COMMISSURE: SURGERY VS RADIOTHERAPY Lucio Rucci, MD, Oreste Gallo, MD, and Omero Fini-Storchi, MD
A retrospective review of 182 patients with glottic cancer involving the anterior commissure (AC) is presented. of these, 123 patients were first treated with conservative surgery and 59 underwent radiotherapy. Patients were staged according to the AJCC system and by the modality of neoplastic involvement of AC (pure AC cancer, glottic cancer involving AC up to the midline, and beyond the midline). Our results indicate a higher rate of local control and of specific-disease survival in the group of patients first treated with surgery than those treated with radiotherapy (86% vs 74% and 97.5% vs 84%, rppectively) @ c 0.05). For pure AC cancers, our results show better local control with primary radiotherapy than with conservation surgery (82% vs 76.5%), but surgical failures have been more successfully salvaged than have radiotherapy recurrences (ultimate local control, 97.5% vs 820% respectively). These data suggest that the treatment of choice for AC cancers is conservation surgery, particularly frontolateral laryngectomy. HEAD 8 NECK 1991;13:403410
T h e anterior commissure (AC) of the larynx constitutes a transitional zone between the supraglottic and glottic region and is frequently involved by tumor. The neoplastic involvement of the AC is rarely an isolated cancer growth in the
From the llnd Otorhinolaryngologic Clinic, University of Florence, Florence, Italy. Address reprint requests to Dr. Rucci at the II Clinica ORL, Universita di Firenze. Careggi, Viale Morgagni, 85. 50134-Firenze, Italia. Accepted for publication February 11, 1991. CCC 0148-6403/91/050403-08 $04.00 0 1991 John Wiley & Sons, Inc.
Treatment of Glottic Cancer Involving AC
midline larynx; most frequently, it is the site of spread from cancers of one of the vocal cords. Of the various regions of the larynx, the AC provides perhaps the greatest challenge to investigators; there is no agreement concerning its boundaries, and its morphology is also controver~ i a l . l -Therefore, ~ many authors have studied AC in an attempt to better define its anatomic structures and the mechanical factors influencing tumor growth and In agreement with o t h e r ~ ,our ~ ~clinical ~ * ~ experience shows that cancer behavior in this zone seems variable. The anatomy of AC is such that an apparent T1 lesion may actually be a T4 lesion if it involves the thyroid cartilage. The presence of fibrous structures (Broyle’s tendom or “ X space of Bagatella) at the anterior attachment of the vocal cords may actually influence the modes of growth and spread of laryngeal tumors.6 These structures act as a barrier, so that invasion of the adjacent thyroid cartilage has not been observed in cancers that remain limited to the glottic level on the surface.2i435 If the cancer extends upward or downward at the anterior commissure, the invasion and destruction of the adjacent thyroid cartilage can be The possible spread of glottic cancers exceeding these anatomic structures is very difficult to appreciate by the two-dimensional picture given by laryngoscopy,4 justifying a different behavior of same staged cancers. Therefore, these elements in addition to the absence of a univer-
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403
sally accepted clinical definition of the boundaries of AC, justify the diagnostic, pathologic, and therapeutic problems linked to AC carcinoma. In this article we define the boundaries of AC on the basis of the anatomic studies of Nicelli7 and Tucker' as the lower tip of the epiglottic cartilage (5 mm) above, the ventricular folds and the vocal cords (113) on the sides, and the subglottic region (5 mm) below. We review the results of primary surgical therapy in selected patients with AC carcinoma (pure AC carcinoma and glottic carcinoma extending into the AC), and compare these data to results of radiotherapy. PATIENTS AND METHODS
