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Surgical treatment of carcinoma of the larynx
Cancer 7ieutment Reviews ( 1986) 13,45&O
Surgical
treatment
of carcinoma
of the larynx
D. F. N. Harrison Professorial
Unit, The Royal National
Throat, .Nose & Ear Hospital,
London, U.K.
Although varying to some extent within different ethnic populations, cancer of the head and neck comprises about 8% ofall cancers diagnosed in men and 3% of those diagnosed in women. The commonest malignant tumour is found within the larynx with an age-adjusted incidence of4 per 100,000 population in the United Kingdom, predominantly male. There is good evidence that although incidence rates are decreasing for white males, they are increasing amongst black and white females and black males (15), although observations amongst the South African urban blacks suggest an incidence of only 3.73 per 100,000 population ( 19). Separation of tumours within the larynx and pharynx for the purpose of classification and statistical analysis has only occurred within the last 20 years. This makes accurate comparisons of incidence rates difficult, although it does appear that in white males there has not been the same dramatic rise in the incidence of laryngeal cancer as that of other tobacco related neoplasms. Unfortunately, the same may not be true of the female population. The majority of laryngeal cancers are squamous carcinomata varying in degrees of differentiation. Relative survival rates, that is the ratio of the probability ofsurviving after diagnosis to the probability of surviving if the disease had not been present, for laryngeal cancer over a 5-year period has improved from 54% to 63% (1960-1970). Relative 5-year survival has continued to improve through 1980 to 67% (27) although often at the expense ofsurgical loss of the larynx. As with other malignancies affecting the oral, pharyngeal and oesophageal mucosa, follow-up studies show an increased risk of laryngeal cancer in alcoholics and heavy smokers. The relative effects of joint exposure to alcohol and tobacco are not easy to quantify, although many studies have found that risk increases with greater alcohol consumption at every level of smoking (30). Rothman (24) developed an index of interaction or synergy to measure the combined effects of such agents as alcohol and tobacco on cancer production. This is defined as the observed effect with joint exposure divided by the effect expected for joint exposure assuming additivity of the effects. No interaction would correspond to a ratio of 1. For cancer of the larynx the figure was
0305-7372/86/100045+
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1986 Academic
Press Inc.
(London)
Limited
46
D. F. N. HARRISON
estimated as 2.5 and although such calculations must inevitably be limited in accuracy they do support clinical impressions (9). Such findings demonstrate a substantial degree of interaction between several risk factors. Exposure to more than one elevates the risk of laryngeal cancer more than additively so that any avoidance will probably reduce the overall risk. Exposure to various occupational risk factors whilst probably playing a minor role compared with alcohol and / tobacco, have been shown to be associated with the development of laryngeal cancer. This particularly applies to asbestos, mustard gas production and nickel refining. However, figures must be adjusted for tobacco and alcohol consumption to reveal the true risk factor. It might well be thought that laryngeal cancer is therefore a largely preventable disease, although individual’s varying ability to control their exposure to tobacco and alcohol, ensures that it will remain a continuing challenge to the laryngologist. Since persistent and progressive hoarseness is the commonest presentation of laryngeal cancer irrespective of the site of origin, it might be expected that diagnosis would be early and cure rates high. Pain is a late symptom occurring only when ulceration and infection have taken place. Often this is aggravated by swallowing and referred to the ear. Since many heavy smokers have thickened keratotic vocal cords, huskiness may be accepted as normal resulting in many patients being diagnosed only when their cancer is at an advanced stage. It is of some interest to both epidemiologist and oncologist that laryngeal and lung cancer are rarely found to occur simultaneously, despite an assumed exposure of the whole upper respiratory tract epithelium to the same carcinogens. However, approximately 10% of patients successfully treated for laryngeal cancer subsequently develop lung cancer even though usage of tobacco has ceased. Since preservation of voice, even at the expense of a relatively inefficient protective sphincter, is obviously desirable, radiotherapy has always been an attractive form of therapy, and with early tumours, highly effective. However, surgical resection of the whole or part of the larynx, whether as primary treatment or following failed radiotherapy has developed considerably within the last two decades as a result of a better understanding of the pathways of spread of cancer within the larynx. The management of each individual patient can no longer be rationalized into a standard pattern and in many countries surgery is now playing an increasingly dominant role, except for the really early tumour. As with most other head and neck malignancies, therapeutic decisions will be made in relation to such factors as availability of radiotherapeutic and surgical facilities, estimations of tumour extent, individual experience, socio-economic factors and, hopefully, the patients own contribution to the final assessment. Since laryngeal cancers are found throughout the world it might be expected that general agreement as to treatment policy and expected cure rate would have been reached, at least in the more developed countries. The underlying reasons for the lack of concensus is multifactorial and will be discussed in relation to the place of surgery in the management of laryngeal cancer.
Surgical
anatomy
and classification
A study of the growth and pattern of spread of laryngeal cancer depends primarily upon a detailed knowledge of the intricate anatomy of this organ. Although the morphological anatomy was well known, the importance of intrinsic membranes, ligaments and compartments has only been appreciated since the work of Tucker in 196 1 (3 1) and others utilizing techniques for serially sectioning total laryngectomy specimens. This de-
SURGICAL
TREATMENT
OF
CARCINOMA
OF
THE
LARYNX
47
monstrated the importance ofconnective tissue barriers dividing the larynx into a variety of compartments which influenced the spread of cancer within the larynx. Although these partitions present no permanent barrier to the eventual spread of the malignancy, they provided the rationale for the development of a variety of quite sophisticated conservation surgical techniques whose purpose was to preserve some function whilst effectively resecting tumour. The efficacy of these operations depends largely upon an accurate assessment of tumour extent utilizing both clinical and radiological assessment. It is obvious that there is considerable difficulty in estimating a three dimensional disease by two dimensional means and conservation surgery remains restricted to the experienced laryngologist. Division of the larynx into three anatomical regions-the glottis, supraglottis and subglottis-recognizes that prognosis in laryngeal cancer is related not only to tumour size but also to site of origin. However, the boundaries of the glottic region were only discussed in detail at the Centennial Conference on Laryngeal Cancer in May 1974 (6) and as yet are not part of any classification system. The potential errors in attempting to apply these divisions into clinical practice in the absence of clearly defined and accepted anatomical boundaries are obvious, but largely ignored in most statistical analysis. By academic training, natural inclination or simple pragmatism, we have learnt to express much of our thinking numerically. In this we are encouraged by statisticians and the computers they serve, even if the basis of calculation is suspect. Within the area of clinical oncology we use the system of TNM classification of malignant disease to quantify, classify and give statistical respectability to our diagnostic and prognostic approach to individual tumours. Desirable though this may be, such systems possess inherent limitations and unspecified errors which vary with each anatomical site. All classification systems are based on ill-defined anatomical sites and regions, although malignant tumours rarely respect such boundaries. In most, histological classification is omitted despite its considerable potential effect on ultimate prognosis. The underlying purpose of classifying malignant tumours is to obtain homogenous, statistically equivalent groups of patients for the purpose of assessing, evaluating and comparing various therapeutic modalities, as well as indicating possible prognosis. By definition, the TNM system is a clinical classification and as such is dependent upon clinical expertise and integrity of the reporting oncologist. Within the larynx it is necessary to ask whether it is possible to evaluate the available information with sufficient accuracy to describe the real extent of the primary tumour. How important are errors of assessment and is the criteria adequate to formulate a prognosis. Can the data be recorded accurately enough to allow analysis? Such questions are not purely academic but reflect an anxiety that many reports and statistical analysis possess significant but unmeasured intrinsic errors which may nuliify suggested improvements in therapy. When the vagaries of measurements and the possible nuances of interpretation are considered it is difficult to consider the classification of laryngeal cancer as more than an exercise in observation and a possible guide to therapy. Despite this somewhat pessimistic conclusion there is surprisingly good correlation between staging of laryngeal cancer and prognosis. It is possible that most systems are too sophisticated and only one or two factors play a really important role in determining prognosis. My own studies on 145 total laryngectomy specimens studied by whole organ serial sectioning, suggests that only the presence of regional lymph node metastasis or extension of tumour outside the laryngeal framework markedly affect prognosis when the primary lesion is treated by radical excision (13). However, the problems of effective conservation surgery lie in determining these boundaries and require more detailed analysis. Even so the indeterminate errors in classification together with variations in the
48
D.
F. N.
HARRISON
means adopted for end stage reporting make realistic comparisons of the efficacy various treatment modalities for laryngeal cancer virtually impossible ( 12).
Preoperative
of the
radiotherapy
If maximum benefit is to be derived from the selection of treatment modality whether it be surgery or radiotherapy, then each specialist must understand the underlying principles of each others technique. In the earliest laryngeal cancer irrespective of site of origin, megavoltage radiotherapy, when skilfully given, should result in a functionally normal larynx. Surgical excision for the small percentage which fail or recur may need to be radical or conservative depending upon site and results in good salvage rates. With more advanced lesions the problem is more complicated for there is conflicting evidence regarding cure rates following a policy of radiotherapy followed by salvage surgery compared with primary surgery alone. A policy of real ‘combined’ therapy necessitating radical surgery following curative dosage of radiotherapy without a positive biopsy, is now rarely practised since pathological examination of some excised larynges failed to show residual cancer-a potential source of litigation in some countries! Since total laryngectomy and some conservation techniques carry little in the way of increased morbidity following skilled megavoltage radiotherapy, advocates of initial radiotherapy will claim that this approach prevents a variable number of unnecessary operations. Unfortunately, post-radiation oedema together with mucosal healing frequently makes residual tumour difficult to detect, persistent vocal cord fixation may be secondary to fibrosis rather than residual tumour (Figure 1) and if thyroid cartilage was originally involved radiation necrosis may occur. Postoperative radiotherapy, at least to the primary site, suggests inadequate surgical excision frequently resulting in severe fibrosis of neck skin and considerable morbidity. Its use in the control of the high risk clinically NO neck is more rational. However, the debate continues without a clear conclusion, possibly because of some of the factors previously mentioned which would allow meaningful comparisons of similar tumours treated by different regimes.
