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Endoscopic CO laser excision for Tis, T1, and T2 glottic carcinomas: Cure rate and prognostic factors
Endoscopic CO2 laser excision for Tis, T1, and T2 glottic carcinomas: Cure rate and prognostic factors GIORGIO PERETTI, MD, PIERO NICOLAI, MD, LUCA OSCAR REDAELLI DE ZINIS, MD, MARCO BERLUCCHI, MD, TULLIA BAZZANA, MD, FILIPPO BERTONI, MD, and ANTONINO ROBERTO ANTONELLI, MD, Brescia, Italy
We present the results of a retrospective study based on a cohort of 140 patients who underwent endoscopic CO2 laser excision for previously untreated early glottic cancer (21 Tis, 96 T1, and 23 T2). This study used univariate analysis to review the impact on disease-free survival of 15 factors related to the host, the tumor, and the treatment. Recurrent cancer developed in 28 patients with an average interval to recurrence of 37.5 months. Retreatment consisted of different procedures, including laser excision, partial or total laryngectomy, and/or radiotherapy. The larynx was definitively preserved in 96% of patients. By the end of the study, 14 patients had died, but only 2 of them had died of the disease. Five-year overall survival and determinate survival were 93% and 98%, respectively. Ultimate local control at 5 years with CO2 laser excision alone was 95% for Tis, 87% for T1, and 91% for T2 lesions. Only involvement of the anterior third of the vocal cord (P = 0.02), involvement of the false vocal cord (P = 0.02), and infiltration of the vocalis muscle (P = 0.004) showed a significant negative impact on disease-free survival. (Otolaryngol Head Neck Surg 2000;123:124-31.)
T
he term early glottic cancer usually refers to Tis, T1, and T2 carcinomas and encompasses a wide spectrum of lesions, ranging from epithelial abnormalities involving a segment of a true vocal cord to large bulky tumors extending from the vocal cord to the anterior commissure, contralateral true vocal cord, supraglottis, and/or subglottis, with or without impairment of vocal cord mobility. The goals of the treatment of such lesions are
From the Departments of Otolaryngology (Drs Peretti, Nicolai, Redaelli de Zinis, Berlucchi, Bazzana, and Antonelli) and Radiotherapy (Dr Bertoni), University of Brescia. Reprint requests: Giorgio Peretti, MD, Department of Otolaryngology, University of Brescia, Piazza Spedali Civili, 1, 25123, Brescia, Italy. Copyright © 2000 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2000/$12.00 + 0 23/77/104523 doi:10.1067/mhn.2000.104523 124
cure of the cancer with a low risk of complications, laryngeal preservation, and good voice quality. Because the spread of tumor to regional nodes and/or distant sites is unlikely, control of the primary lesion is usually equivalent to cure. Radiotherapy, conservation surgery, and endoscopic resection are the most common treatment options. The ideal treatment for Tis, T1, and T2 glottic carcinoma, however, is still unsettled and a matter of debate. The treatment should be tailored to each patient, depending on his or her own choice, general conditions, characteristics of the lesion, vocal function, occupation, treatment facilities, cost-effectiveness ratio, and quality of the technique. In recent years the development of laser technology and innovations in laryngoscopic instrumentation and endoscopic surgical techniques have markedly increased the popularity of CO2 laser treatment for selected glottic carcinomas. There is convincing evidence in the literature that the procedure is as effective as other conventional methods, such as open neck functional laryngectomy and/or radiation treatment, in terms of cure rate and functional results.1,2 This article focuses on the results of a retrospective study based on a cohort of 140 patients with Tis, T1, or T2 previously untreated glottic carcinoma, who underwent endoscopic surgery by CO2 laser, with depth and extension of the excision graded from I to V according to our own classification system. The prognostic impact on disease-free survival of several factors (related to the host, tumor, and treatment) is discussed. METHODS AND PATIENTS Patients and Treatment From January 1987 to December 1994, 155 patients with glottic carcinoma underwent endoscopic CO2 laser excision at the Department of Otorhinolaryngology, University of Brescia, Italy. Fifteen patients with glottic cancer recurrent after radiotherapy were excluded from the study; a total of 140 patients with previously untreated glottic carcinoma (21 Tis, 96 T1, and 23 T2) formed the basis of the analysis. There were 135 men and 5 women, with a mean age of 60.5 years (range 3480 years). At the time of the diagnosis, 120 men and 4 women were cigarette smokers, and 15 men and 1 woman had never smoked. The basic criterion for inclusion was the possibility of obtaining a wide endoscopic exposure of the glottis.
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Table 1. Primary treatment modality (N = 140) Excision type
Extension of excision
No. of patients
I II III IV V
Superficial layer of lamina propria Superficial portion of vocalis muscle Medial portion of vocalis muscle Inner perichondrium of thyroid lamina Surrounding laryngeal subsites
16 19 46 17 42
Further criteria for T2 lesions were (1) no supraglottic spread at the level of the anterior commissure, (2) anterior subglottic extension of the tumor not exceeding 5 mm from the free edge of the vocal cord, (3) no posterior subglottic extension, (4) no involvement of the posterior paraglottic space and/or arytenoid cartilage, and (5) a lateral upper limit of the neoplasm not higher than the free edge of the false cord. All procedures were performed with patients under general anesthesia. The Dedo or Ossoff-Holinger laser laryngoscope and Boston University suspension system were used with microlaryngoscopy, with the CO2 laser set on superpulse mode (1-3 W, 270 µm spot size). Patients with T1 glottic carcinoma with anterior commissure involvement and those with T2 carcinoma underwent preoperative CT scan. Intraoperative endoscopy was performed in all patients by 0°, 30°, 70°, and 120° rigid telescopes to explore hidden regions, such as the subglottic portion of the anterior commissure. Exploring hidden regions improved the definition and identification of the characteristics of the lesions in regions such as the anterior commissure, ventricle, and subglottis, and allowed a more detailed inspection of the location, shape, dimensions, boundaries, extension, color, relief, and surface vascular patterns of the lesions. Infusion of saline solution and 1/10,000 epinephrine into the superficial lamina propria was used in patients with superficial lesions apparently limited to the mucosa to determine whether the epithelial lesion had transgressed the superficial lamina propria to or through the vocal ligament. Intraoperative supravital staining with 2% toluidine blue was also used routinely to identify the precise surface extent of the tumor and to demonstrate superficial areas of cellular atypia. Patients underwent different types of resections (type I, mucosectomy; type II, superficial cordectomy; type III, partial cordectomy; type IV, total cordectomy; type V, extended cordectomy) (Fig 1), which were classified according to a personal system based on the endoscopic appearance, radiologic findings of the lesion, results of saline infusion into the superficial lamina propria, and results of supravital staining with toluidine blue. We carried out mucosectomy (type I) limited to the epithelium and to the superficial layer of the lamina propria in 16 patients and superficial cordectomy (type II) extended to the vocal ligament and the superficial portion of the vocalis
Fig 1. Coronal view of a laryngeal specimen depicting the 5 types of resection (I, mucosectomy; II, superficial cordectomy; III, partial cordectomy; IV, total cordectomy; V, extended cordectomy).
muscle in 19. Partial cordectomy (type III), with conservation of the lateral portion of the vocalis muscle, was used in 46 patients in whom microinvasive carcinoma had been diagnosed previously or in whom invasive carcinoma without impairment of vocal cord mobility was suspected. Total cordectomy (type IV), limited to the vocal cord but including the inner perichondrium of the thyroid lamina, was performed in 17 patients, in whom infiltration of the vocalis muscle was preoperatively inferred by the impairment of vocal cord mobility or histologically demonstrated by a previous biopsy. Extended cordectomy (type V) was used in 42 patients with involvement of the false cord, the ventricle, a part of the contralateral cord, or the anterior commissure (Table 1). Partial ventriculotomy was performed in 53% (74/140) of patients to expose the floor of the ventricle and to evaluate the lateral extension of the tumor. For histologic evaluation, the surgical specimen was oriented by staining of the superior edge with marking ink. Multiple sections were cut along the transverse axis, and the depth of infiltration of the vocalis muscle was estimated. Two different policies were followed in cases of positive margins during the observation period: 10 patients (19871991) underwent complementary radiotherapy, and 13 (19921994) underwent laser re-excision.