Between 1968 and 1988, 182 patients with neoplastic involvement of AC were treated with curative intent at the ENT Clinic of the University of Florence. During this 20-year period, a selected number of patients (123) underwent conservation procedures, while the others (59) received primary radiotherapy. The mean age of patients was 59 years (range, 38-78 years). Patients were retrospectively staged according to the TNM system of the American Joint Committee on Cancer (198718 for glottic cancer, using preoperative clinical records, radiologic studies, and endoscopic and operative findings, as follows: Tla, involvement of one true vocal cord with AC spread; Tlb, involvement of both true vocal cords; T2, cancer lesion with extraglottic extension: T2a, with normal mobility, and T2b, with reduced mobility of the true vocal cord. According to the TNM system, the 182 AC cancers were classified as follows: 76 Tla, 71 Tlb, 24 T2a, and 11 T2b. The number of positive neck nodes (Nl) at diagnosis was 0 of 76 Tla, 1 of 71 Tlb, 0 of 24 T2a, and 1 of 11 T2b. In 3 cases, a delayed homolateral neck involvement was observed. On the whole, 5 of 182 (2.7%) patients were affected by laterocervical metastases. Considering the causes of death in this population, with particular reference to distant metastases and subsequent primary cancers, the criteria we considered for distinguishing lung metastases from the primary laryngeal cancer and second primary lung cancer were: (a) time greater than 5 years to development of lung lesion; and (b) different clinical and histopathologic - features. Thus, after successful Primary
treatment Of the dotticcancer* Of (4'4') patients with AC carcinoma suffered distant pul-
404
Treatment of Glottic Cancer Involving AC
monary metastases (ranging from 11 to 22 months after primary treatment), whereas another 9 patients (5%) presented with a second cancer (3 of the larynx, 3 of the lung, 2 of the large bowel, and 1 of the bladder). The method of primary treatment by T stage is shown in Table 1. In the group of patients first treated with surgery, 82 underwent frontolateral laryngectomies (in Tla, Tlb, T2a, T2b cases); 33 cordectomies (in T l a cases); 3 frontal anterior laryngectomies (in T1, T2a cases); 3 horizontal glottectomies (in T l b cases); and 2 subtotal laryngectomies with cricohyoidopexy (in Tlb, T2 cases). Radiotherapy was given with the same technique to all patients, using a cobalt 60 source. Two anterior oblique, 6 x 7 cm wedged fields were used. All patients had external fixation of the head and neck. A total dose in the range of 5,600-6,700 cGy was delivered in fractions of 200 cGy, 5 days a week. Patients were set up each day on the treatment machine by a physician; the fields were marked on the patients daily using the anatomic landmarks of the thyroid and cricoid cartilages. The reason for selection of surgery or radiotherapy was mostly subjective. Usually irradiation was employed in patients with small AC lesions, in older patients, and in patients in unsatisfactory general condition. All patients were subdivided in 3 groups, according to the modalities of AC neoplastic involvement: 41 patients with pure AC carcinoma; 83 patients with glottic carcinoma extending into AC up to the midline; and 58 patients with glottic carcinoma extending into AC beyond the midline. Patients had a 2-year minimum follow-up and 102 (56%) had at least 5 years' follow-up. A detailed analysis of the subgroups was carried out to determine survival rates, pattern of relapse and treatment complications, and to com-
Table 1. Method of treatment by tumor stage. Primary treatment T stage T1a Tb l T2a ~ 2 b Total
Conservation 71 (38 FL, 33 C) 32 (28 FL, 4 0s) 11 (8 FL, 3 0s) 9 (8 FL, 1 0s) 123
Radiotherapy
Total
5 39 13 2
76 71 24 11 182
59
FL, frontolateral laryngectomy; C, cordectomy; as,other conservation surgery.
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September/October 1991
pare these results according to tumor extension and method of treatment. Patients who died within 2 years and with a continuously diseasefree primary site were excluded. They were considered, however, in the actuarial analysis. These data were analyzed using the actuarial method, and statistical differences in survival rates were determined by the z - t e ~ t Only . ~ significant differences of p < 0.05 are noted for each analysis.