Glottic
cancer
If a realistic attempt is to be made to apply a system of classification, and Table 1 illustrates the UICC 1978 system for glottic cancer, then the boundaries of this region must be clearly
Table Tis TO Tl
T2 T3 T4 TX
1. UICC
staging
for
subglottic
cancer
Pre-invasive carcinoma (carcinoma in situ) No evidence ofprimary tumour Tumour confined to the region T 1 a Tumour confined to one side of the region Tlb Tumour with extension to both sides of the region Tumour confined to the larynx with extension to one or both cords with normal or impaired Tumour confined to the larynx with fixation of one or both cords Tumour with destruction of cartilage and/or with direct extension beyond the larynx The minimum requirements to assess the primary tumour can not be met
mobility
SURGICAL
Figure
1. Coronal
section
TREATMENT
through
larynx
OF
CARCINOMA
to show post-radiation transglottically.
OF
fibrosis
THE
LARYNX
in paraglottic
49
space
extending
defined. Although not internationally accepted, the relevant Workshop at the Toronto Centennial Conference on Laryngeal Cancer in 1974 defined these as ‘that portion of the vocal cord which approximates to its neighbour during phonation and which is normally covered with squamous epithelium. It extends from the anterior commissure to the tip of the vocal process of the arytenoid, having a vertical height in the male of 5 mm at its midpoint but only 2 mm anteriorly’. Busuttil et al. (4) measured the length of the true cord in relation to the length of the vocal process and body of the arytenoid in 93 human larynges (I am currently performing this exercise in 650 non-humanoid mammalian larynges). Almost one half of the glottis was made up of cartilage (Figure 2) and true glottic carcinoma is therefore limited to the anterior half of the glottis. Consequently, any tumour more than 1 cm in antero-posterior length must inevitably involve cartilage either at the anterior commissure or arytenoid-rarely possible to detect clinically. Where then is the upper surface of the vocal cord, for it forms the floor of the laryngeal ventricle with its boundary the lateral angle of the ventricular space?
50
D. F. N. HARRISON
Figure 2. Transverse
section
showing
glottic
aperture
and relationship
of vocal
cord to body
of arytenoid.
With no clear guidelines for defining vocal cord, not to say anterior and posterior commissure, the potential inaccuracies for recording the primary site within the glottisand consequently subglottis and supraglottis-are considerable. Various interpretations exist both nationally and internationally regarding regional boundaries within the larynx and together with the intrinsic difficulties ofvisualizing many neoplasms may well account for variations in treatment success. Further difficulties exist in translating clinical and radiological assessment into relevant T and N categories, although comparisons between clinical and subsequent histopathological staging has (12, 13, 23) highlighted the magnitude and source of these errors. Pretreatment clinical assessment is based upon clinical, endoscopic and occasionally, radiological findings. Indirect laryngoscopy, now aided by fibre-optic instrumentation, stroboscopic light together with video recording, has markedly advanced our accuracy in determining site and cord movement. However, direct laryngoscopy with biopsies taken from the body of the tumour remains the principle diagnostic means of assessment. However, not all larynges are easy to examine even with the most sophisticated instrumentation, and vocal cord movement, so important in classification and prognosis, is notoriously difficult to interpret. Surface extension of tumour may be accurately viewed by clinical and radiological means whereas deep invasion is not easily assessed. Radiological detection of anything less than gross destruction of cartilage is unlikely even with the help of computerized tomography. These deficiencies and difficulties are of considerable importance when considering the accuracy of classification and also in interpreting deep extension essential when contemplating conservation surgery. An added complication is the potential for regional lymph node metastasis. This is minimal whilst the tumour is confined to the area superficial
SURGICAL
Figure 3
Coronal
section
showing
TREATMENT
large
OF
CARCINOMA
OF
carcinoma of the vocal cord which thyroarytenoideus muscle.
to the conus elasticus. Invasion of the thyroarytenoideus cord movement, markedly increases the risk of regional
THE
LARYNX
has extended
laterally
muscle, with limitation metastasis (Figure 3).
51
to involve
the
or fixity of
TI glottic For most systems Tl represents the earliest, smallest and most favourable tumour. However, in the larynx (UICC) this has been subdivided into what are in fact two different lesions. Tl a represents the smallest detectable cancer for ifgreater than 1 cm in length it will involve cartilage. This may occur without interfering with cord movement and is not considered when classifying unless there is extra laryngeal spread. However Tl b involves both vocal cords and crosses the anterior commissure. The latter, an ‘area’ between the anterior extent of the cords is a weak point since only the anterior commissure tendon separates it from underlying thyroid cartilage. There is no internal perichondrium or periostium, for this region is usually ossified, to resist invasion. Obviously, collating all Tla and T 1b tumours together for analysis of T 1 glottic cancers introduces yet another error.
52
D. F. N. HARRISON
With the possible exception of young patients who might later develop radiationinduced carcinoma, heavy smokers with long standing keratosis and in certain socioeconomic situations, Tl NO glottic tumours are usually treated with radiotherapy. The voice should return to normal and in most instances the possible disadvantages of duration of therapy, dryness of the mouth and the inability to give further radiotherapy to this region, are acceptable. 5-year survival figures are influenced by the proportion of Tlb tumours but approximate to 92%. Resection with the carbon dioxide laser for the smallest Tla lesions is reported by Hiram0 et al. (16) to give as good a cure rate although there may be some postoperative lack of vibration of the operated cord due to scar formation. Between 7% and 10% (29) of the Tl tumours suffer a primary recurrence following radiotherapy. Hordijk (17) attempted to predict these potential failures by using eight different microscopical measurements on biopsy material. Although a positive correlation exists between poor differentiation and prognosis, confirmed in my own series ( 13)) there was no relationship between a high malignancy score and local recurrence of tumour. Salvage of these irradiation failures may be by total or partial laryngectomy. In many centres total laryngectomy has been the most frequent operation providing wide margins of excision, simplifying follow-up and avoiding the exposure of irradiated cartilage. Russ et al. (25) and Robbins & Michaels (23) have both examined total laryngectomy specimens to determine whether post-irradiation conservation surgery would have been possible. They concluded that between 5% and 11 o/o of tumours could have had a partial vertical laryngectomy. However, histopathological examination utilizing serially sectioned specimens provides a great deal more information than examination of the larynx in situ. Biller et al. (3) have described the criteria which are helpful in deciding the feasibility of vertical partial laryngectomy following irradiation. 1. 2. 3. 4. 5. 6. 7.
Tumour extension to the contralateral vocal cord should not exceed 3mm. The arytenoid, except for the vocal process, should be free of tumour. Subglottic extension should not exceed 5 mm. Supraglottic tumour should extend no further than the lateral extent of the ventricle. The vocal cords should not be fixed. No cartilage involvement. Recurrence should correlate with the site and extent of the original lesion.
Applying this criteria Croll et al. (7) treated 26 patients by vertical partial laryngectomy following radiotherapy. Local tumour recurrence occurred in 2 patients, one of whom was salvaged by total laryngectomy. There are differentials in the amount oflarynx removed by vertical partial laryngectomy techniques ranging from removal of thyroid cartilage overlying the anterior commissure to removal of the whole lamina together with arytenoid. The variations in technique, with consequent problems in postoperative morbidity and rehabilitation are multitudinous, and these operations require considerable judgment and technical expertise. Reference should be made to Silver’s Surgery for cancer of the larynx for graphical illustration of the various choices (26)! Depending upon such factors as the intensity of irradiation, duration between completion and local recurrence, ease of examination and accuracy of original assessment, the accepted criteria for conservative surgery can be applied with varying success. Others such as cartilage invasion are more problematical and it is surprising that the incidence of postoperative recurrence is not greater. Follow-up is essential since removal of the protective cartilaginous barrier provided by the thyroid lamina allows further disease to spread into the neck. Apart from
SURGICAL
survival surgery. 1. 2. 3. 4. 5.
TREATMENT
OF
CARCINOMA
OF
rates consideration must also be given to the quality Maceri et al. (2 1) evaluated this in 63 patients with
THE
LARYNX
of life following regard to:
53
conservation
Need for completiontotal laryngectomy. Incidence of successful decannulation. Aspiration. Problems with deglutition. Quality of voice.
