field for T1 cancers encompasses a small portal to the glottis, sparing the arytenoids and the rest of the neck, thus minimizing the impact on voice quality and swallowing.

Radiotherapy cannot be given again for treating a recurrence. For a localized recurrence, voice conservation surgery maybe performed provided the surrounding tissues are supple and nonedematous. Most recurrences after radiotherapy will need a total laryngectomy.

Radiotherapy is best avoided in the very young, in non-squamous histologies and in patients who have previously received radiation to the neck. In such cases when TLM is not possible, OPL is the preferred treatment. Surgical treatment of a midcord lesion would entail a laryngo-fissure and cordectomy (Fig. 6) while for a tumor involving the anterior commissure it would require a frontolateral laryngectomy (Fig. 7).

Fig. 6: Laryngofissure and cordectomy-extent of resection as viewed in the horizontal plane

Fig. 7: Frontolateral laryngectomy for lesion involving the anterior commissure-extent of resection as viewed in the horizontal plane

T2 GLOTTIC CANCER

Radiation therapy is the preferred modality of treatment in majority of T2 glottic cancers. The radiation field encompasses the entire larynx and nodes at risk of metastasis (Levels II-VI).

For bulky T2 lesions or lesions that have caused an impaired cord mobility, combined chemoradiation is preferred over radiation therapy alone (Fig. 8).

Fig. 8: T2 glottic cancer with impaired cord mobility involving the anterior commissure

Open partial laryngectomy was earlier considered as the treatment of choice in T2 glottic cancers, but today it is very infrequently used. In the very young, in those previously treated with radiation to the same region and in nonsquamous histologies, OPL is the preferred treatment of T2 cancers. For a lateralized T2 lesion with impaired cord mobility a hemilaryngectomy is the procedure of choice (Fig. 9); while for a T2 lesion involving the anterior commissure, extending onto the petiole of epiglottis, a supracricoid partial laryngectomy (SCPL) is required. The postoperative course in patients who have undergone a SCPL is very stressful. Hence it should only be done in the young with good pulmonary functions.

Fig. 9: Hemilaryngectomy for a lateralized T2 cancer-extent of resection as viewed in the horizontal plane

Transoral Laser Microsurgery has a very limited role in T2 glottic cancers. An exophytic glottic cancer extending onto the mucosa over the arytenoid posteriorly can be resected very satisfactorily with the laser. The magnification of the operating microscope and the precision of the CO2 laser cut will enable such a lesion to be resected with tumor free margins, cutting through the supple submucosal tissues. The cartilage need not be resected in such cases, thus preventing aspiration while preserving a good quality of voice. In all other T2 lesions TLM is not ideal. A lateralized T2 glottic cancer extending transventricularly onto the false cords can be resected transorally with the CO2 laser, but the margin of safety in the region of the ventricle is not good due to the proximity of the ventricular mucosa to the inner perichondrium.

MANAGEMENT OF CERVICAL LYMPH NODES

Lymphatic spread of early glottic cancers is rare. For T1 glottic cancers, there is no role of prophylactic radiation/dissection of the cervical lymph nodes. For T2 cancers, the radiation field encompasses the lymph nodes at risk of metastasis (levels II-VI). For T2 cancers being treated with TLM or OPL, there is no role of prophylactic neck dissection.

SUMMARY

Glottic cancer lends itself to early detection because of the symptom of persistent hoarseness. The advances in the evaluation of these cancers include excellent endoscopic assessment and good imaging.

For in situ cancer, microlaryngoscopic excision either with cold steel or CO2 laser is the treatment of choice. The patient is advised to refrain from smoking and kept on a regular follow-up. Radiation therapy is reserved only for cases where microlaryngoscopic exposure is inadequate or recurrences are very frequent.

In T1 glottic cancers, the treatment trends have swung significantly towards TLM, away from both RT and OPL. Radiation therapy is the next best option.

In T2 cancers, radiation therapy is the mainstay of treatment in majority of the cases. Combined chemoradiation is used in bulky T2 tumors and those with impaired cord mobility. OPL and TLM have limited indications in the treatment of T2 glottic cancers.

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