0
Surgery Radiotherapy
4
5
o i 0
I
1
3
2
Vearr
RESULTS
for the total group of patients survival are shown in Figures 1 and 2 according to tumor stage and primary treatment method, respectively. There were significant differences between actuarial survival curves after surgery and after radiotherapy ( p < 0.05). Recurrence-free survival according to primary treatment is shown in Figure 3. There was a significant difference between radiotherapy and surgery ( p < 0.05). Results of our series after surgery or radiotherapy are shown in detail in Tables 2 and 3, respectively. The group of 123 patients primarily treated with surgery were classified as follows: 18 patients with pure AC, 75 patients with glottic carcinoma involving the AC up to the midline, and 30 patients with glottic carcinoma involving the AC beyond the midline. Two patients in this group died of other causes and were excluded. Control of the primary tumor was achieved in 104 of 121 patients (86%).In this group 17 patients had a local recurrence within 5 years (75%appeared within 2 years). In 16 of these 17 local recurrences, a salvage (2 radiotherapy, 1 subtotal laryngectomy with cricohyoidopexy, 13 total laryngectomies)
I I
rn 0
Tla Tlb T2a T2b
FIGURE 2. Global actuarial corrected survival according to primary treatment.
was attempted, unsuccessfully in 2 cases. Thus, the ultimate local control rate for the entire group was 118 of 121 (97.5%). Considering the modality of AC involvement, 5-year local control was achieved by surgery in 13 of 17 (76.5%)pure AC carcinomas (Table 4), 56 of 74 (89%)with glottic carcinoma involving the AC up to the midline (Table 5), and 25 of 30 (83%) with glottic carcinoma involving the AC beyond the midline (Table 6). Surgical salvage was attempted in 4 patients with pure AC cancer (unsuccessfully in 1 case), in 6 patients with AC cancer up to the midline (unsuccessfully in 1 case), and successfully in 4 patients with AC cancer beyond the midline, whose primary conservative surgical procedures failed. Moreover, radiotherapy was employed in another 2 patients with recurrence (1with AC cancer up to the midline, 1 with AC cancer beyond the midline) with a favorable result in the first patient. The 5-year recurrence-free survival of frontolateral laryngectomy, which was the most com-
0
Surgery Radiotherapy
20 0 4
0
0
I
1
3
2
4
5
veerr Year.
FIGURE 1. Actuarial survival results of total group by T stage.
Treatment of Glottic Cancer Involving AC
FIGURE 3. Recurrence-free survival according to primary treatment.
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September/October 1991
405
Table 2. Surgical local control in 123 patients with glottic cancer involving the AC. No. salvagedINo. attempted T stage
T1a Tlb T2a T2b Total
Subgroup
Excluded
Local control(%)
Total laryng.
38 FL 33 c 28 FL 4 0s 8 FL 3 0s 8 FL 1 0s 123
1 1
35/38 (92%) 27/32 (84.5%) 23/27 (85%) 414 418 (50%) 313 718 (87.5%) 111 1041121 (86%)
212 415 313 -
2
Ultimate local control(5)
Other
38/38 (100%) 31/32 (97%) 26/27 (96%) 414 718 (87.5%) 313 718 (87.5%) 1I1 1161121 (97.5%)
-
-
11/13
FL, frontolateral laryngectomy; C, cordectomy;os, other conservation surgery 'Radiotherapy-salvage.
mon surgical procedure for tumors involving AC, is shown in Figure 4. The data show that this procedure was successfully used in the control of glottic tumors extending into AC, but not in pure AC carcinomas. In fact, 4 of 17 (23.5%)local recurrences were observed within 5 years in the group of patients with pure AC involvement. Moreover, with surgical (2 cases) and radiotherapy (1 case) salvage, the ultimate local control in patients with AC carcinoma first treated with frontolateral laryngectomy was 10 of 11 (91%). The 59 patients treated with radiotherapy are classified, according to tumor extension, as follows: 23 patients with pure AC carcinoma; 28 patients with glottic carcinoma involving AC up to the midline, and 8 patients with glottic carcinoma involving AC beyond the midline. Two disease-free patients died of other causes within 2 years after surgery and were excluded. Control of the primary tumor was achieved in 42 of 57 patients (74%) (Table 3). The 5-year follow-up in this group showed 15 local recurrences (62%within 2 years). In fact, control of the tu-
mor by radiotherapy was achieved in 18 of 22 (82%) patients with pure AC cancer, in 5 of 8 with cancer extending up to the midline, and in 19 of 27 (70%) with cancer extending beyond the midline. Moreover, in 8 of 15 local recurrences a surgical salvage was attempted (7total laryngectomies and 1 conservative laryngectomy with cricohyoidopexy), without success in 2 cases. Thus, the ultimate local control rate of patients initially treated with radiotherapy was 48 of 57 (84%).Seven patients with extensive local recurrences (5 patients) or distant metastases (2 patients) did not consent to any salvage and died of disease. Considering the disease-free rates according to the 3 subgroups mentioned above (Figure 51, it was observed that, at 5 years, local control of the primary tumor by radiotherapy was achieved in 18 of 22 (82%)patients with pure AC, 5 of 8 with glottic cancer extending into the AC up to the midline, and 19 of 27 (70%) with glottic cancer extending into the AC beyond the midline. Radiotherapy seemed to control successfully only pure AC carcinomas. On the other hand, it
Table 3. Radiotherapy-local control in 59 patients with glottic cancer involving the AC. No. salvagedlNo. attempted T stage T1a Tlb T2a T2b Total
Subgroup
Excluded
Local control (%)
Total laryng.