The more extensive the surgery the more frequent were post operative problems particularly with removal of the arytenoid. Poor pulmonary reserve, a FEV, of less than 60% of expected values increased morbidity rates as did surgery in the over 70 years old patient. Both dyspnoea and aspiration may occur in the more extensive procedures and with the expected harsh voice many of these patients will be better served by total laryngectomy-perhaps with use of the better voice prosthesis. Morbidity
and mortality
after total ldpgectomy
Many patients will ultimately be treated by total laryngectomy, following failed radiotherapy or conservation surgery or because of the extent of the primary tumour. There are few detailed analyses of the complications and risks of this operation when carried out under ideal conditions. A recent analysis of 374 total laryngectomy operations carried out in my own Unit (as yet unpublished) over a 22 year period has shown a fall in salivary fistula rate from 37% to 10%. The medium duration of hospitalization is now 15 days with a hospital mortality rate of 4%. This figure has dropped to 0.6% since 1978. If even minor wound and urinary infections are considered the morbidity is about 25% of which only 8% could be considered serious. Routine peri-operative coverage with metronidazole as well as ampicillin and flucloxacillin has been largely responsible for the drop in salivary fistula production and our figures show that previous radiotherapy and age greater than 70 years no longer materially affect operative morbidity or mortality. The fear of permanent loss of voice following total laryngectomy obviously effects the initial choice of radiotherapy or conservation surgery despite the considerable success in acquisition of effective oesophageal speech. How successful this technique is depends upon age, previous radiotherapy, motivation, availability of skilled help as well as sex. Language plays a less important role and my own best speakers are Greek! Attempts have been made to restore voice by means of various techniques for almost as long as the operation of total laryngectomy. Few have stood the test of time, many were frankly dangerous. However, the work of Singer & Blom in 1978 (28) who established a trachea-oesophageal fistula maintained with a silicone valve stent has proved most successful in carefully chosen patients. Success rates of around 90% have been reported, although as with other innovations this will vary with the enthusiasm shown by patient and therapeutic team. I-.. glottic The problems in accurately classifying more advanced glottic carcinomata are not overtly different from the earlier lesions. Whereas extension to surrounding regions is usually visible with accuracy dependent primarily upon boundary definitions, impaired movement is largely conjectural. Its significance lies in the involvement of underlying thyroarytenoideus muscle for cricoarytenoid joint involvement is not found without intrinsic muscle tumour.
54
D. F. N. HARRISON
Impairment must precede fixation and it is not known whether the degree of muscular involvement markedly influences the risk of regional lymph node metastasis. Stroboscopic evaluation of cord movement has introduced a degree of objectivity to this important clinical sign but is not universally used nor does it differentiate limitation secondary to tumour bulk. Harwood & de Boer (14) found a local control rate of only 51 y0 for T2 NO glottic tumours with impaired mobility compared with 77% when mobility was judged normal and upgrading was secondary to local extension. Radiotherapy with surgical salvage is effective for T2 glottic tumours with normal mobility frequently allowing a conservation procedure to be carried out. Cure rates in this group are little different from the total Tl glottic group. The decision is more complex when there is impairment of movement for although radiotherapy will heal the mucosal disease, post-irradiation fibrosis may leave cord movement impaired. Conservation surgery in these cases carries a risk of inadequate tumour excision although there is some evidence that positive margins do not always result in recurrent disease (7). Primary vertical partial laryngectomy is frequently advocated for these patients particularly in North America, although not popular in the United Kingdom where salvage total laryngectomy usually follows failed radiotherapy. T3 and T4 glottic Vocal cord fixation always indicates invasion of the thyroarytenoid muscle and may be associated with destruction of arytenoid, cricoarytenoid joint and possibly invasion of the laryngeal intrinsic musculature (Figure 4). My own experience supports that of Kirchner (20) in that almost one-third of patients operated upon with cord fixation have transglottic tumours. Invasion of the paraglottic space with extensions above and below the ventricle are called transglottic-many invade thyroid cartilage and extend outside the larynx (Figure 5). These should have been upgraded to T4 although these extensions are often not visible radiologically. Long term cure rates vary considerably with T3 glottic tumours possibly depending upon the accuracy with which the original classification is made. Several options are available with prognosis largely depending upon the presence or development of cervical lymph node metastases. Harwood et al. (15) in 1980 described 112 patients with T3 NO glottic cancer treated with radiotherapy and salvage total laryngectomy. They emphasized that of those patients dying from glottic cancer 94% had disease at the primary site or in the neck. Using moderate dosage of 5500 rads in 5 weeks there were no problems in subsequent surgery although diagnosis of recurrent or residual tumour required monthly follow up, most recurrences occur within the first year. Five-year salvage rate was 50% but this paper gives no account of the pathological findings in the operative specimens. Success rates for primary total laryngectomy are much higher-80% in DeSanto’s series (8) with the disadvantage of possibly losing power of speech. It might be thought that it is better to be alive without a larynx than dead with one! More recently, Pearson (22) has advocated a near total laryngectomy procedure for advanced glottic cancers claiming good tumour control with reasonable glottic function. This technique is dependent upon high quality frozen section control of the excision at time of surgery and in my own series would not be feasible because of understaging in most T3 glottic tumours. In none of my own specimens studied by serial sectioning (13) nor in those reported by others (23, 25) were any T3 glottic tumours judged suitable for conservation surgery. T4 classification covers a wide range of pathologies and salvage depends on the
SURGICAL
Figure
4. Tumour
has destroyed
TREATMENT
arytenoid
OF
CARCINOMA
and upper interarytenoideus
OF
margin of cricoid muscle.
THE
LARYNX
cartilage.
Some
55
invasion
of the
presence of controllable disease both locally and within the neck. Radical excision combined with postoperative radiotherapy is most commonly used with control rates ranging from 45% to 58% depending on the presence of positive neck nodes. However, it is doubtful if any published figures do more than offer general guide lines since few patients will be cured with radiotherapy alone, prognosis will be dependent upon the surgeons ability to control the local disease.
Supraglottic
cancer
Difficulties and confusion exist in the application of the UICC supraglottic classification because of the division of this region into epilarynx, which bears a close relationship to the hypopharynx, and supraglottis proper. Tumours of the epilarynx tend to invade tongue base and pyriform fossa rather than the pre-epiglottic space. Provision for recognition of the importance of cord fixation is useful although extensive and serious spread from region to
56
D. F. N. HARRISON
Figure 5. Large
transglottic
cancer
invading
thyroid
cartilage
and external
laryngeal
musculature.
region is common without necessarily cord fixation. Tumours of the infrahyoid epiglottisthe impracticability of using the unseen hyoid bone as a dividing line is obvious, easily extend into the pre-epiglottic space by direct invasion or through pre-existing pits (Figure 6). Every tumour at this site is potentially T4!! The abundant lymphatic system of the supraglottic larynx leads to an incidence of regional metastatic disease of about 40% reducing survival by 50%. However, this is thought to be related to site of origin with epilaryngeal tumours being more exophytic with a propensity for lymphatic metastases. Tumour arising from the infrahyoid epiglottis and false cords invade locally but with less risk of neck metastasis. Five-year survival rates for Tl supraglottic tumour presenting without nodes is close to 80% when treated with radiotherapy. The same lesion with suspected positive neck nodes probably requires surgery, for the lesion is often more extensive than suspected. Conservation surgery is based upon the concept that a barrier exists at the level of the anterior commissure and ventricles that impedes the downward extension of cancer of the epiglottis and false cords. Horizontal supraglottic laryngectomy has been practised since 1947 with varying success dependent upon good case selection and
SURGICAL
Figure 6. Tumour
extending
TREATMENT
from
laryngeal
OF
CARCINOMA
surface
epiglottis
OF
through
THE
LARYNX
pits into the pre-epiglottic
57
space.
skilled surgical expertise. Five-year cure rates of between 65% and 90% are claimed by Bocca et al. (2) for all stages of disease which comfortably exceeds what might be expected for total laryngectomy! Apart from the difficulties of case selection, supraglottic laryngectomy is frequently complicated by aspiration in some instances requiring secondary total laryngectomy. Failure to decannulate patients is reported particularly when treating advanced supraglottic tumours involving surgery to the crico-arytenoid joint or following preoperative radiotherapy. Persistent oedema or a need for repeat tracheostomy is associated with residual or recurrent tumour in at least 60% of patients (21). The problems of accurate assessment, good tumour margins and the increased postoperative morbidity reported when horizontal supraglottic laryngectomy follows curative dosage of radiotherapy. However, Tucker et al. (32) in 1984 reported 84 patients treated by 5500 rads to the primary lesion and 4500 rads to both sides of the neck followed in each instance by the appropriate conservation surgery. Three-year survival without recurrence for the whole group covering all stages of disease was 68.8%. The difficulties of
58
D. F. N. HARRISON
true planned combined therapy where surgery may be carried out without evidence of residual disease have already been discussed. These may not be so relevant when preservation of voice is possible and morbidity rates are quoted as being no different from those found when supraglottic laryngectomy is followed by radiotherapy. In their examination of excised larynges, Robbins & Michaels (23) found 12 of the 62 specimens would have been suitable for conservation surgery. Most were confined to the epiglottis and they emphasised the clinical problems of accurate assessing and staging these tumours. Better use of laryngeal tomography and C.T. scanning may enhance clinical accuracy although the presence of irradiation induced oedema adds to the difficulties. With the more advanced tumours, particularly with extension outside of the larynx to tongue base or pyriform fossa, primary total laryngectomy associated with neck dissection or postoperative radiotherapy is still favoured in the majority of patients.