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Table 2. Univariate survival analysis for prognostic factors (log rank test)
Variable
Sex Male Female Preoperative smoker No Yes Pathologic T category Tis T1 T2 Anterior 3rd true vocal cord involvement No Yes Middle 3rd true vocal cord involvement No Yes Posterior 3rd true vocal cord involvement No Yes Anterior commissure involvement No Yes Ventricle floor involvement No Yes False vocal cord involvement No Yes Vocal muscle involvement No Yes Neoplastic involvement of surgical margins No Yes Complementary treatment No Yes Degree of differentiation Tis 1 2 3 Postoperative smoker No Yes *Survival
No. of patients
Estimated 5-year disease-free survival (%) P
All patients subsequently returned for follow-up visits with a flexible fiberoptic laryngoscope or a rigid 90° telescope for a period ranging from 48 to 132 months (mean 76 months). Microlaryngeal examination was repeated only when suspicious areas were noticed. Statistical Analysis
129 9
78 ± 4 *
0.1
21 117
90 ± 6 77 ± 4
0.2
20 95 23
78 ± 10 81 ± 4 73 ± 9
0.7
34 104
94 ± 4 75 ± 4
0.02†
25 113
76 ± 9 80 ± 4
0.6
95 43
76 ± 4 86 ± 5
0.2
98 40
82 ± 4 72 ± 7
0.2
115 23
81 ± 4 73 ± 9
0.4
135 3
80 ± 3 33 ± 27‡
0.02†
125 13
82 ± 3 54 ± 14
0.004†
93 45
78 ± 4 82 ± 6
0.6
115 23
79 ± 4 82 ± 8
0.7
20 47 65 6
78 ± 10 74 ± 6 81 ± 5 *
0.5
118 20
81 ± 4 70 ± 10
0.2
estimates could not be calculated because all observations were censored. †Statistically significant. ‡Four-year disease-free survival.
Statistical analysis was performed with the SPSS statistical package. Survival curves were calculated from the date of the diagnosis by the Kaplan-Meier method. The end point for overall survival was the date of death (regardless of the cause) or the date of the last consultation for censored observations. For the analysis of determinate survival, patients who died of unrelated causes were considered as censored observations at the date of death. The end point for disease-free survival was the date of the first locoregional recurrence. For ultimate local control with laser alone, patients who had a relapse at the primary site and who were subsequently cured by further laser treatment were considered censored at the date of the last consultation. Four factors were related to the host (age, sex, preoperative and postoperative smoking habits), 9 to the tumor (pT category; localization of the tumor on the anterior, middle, or posterior third of the vocal cord; involvement of the anterior commissure, floor of the ventricle, or false vocal cord; histologic infiltration of the vocal muscle; histologic grading), and 2 to the treatment (positive margins, complementary therapy). The impact of all these factors on disease-free survival was analyzed by univariate analysis with the log rank test (Table 2). Age was evaluated as a continuous variable. Patients who died of other causes or who were lost to follow-up less than 2 years after primary treatment were excluded from statistical analysis. RESULTS
When the study ended, 28 recurrences, with a 37month average interval to the event, had been observed (Table 3). The rate of recurrences, in relation to pT category, was as follows: 19% in Tis (4/21), 18% in T1 (18/96), and 26% in T2 (6/23). Local recurrence was observed in 24% (26/106), 67% (2/3), and 49% (6/14) of patients with involvement of the anterior third of the true vocal cord, false vocal cord, and vocal muscle, respectively. The primary tumor involved more than one of the aforementioned sites in 7 patients. In only 2 patients was the primary lesion limited to the middle and the posterior third of the true vocal cord (Table 3). Retreatment consisted of the following: laser excision in 14 patients; laser excision plus postoperative radiotherapy in 5; partial laryngectomy in 2; total laryngectomy in 4; total laryngectomy extended to the thyroid gland, perilaryngeal soft tissues, and neck skin, with
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bilateral neck dissection plus postoperative radiotherapy in 1; and radiotherapy alone in 1. One patient, in whom a second cancer developed in the lung, was not considered suitable for any kind of treatment (Table 3). Six patients had a second recurrence, which was salvaged in 4. Three underwent a third laser excision, and 1 underwent laser excision plus radiotherapy. Two patients died of the disease: one patient who had received extended total laryngectomy for the first recurrence died of a persistent neck tumor that had been treated unsuccessfully with chemotherapy; a second, who underwent salvage surgery for the first recurrence with laser excision, died of regional recurrence after radical neck dissection for lymph node metastases with extracapsular spread (Table 3). Twelve patients died of other causes. Two patients were excluded from statistical analysis: one who died of myocardial infarction at 11 months, and another who was lost to follow-up 15 months after primary treatment. Five-year overall survival, determinate survival, and disease-free survival of the remaining 138 patients were 93%, 98%, and 79%, respectively. Ultimate local control at 5 years with CO2 laser excision alone was 89%: according to pT category, it was 95% for Tis, 87% for T1, and 91% for T2. The larynx was preserved in 135 cases (96%). Analysis of the impact of 1 continuous and 14 categorical variables showed a significant decline in the disease-free survival rate of patients with involvement of the anterior third of the true vocal cord (75% vs 94%; P = 0.02), false vocal cord involvement (33% vs 80%; P = 0.02), and vocal muscle infiltration (54% vs 82%; P = 0.004) (Table 2). Because of the sample size, the probability of having a false-negative result for the variables that did not significantly influence survival with the log rank test was greater than the commonly accepted value of 0.20. DISCUSSION
The definition of carcinoma in situ should be restricted to lesions of the epithelium that have not transgressed the basement membrane and therefore do not involve the lamina propria. The reported incidence of carcinoma in situ without coexisting invasive carcinoma varies widely from 1% to 16% of laryngeal malignancies.3 Ferlito et al4 found marked international variation in treatment policy. After introduction of the microlaryngeal surgical technique by Kleinsasser5 in 1968 and the CO2 surgical laser by Strong6 in 1975, open procedures, and to a lesser extent radiotherapy, have largely given way to endoscopic techniques. An en bloc excisional biopsy provides an accurate diagnosis
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and an effective treatment in a 1-stage procedure. Histologic examination of the entire specimen with multiple sections prevents overtreatment or undertreatment of small glottic lesions. If necessary, the treatment can be repeated and does not preclude further therapy. In addition, during microlaryngeal surgery it is possible to inspect the endolarynx with rigid and contact endoscopy, which offers a multiperspective view of the lesion and in vivo and in situ observations of the superficial layers of the epithelium. T1 and T2 glottic carcinoma should be classified by a careful microscopic pathologic evaluation into microinvasive, superficial extending, and deeply invasive carcinomas to avoid an inadequate or overzealous approach to treatment and prognosis. The term early glottic cancer should be restricted to those carcinomas that involve the lamina and do not invade muscle or cartilaginous structures, but are still capable of metastasis.7 Impairment of vocal cord mobility is generally related to invasion of the underlying intrinsic muscles and/or cricoarytenoid joint and coincides with a deeply infiltrating neoplasm. Hirano