Other
5 RT 39 RT 13 RT 2 RT 59
2 2
415 (80%) 28/37 (76%) 9113 (69%) 112 (50%) 42/57 (74%)
111 414 1I2 617
-
011* 011*
Ultimate local control (%)
5/51 32/37 (86%) 10113 (77%) 112 48/57 (84%)
RT, treated with radiotherapy. 'Surgical salvage with partial /aryngectomy with cficohyioidopexy.
406
Treatment of Glottic Cancer Involving AC
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SeptemberlOctober 1991
Table 4. Surgical local control in 18 patients with pure AC cancer. No. salvaged/No. attempted T stage
T1 a Tlb T2a
Subgroup
Excluded
1 FL 8 FL 4 0s 3 FL
1 1
2 0s -
T2b Total
18
Local control (%)
Total laryng.
Other
Ultimate local control (%)
-
-
111
517 (71.5%)
212
-
414 1/3
-
-
011
1 */1*
717 414 213
-
-
-
212 -
213
1 *I1
111
212 -
13/17(76.5%)
1611 7 (94%)
FL, fronfolateral laryngectomy; 0s. other conservation surgery. 'Surgical salvage with partial laryngectomy with cricohyioidopexy
should be noted that in the 4 cases in which a local recurrence was seen, it was not possible to attempt any surgical salvage. In contrast, surgical salvage was attempted in 2 of 3 patients with glottic cancer extending into the AC up to the midline and in 6 of 8 patients with glottic cancer extending into the AC beyond the midline, whose primary radiotherapy failed. Local- regional disease control by surgical salvage was achieved in 6 of 8 (75%) patients. Moreover, the low number of patients with glottic cancer extending into the AC up to the midline (only 8) makes impossible any comparative analysis with surgery or with other reports. CONCLUSION
Involvement of the AC as a primary event or as a complication of unilateral or bilateral vocal cord cancer has been extensively studied.'-7sf0 Tumor at this site is very close to the thyroid cartilage being separated from it only by a fibrous structure (AC tendom and/or " X space).
The exact pretreatment evaluation of AC tumors, particularly with regard to deep infiltration, is very difficult even with direct laryngoscopy and also with TC and Furthermore, the treatment method of choice (radiotherapy or conservation surgery) for these particular cancers has long been discussed. The literature with regard to radiotherapy varies widely as to local-regional control rates ranging from 61% to 93% in patients primarily treated with radi~therapy."-~' This is evident in the review presented in Table 7 of previously published series of glottic carcinomas involving the AC treated by radi~therapy."-~' Although heterogeneity in the stage, extent, and modality of treatment of tumors among these series exists, our local control rate in T1 and T2 lesions is not very dissimilar from the overall local control of the all cases reported (76% vs 80% in T1 and 67% vs 70% in T2 cancers, respectively). Furthermore, the analysis of several reports evidences that the involvement of the AC was a
Table 5. Surgical local control in 75 patients with glottic cancer extending into the AC up to the midline. No. salvaged/No. attempted T stage
Total laryng.
Other
-
33/35(94%)
1 *I1* -
-
27/32 (84.5%) 212
1 I1 415
213
1
-
-
19/20 (95%)
-
-
-
415
-
-
313 111 313
1
66/74(89%)
516
Excluded
35 FL 33 c
Tlb T2a
2 FL
T2b
5 FL
Total
75
Tl a
Ultimate local control (%)
Local control (%)
Subgroup
111
l'll*
72/74(97%)
FL, fronfolateral laryngectomy; C, cordectomy. 'Radiotherapy-salvage.