Subglottic
cancer
The absence of clearly defined boundaries for the vocal cords has led to confusion regarding the upper limits of the subglottis. The only structure acting as a barrier between glottic and subglottic regions is the conus elasticus, any tumour starting more than 5 mm below the free edge of the cord must therefore be in the subglottis. Extension through the conus, whether arising primarily from glottis or subglottis, will lead to reduction in cord mobility and fixation. The pathways of spread from these subglottic extensions from the glottis or from primary subglottic tumours has been discussed by Harrison with particular reference to the Delphian and paratracheal lymph nodes as well as the thyroid gland (10, 11). Most primary subglottic tumours rapidly become circumferential and true unilateral disease is unlikely to be diagnosed. It is difficult to see the purpose ofseparating Tl lesions (see Table 1) or T2 from T3. However, T4 is often impossible to diagnose and might well be joined with T3 for simplicity. In essence Tl for relatively early tumours to be treated with radiotherapy, T3 for those with fixation. Extension inferiorly into the trachea and potential spread to the prelaryngeal (Delphian) and paratracheal nodes necessitates total laryngectomy being combined with total thyroidectomy and if necessary manubrial resection (11). The latter allows low resection of the trachea and clearance of the upper paratracheal lymph nodes. This should be followed by postoperative radiotherapy if positive nodes are found at surgery and minimizes the risk of stoma1 recurrence.
Discussion Laryngeal cancer has been recognized for over 150 years and during this time great advances have been made in diagnostic accuracy and management. Our understanding of the natural history of the disease followed the use of serial sectioning techniques for studying operative specimens which provide the foundation for conservation surgery. However, our knowledge of the many factors which govern intrinsic growth rate and tumour-host relationships remains poor. Even so, there appears to be little excuse for the development of the many unrealistic systems of classification in use today which make it almost impossible to compare the efficacy of the various treatment modalities ( 12). Although early carcinoma can be effectively cured by radiotherapy or voice-sparing conservation surgery, many laryngeal cancers continue to be diagnosed late. Indeed, since
SURGICAL
TREATMENT
OF
CARCINOMA
OF
THE
LARYNX
59
smoking has been clearly identified as a major causative agent, most glottic cancers are probably avoidable! One interesting aspect remains to be considered-the influence of age on choice of therapy, for we live in an ageing population. A retrospective study of 18 patients with primary glottic tumours diagnosed between the ages of 19 and 35 years in my own Unit (3% ofa total of600 cases between 1960 and 1981) provided survival figures comparable with results reported from much older patients with similar lesions. This is despite the usual lengthy history of smoking but of course may be associated with an eventual incidence of irradiation induced cancer. Such cases would now receive conservation surgery. Huygen et al. (18) examined the records of 37 1 patients with laryngeal cancer treated over a 17-year period with reference to the prognostic significance of age. If the risks associated with extensive disease were eliminated they found a significant correlation between the age of the patient on admission and the chance of death from tumour within the first 3 years after treatment. In older patients survival was significantly lower than in younger individuals. Similar findings have been reported previously with the explanation that it was related to ‘impairment of cellular immunity in the elderly”. However, additional risks are certainly associated with many of the conservation surgical procedures in the older patient (1). Reduction of more than 50% of predicted values for pulmonary function tests invariably results in severe or fatal postoperative chest infection. Deglutition is often seriously impaired and the effect of these complications on the psychological attitude of elderly patients may be disastrous. Total laryngectomy if uncomplicated by prolonged hospitalization avoids most of these problems and even the elderly can utilize a simple hand held vibrator for the purpose of communication. For many laryngeal cancers there is a choice of treatment with little in the way of valid evidence to judge the efficacy of the various modalities. It is essential therefore that as with all other malignant tumours each patient must be considered as an individual with specific needs. Only in this way can they be offered the best chance of cure with meaningful rehabilitation. References 1. Alasmo, E., Fini-Storchi, O., Agostini, V. & Polli, G. (1985) Conservation surgery for cancer of the larynx in the elderly. f,ur~goscopc 95: 203-205. 2. Bocca, D., Pignataro, 0. & Oldini, C. (1983) Supraglottic laryngectomy. 30 years of experience. Ann. Otol. Rhinol. Laryngol. 92: 14-18. 3. Biller, H. F., Barnhill, F. R., Ogura, J. H. & Perez, A. C. (1970) Hemilaryngectomy following radiation failure for carcinoma of the vocal cords. Laryngoscope 80: 249-253. 4. Bussittil, A., Davis, B. C. & Maran, A. (1981) The soft tissue/cartilage relationship in the laryngeal glottis. j’. Laryngol. Otol. 95: 385-391. 5. Cann, C. I. & Fried, M. P. (1984) Determinants and prognosis of laryngeal cancer. Otolaryngol. Clin. North Amer. 17: 13%150. 6. Centennial Conference on Laryngeal Cancer (1974). Workshop I. New York: Appleton-Century-Crofts. 7. Croll, G. A., Tiwari, R. M. & Manni, J. S. (1984) Vertical partial laryngectomy for recurrent glottic carcinoma after irradiation. Head .Neck Surg. 7: 390-393. 8. DeSanto, L. W. (1984) T3 glottic cancer. Options and consequences of the options. Larygoscope 94: 131 l1315. 9. Flanders, W. D. & Rothman, K. S. (1982) Interaction of alcohol and tobacco in laryngeal cancer. Am. 3. Epidermiol. 115: 371-379. 10. Harrison, D. F. N. (1971) The pathology and management ofsubglotticcancer. Ann. Otol. Rhinol. Laryngol. 84: l-7.
60
D.
F. N. HARRISON
11. Harrison, D. F. N. (1973) Thyroid gland in the management of laryngopharyngeal cancer. Arch. Otolarpgol. 97: 301-302. 12. Harrison, D. F. N. (1979) Intrinsic weakness of the TNM System for classification oflaryngeal cancer. ORL 41: 241-251. 13. Harrison, D. F. N. (1984) Significance of errors in classification for laryngeal cancer. Analysis of 145 total laryngectomy specimens. Ph.D. Thesis. University of London. 14. Harwood, A. R. & de Boer, C. (1980) Prognostic factors in T glottic cancer. Cancer 45: 991-995. 15. Harwood, A. R., Bryce, D. P. & Rider, W. D. (1980) Management ofT3 glottic cancer. Arch. Otolarygol. 106: 697-699. 16. Hirano, M., Hirade, Y. & Kawasaki, H. (1985) Vocal function following carbon dioxide laser surgery for glottic carcinoma: does partial laryngectomy have a place. Ann. Otol. Rhinol. Luryngol. 94: 232-235. 17. Hordijk, G. S. (1980) The high-risk group in early glottic carcinoma. Arch. Otolaryngol. 106: 621-622. 18. Huygen, P. L. M., Van Den Broek, P. & Kazem, I. (1980) Age and mortality in laryngeal cancer. Clin. Otolqngol. 5: 129137. 19. Isaacson, C., Seizer, G., Kaye, V., Greenberg, M., Woodruff, J. D., Davies, J., Ninian, D., Vetten, D. & Andrew, M. (1978) Cancer in the urban blacks of South Africa. S.A. Cancer Bull. 22: 4%84. 20. Kirchner, N. A. (1969) One hundred laryngeal cancers studied by serial section. Ann. Otol. Rhinol. Laryngol. 78: 689-709. 21. Maceri, D. R., Lampe, H. B., Makielski, K. H., Cassamani, P. P. & Krause, J. (1985) Conservation laryngeal surgery. Arch. Otolaryzgol. 111: 361-365. 22. Pearson, B. W. (1981) Subtotal laryngectomy. Larpgoscope 91: 190441912. 23. Robbins, K. T. & Michaels, L. (1984) A study of whole organ cancerous larynges to determine resectability by conservation surgery. Head Neck Surg. 7: 2-7. 24. Rothman, K. J. (1974) Synergy and antagonism in cause-effect relationships. Am. j. Epidemiol. 99: 385388. surgery of the larynx: a 25. Russ, J. E., Sullivan, C., Gallager, H. S. & J esse, R. H. (1979) Conservation reappraisal based on whole organ study. Am. 3. Surg. 183: 588-596. 26. Silver, C. E. (1981) Surgeryfor cancer ofthe larynx. Edinburgh: Churchill Livingstone. 27. Silverberg, E. (1984) Cancer statistics. Cancer 3. Clin. 34~ 7-23. 28. Singer, M. L. & Blom, E. D. (1980) An endoscopic technique for restoration ofvoice after laryngectomy. Ann. Otol. Rhinol. Lqngol. 89: 529-533. 29. Stell, P. M. & Dalby, J. E. (1985) The treatment ofearly (Tl) glottic and supraglottic carcinoma: does partial laryngectomy have a place. Eur. 3. Surg. Oncol. 11: 263-266. 30. Stevens, M. H., Gardner, J. W. & Parkin, J. L. (1983) Head and neck cancer survival and life-style change. Arch. Otolaryngol. 109: 746-749. 3 1. Tucker, G. F. (196 1) A histological method for the study of the spread of cancer within the larynx. Ann. Otol. Rhinol. Layngol. 70: 9 l&92 1. 32. Tucker, H. M., Levine, H., Wood, B. G., Lavertu, P. &Thomas, F. J. (1984) Planned high dose preoperative radiotherapy and definitive surgery for carcinoma of the supraglottic larynx. 7ran.r. Am. Lqngol. Assoc. 105: 115-118.