et al8 reported that invasion of one fourth to three fourths of the thyroarytenoid muscle resulted in impaired motion, whereas invasion of more than three fourths of the thyroarytenoid muscle caused fixation of the true vocal cord. Impaired vocal cord mobility in stage II glottic carcinoma is the most significant prognostic tumor-related factor in predicting response to primary and/or salvage therapy.9 For T1 lesions, a cure rate in the range of 80% to 98%, regardless of the treatment, has been reported.1,10-14 However, endoscopic resection1,10 and irradiation11-13 are the most frequently recommended options because of the favorable cost-effectiveness ratio and good voice quality.2,15,16 For T2 lesions with freely mobile cords, the results are comparable with those achieved with T1 with radiotherapy and open surgery.9 Instead, for T2 lesions with impaired mobility, the cure rate obtained with radiotherapy ranges from 52% to 76%,17-19 whereas surgery including vertical partial laryngectomy or hemilaryngectomy still guarantees a cure rate of 56% to 84%.9,20,21 Moreover, in a retrospective study focused on patients with glottic carcinoma with impaired motion of the true vocal cord, Chevalier et al22 reported 5-year absolute survival, cause-specific survival, and local control rates of 81%, 96%, and 94%, respectively. On the basis of their results, they favor the use of cricohyoidoepiglottopexy instead of radiotherapy and vertical partial laryngectomy. Considering the excellent long-term results obtained
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Table 3. Analysis of the patients with recurrences 1st recurrence Initial involved structures
Type of excision
1 2 3 4
Anterior and middle 3rd TVC Anterior and middle 3rd TVC, AC Anterior and middle 3rd TVC Anterior and middle 3rd TVC, vocal muscle
3 5 3 3
5 6 7 8
11
Middle and posterior 3rd TVC, ventricle floor Anterior 3rd TVC Anterior, middle, and posterior TVC, AC Anterior and middle 3rd TVC, AC, ventricle floor, vocal muscle Anterior and middle 3rd TVC Anterior, middle, and posterior TVC, AC, ventricle floor, FVC Anterior 3rd TVC, AC, vocal muscle
12
Anterior and middle 3rd TVC, AC
5
13 14
Anterior 3rd TVC Anterior and middle 3rd TVC, ventricle floor, FVC, vocal muscle Anterior and middle 3rd TVC, AC Anterior and middle 3rd TVC, ventricle floor, vocal muscle Anterior 3rd TVC, AC Middle 3rd TVC Anterior, middle, and posterior TVC, AC, ventricle floor Anterior 3rd TVC Anterior and middle 3rd TVC Anterior and middle 3rd TVC, AC Anterior 3rd TVC Anterior, middle, and posterior TVC Anterior and middle 3rd TVC, AC, vocal muscle Anterior and middle 3rd TVC Anterior and middle 3rd TVC Anterior, middle, and posterior TVC
9 10
15 16 17 18 19 20 21 22 23 24 25 26 27 28
Site
Time (mo)
Treatment
30 8 25 15
PL LE LE + RT TL
3 3 5 5
Homolateral TVC Homolateral TVC Contralateral TVC Homolateral TVC, paraglottic space, posterior commissure Homolateral TVC Contralateral TVC Homolateral TVC AC
43 50 27 11
LE LE + RT LE RT
3 5
Homolateral TVC, AC Homolateral TVC, subglottis
19 34
LE + RT Not treated*
5
3 5
Homolateral TVC, subglottis, thyroid cartilage invasion Homolateral TVC, subglottis, thyroid cartilage invasion Homolateral TVC, AC Homolateral TVC
5 3
Contralateral TVC Homolateral TVC, thyroid cartilage invasion
5 3 5
Contralateral TVC Homolateral TVC Contralateral TVC
2 2 5 4 2 5 2 3 4
Homolateral TVC Homolateral TVC Homolateral TVC, AC Homolateral TVC, AC Homolateral TVC, AC AC, supraglottis Homolateral TVC Homolateral TVC, AC Homolateral TVC, thyroid cartilage invasion
7
TL
23
TL
3 5
LE LE
20 7
LE TL
7 6 9
LE LE LE
30 16 54 12 12 21 12 43 9
LE LE LE LE + RT LE + RT PL LE LE TL + BFND + RT
TVC, True vocal cord; AC,anterior commissure; FVC, false vocal cord; PL, partial laryngectomy; LE, laser excision; RT, radiotherapy; RND, radical neck dissection; TL, total laryngectomy; PL, partial laryngectomy; BFND, bilateral functional neck dissection; CX, chemotherapy; A&W, alive and well; DOC, dead of other causes; DOD, dead of disease; LFU, lost to follow-up. *Patient had a slow-growing laryngeal recurrence and a second cancer in the lung, which was deemed inoperable and was considered to be the final cause of death.
with CO2 laser microsurgical treatment in Tis and T1 glottic carcinomas, several authors have extended the indications to include T2 glottic carcinomas and T1-T2 glottic carcinomas recurrent after radiotherapy.23,24 The cure rates for T2 glottic carcinomas treated endoscopically with laser, regardless of vocal cord mobility, range from 76% to 85%.24-26 Laser surgery has several advantages over radiotherapy and open surgery. The procedure is brief with a shorter hospitalization time, less morbidity, and fewer side effects. Each excision can be adapted individually to the size of the lesion. Working in a bloodless surgical
field ensures a precise and safe resection of the tumor. Residual or recurrent tumor can be detected earlier than it can after open surgery or radiotherapy. The favorable cost-effectiveness ratio of laser surgery has been demonstrated.15,16 Recently, the concept of ultraconservative endoscopic treatment has been emphasized by several authors2,25,27,28 who presented different modalities of resection in relation to the extent and depth of invasion of the tumor. Partial cordectomy, aimed at saving the entire or part of the vocalis muscle, allows good phonatory results by combining the principles of surgical oncology with those of voice preservation. Recently,
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2nd recurrence
3rd recurrence
Time (mo)
Treatment
Site
Time (mo)
Treatment
— — — —
— — — —
— — — —
— — — —
— — — —
— — — —
A&W (132) A&W (132) A&W (83) A&W (113)
— — — —
— — — —
— — — —
— — — —
— — — —
— — — —
A&W (119) A&W (100) A&W (75) A&W (122)
— —
— —
— —
— —
— —
— —
A&W (107) DOC (lung cancer) (42)
—
—
—
—
—
—
LFU (8)
—
—
—
—
—
—
DOC (lung cancer) (53)
— Contralateral TVC
— 8
— LE
— —
— —
— —
A&W (70) A&W (74)
— —
— —
— —
— —
— —
— —
A&W (74) A&W (77)
Homolateral TVC AC —
35 34 —
LE LE + RT —
— Neck metastases —
— 19 —
— RND + RT —
AC — — — — — Homolateral TVC — Neck spread
23 — — — — — 13 — 5
LE — — — — — PL + RT — CX
— — — — — — — — —
— — — — — — — — —
— — — — — — — — —
Site
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Lai and Zeitels29 stressed the validity of phonomicrosurgical treatment for in situ and microinvasive glottic carcinoma by trying to minimize the resected margin of normal tissue and thereby maximizing the preservation of the vocal fold’s layered microstructure, to optimize the vocal outcome. Furthermore, Steiner24 introduced also for advanced tumors an unconventional surgical technique, based on transtumoral incisions, to achieve an oncologically safe resection and, at the same time, a maximal preservation of organ function. In the last 5 years, we have extended our previous indications for laser surgery30 to include the treatment
Outcome (mo after primary treatment)
A&W (130) DOD (brain metastases) (62) A&W (74) A&W (100) A&W (92) A&W (130) A&W (69) A&W (62) A&W (60) A&W (95) A&W (104) DOD (neck spread) (17)
of T1 glottic carcinomas involving the anterior commissure, selected T2 glottic carcinomas, and T1-T2 glottic carcinomas recurrent after radiotherapy. In the group of 138 patients examined in this study, the probability of remaining free of locoregional recurrence 5 years after primary surgery was estimated to be 79%. Moreover, in 14 of 28 (50%) cases requiring retreatment, the second laser resection was successful. Three of 6 (50%) patients who had a second recurrence underwent a third laser excision. Therefore the probability of ultimate local control with CO2 laser excision alone at 5 years was 89% (Tis, 95%; T1, 87%; T2, 91%).