Treatment of Glottic Cancer Involving AC
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September/October 1991
407
Table 6. Surgical local control in 30 patients with glottic cancer extending into the AC beyond the midline. ~
~
~~~
T stage T1a Tlb T2a T2b Total
Subgroup
Excluded
Local control (%)
2 FL 20 FL 3 FL 1 0s 3 FL 1 0s 30
-
112 18/20 (90%) 113 111 313 1I1 25/30 (83%)
-
No. salvage1 No. attempts
Total laryng.1 Other
Ultimate local control (%)
111 111 212
-
011"
-
-
-
-
-
011*
2/2 .I9120 (95%) 313 1I1 313 111 29/30 (97%)
-
414
FL, frontolateral laryngectomy; 0s. other conservation surgery. 'Radiotherapy- salvage.
cause of increased local recurrence in glottic cancer.11,14i16,20i22*24i30i32 Therefore, recently many a ~ t h o r s have ~ ~ - suggested ~~ a primary surgical approach for the treatment of AC lesions, employing various conservative procedures as partial fronto-anterior laryngectomy, partial frontolateral laryngectomy, hemilaryngectomy,14 and others. Laser surgery has also been suggested in the treatment of such cancers, but there is no ~ ~ > the ~~ agreement concerning its r e s ~ l t s .Thus, problem remains open. We have analyzed our experience in the treatment of 182 patients with glottic carcinoma involving AC (41 pure AC carcinomas and 141 extending from 1vocal cord). In contrast with almost all the above-mentioned reports, in our series we considered 3 different modalities of neoplastic involvement of AC (pure AC cancers, AC cancers involving 1 or both cords) and not only T l b but also T2 glottic tumors extending into the AC . Our overall results evidence a higher rate of local control of neoplastic disease with surgical
Dure AC glonlc up to AC glonlc beyond AC
I:
.
,
.
,
,
,
.
0
pure AC glonic , beyond , AC
,
0
0
0
3
2 Years
FIGURE 4. Recurrence-free survival after frontolateral laryngectomy by the modalities of AC involvement.
408
treatment than with irradiation (86%vs 74%) (p < 0.05). These data are more significant if we consider the results of salvage after local failures. In 16 of 17 patients with local recurrence after conservative surgery, a surgical (14 cases) or radiotherapy (2 cases) salvage was possible with an ultimate local control of 97.5% (118 of 121). In 15 patients with local recurrence after irradiation only 7 could be surgically retreated, but 2 died of the disease. Therefore, our patients with a local recurrence have been more successfully treated when surgery was the initial therapeutic approach, rather than radiotherapy. Moreover, in patients with pure AC lesions, the local control rate was superior by radiotherapy (82% vs 76.5%). These data could be explained considering that in head and neck cancers one of the major advantages of irradiation compared with surgery is the ability to cover potential subclinical avenues of spread with less m~rbidity.~' It has been reported that tumors of the vocal cord spreading to the AC almost always involve
Treatment of Glottic Cancer Involving AC
0
1
3
2
4
5
YMrl
FIGURE 5. Recurrence-free survival after radiotherapy by the modalities of AC involvement.