Surgical
treatment
of carcinoma
of the larynx
D. F. N. Harrison Professorial
Unit, The Royal National
Throat, .Nose & Ear Hospital,
London, U.K.
Although varying to some extent within different ethnic populations, cancer of the head and neck comprises about 8% ofall cancers diagnosed in men and 3% of those diagnosed in women. The commonest malignant tumour is found within the larynx with an age-adjusted incidence of4 per 100,000 population in the United Kingdom, predominantly male. There is good evidence that although incidence rates are decreasing for white males, they are increasing amongst black and white females and black males (15), although observations amongst the South African urban blacks suggest an incidence of only 3.73 per 100,000 population ( 19). Separation of tumours within the larynx and pharynx for the purpose of classification and statistical analysis has only occurred within the last 20 years. This makes accurate comparisons of incidence rates difficult, although it does appear that in white males there has not been the same dramatic rise in the incidence of laryngeal cancer as that of other tobacco related neoplasms. Unfortunately, the same may not be true of the female population. The majority of laryngeal cancers are squamous carcinomata varying in degrees of differentiation. Relative survival rates, that is the ratio of the probability ofsurviving after diagnosis to the probability of surviving if the disease had not been present, for laryngeal cancer over a 5-year period has improved from 54% to 63% (1960-1970). Relative 5-year survival has continued to improve through 1980 to 67% (27) although often at the expense ofsurgical loss of the larynx. As with other malignancies affecting the oral, pharyngeal and oesophageal mucosa, follow-up studies show an increased risk of laryngeal cancer in alcoholics and heavy smokers. The relative effects of joint exposure to alcohol and tobacco are not easy to quantify, although many studies have found that risk increases with greater alcohol consumption at every level of smoking (30). Rothman (24) developed an index of interaction or synergy to measure the combined effects of such agents as alcohol and tobacco on cancer production. This is defined as the observed effect with joint exposure divided by the effect expected for joint exposure assuming additivity of the effects. No interaction would correspond to a ratio of 1. For cancer of the larynx the figure was
0305-7372/86/100045+
16 $03.00/O
0 45
1986 Academic
Press Inc.
(London)
Limited
46
D. F. N. HARRISON
estimated as 2.5 and although such calculations must inevitably be limited in accuracy they do support clinical impressions (9). Such findings demonstrate a substantial degree of interaction between several risk factors. Exposure to more than one elevates the risk of laryngeal cancer more than additively so that any avoidance will probably reduce the overall risk. Exposure to various occupational risk factors whilst probably playing a minor role compared with alcohol and / tobacco, have been shown to be associated with the development of laryngeal cancer. This particularly applies to asbestos, mustard gas production and nickel refining. However, figures must be adjusted for tobacco and alcohol consumption to reveal the true risk factor. It might well be thought that laryngeal cancer is therefore a largely preventable disease, although individual’s varying ability to control their exposure to tobacco and alcohol, ensures that it will remain a continuing challenge to the laryngologist. Since persistent and progressive hoarseness is the commonest presentation of laryngeal cancer irrespective of the site of origin, it might be expected that diagnosis would be early and cure rates high. Pain is a late symptom occurring only when ulceration and infection have taken place. Often this is aggravated by swallowing and referred to the ear. Since many heavy smokers have thickened keratotic vocal cords, huskiness may be accepted as normal resulting in many patients being diagnosed only when their cancer is at an advanced stage. It is of some interest to both epidemiologist and oncologist that laryngeal and lung cancer are rarely found to occur simultaneously, despite an assumed exposure of the whole upper respiratory tract epithelium to the same carcinogens. However, approximately 10% of patients successfully treated for laryngeal cancer subsequently develop lung cancer even though usage of tobacco has ceased. Since preservation of voice, even at the expense of a relatively inefficient protective sphincter, is obviously desirable, radiotherapy has always been an attractive form of therapy, and with early tumours, highly effective. However, surgical resection of the whole or part of the larynx, whether as primary treatment or following failed radiotherapy has developed considerably within the last two decades as a result of a better understanding of the pathways of spread of cancer within the larynx. The management of each individual patient can no longer be rationalized into a standard pattern and in many countries surgery is now playing an increasingly dominant role, except for the really early tumour. As with most other head and neck malignancies, therapeutic decisions will be made in relation to such factors as availability of radiotherapeutic and surgical facilities, estimations of tumour extent, individual experience, socio-economic factors and, hopefully, the patients own contribution to the final assessment. Since laryngeal cancers are found throughout the world it might be expected that general agreement as to treatment policy and expected cure rate would have been reached, at least in the more developed countries. The underlying reasons for the lack of concensus is multifactorial and will be discussed in relation to the place of surgery in the management of laryngeal cancer.
Surgical
anatomy
and classification
A study of the growth and pattern of spread of laryngeal cancer depends primarily upon a detailed knowledge of the intricate anatomy of this organ. Although the morphological anatomy was well known, the importance of intrinsic membranes, ligaments and compartments has only been appreciated since the work of Tucker in 196 1 (3 1) and others utilizing techniques for serially sectioning total laryngectomy specimens. This de-
SURGICAL
TREATMENT
OF
CARCINOMA
OF
THE
LARYNX
47
monstrated the importance ofconnective tissue barriers dividing the larynx into a variety of compartments which influenced the spread of cancer within the larynx. Although these partitions present no permanent barrier to the eventual spread of the malignancy, they provided the rationale for the development of a variety of quite sophisticated conservation surgical techniques whose purpose was to preserve some function whilst effectively resecting tumour. The efficacy of these operations depends largely upon an accurate assessment of tumour extent utilizing both clinical and radiological assessment. It is obvious that there is considerable difficulty in estimating a three dimensional disease by two dimensional means and conservation surgery remains restricted to the experienced laryngologist. Division of the larynx into three anatomical regions-the glottis, supraglottis and subglottis-recognizes that prognosis in laryngeal cancer is related not only to tumour size but also to site of origin. However, the boundaries of the glottic region were only discussed in detail at the Centennial Conference on Laryngeal Cancer in May 1974 (6) and as yet are not part of any classification system. The potential errors in attempting to apply these divisions into clinical practice in the absence of clearly defined and accepted anatomical boundaries are obvious, but largely ignored in most statistical analysis. By academic training, natural inclination or simple pragmatism, we have learnt to express much of our thinking numerically. In this we are encouraged by statisticians and the computers they serve, even if the basis of calculation is suspect. Within the area of clinical oncology we use the system of TNM classification of malignant disease to quantify, classify and give statistical respectability to our diagnostic and prognostic approach to individual tumours. Desirable though this may be, such systems possess inherent limitations and unspecified errors which vary with each anatomical site. All classification systems are based on ill-defined anatomical sites and regions, although malignant tumours rarely respect such boundaries. In most, histological classification is omitted despite its considerable potential effect on ultimate prognosis. The underlying purpose of classifying malignant tumours is to obtain homogenous, statistically equivalent groups of patients for the purpose of assessing, evaluating and comparing various therapeutic modalities, as well as indicating possible prognosis. By definition, the TNM system is a clinical classification and as such is dependent upon clinical expertise and integrity of the reporting oncologist. Within the larynx it is necessary to ask whether it is possible to evaluate the available information with sufficient accuracy to describe the real extent of the primary tumour. How important are errors of assessment and is the criteria adequate to formulate a prognosis. Can the data be recorded accurately enough to allow analysis? Such questions are not purely academic but reflect an anxiety that many reports and statistical analysis possess significant but unmeasured intrinsic errors which may nuliify suggested improvements in therapy. When the vagaries of measurements and the possible nuances of interpretation are considered it is difficult to consider the classification of laryngeal cancer as more than an exercise in observation and a possible guide to therapy. Despite this somewhat pessimistic conclusion there is surprisingly good correlation between staging of laryngeal cancer and prognosis. It is possible that most systems are too sophisticated and only one or two factors play a really important role in determining prognosis. My own studies on 145 total laryngectomy specimens studied by whole organ serial sectioning, suggests that only the presence of regional lymph node metastasis or extension of tumour outside the laryngeal framework markedly affect prognosis when the primary lesion is treated by radical excision (13). However, the problems of effective conservation surgery lie in determining these boundaries and require more detailed analysis. Even so the indeterminate errors in classification together with variations in the
48
D.
F. N.
HARRISON
means adopted for end stage reporting make realistic comparisons of the efficacy various treatment modalities for laryngeal cancer virtually impossible ( 12).
Preoperative
of the
radiotherapy
If maximum benefit is to be derived from the selection of treatment modality whether it be surgery or radiotherapy, then each specialist must understand the underlying principles of each others technique. In the earliest laryngeal cancer irrespective of site of origin, megavoltage radiotherapy, when skilfully given, should result in a functionally normal larynx. Surgical excision for the small percentage which fail or recur may need to be radical or conservative depending upon site and results in good salvage rates. With more advanced lesions the problem is more complicated for there is conflicting evidence regarding cure rates following a policy of radiotherapy followed by salvage surgery compared with primary surgery alone. A policy of real ‘combined’ therapy necessitating radical surgery following curative dosage of radiotherapy without a positive biopsy, is now rarely practised since pathological examination of some excised larynges failed to show residual cancer-a potential source of litigation in some countries! Since total laryngectomy and some conservation techniques carry little in the way of increased morbidity following skilled megavoltage radiotherapy, advocates of initial radiotherapy will claim that this approach prevents a variable number of unnecessary operations. Unfortunately, post-radiation oedema together with mucosal healing frequently makes residual tumour difficult to detect, persistent vocal cord fixation may be secondary to fibrosis rather than residual tumour (Figure 1) and if thyroid cartilage was originally involved radiation necrosis may occur. Postoperative radiotherapy, at least to the primary site, suggests inadequate surgical excision frequently resulting in severe fibrosis of neck skin and considerable morbidity. Its use in the control of the high risk clinically NO neck is more rational. However, the debate continues without a clear conclusion, possibly because of some of the factors previously mentioned which would allow meaningful comparisons of similar tumours treated by different regimes.