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From our analysis, infiltration of the vocalis muscle, documented in 13 cases (9%), proved to be a significant prognostic factor for disease-free survival (P = 0.004) (Table 2). On the basis of our data, whenever infiltration of the vocalis muscle is preoperatively suspected by videostroboscopy or histologically demonstrated by a previous excision, total (type IV) or extended (type V) cordectomy should be performed, whereas a mucosectomy and superficial cordectomy should be reserved for Tis and microinvasive carcinoma, respectively. Involvement of the anterior third of the true vocal cord, which was present in 104 patients (75%), was another significant prognostic factor (P = 0.02) (Table 2). The high rate of recurrence observed in this group of patients could be explained by the ultraconservative resection of the lesion, which was aimed at saving the vocalis muscle and achieving a good phonatory result. Such a hypothesis suggests that a total or extended cordectomy with anterior ventriculotomy should be performed when the lesion involves the anterior third of the true vocal cord. In fact, anterior commissure involvement, observed in 40 patients (29%) who underwent a more radical resection, did not show, within the limits of our sample size, a significant impact on local recurrence. Involvement of the false vocal cord was observed in only 3 patients (2%). Two of them had a recurrence 1 year later on the contralateral true vocal cord and 3 years later on the same side of the larynx as the primary tumor. Although the variable showed prognostic significance (P = 0.02) (Table 2), the small number of observations and the pattern of recurrence do not allow us to draw a definitive conclusion. However, endoscopic resection should be reasonably restricted to the very rare lesions with superficial growth and minimal involvement of the false vocal cord, whereas tumors encroaching on the ventricle with a more extensive involvement of the false vocal cord are more appropriately treated with supracricoid laryngectomy. Our data support the concept expressed by other authors1,16,24 that laser surgery can be considered an excellent tool for treating Tis, T1, and selected T2 glottic carcinomas. Moreover, it can be used successfully as a salvage therapy in most cases requiring a retreatment, provided that the selection criteria indicated for the primary treatment are respected. The indications for mucosectomy (type I) and/or superficial cordectomy (type II) should be restricted to Tis and microinvasive carcinoma of the middle portion of the vocal cord without infiltration of the vocalis muscle, whereas total (type IV) or extended cordectomy (type V) should be performed in cases of involvement of the anterior third of the vocal cord and anterior commissure or infiltration of the
vocalis muscle. In these cases, ventriculotomy should be used to obtain better control of the lateral extension of the tumor. In cases of positive margins of the surgical specimen after type I or type II resection, partial cordectomy (type III) should be performed. In our study, T1-T2 glottic lesions with infiltration of the vocalis muscle behaved more like advanced than early cancers. In such cases meticulous patient selection, with preoperative radiologic assessment, videostroboscopy, and endoscopic evaluation during microlaryngoscopy, is necessary to optimize local control. Moreover, a staged microlaryngoscopy at 2 months to evaluate possible suspicious areas is recommended after total and extended cordectomy. Even though phonatory results were not studied in our series, it is evident from the experience of other authors that the degree of voice abnormalities is related to the extension of the resection.2,27,28 The probability of persistent dysphonia before total and extended cordectomy or re-excision should be included in the patient counseling. Our conclusions are based on a retrospective analysis of the results. Meticulous preoperative and intraoperative diagnostic workup could improve the diagnostic accuracy and reduce the risk of undertreatment or overtreatment when minimal excision of the tumor is performed. REFERENCES 1. Ossoff RH, Sisson GA, Shapshay SM. Endoscopic management of selected early vocal cord carcinoma. Ann Otol Rhinol Laryngol 1985;94:560-4. 2. McGuirt FW, Blalock D, Koufman JA, et al. Comparative voice results after laser resection or irradiation of T1 vocal cord carcinoma. Arch Otolaryngol Head Neck Surg 1994;120:951-5. 3. Murty GE, Diver JP, Bradley PJ. Carcinoma in situ of the glottis: radiotherapy or excision biopsy? Ann Otol Rhinol Laryngol 1993;102:592-5. 4. Ferlito A, Polidoro F, Rossi M. Pathological basis and clinical aspects of treatment policy in carcinoma in situ of the larynx. J Laryngol Otol 1981;95:141-54. 5. Kleinsasser O. Mikrolaryngoskopie und Endolarungeale Mikrochirurgie Technik und Typishe Befund. Stuttgart: FK SchattauerVerlang; 1968. 6. Strong MS. Laser excision of carcinoma of the larynx. Laryngoscope 1975;85:1286-9. 7. Ferlito A, Carbone A, De Santo LW, et al. “Early” cancer of the larynx: the concept as defined by clinicians, pathologists, and biologists. Ann Otol Rhinol Laryngol 1996;105:245-50. 8. Hirano M, Kurita S, Matsuoka H, et al. Vocal cord fixation in laryngeal carcinomas. Acta Otolaryngol (Stockh) 1991;111:44954. 9. Kaplan MJ, Johns ME, Mc Lean WC, et al. Stage II glottic carcinoma: prognostic factors and management. Laryngoscope 1983;93:725-8. 10. Blakeslee D, Vaughan CW, Shapshay SM, et al. Excisional biopsy in the selective management of T1 glottic cancer: a three-year follow-up study. Laryngoscope 1984;94:488-94. 11. Olszewski SJ, Vaeth JM, Green JP, et al. The influence of the field size, treatment modality, commissure involvement and his-
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tology in the treatment of the early vocal cord cancer with irradiation. Int J Radiat Oncol Biol Phys 1985;11:1333-7. Rudoltz MS, Benammar A, Mohiuddin M. Prognostic factors for local control and survival in T1 squamous cell carcinoma of the glottis. Int J Radiat Oncol Biol Phys 1993;26:767-72. Morris MR, Canonico D, Blank C. A critical review of radiotherapy in the management of T1 glottic carcinoma. Am J Otolaryngol 1994;15:276-80. Thomas JV, Olsen KD, Neel III BH, et al. Early glottic carcinoma treated with open laryngeal procedures. Arch Otolaryngol Head Neck Surg 1994;120:264-8. Cragle SP, Brandenburg JH. Laser cordectomy or radiotherapy: cure rates, communication, and cost. Otolaryngol Head Neck Surg 1993;108:648-54. Myers EN, Wagner RL, Johnson JT. Microlaryngoscopic surgery for T1 glottic lesions: a cost-effective option. Ann Otol Rhinol Laryngol 1994;103:28-30. Harwood AR, De Boer G. Prognostic factor in T2 glottic cancer. Cancer 1980;54:991-5. Inoue T, Inoue T, Ikeda H, et al. Prognostic factor of telecobalt therapy for early glottic carcinoma. Cancer 1992;70:2797-801. Fein DA, Mendenhall WM, Parsons JT, et al. T1-T2 squamous cell carcinoma of the glottic larynx treated with radiotherapy: a multivariate analysis of variables potentially influencing local control. Int J Radiat Oncol Biol Phys 1993;25:605-11. Laccourreye O, Weinstein G, Brasnu D, et al. Vertical partial laryngectomy: a critical analysis of local recurrence. Ann Otol Rhinol Laryngol 1991;100:68-71.
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21. Sheen T-S, Ko J-Y, Chang Y-L. Partial vertical laryngectomy in the treatment of early glottic cancer. Ann Otol Rhinol Laryngol 1998;107:593-7. 22. Chevalier D, Laccourreye O, Brasnu D, et al. Cricohyoidoepiglottopexy for glottic carcinoma with fixation or impaired motion of the true vocal cord: 5-year oncologic results with 112 patients. Ann Otol Rhinol Laryngol 1997;106:364-9. 23. Casiano RR, Cooper JD, Lundy DS, et al. Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings. Otolaryngol Head Neck Surg 1991;104:831-7. 24. Steiner W. Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 1993;14:116-21. 25. Eckel HE, Thumfart WS. Laser surgery for the treatment of larynx carcinoma: indications, techniques, and preliminary results. Ann Otol Rhinol Laryngol 1992;101:113-8. 26. Motta G, Villari G, Motta S, et al. L’impiego del laser a CO2 nella chirurgia conservativa dei tumori glottici. Acta Otorhinolaryngol Ital 1991;11:25-34. 27. Hirano M, Hirade Y. CO2 laser for treating glottic carcinoma. Acta Otolaryngol Suppl (Stockh) 1988;458:154-7. 28. Remacle M, Lawson G, Jamart J, et al. CO2 laser in the diagnosis and treatment of early cancer of the vocal fold. Eur Arch Otorhinolaryngol 1997;254:169-76. 29. Lai A, Zeitels SM. Endoscopic treatment of early glottic carcinoma. Curr Opin Otolaryngol Head Neck Surg 1996;4:126-33. 30. Peretti G, Cappiello J, Nicolai P, et al. Endoscopic laser excisional biopsy for selected glottic carcinomas. Laryngoscope 1994;104:1276-9.