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SeptemberlOctober 1991
Table 7. Review of previously published series of glottic cancer extending into the AC treated with radiotherapy. Author Oloffson et al.” Horiot et a1.12 Fletcher et aI.l3 Sessions et a1.14 Ennuyer and Bataini15 Sung et a1.16 Mills” Harwood et al.” Woodhouse et al.” Chacko et aL20 Dickens et Mantravadi et aL2* Mittal et aLz3 Olszewski et al.24 Amornmarn et al.25 Karim et aLZ6 Mendenhall et al.27 Schwaibold et aL2’ Teshima et al.” Fernberg et aL3’ Lusinchi et aL3’ Total
No. of Datients
T staae
% Local control
57 36 28 39 31 20
T l b + T2 Tlb Tlb T2 Tlb Tlb
80 (45/57) 91 (33/36) 85 (24/28) 71 (28139) 61 (19/31) 80 (16/20)
20 16 50 45
Tlb Tlb Tlb Tlb
32 16 20 31 21 58 35 34 45 31 13 13 9 22
Tlb Tlb T2 Tlb T2 Tlb Tlb Tlb T2 Tlb Tlb Tlb Tlb Tlb
70 (14/20) 75 (12/16) 82 (41/50) 80 (36/45) 64 (16/25) 87.5 (28/32) 81 (13/16) 55 (11/20) 71 (22131) 69 (16/21) 79 (46158) 74 (26/35) 91 (31/34) 75 (34/45) 93 (29/31) 84 (11/13) 84 (1 1/13) 66 (619) 80 (17/22)
597 150
Tlb T2
80 (480/597) 70 (105/150)
this structure superficially, whereas cancer growths in the midline larynx frequently show a deep infiltration.2i6 Therefore, radiotherapy could give better results in the treatment of infiltrative lesions, often not correctly assessed and staged by the two-dimensional picture given by laryngos~opy.~.~~ In pure AC cancers, these data are more significant, due to the well-distinguished modality of local recurrence linked to primary treatment. Generally, when irradiation is unsuccessful in treating a primary lesion, the disease almost always recurs at the site of the original lesion; disease recurring at the margins of the primary lesion is uncommon. Surgical recurrences usually
develop at the margins of the resection. These elements indicate that the surgical salvage of irradiation failure is usually more likely to succeed than the salvage of a surgical failure by surgery, radiotherapy, or both.38 On the contrary, in AC cancers a central recurrence is far worse than a recurrence at the margins of the surgical resection: in the midline larynx, a recurrent tumor is difficult to distinguish and the diagnosis of recurrence is often delayed, with less success in surgical salvage, because of an easy anterior extralaryngeal spreading through the thyroid cartilage. Considering the different conservative surgical techniques, our experience confirms that the treatment of choice for cancers involving the AC is frontolateral laryngectomy, as evidenced above by rates of local control. Regarding tumor extension, the results of local failures after frontolateral laryngectomy need to be analyzed. When a tumor involved the AC from an adjacent true vocal cord, this conservative technique successfully controlled the disease (but if the tumor did not cross the midline, the rate of local control was obviously similar for frontolateral laryngectomy and cordectomy). On the contrary, pure AC carcinoma treated with frontolateral laryngectomy had a high rate of local recurrence (34%), but the successful surgical salvage (ultimate local control rate of 97.5%%) enabled us to avoid the use of primary demolitive laryngeal surgery and radiotherapy in these patients. Because of the different clinical behavior of pure AC cancer, a very strict control for patients with pure AC carcinoma primarily treated with frontolateral laryngectomy is recommended. In our study we also found that glottic AC cancers (usually all staged as Tlb), in relation to the different involvement of the AC, have a variable behavior and prognosis. Therefore, we emphasize the need to define universally the AC region and, in staging laryngeal glottic tumors, to consider separately its different modalities of involvement in well-distinguished T categories with a possibly better therapeutic approach.
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Treatment of Glottic Cancer Involving AC
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A retrospective review of 182 patients with glottic cancer involving the anterior commissure (AC) is presented. of these, 123 patients were first treated with conservative surgery and 59 underwent radiotherapy. Patients were staged according to the AJCC system and by the modality of neoplastic involvement of AC (pure AC cancer, glottic cancer involving AC up to the midline, and beyond the midline). Our results indicate a higher rate of local control and of specific-disease survival in the group of patients first treated with surgery than those treated with radiotherapy (86% vs 74% and 97.5% vs 84%, rppectively) @ c 0.05). For pure AC cancers, our results show better local control with primary radiotherapy than with conservation surgery (82% vs 76.5%), but surgical failures have been more successfully salvaged than have radiotherapy recurrences (ultimate local control, 97.5% vs 820% respectively). These data suggest that the treatment of choice for AC cancers is conservation surgery, particularly frontolateral laryngectomy. HEAD 8 NECK 1991;13:403410
T h e anterior commissure (AC) of the larynx constitutes a transitional zone between the supraglottic and glottic region and is frequently involved by tumor. The neoplastic involvement of the AC is rarely an isolated cancer growth in the
From the llnd Otorhinolaryngologic Clinic, University of Florence, Florence, Italy. Address reprint requests to Dr. Rucci at the II Clinica ORL, Universita di Firenze. Careggi, Viale Morgagni, 85. 50134-Firenze, Italia. Accepted for publication February 11, 1991. CCC 0148-6403/91/050403-08 $04.00 0 1991 John Wiley & Sons, Inc.