Glottic
cancer
If a realistic attempt is to be made to apply a system of classification, and Table 1 illustrates the UICC 1978 system for glottic cancer, then the boundaries of this region must be clearly
Table Tis TO Tl
T2 T3 T4 TX
1. UICC
staging
for
subglottic
cancer
Pre-invasive carcinoma (carcinoma in situ) No evidence ofprimary tumour Tumour confined to the region T 1 a Tumour confined to one side of the region Tlb Tumour with extension to both sides of the region Tumour confined to the larynx with extension to one or both cords with normal or impaired Tumour confined to the larynx with fixation of one or both cords Tumour with destruction of cartilage and/or with direct extension beyond the larynx The minimum requirements to assess the primary tumour can not be met
mobility
SURGICAL
Figure
1. Coronal
section
TREATMENT
through
larynx
OF
CARCINOMA
to show post-radiation transglottically.
OF
fibrosis
THE
LARYNX
in paraglottic
49
space
extending
defined. Although not internationally accepted, the relevant Workshop at the Toronto Centennial Conference on Laryngeal Cancer in 1974 defined these as ‘that portion of the vocal cord which approximates to its neighbour during phonation and which is normally covered with squamous epithelium. It extends from the anterior commissure to the tip of the vocal process of the arytenoid, having a vertical height in the male of 5 mm at its midpoint but only 2 mm anteriorly’. Busuttil et al. (4) measured the length of the true cord in relation to the length of the vocal process and body of the arytenoid in 93 human larynges (I am currently performing this exercise in 650 non-humanoid mammalian larynges). Almost one half of the glottis was made up of cartilage (Figure 2) and true glottic carcinoma is therefore limited to the anterior half of the glottis. Consequently, any tumour more than 1 cm in antero-posterior length must inevitably involve cartilage either at the anterior commissure or arytenoid-rarely possible to detect clinically. Where then is the upper surface of the vocal cord, for it forms the floor of the laryngeal ventricle with its boundary the lateral angle of the ventricular space?
50
D. F. N. HARRISON
Figure 2. Transverse
section
showing
glottic
aperture
and relationship
of vocal
cord to body
of arytenoid.
With no clear guidelines for defining vocal cord, not to say anterior and posterior commissure, the potential inaccuracies for recording the primary site within the glottisand consequently subglottis and supraglottis-are considerable. Various interpretations exist both nationally and internationally regarding regional boundaries within the larynx and together with the intrinsic difficulties ofvisualizing many neoplasms may well account for variations in treatment success. Further difficulties exist in translating clinical and radiological assessment into relevant T and N categories, although comparisons between clinical and subsequent histopathological staging has (12, 13, 23) highlighted the magnitude and source of these errors. Pretreatment clinical assessment is based upon clinical, endoscopic and occasionally, radiological findings. Indirect laryngoscopy, now aided by fibre-optic instrumentation, stroboscopic light together with video recording, has markedly advanced our accuracy in determining site and cord movement. However, direct laryngoscopy with biopsies taken from the body of the tumour remains the principle diagnostic means of assessment. However, not all larynges are easy to examine even with the most sophisticated instrumentation, and vocal cord movement, so important in classification and prognosis, is notoriously difficult to interpret. Surface extension of tumour may be accurately viewed by clinical and radiological means whereas deep invasion is not easily assessed. Radiological detection of anything less than gross destruction of cartilage is unlikely even with the help of computerized tomography. These deficiencies and difficulties are of considerable importance when considering the accuracy of classification and also in interpreting deep extension essential when contemplating conservation surgery. An added complication is the potential for regional lymph node metastasis. This is minimal whilst the tumour is confined to the area superficial
SURGICAL
Figure 3
Coronal
section
showing
TREATMENT
large
OF
CARCINOMA
OF
carcinoma of the vocal cord which thyroarytenoideus muscle.
to the conus elasticus. Invasion of the thyroarytenoideus cord movement, markedly increases the risk of regional
THE
LARYNX
has extended
laterally
muscle, with limitation metastasis (Figure 3).
51
to involve
the
or fixity of
TI glottic For most systems Tl represents the earliest, smallest and most favourable tumour. However, in the larynx (UICC) this has been subdivided into what are in fact two different lesions. Tl a represents the smallest detectable cancer for ifgreater than 1 cm in length it will involve cartilage. This may occur without interfering with cord movement and is not considered when classifying unless there is extra laryngeal spread. However Tl b involves both vocal cords and crosses the anterior commissure. The latter, an ‘area’ between the anterior extent of the cords is a weak point since only the anterior commissure tendon separates it from underlying thyroid cartilage. There is no internal perichondrium or periostium, for this region is usually ossified, to resist invasion. Obviously, collating all Tla and T 1b tumours together for analysis of T 1 glottic cancers introduces yet another error.
52
D. F. N. HARRISON
With the possible exception of young patients who might later develop radiationinduced carcinoma, heavy smokers with long standing keratosis and in certain socioeconomic situations, Tl NO glottic tumours are usually treated with radiotherapy. The voice should return to normal and in most instances the possible disadvantages of duration of therapy, dryness of the mouth and the inability to give further radiotherapy to this region, are acceptable. 5-year survival figures are influenced by the proportion of Tlb tumours but approximate to 92%. Resection with the carbon dioxide laser for the smallest Tla lesions is reported by Hiram0 et al. (16) to give as good a cure rate although there may be some postoperative lack of vibration of the operated cord due to scar formation. Between 7% and 10% (29) of the Tl tumours suffer a primary recurrence following radiotherapy. Hordijk (17) attempted to predict these potential failures by using eight different microscopical measurements on biopsy material. Although a positive correlation exists between poor differentiation and prognosis, confirmed in my own series ( 13)) there was no relationship between a high malignancy score and local recurrence of tumour. Salvage of these irradiation failures may be by total or partial laryngectomy. In many centres total laryngectomy has been the most frequent operation providing wide margins of excision, simplifying follow-up and avoiding the exposure of irradiated cartilage. Russ et al. (25) and Robbins & Michaels (23) have both examined total laryngectomy specimens to determine whether post-irradiation conservation surgery would have been possible. They concluded that between 5% and 11 o/o of tumours could have had a partial vertical laryngectomy. However, histopathological examination utilizing serially sectioned specimens provides a great deal more information than examination of the larynx in situ. Biller et al. (3) have described the criteria which are helpful in deciding the feasibility of vertical partial laryngectomy following irradiation. 1. 2. 3. 4. 5. 6. 7.
Tumour extension to the contralateral vocal cord should not exceed 3mm. The arytenoid, except for the vocal process, should be free of tumour. Subglottic extension should not exceed 5 mm. Supraglottic tumour should extend no further than the lateral extent of the ventricle. The vocal cords should not be fixed. No cartilage involvement. Recurrence should correlate with the site and extent of the original lesion.
Applying this criteria Croll et al. (7) treated 26 patients by vertical partial laryngectomy following radiotherapy. Local tumour recurrence occurred in 2 patients, one of whom was salvaged by total laryngectomy. There are differentials in the amount oflarynx removed by vertical partial laryngectomy techniques ranging from removal of thyroid cartilage overlying the anterior commissure to removal of the whole lamina together with arytenoid. The variations in technique, with consequent problems in postoperative morbidity and rehabilitation are multitudinous, and these operations require considerable judgment and technical expertise. Reference should be made to Silver’s Surgery for cancer of the larynx for graphical illustration of the various choices (26)! Depending upon such factors as the intensity of irradiation, duration between completion and local recurrence, ease of examination and accuracy of original assessment, the accepted criteria for conservative surgery can be applied with varying success. Others such as cartilage invasion are more problematical and it is surprising that the incidence of postoperative recurrence is not greater. Follow-up is essential since removal of the protective cartilaginous barrier provided by the thyroid lamina allows further disease to spread into the neck. Apart from
SURGICAL
survival surgery. 1. 2. 3. 4. 5.
TREATMENT
OF
CARCINOMA
OF
rates consideration must also be given to the quality Maceri et al. (2 1) evaluated this in 63 patients with
THE
LARYNX
of life following regard to:
53
conservation
Need for completiontotal laryngectomy. Incidence of successful decannulation. Aspiration. Problems with deglutition. Quality of voice.