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We present the results of a retrospective study based on a cohort of 140 patients who underwent endoscopic CO2 laser excision for previously untreated early glottic cancer (21 Tis, 96 T1, and 23 T2). This study used univariate analysis to review the impact on disease-free survival of 15 factors related to the host, the tumor, and the treatment. Recurrent cancer developed in 28 patients with an average interval to recurrence of 37.5 months. Retreatment consisted of different procedures, including laser excision, partial or total laryngectomy, and/or radiotherapy. The larynx was definitively preserved in 96% of patients. By the end of the study, 14 patients had died, but only 2 of them had died of the disease. Five-year overall survival and determinate survival were 93% and 98%, respectively. Ultimate local control at 5 years with CO2 laser excision alone was 95% for Tis, 87% for T1, and 91% for T2 lesions. Only involvement of the anterior third of the vocal cord (P = 0.02), involvement of the false vocal cord (P = 0.02), and infiltration of the vocalis muscle (P = 0.004) showed a significant negative impact on disease-free survival. (Otolaryngol Head Neck Surg 2000;123:124-31.)
T
he term early glottic cancer usually refers to Tis, T1, and T2 carcinomas and encompasses a wide spectrum of lesions, ranging from epithelial abnormalities involving a segment of a true vocal cord to large bulky tumors extending from the vocal cord to the anterior commissure, contralateral true vocal cord, supraglottis, and/or subglottis, with or without impairment of vocal cord mobility. The goals of the treatment of such lesions are
From the Departments of Otolaryngology (Drs Peretti, Nicolai, Redaelli de Zinis, Berlucchi, Bazzana, and Antonelli) and Radiotherapy (Dr Bertoni), University of Brescia. Reprint requests: Giorgio Peretti, MD, Department of Otolaryngology, University of Brescia, Piazza Spedali Civili, 1, 25123, Brescia, Italy. Copyright © 2000 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/2000/$12.00 + 0 23/77/104523 doi:10.1067/mhn.2000.104523 124
cure of the cancer with a low risk of complications, laryngeal preservation, and good voice quality. Because the spread of tumor to regional nodes and/or distant sites is unlikely, control of the primary lesion is usually equivalent to cure. Radiotherapy, conservation surgery, and endoscopic resection are the most common treatment options. The ideal treatment for Tis, T1, and T2 glottic carcinoma, however, is still unsettled and a matter of debate. The treatment should be tailored to each patient, depending on his or her own choice, general conditions, characteristics of the lesion, vocal function, occupation, treatment facilities, cost-effectiveness ratio, and quality of the technique. In recent years the development of laser technology and innovations in laryngoscopic instrumentation and endoscopic surgical techniques have markedly increased the popularity of CO2 laser treatment for selected glottic carcinomas. There is convincing evidence in the literature that the procedure is as effective as other conventional methods, such as open neck functional laryngectomy and/or radiation treatment, in terms of cure rate and functional results.1,2 This article focuses on the results of a retrospective study based on a cohort of 140 patients with Tis, T1, or T2 previously untreated glottic carcinoma, who underwent endoscopic surgery by CO2 laser, with depth and extension of the excision graded from I to V according to our own classification system. The prognostic impact on disease-free survival of several factors (related to the host, tumor, and treatment) is discussed. METHODS AND PATIENTS Patients and Treatment From January 1987 to December 1994, 155 patients with glottic carcinoma underwent endoscopic CO2 laser excision at the Department of Otorhinolaryngology, University of Brescia, Italy. Fifteen patients with glottic cancer recurrent after radiotherapy were excluded from the study; a total of 140 patients with previously untreated glottic carcinoma (21 Tis, 96 T1, and 23 T2) formed the basis of the analysis. There were 135 men and 5 women, with a mean age of 60.5 years (range 3480 years). At the time of the diagnosis, 120 men and 4 women were cigarette smokers, and 15 men and 1 woman had never smoked. The basic criterion for inclusion was the possibility of obtaining a wide endoscopic exposure of the glottis.
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Table 1. Primary treatment modality (N = 140) Excision type
Extension of excision
No. of patients
I II III IV V
Superficial layer of lamina propria Superficial portion of vocalis muscle Medial portion of vocalis muscle Inner perichondrium of thyroid lamina Surrounding laryngeal subsites
16 19 46 17 42
Further criteria for T2 lesions were (1) no supraglottic spread at the level of the anterior commissure, (2) anterior subglottic extension of the tumor not exceeding 5 mm from the free edge of the vocal cord, (3) no posterior subglottic extension, (4) no involvement of the posterior paraglottic space and/or arytenoid cartilage, and (5) a lateral upper limit of the neoplasm not higher than the free edge of the false cord. All procedures were performed with patients under general anesthesia. The Dedo or Ossoff-Holinger laser laryngoscope and Boston University suspension system were used with microlaryngoscopy, with the CO2 laser set on superpulse mode (1-3 W, 270 µm spot size). Patients with T1 glottic carcinoma with anterior commissure involvement and those with T2 carcinoma underwent preoperative CT scan. Intraoperative endoscopy was performed in all patients by 0°, 30°, 70°, and 120° rigid telescopes to explore hidden regions, such as the subglottic portion of the anterior commissure. Exploring hidden regions improved the definition and identification of the characteristics of the lesions in regions such as the anterior commissure, ventricle, and subglottis, and allowed a more detailed inspection of the location, shape, dimensions, boundaries, extension, color, relief, and surface vascular patterns of the lesions. Infusion of saline solution and 1/10,000 epinephrine into the superficial lamina propria was used in patients with superficial lesions apparently limited to the mucosa to determine whether the epithelial lesion had transgressed the superficial lamina propria to or through the vocal ligament. Intraoperative supravital staining with 2% toluidine blue was also used routinely to identify the precise surface extent of the tumor and to demonstrate superficial areas of cellular atypia. Patients underwent different types of resections (type I, mucosectomy; type II, superficial cordectomy; type III, partial cordectomy; type IV, total cordectomy; type V, extended cordectomy) (Fig 1), which were classified according to a personal system based on the endoscopic appearance, radiologic findings of the lesion, results of saline infusion into the superficial lamina propria, and results of supravital staining with toluidine blue. We carried out mucosectomy (type I) limited to the epithelium and to the superficial layer of the lamina propria in 16 patients and superficial cordectomy (type II) extended to the vocal ligament and the superficial portion of the vocalis
Fig 1. Coronal view of a laryngeal specimen depicting the 5 types of resection (I, mucosectomy; II, superficial cordectomy; III, partial cordectomy; IV, total cordectomy; V, extended cordectomy).
muscle in 19. Partial cordectomy (type III), with conservation of the lateral portion of the vocalis muscle, was used in 46 patients in whom microinvasive carcinoma had been diagnosed previously or in whom invasive carcinoma without impairment of vocal cord mobility was suspected. Total cordectomy (type IV), limited to the vocal cord but including the inner perichondrium of the thyroid lamina, was performed in 17 patients, in whom infiltration of the vocalis muscle was preoperatively inferred by the impairment of vocal cord mobility or histologically demonstrated by a previous biopsy. Extended cordectomy (type V) was used in 42 patients with involvement of the false cord, the ventricle, a part of the contralateral cord, or the anterior commissure (Table 1). Partial ventriculotomy was performed in 53% (74/140) of patients to expose the floor of the ventricle and to evaluate the lateral extension of the tumor. For histologic evaluation, the surgical specimen was oriented by staining of the superior edge with marking ink. Multiple sections were cut along the transverse axis, and the depth of infiltration of the vocalis muscle was estimated. Two different policies were followed in cases of positive margins during the observation period: 10 patients (19871991) underwent complementary radiotherapy, and 13 (19921994) underwent laser re-excision.