Treatment of Glottic Cancer Involving AC
midline larynx; most frequently, it is the site of spread from cancers of one of the vocal cords. Of the various regions of the larynx, the AC provides perhaps the greatest challenge to investigators; there is no agreement concerning its boundaries, and its morphology is also controver~ i a l . l -Therefore, ~ many authors have studied AC in an attempt to better define its anatomic structures and the mechanical factors influencing tumor growth and In agreement with o t h e r ~ ,our ~ ~clinical ~ * ~ experience shows that cancer behavior in this zone seems variable. The anatomy of AC is such that an apparent T1 lesion may actually be a T4 lesion if it involves the thyroid cartilage. The presence of fibrous structures (Broyle’s tendom or “ X space of Bagatella) at the anterior attachment of the vocal cords may actually influence the modes of growth and spread of laryngeal tumors.6 These structures act as a barrier, so that invasion of the adjacent thyroid cartilage has not been observed in cancers that remain limited to the glottic level on the surface.2i435 If the cancer extends upward or downward at the anterior commissure, the invasion and destruction of the adjacent thyroid cartilage can be The possible spread of glottic cancers exceeding these anatomic structures is very difficult to appreciate by the two-dimensional picture given by laryngoscopy,4 justifying a different behavior of same staged cancers. Therefore, these elements in addition to the absence of a univer-
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403
sally accepted clinical definition of the boundaries of AC, justify the diagnostic, pathologic, and therapeutic problems linked to AC carcinoma. In this article we define the boundaries of AC on the basis of the anatomic studies of Nicelli7 and Tucker' as the lower tip of the epiglottic cartilage (5 mm) above, the ventricular folds and the vocal cords (113) on the sides, and the subglottic region (5 mm) below. We review the results of primary surgical therapy in selected patients with AC carcinoma (pure AC carcinoma and glottic carcinoma extending into the AC), and compare these data to results of radiotherapy. PATIENTS AND METHODS
Between 1968 and 1988, 182 patients with neoplastic involvement of AC were treated with curative intent at the ENT Clinic of the University of Florence. During this 20-year period, a selected number of patients (123) underwent conservation procedures, while the others (59) received primary radiotherapy. The mean age of patients was 59 years (range, 38-78 years). Patients were retrospectively staged according to the TNM system of the American Joint Committee on Cancer (198718 for glottic cancer, using preoperative clinical records, radiologic studies, and endoscopic and operative findings, as follows: Tla, involvement of one true vocal cord with AC spread; Tlb, involvement of both true vocal cords; T2, cancer lesion with extraglottic extension: T2a, with normal mobility, and T2b, with reduced mobility of the true vocal cord. According to the TNM system, the 182 AC cancers were classified as follows: 76 Tla, 71 Tlb, 24 T2a, and 11 T2b. The number of positive neck nodes (Nl) at diagnosis was 0 of 76 Tla, 1 of 71 Tlb, 0 of 24 T2a, and 1 of 11 T2b. In 3 cases, a delayed homolateral neck involvement was observed. On the whole, 5 of 182 (2.7%) patients were affected by laterocervical metastases. Considering the causes of death in this population, with particular reference to distant metastases and subsequent primary cancers, the criteria we considered for distinguishing lung metastases from the primary laryngeal cancer and second primary lung cancer were: (a) time greater than 5 years to development of lung lesion; and (b) different clinical and histopathologic - features. Thus, after successful Primary
treatment Of the dotticcancer* Of (4'4') patients with AC carcinoma suffered distant pul-
404
Treatment of Glottic Cancer Involving AC