The more extensive the surgery the more frequent were post operative problems particularly with removal of the arytenoid. Poor pulmonary reserve, a FEV, of less than 60% of expected values increased morbidity rates as did surgery in the over 70 years old patient. Both dyspnoea and aspiration may occur in the more extensive procedures and with the expected harsh voice many of these patients will be better served by total laryngectomy-perhaps with use of the better voice prosthesis. Morbidity
and mortality
after total ldpgectomy
Many patients will ultimately be treated by total laryngectomy, following failed radiotherapy or conservation surgery or because of the extent of the primary tumour. There are few detailed analyses of the complications and risks of this operation when carried out under ideal conditions. A recent analysis of 374 total laryngectomy operations carried out in my own Unit (as yet unpublished) over a 22 year period has shown a fall in salivary fistula rate from 37% to 10%. The medium duration of hospitalization is now 15 days with a hospital mortality rate of 4%. This figure has dropped to 0.6% since 1978. If even minor wound and urinary infections are considered the morbidity is about 25% of which only 8% could be considered serious. Routine peri-operative coverage with metronidazole as well as ampicillin and flucloxacillin has been largely responsible for the drop in salivary fistula production and our figures show that previous radiotherapy and age greater than 70 years no longer materially affect operative morbidity or mortality. The fear of permanent loss of voice following total laryngectomy obviously effects the initial choice of radiotherapy or conservation surgery despite the considerable success in acquisition of effective oesophageal speech. How successful this technique is depends upon age, previous radiotherapy, motivation, availability of skilled help as well as sex. Language plays a less important role and my own best speakers are Greek! Attempts have been made to restore voice by means of various techniques for almost as long as the operation of total laryngectomy. Few have stood the test of time, many were frankly dangerous. However, the work of Singer & Blom in 1978 (28) who established a trachea-oesophageal fistula maintained with a silicone valve stent has proved most successful in carefully chosen patients. Success rates of around 90% have been reported, although as with other innovations this will vary with the enthusiasm shown by patient and therapeutic team. I-.. glottic The problems in accurately classifying more advanced glottic carcinomata are not overtly different from the earlier lesions. Whereas extension to surrounding regions is usually visible with accuracy dependent primarily upon boundary definitions, impaired movement is largely conjectural. Its significance lies in the involvement of underlying thyroarytenoideus muscle for cricoarytenoid joint involvement is not found without intrinsic muscle tumour.
54
D. F. N. HARRISON
Impairment must precede fixation and it is not known whether the degree of muscular involvement markedly influences the risk of regional lymph node metastasis. Stroboscopic evaluation of cord movement has introduced a degree of objectivity to this important clinical sign but is not universally used nor does it differentiate limitation secondary to tumour bulk. Harwood & de Boer (14) found a local control rate of only 51 y0 for T2 NO glottic tumours with impaired mobility compared with 77% when mobility was judged normal and upgrading was secondary to local extension. Radiotherapy with surgical salvage is effective for T2 glottic tumours with normal mobility frequently allowing a conservation procedure to be carried out. Cure rates in this group are little different from the total Tl glottic group. The decision is more complex when there is impairment of movement for although radiotherapy will heal the mucosal disease, post-irradiation fibrosis may leave cord movement impaired. Conservation surgery in these cases carries a risk of inadequate tumour excision although there is some evidence that positive margins do not always result in recurrent disease (7). Primary vertical partial laryngectomy is frequently advocated for these patients particularly in North America, although not popular in the United Kingdom where salvage total laryngectomy usually follows failed radiotherapy. T3 and T4 glottic Vocal cord fixation always indicates invasion of the thyroarytenoid muscle and may be associated with destruction of arytenoid, cricoarytenoid joint and possibly invasion of the laryngeal intrinsic musculature (Figure 4). My own experience supports that of Kirchner (20) in that almost one-third of patients operated upon with cord fixation have transglottic tumours. Invasion of the paraglottic space with extensions above and below the ventricle are called transglottic-many invade thyroid cartilage and extend outside the larynx (Figure 5). These should have been upgraded to T4 although these extensions are often not visible radiologically. Long term cure rates vary considerably with T3 glottic tumours possibly depending upon the accuracy with which the original classification is made. Several options are available with prognosis largely depending upon the presence or development of cervical lymph node metastases. Harwood et al. (15) in 1980 described 112 patients with T3 NO glottic cancer treated with radiotherapy and salvage total laryngectomy. They emphasized that of those patients dying from glottic cancer 94% had disease at the primary site or in the neck. Using moderate dosage of 5500 rads in 5 weeks there were no problems in subsequent surgery although diagnosis of recurrent or residual tumour required monthly follow up, most recurrences occur within the first year. Five-year salvage rate was 50% but this paper gives no account of the pathological findings in the operative specimens. Success rates for primary total laryngectomy are much higher-80% in DeSanto’s series (8) with the disadvantage of possibly losing power of speech. It might be thought that it is better to be alive without a larynx than dead with one! More recently, Pearson (22) has advocated a near total laryngectomy procedure for advanced glottic cancers claiming good tumour control with reasonable glottic function. This technique is dependent upon high quality frozen section control of the excision at time of surgery and in my own series would not be feasible because of understaging in most T3 glottic tumours. In none of my own specimens studied by serial sectioning (13) nor in those reported by others (23, 25) were any T3 glottic tumours judged suitable for conservation surgery. T4 classification covers a wide range of pathologies and salvage depends on the
SURGICAL
Figure
4. Tumour
has destroyed
TREATMENT
arytenoid
OF
CARCINOMA
and upper interarytenoideus
OF
margin of cricoid muscle.
THE
LARYNX
cartilage.
Some
55
invasion
of the
presence of controllable disease both locally and within the neck. Radical excision combined with postoperative radiotherapy is most commonly used with control rates ranging from 45% to 58% depending on the presence of positive neck nodes. However, it is doubtful if any published figures do more than offer general guide lines since few patients will be cured with radiotherapy alone, prognosis will be dependent upon the surgeons ability to control the local disease.
Supraglottic
cancer
Difficulties and confusion exist in the application of the UICC supraglottic classification because of the division of this region into epilarynx, which bears a close relationship to the hypopharynx, and supraglottis proper. Tumours of the epilarynx tend to invade tongue base and pyriform fossa rather than the pre-epiglottic space. Provision for recognition of the importance of cord fixation is useful although extensive and serious spread from region to
56
D. F. N. HARRISON
Figure 5. Large
transglottic
cancer
invading
thyroid
cartilage
and external
laryngeal
musculature.
region is common without necessarily cord fixation. Tumours of the infrahyoid epiglottisthe impracticability of using the unseen hyoid bone as a dividing line is obvious, easily extend into the pre-epiglottic space by direct invasion or through pre-existing pits (Figure 6). Every tumour at this site is potentially T4!! The abundant lymphatic system of the supraglottic larynx leads to an incidence of regional metastatic disease of about 40% reducing survival by 50%. However, this is thought to be related to site of origin with epilaryngeal tumours being more exophytic with a propensity for lymphatic metastases. Tumour arising from the infrahyoid epiglottis and false cords invade locally but with less risk of neck metastasis. Five-year survival rates for Tl supraglottic tumour presenting without nodes is close to 80% when treated with radiotherapy. The same lesion with suspected positive neck nodes probably requires surgery, for the lesion is often more extensive than suspected. Conservation surgery is based upon the concept that a barrier exists at the level of the anterior commissure and ventricles that impedes the downward extension of cancer of the epiglottis and false cords. Horizontal supraglottic laryngectomy has been practised since 1947 with varying success dependent upon good case selection and
SURGICAL
Figure 6. Tumour
extending
TREATMENT
from
laryngeal
OF
CARCINOMA
surface
epiglottis
OF
through
THE
LARYNX
pits into the pre-epiglottic
57
space.
skilled surgical expertise. Five-year cure rates of between 65% and 90% are claimed by Bocca et al. (2) for all stages of disease which comfortably exceeds what might be expected for total laryngectomy! Apart from the difficulties of case selection, supraglottic laryngectomy is frequently complicated by aspiration in some instances requiring secondary total laryngectomy. Failure to decannulate patients is reported particularly when treating advanced supraglottic tumours involving surgery to the crico-arytenoid joint or following preoperative radiotherapy. Persistent oedema or a need for repeat tracheostomy is associated with residual or recurrent tumour in at least 60% of patients (21). The problems of accurate assessment, good tumour margins and the increased postoperative morbidity reported when horizontal supraglottic laryngectomy follows curative dosage of radiotherapy. However, Tucker et al. (32) in 1984 reported 84 patients treated by 5500 rads to the primary lesion and 4500 rads to both sides of the neck followed in each instance by the appropriate conservation surgery. Three-year survival without recurrence for the whole group covering all stages of disease was 68.8%. The difficulties of
58
D. F. N. HARRISON
true planned combined therapy where surgery may be carried out without evidence of residual disease have already been discussed. These may not be so relevant when preservation of voice is possible and morbidity rates are quoted as being no different from those found when supraglottic laryngectomy is followed by radiotherapy. In their examination of excised larynges, Robbins & Michaels (23) found 12 of the 62 specimens would have been suitable for conservation surgery. Most were confined to the epiglottis and they emphasised the clinical problems of accurate assessing and staging these tumours. Better use of laryngeal tomography and C.T. scanning may enhance clinical accuracy although the presence of irradiation induced oedema adds to the difficulties. With the more advanced tumours, particularly with extension outside of the larynx to tongue base or pyriform fossa, primary total laryngectomy associated with neck dissection or postoperative radiotherapy is still favoured in the majority of patients.