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Table 2. Univariate survival analysis for prognostic factors (log rank test)
Variable
Sex Male Female Preoperative smoker No Yes Pathologic T category Tis T1 T2 Anterior 3rd true vocal cord involvement No Yes Middle 3rd true vocal cord involvement No Yes Posterior 3rd true vocal cord involvement No Yes Anterior commissure involvement No Yes Ventricle floor involvement No Yes False vocal cord involvement No Yes Vocal muscle involvement No Yes Neoplastic involvement of surgical margins No Yes Complementary treatment No Yes Degree of differentiation Tis 1 2 3 Postoperative smoker No Yes *Survival
No. of patients
Estimated 5-year disease-free survival (%) P
All patients subsequently returned for follow-up visits with a flexible fiberoptic laryngoscope or a rigid 90° telescope for a period ranging from 48 to 132 months (mean 76 months). Microlaryngeal examination was repeated only when suspicious areas were noticed. Statistical Analysis
129 9
78 ± 4 *
0.1
21 117
90 ± 6 77 ± 4
0.2
20 95 23
78 ± 10 81 ± 4 73 ± 9
0.7
34 104
94 ± 4 75 ± 4
0.02†
25 113
76 ± 9 80 ± 4
0.6
95 43
76 ± 4 86 ± 5
0.2
98 40
82 ± 4 72 ± 7
0.2
115 23
81 ± 4 73 ± 9
0.4
135 3
80 ± 3 33 ± 27‡
0.02†
125 13
82 ± 3 54 ± 14
0.004†
93 45
78 ± 4 82 ± 6
0.6
115 23
79 ± 4 82 ± 8
0.7
20 47 65 6
78 ± 10 74 ± 6 81 ± 5 *
0.5
118 20
81 ± 4 70 ± 10
0.2
estimates could not be calculated because all observations were censored. †Statistically significant. ‡Four-year disease-free survival.
Statistical analysis was performed with the SPSS statistical package. Survival curves were calculated from the date of the diagnosis by the Kaplan-Meier method. The end point for overall survival was the date of death (regardless of the cause) or the date of the last consultation for censored observations. For the analysis of determinate survival, patients who died of unrelated causes were considered as censored observations at the date of death. The end point for disease-free survival was the date of the first locoregional recurrence. For ultimate local control with laser alone, patients who had a relapse at the primary site and who were subsequently cured by further laser treatment were considered censored at the date of the last consultation. Four factors were related to the host (age, sex, preoperative and postoperative smoking habits), 9 to the tumor (pT category; localization of the tumor on the anterior, middle, or posterior third of the vocal cord; involvement of the anterior commissure, floor of the ventricle, or false vocal cord; histologic infiltration of the vocal muscle; histologic grading), and 2 to the treatment (positive margins, complementary therapy). The impact of all these factors on disease-free survival was analyzed by univariate analysis with the log rank test (Table 2). Age was evaluated as a continuous variable. Patients who died of other causes or who were lost to follow-up less than 2 years after primary treatment were excluded from statistical analysis. RESULTS
When the study ended, 28 recurrences, with a 37month average interval to the event, had been observed (Table 3). The rate of recurrences, in relation to pT category, was as follows: 19% in Tis (4/21), 18% in T1 (18/96), and 26% in T2 (6/23). Local recurrence was observed in 24% (26/106), 67% (2/3), and 49% (6/14) of patients with involvement of the anterior third of the true vocal cord, false vocal cord, and vocal muscle, respectively. The primary tumor involved more than one of the aforementioned sites in 7 patients. In only 2 patients was the primary lesion limited to the middle and the posterior third of the true vocal cord (Table 3). Retreatment consisted of the following: laser excision in 14 patients; laser excision plus postoperative radiotherapy in 5; partial laryngectomy in 2; total laryngectomy in 4; total laryngectomy extended to the thyroid gland, perilaryngeal soft tissues, and neck skin, with
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bilateral neck dissection plus postoperative radiotherapy in 1; and radiotherapy alone in 1. One patient, in whom a second cancer developed in the lung, was not considered suitable for any kind of treatment (Table 3). Six patients had a second recurrence, which was salvaged in 4. Three underwent a third laser excision, and 1 underwent laser excision plus radiotherapy. Two patients died of the disease: one patient who had received extended total laryngectomy for the first recurrence died of a persistent neck tumor that had been treated unsuccessfully with chemotherapy; a second, who underwent salvage surgery for the first recurrence with laser excision, died of regional recurrence after radical neck dissection for lymph node metastases with extracapsular spread (Table 3). Twelve patients died of other causes. Two patients were excluded from statistical analysis: one who died of myocardial infarction at 11 months, and another who was lost to follow-up 15 months after primary treatment. Five-year overall survival, determinate survival, and disease-free survival of the remaining 138 patients were 93%, 98%, and 79%, respectively. Ultimate local control at 5 years with CO2 laser excision alone was 89%: according to pT category, it was 95% for Tis, 87% for T1, and 91% for T2. The larynx was preserved in 135 cases (96%). Analysis of the impact of 1 continuous and 14 categorical variables showed a significant decline in the disease-free survival rate of patients with involvement of the anterior third of the true vocal cord (75% vs 94%; P = 0.02), false vocal cord involvement (33% vs 80%; P = 0.02), and vocal muscle infiltration (54% vs 82%; P = 0.004) (Table 2). Because of the sample size, the probability of having a false-negative result for the variables that did not significantly influence survival with the log rank test was greater than the commonly accepted value of 0.20. DISCUSSION
The definition of carcinoma in situ should be restricted to lesions of the epithelium that have not transgressed the basement membrane and therefore do not involve the lamina propria. The reported incidence of carcinoma in situ without coexisting invasive carcinoma varies widely from 1% to 16% of laryngeal malignancies.3 Ferlito et al4 found marked international variation in treatment policy. After introduction of the microlaryngeal surgical technique by Kleinsasser5 in 1968 and the CO2 surgical laser by Strong6 in 1975, open procedures, and to a lesser extent radiotherapy, have largely given way to endoscopic techniques. An en bloc excisional biopsy provides an accurate diagnosis
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and an effective treatment in a 1-stage procedure. Histologic examination of the entire specimen with multiple sections prevents overtreatment or undertreatment of small glottic lesions. If necessary, the treatment can be repeated and does not preclude further therapy. In addition, during microlaryngeal surgery it is possible to inspect the endolarynx with rigid and contact endoscopy, which offers a multiperspective view of the lesion and in vivo and in situ observations of the superficial layers of the epithelium. T1 and T2 glottic carcinoma should be classified by a careful microscopic pathologic evaluation into microinvasive, superficial extending, and deeply invasive carcinomas to avoid an inadequate or overzealous approach to treatment and prognosis. The term early glottic cancer should be restricted to those carcinomas that involve the lamina and do not invade muscle or cartilaginous structures, but are still capable of metastasis.7 Impairment of vocal cord mobility is generally related to invasion of the underlying intrinsic muscles and/or cricoarytenoid joint and coincides with a deeply infiltrating neoplasm. Hirano et al8 reported that invasion of one fourth to three fourths of the thyroarytenoid muscle resulted in impaired motion, whereas invasion of more than three fourths of the thyroarytenoid muscle caused fixation of the true vocal cord. Impaired vocal cord mobility in stage II glottic carcinoma is the most significant prognostic tumor-related factor in predicting response to primary and/or salvage therapy.9 For T1 lesions, a cure rate in the range of 80% to 98%, regardless of the treatment, has been reported.1,10-14 However, endoscopic resection1,10 and irradiation11-13 are the most frequently recommended options because of the favorable cost-effectiveness ratio and good voice quality.2,15,16 For T2 lesions with freely mobile cords, the results are comparable with those achieved with T1 with radiotherapy and open surgery.9 Instead, for T2 lesions with impaired mobility, the cure rate obtained with radiotherapy ranges from 52% to 76%,17-19 whereas surgery including vertical partial laryngectomy or hemilaryngectomy still guarantees a cure rate of 56% to 84%.9,20,21 Moreover, in a retrospective study focused on patients with glottic carcinoma with impaired motion of the true vocal cord, Chevalier et al22 reported 5-year absolute survival, cause-specific survival, and local control rates of 81%, 96%, and 94%, respectively. On the basis of their results, they favor the use of cricohyoidoepiglottopexy instead of radiotherapy and vertical partial laryngectomy. Considering the excellent long-term results obtained
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Table 3. Analysis of the patients with recurrences 1st recurrence Initial involved structures
Type of excision
1 2 3 4
Anterior and middle 3rd TVC Anterior and middle 3rd TVC, AC Anterior and middle 3rd TVC Anterior and middle 3rd TVC, vocal muscle
3 5 3 3
5 6 7 8
11
Middle and posterior 3rd TVC, ventricle floor Anterior 3rd TVC Anterior, middle, and posterior TVC, AC Anterior and middle 3rd TVC, AC, ventricle floor, vocal muscle Anterior and middle 3rd TVC Anterior, middle, and posterior TVC, AC, ventricle floor, FVC Anterior 3rd TVC, AC, vocal muscle
12
Anterior and middle 3rd TVC, AC
5
13 14
Anterior 3rd TVC Anterior and middle 3rd TVC, ventricle floor, FVC, vocal muscle Anterior and middle 3rd TVC, AC Anterior and middle 3rd TVC, ventricle floor, vocal muscle Anterior 3rd TVC, AC Middle 3rd TVC Anterior, middle, and posterior TVC, AC, ventricle floor Anterior 3rd TVC Anterior and middle 3rd TVC Anterior and middle 3rd TVC, AC Anterior 3rd TVC Anterior, middle, and posterior TVC Anterior and middle 3rd TVC, AC, vocal muscle Anterior and middle 3rd TVC Anterior and middle 3rd TVC Anterior, middle, and posterior TVC
9 10
15 16 17 18 19 20 21 22 23 24 25 26 27 28
Site
Time (mo)
Treatment
30 8 25 15
PL LE LE + RT TL
3 3 5 5
Homolateral TVC Homolateral TVC Contralateral TVC Homolateral TVC, paraglottic space, posterior commissure Homolateral TVC Contralateral TVC Homolateral TVC AC
43 50 27 11
LE LE + RT LE RT
3 5
Homolateral TVC, AC Homolateral TVC, subglottis
19 34
LE + RT Not treated*
5
3 5
Homolateral TVC, subglottis, thyroid cartilage invasion Homolateral TVC, subglottis, thyroid cartilage invasion Homolateral TVC, AC Homolateral TVC
5 3
Contralateral TVC Homolateral TVC, thyroid cartilage invasion
5 3 5
Contralateral TVC Homolateral TVC Contralateral TVC
2 2 5 4 2 5 2 3 4
Homolateral TVC Homolateral TVC Homolateral TVC, AC Homolateral TVC, AC Homolateral TVC, AC AC, supraglottis Homolateral TVC Homolateral TVC, AC Homolateral TVC, thyroid cartilage invasion
7
TL
23
TL
3 5
LE LE
20 7
LE TL
7 6 9
LE LE LE
30 16 54 12 12 21 12 43 9
LE LE LE LE + RT LE + RT PL LE LE TL + BFND + RT
TVC, True vocal cord; AC,anterior commissure; FVC, false vocal cord; PL, partial laryngectomy; LE, laser excision; RT, radiotherapy; RND, radical neck dissection; TL, total laryngectomy; PL, partial laryngectomy; BFND, bilateral functional neck dissection; CX, chemotherapy; A&W, alive and well; DOC, dead of other causes; DOD, dead of disease; LFU, lost to follow-up. *Patient had a slow-growing laryngeal recurrence and a second cancer in the lung, which was deemed inoperable and was considered to be the final cause of death.
with CO2 laser microsurgical treatment in Tis and T1 glottic carcinomas, several authors have extended the indications to include T2 glottic carcinomas and T1-T2 glottic carcinomas recurrent after radiotherapy.23,24 The cure rates for T2 glottic carcinomas treated endoscopically with laser, regardless of vocal cord mobility, range from 76% to 85%.24-26 Laser surgery has several advantages over radiotherapy and open surgery. The procedure is brief with a shorter hospitalization time, less morbidity, and fewer side effects. Each excision can be adapted individually to the size of the lesion. Working in a bloodless surgical
field ensures a precise and safe resection of the tumor. Residual or recurrent tumor can be detected earlier than it can after open surgery or radiotherapy. The favorable cost-effectiveness ratio of laser surgery has been demonstrated.15,16 Recently, the concept of ultraconservative endoscopic treatment has been emphasized by several authors2,25,27,28 who presented different modalities of resection in relation to the extent and depth of invasion of the tumor. Partial cordectomy, aimed at saving the entire or part of the vocalis muscle, allows good phonatory results by combining the principles of surgical oncology with those of voice preservation. Recently,
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2nd recurrence
3rd recurrence
Time (mo)
Treatment
Site
Time (mo)
Treatment
— — — —
— — — —
— — — —
— — — —
— — — —
— — — —
A&W (132) A&W (132) A&W (83) A&W (113)
— — — —
— — — —
— — — —
— — — —
— — — —
— — — —
A&W (119) A&W (100) A&W (75) A&W (122)
— —
— —
— —
— —
— —
— —
A&W (107) DOC (lung cancer) (42)
—
—
—
—
—
—
LFU (8)
—
—
—
—
—
—
DOC (lung cancer) (53)
— Contralateral TVC
— 8
— LE
— —
— —
— —
A&W (70) A&W (74)
— —
— —
— —
— —
— —
— —
A&W (74) A&W (77)
Homolateral TVC AC —
35 34 —
LE LE + RT —
— Neck metastases —
— 19 —
— RND + RT —
AC — — — — — Homolateral TVC — Neck spread
23 — — — — — 13 — 5
LE — — — — — PL + RT — CX
— — — — — — — — —
— — — — — — — — —
— — — — — — — — —
Site
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Lai and Zeitels29 stressed the validity of phonomicrosurgical treatment for in situ and microinvasive glottic carcinoma by trying to minimize the resected margin of normal tissue and thereby maximizing the preservation of the vocal fold’s layered microstructure, to optimize the vocal outcome. Furthermore, Steiner24 introduced also for advanced tumors an unconventional surgical technique, based on transtumoral incisions, to achieve an oncologically safe resection and, at the same time, a maximal preservation of organ function. In the last 5 years, we have extended our previous indications for laser surgery30 to include the treatment
Outcome (mo after primary treatment)
A&W (130) DOD (brain metastases) (62) A&W (74) A&W (100) A&W (92) A&W (130) A&W (69) A&W (62) A&W (60) A&W (95) A&W (104) DOD (neck spread) (17)
of T1 glottic carcinomas involving the anterior commissure, selected T2 glottic carcinomas, and T1-T2 glottic carcinomas recurrent after radiotherapy. In the group of 138 patients examined in this study, the probability of remaining free of locoregional recurrence 5 years after primary surgery was estimated to be 79%. Moreover, in 14 of 28 (50%) cases requiring retreatment, the second laser resection was successful. Three of 6 (50%) patients who had a second recurrence underwent a third laser excision. Therefore the probability of ultimate local control with CO2 laser excision alone at 5 years was 89% (Tis, 95%; T1, 87%; T2, 91%).