Subglottic
cancer
The absence of clearly defined boundaries for the vocal cords has led to confusion regarding the upper limits of the subglottis. The only structure acting as a barrier between glottic and subglottic regions is the conus elasticus, any tumour starting more than 5 mm below the free edge of the cord must therefore be in the subglottis. Extension through the conus, whether arising primarily from glottis or subglottis, will lead to reduction in cord mobility and fixation. The pathways of spread from these subglottic extensions from the glottis or from primary subglottic tumours has been discussed by Harrison with particular reference to the Delphian and paratracheal lymph nodes as well as the thyroid gland (10, 11). Most primary subglottic tumours rapidly become circumferential and true unilateral disease is unlikely to be diagnosed. It is difficult to see the purpose ofseparating Tl lesions (see Table 1) or T2 from T3. However, T4 is often impossible to diagnose and might well be joined with T3 for simplicity. In essence Tl for relatively early tumours to be treated with radiotherapy, T3 for those with fixation. Extension inferiorly into the trachea and potential spread to the prelaryngeal (Delphian) and paratracheal nodes necessitates total laryngectomy being combined with total thyroidectomy and if necessary manubrial resection (11). The latter allows low resection of the trachea and clearance of the upper paratracheal lymph nodes. This should be followed by postoperative radiotherapy if positive nodes are found at surgery and minimizes the risk of stoma1 recurrence.
Discussion Laryngeal cancer has been recognized for over 150 years and during this time great advances have been made in diagnostic accuracy and management. Our understanding of the natural history of the disease followed the use of serial sectioning techniques for studying operative specimens which provide the foundation for conservation surgery. However, our knowledge of the many factors which govern intrinsic growth rate and tumour-host relationships remains poor. Even so, there appears to be little excuse for the development of the many unrealistic systems of classification in use today which make it almost impossible to compare the efficacy of the various treatment modalities ( 12). Although early carcinoma can be effectively cured by radiotherapy or voice-sparing conservation surgery, many laryngeal cancers continue to be diagnosed late. Indeed, since
SURGICAL
TREATMENT
OF
CARCINOMA
OF
THE
LARYNX
59
smoking has been clearly identified as a major causative agent, most glottic cancers are probably avoidable! One interesting aspect remains to be considered-the influence of age on choice of therapy, for we live in an ageing population. A retrospective study of 18 patients with primary glottic tumours diagnosed between the ages of 19 and 35 years in my own Unit (3% ofa total of600 cases between 1960 and 1981) provided survival figures comparable with results reported from much older patients with similar lesions. This is despite the usual lengthy history of smoking but of course may be associated with an eventual incidence of irradiation induced cancer. Such cases would now receive conservation surgery. Huygen et al. (18) examined the records of 37 1 patients with laryngeal cancer treated over a 17-year period with reference to the prognostic significance of age. If the risks associated with extensive disease were eliminated they found a significant correlation between the age of the patient on admission and the chance of death from tumour within the first 3 years after treatment. In older patients survival was significantly lower than in younger individuals. Similar findings have been reported previously with the explanation that it was related to ‘impairment of cellular immunity in the elderly”. However, additional risks are certainly associated with many of the conservation surgical procedures in the older patient (1). Reduction of more than 50% of predicted values for pulmonary function tests invariably results in severe or fatal postoperative chest infection. Deglutition is often seriously impaired and the effect of these complications on the psychological attitude of elderly patients may be disastrous. Total laryngectomy if uncomplicated by prolonged hospitalization avoids most of these problems and even the elderly can utilize a simple hand held vibrator for the purpose of communication. For many laryngeal cancers there is a choice of treatment with little in the way of valid evidence to judge the efficacy of the various modalities. It is essential therefore that as with all other malignant tumours each patient must be considered as an individual with specific needs. Only in this way can they be offered the best chance of cure with meaningful rehabilitation. References 1. Alasmo, E., Fini-Storchi, O., Agostini, V. & Polli, G. (1985) Conservation surgery for cancer of the larynx in the elderly. f,ur~goscopc 95: 203-205. 2. Bocca, D., Pignataro, 0. & Oldini, C. (1983) Supraglottic laryngectomy. 30 years of experience. Ann. Otol. Rhinol. Laryngol. 92: 14-18. 3. Biller, H. F., Barnhill, F. R., Ogura, J. H. & Perez, A. C. (1970) Hemilaryngectomy following radiation failure for carcinoma of the vocal cords. Laryngoscope 80: 249-253. 4. Bussittil, A., Davis, B. C. & Maran, A. (1981) The soft tissue/cartilage relationship in the laryngeal glottis. j’. Laryngol. Otol. 95: 385-391. 5. Cann, C. I. & Fried, M. P. (1984) Determinants and prognosis of laryngeal cancer. Otolaryngol. Clin. North Amer. 17: 13%150. 6. Centennial Conference on Laryngeal Cancer (1974). Workshop I. New York: Appleton-Century-Crofts. 7. Croll, G. A., Tiwari, R. M. & Manni, J. S. (1984) Vertical partial laryngectomy for recurrent glottic carcinoma after irradiation. Head .Neck Surg. 7: 390-393. 8. DeSanto, L. W. (1984) T3 glottic cancer. Options and consequences of the options. Larygoscope 94: 131 l1315. 9. Flanders, W. D. & Rothman, K. S. (1982) Interaction of alcohol and tobacco in laryngeal cancer. Am. 3. Epidermiol. 115: 371-379. 10. Harrison, D. F. N. (1971) The pathology and management ofsubglotticcancer. Ann. Otol. Rhinol. Laryngol. 84: l-7.
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11. Harrison, D. F. N. (1973) Thyroid gland in the management of laryngopharyngeal cancer. Arch. Otolarpgol. 97: 301-302. 12. Harrison, D. F. N. (1979) Intrinsic weakness of the TNM System for classification oflaryngeal cancer. ORL 41: 241-251. 13. Harrison, D. F. N. (1984) Significance of errors in classification for laryngeal cancer. Analysis of 145 total laryngectomy specimens. Ph.D. Thesis. University of London. 14. Harwood, A. R. & de Boer, C. (1980) Prognostic factors in T glottic cancer. Cancer 45: 991-995. 15. Harwood, A. R., Bryce, D. P. & Rider, W. D. (1980) Management ofT3 glottic cancer. Arch. Otolarygol. 106: 697-699. 16. Hirano, M., Hirade, Y. & Kawasaki, H. (1985) Vocal function following carbon dioxide laser surgery for glottic carcinoma: does partial laryngectomy have a place. Ann. Otol. Rhinol. Luryngol. 94: 232-235. 17. Hordijk, G. S. (1980) The high-risk group in early glottic carcinoma. Arch. Otolaryngol. 106: 621-622. 18. Huygen, P. L. M., Van Den Broek, P. & Kazem, I. (1980) Age and mortality in laryngeal cancer. Clin. Otolqngol. 5: 129137. 19. Isaacson, C., Seizer, G., Kaye, V., Greenberg, M., Woodruff, J. D., Davies, J., Ninian, D., Vetten, D. & Andrew, M. (1978) Cancer in the urban blacks of South Africa. S.A. Cancer Bull. 22: 4%84. 20. Kirchner, N. A. (1969) One hundred laryngeal cancers studied by serial section. Ann. Otol. Rhinol. Laryngol. 78: 689-709. 21. Maceri, D. R., Lampe, H. B., Makielski, K. H., Cassamani, P. P. & Krause, J. (1985) Conservation laryngeal surgery. Arch. Otolaryzgol. 111: 361-365. 22. Pearson, B. W. (1981) Subtotal laryngectomy. Larpgoscope 91: 190441912. 23. Robbins, K. T. & Michaels, L. (1984) A study of whole organ cancerous larynges to determine resectability by conservation surgery. Head Neck Surg. 7: 2-7. 24. Rothman, K. J. (1974) Synergy and antagonism in cause-effect relationships. Am. j. Epidemiol. 99: 385388. surgery of the larynx: a 25. Russ, J. E., Sullivan, C., Gallager, H. S. & J esse, R. H. (1979) Conservation reappraisal based on whole organ study. Am. 3. Surg. 183: 588-596. 26. Silver, C. E. (1981) Surgeryfor cancer ofthe larynx. Edinburgh: Churchill Livingstone. 27. Silverberg, E. (1984) Cancer statistics. Cancer 3. Clin. 34~ 7-23. 28. Singer, M. L. & Blom, E. D. (1980) An endoscopic technique for restoration ofvoice after laryngectomy. Ann. Otol. Rhinol. Lqngol. 89: 529-533. 29. Stell, P. M. & Dalby, J. E. (1985) The treatment ofearly (Tl) glottic and supraglottic carcinoma: does partial laryngectomy have a place. Eur. 3. Surg. Oncol. 11: 263-266. 30. Stevens, M. H., Gardner, J. W. & Parkin, J. L. (1983) Head and neck cancer survival and life-style change. Arch. Otolaryngol. 109: 746-749. 3 1. Tucker, G. F. (196 1) A histological method for the study of the spread of cancer within the larynx. Ann. Otol. Rhinol. Layngol. 70: 9 l&92 1. 32. Tucker, H. M., Levine, H., Wood, B. G., Lavertu, P. &Thomas, F. J. (1984) Planned high dose preoperative radiotherapy and definitive surgery for carcinoma of the supraglottic larynx. 7ran.r. Am. Lqngol. Assoc. 105: 115-118.