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From our analysis, infiltration of the vocalis muscle, documented in 13 cases (9%), proved to be a significant prognostic factor for disease-free survival (P = 0.004) (Table 2). On the basis of our data, whenever infiltration of the vocalis muscle is preoperatively suspected by videostroboscopy or histologically demonstrated by a previous excision, total (type IV) or extended (type V) cordectomy should be performed, whereas a mucosectomy and superficial cordectomy should be reserved for Tis and microinvasive carcinoma, respectively. Involvement of the anterior third of the true vocal cord, which was present in 104 patients (75%), was another significant prognostic factor (P = 0.02) (Table 2). The high rate of recurrence observed in this group of patients could be explained by the ultraconservative resection of the lesion, which was aimed at saving the vocalis muscle and achieving a good phonatory result. Such a hypothesis suggests that a total or extended cordectomy with anterior ventriculotomy should be performed when the lesion involves the anterior third of the true vocal cord. In fact, anterior commissure involvement, observed in 40 patients (29%) who underwent a more radical resection, did not show, within the limits of our sample size, a significant impact on local recurrence. Involvement of the false vocal cord was observed in only 3 patients (2%). Two of them had a recurrence 1 year later on the contralateral true vocal cord and 3 years later on the same side of the larynx as the primary tumor. Although the variable showed prognostic significance (P = 0.02) (Table 2), the small number of observations and the pattern of recurrence do not allow us to draw a definitive conclusion. However, endoscopic resection should be reasonably restricted to the very rare lesions with superficial growth and minimal involvement of the false vocal cord, whereas tumors encroaching on the ventricle with a more extensive involvement of the false vocal cord are more appropriately treated with supracricoid laryngectomy. Our data support the concept expressed by other authors1,16,24 that laser surgery can be considered an excellent tool for treating Tis, T1, and selected T2 glottic carcinomas. Moreover, it can be used successfully as a salvage therapy in most cases requiring a retreatment, provided that the selection criteria indicated for the primary treatment are respected. The indications for mucosectomy (type I) and/or superficial cordectomy (type II) should be restricted to Tis and microinvasive carcinoma of the middle portion of the vocal cord without infiltration of the vocalis muscle, whereas total (type IV) or extended cordectomy (type V) should be performed in cases of involvement of the anterior third of the vocal cord and anterior commissure or infiltration of the
vocalis muscle. In these cases, ventriculotomy should be used to obtain better control of the lateral extension of the tumor. In cases of positive margins of the surgical specimen after type I or type II resection, partial cordectomy (type III) should be performed. In our study, T1-T2 glottic lesions with infiltration of the vocalis muscle behaved more like advanced than early cancers. In such cases meticulous patient selection, with preoperative radiologic assessment, videostroboscopy, and endoscopic evaluation during microlaryngoscopy, is necessary to optimize local control. Moreover, a staged microlaryngoscopy at 2 months to evaluate possible suspicious areas is recommended after total and extended cordectomy. Even though phonatory results were not studied in our series, it is evident from the experience of other authors that the degree of voice abnormalities is related to the extension of the resection.2,27,28 The probability of persistent dysphonia before total and extended cordectomy or re-excision should be included in the patient counseling. Our conclusions are based on a retrospective analysis of the results. Meticulous preoperative and intraoperative diagnostic workup could improve the diagnostic accuracy and reduce the risk of undertreatment or overtreatment when minimal excision of the tumor is performed. REFERENCES 1. Ossoff RH, Sisson GA, Shapshay SM. Endoscopic management of selected early vocal cord carcinoma. Ann Otol Rhinol Laryngol 1985;94:560-4. 2. McGuirt FW, Blalock D, Koufman JA, et al. Comparative voice results after laser resection or irradiation of T1 vocal cord carcinoma. Arch Otolaryngol Head Neck Surg 1994;120:951-5. 3. Murty GE, Diver JP, Bradley PJ. Carcinoma in situ of the glottis: radiotherapy or excision biopsy? Ann Otol Rhinol Laryngol 1993;102:592-5. 4. Ferlito A, Polidoro F, Rossi M. Pathological basis and clinical aspects of treatment policy in carcinoma in situ of the larynx. J Laryngol Otol 1981;95:141-54. 5. Kleinsasser O. Mikrolaryngoskopie und Endolarungeale Mikrochirurgie Technik und Typishe Befund. Stuttgart: FK SchattauerVerlang; 1968. 6. Strong MS. Laser excision of carcinoma of the larynx. Laryngoscope 1975;85:1286-9. 7. Ferlito A, Carbone A, De Santo LW, et al. “Early” cancer of the larynx: the concept as defined by clinicians, pathologists, and biologists. Ann Otol Rhinol Laryngol 1996;105:245-50. 8. Hirano M, Kurita S, Matsuoka H, et al. Vocal cord fixation in laryngeal carcinomas. Acta Otolaryngol (Stockh) 1991;111:44954. 9. Kaplan MJ, Johns ME, Mc Lean WC, et al. Stage II glottic carcinoma: prognostic factors and management. Laryngoscope 1983;93:725-8. 10. Blakeslee D, Vaughan CW, Shapshay SM, et al. Excisional biopsy in the selective management of T1 glottic cancer: a three-year follow-up study. Laryngoscope 1984;94:488-94. 11. Olszewski SJ, Vaeth JM, Green JP, et al. The influence of the field size, treatment modality, commissure involvement and his-
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tology in the treatment of the early vocal cord cancer with irradiation. Int J Radiat Oncol Biol Phys 1985;11:1333-7. Rudoltz MS, Benammar A, Mohiuddin M. Prognostic factors for local control and survival in T1 squamous cell carcinoma of the glottis. Int J Radiat Oncol Biol Phys 1993;26:767-72. Morris MR, Canonico D, Blank C. A critical review of radiotherapy in the management of T1 glottic carcinoma. Am J Otolaryngol 1994;15:276-80. Thomas JV, Olsen KD, Neel III BH, et al. Early glottic carcinoma treated with open laryngeal procedures. Arch Otolaryngol Head Neck Surg 1994;120:264-8. Cragle SP, Brandenburg JH. Laser cordectomy or radiotherapy: cure rates, communication, and cost. Otolaryngol Head Neck Surg 1993;108:648-54. Myers EN, Wagner RL, Johnson JT. Microlaryngoscopic surgery for T1 glottic lesions: a cost-effective option. Ann Otol Rhinol Laryngol 1994;103:28-30. Harwood AR, De Boer G. Prognostic factor in T2 glottic cancer. Cancer 1980;54:991-5. Inoue T, Inoue T, Ikeda H, et al. Prognostic factor of telecobalt therapy for early glottic carcinoma. Cancer 1992;70:2797-801. Fein DA, Mendenhall WM, Parsons JT, et al. T1-T2 squamous cell carcinoma of the glottic larynx treated with radiotherapy: a multivariate analysis of variables potentially influencing local control. Int J Radiat Oncol Biol Phys 1993;25:605-11. Laccourreye O, Weinstein G, Brasnu D, et al. Vertical partial laryngectomy: a critical analysis of local recurrence. Ann Otol Rhinol Laryngol 1991;100:68-71.
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21. Sheen T-S, Ko J-Y, Chang Y-L. Partial vertical laryngectomy in the treatment of early glottic cancer. Ann Otol Rhinol Laryngol 1998;107:593-7. 22. Chevalier D, Laccourreye O, Brasnu D, et al. Cricohyoidoepiglottopexy for glottic carcinoma with fixation or impaired motion of the true vocal cord: 5-year oncologic results with 112 patients. Ann Otol Rhinol Laryngol 1997;106:364-9. 23. Casiano RR, Cooper JD, Lundy DS, et al. Laser cordectomy for T1 glottic carcinoma: a 10-year experience and videostroboscopic findings. Otolaryngol Head Neck Surg 1991;104:831-7. 24. Steiner W. Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 1993;14:116-21. 25. Eckel HE, Thumfart WS. Laser surgery for the treatment of larynx carcinoma: indications, techniques, and preliminary results. Ann Otol Rhinol Laryngol 1992;101:113-8. 26. Motta G, Villari G, Motta S, et al. L’impiego del laser a CO2 nella chirurgia conservativa dei tumori glottici. Acta Otorhinolaryngol Ital 1991;11:25-34. 27. Hirano M, Hirade Y. CO2 laser for treating glottic carcinoma. Acta Otolaryngol Suppl (Stockh) 1988;458:154-7. 28. Remacle M, Lawson G, Jamart J, et al. CO2 laser in the diagnosis and treatment of early cancer of the vocal fold. Eur Arch Otorhinolaryngol 1997;254:169-76. 29. Lai A, Zeitels SM. Endoscopic treatment of early glottic carcinoma. Curr Opin Otolaryngol Head Neck Surg 1996;4:126-33. 30. Peretti G, Cappiello J, Nicolai P, et al. Endoscopic laser excisional biopsy for selected glottic carcinomas. Laryngoscope 1994;104:1276-9.
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