monary metastases (ranging from 11 to 22 months after primary treatment), whereas another 9 patients (5%) presented with a second cancer (3 of the larynx, 3 of the lung, 2 of the large bowel, and 1 of the bladder). The method of primary treatment by T stage is shown in Table 1. In the group of patients first treated with surgery, 82 underwent frontolateral laryngectomies (in Tla, Tlb, T2a, T2b cases); 33 cordectomies (in T l a cases); 3 frontal anterior laryngectomies (in T1, T2a cases); 3 horizontal glottectomies (in T l b cases); and 2 subtotal laryngectomies with cricohyoidopexy (in Tlb, T2 cases). Radiotherapy was given with the same technique to all patients, using a cobalt 60 source. Two anterior oblique, 6 x 7 cm wedged fields were used. All patients had external fixation of the head and neck. A total dose in the range of 5,600-6,700 cGy was delivered in fractions of 200 cGy, 5 days a week. Patients were set up each day on the treatment machine by a physician; the fields were marked on the patients daily using the anatomic landmarks of the thyroid and cricoid cartilages. The reason for selection of surgery or radiotherapy was mostly subjective. Usually irradiation was employed in patients with small AC lesions, in older patients, and in patients in unsatisfactory general condition. All patients were subdivided in 3 groups, according to the modalities of AC neoplastic involvement: 41 patients with pure AC carcinoma; 83 patients with glottic carcinoma extending into AC up to the midline; and 58 patients with glottic carcinoma extending into AC beyond the midline. Patients had a 2-year minimum follow-up and 102 (56%) had at least 5 years' follow-up. A detailed analysis of the subgroups was carried out to determine survival rates, pattern of relapse and treatment complications, and to com-
Table 1. Method of treatment by tumor stage. Primary treatment T stage T1a Tb l T2a ~ 2 b Total
Conservation 71 (38 FL, 33 C) 32 (28 FL, 4 0s) 11 (8 FL, 3 0s) 9 (8 FL, 1 0s) 123
Radiotherapy
Total
5 39 13 2
76 71 24 11 182
59
FL, frontolateral laryngectomy; C, cordectomy; as,other conservation surgery.
HEAD 8, NECK
September/October 1991
pare these results according to tumor extension and method of treatment. Patients who died within 2 years and with a continuously diseasefree primary site were excluded. They were considered, however, in the actuarial analysis. These data were analyzed using the actuarial method, and statistical differences in survival rates were determined by the z - t e ~ t Only . ~ significant differences of p < 0.05 are noted for each analysis.
0
Surgery Radiotherapy
4
5
o i 0
I
1
3
2
Vearr
RESULTS
for the total group of patients survival are shown in Figures 1 and 2 according to tumor stage and primary treatment method, respectively. There were significant differences between actuarial survival curves after surgery and after radiotherapy ( p < 0.05). Recurrence-free survival according to primary treatment is shown in Figure 3. There was a significant difference between radiotherapy and surgery ( p < 0.05). Results of our series after surgery or radiotherapy are shown in detail in Tables 2 and 3, respectively. The group of 123 patients primarily treated with surgery were classified as follows: 18 patients with pure AC, 75 patients with glottic carcinoma involving the AC up to the midline, and 30 patients with glottic carcinoma involving the AC beyond the midline. Two patients in this group died of other causes and were excluded. Control of the primary tumor was achieved in 104 of 121 patients (86%).In this group 17 patients had a local recurrence within 5 years (75%appeared within 2 years). In 16 of these 17 local recurrences, a salvage (2 radiotherapy, 1 subtotal laryngectomy with cricohyoidopexy, 13 total laryngectomies)
I I
rn 0
Tla Tlb T2a T2b
FIGURE 2. Global actuarial corrected survival according to primary treatment.
was attempted, unsuccessfully in 2 cases. Thus, the ultimate local control rate for the entire group was 118 of 121 (97.5%). Considering the modality of AC involvement, 5-year local control was achieved by surgery in 13 of 17 (76.5%)pure AC carcinomas (Table 4), 56 of 74 (89%)with glottic carcinoma involving the AC up to the midline (Table 5), and 25 of 30 (83%) with glottic carcinoma involving the AC beyond the midline (Table 6). Surgical salvage was attempted in 4 patients with pure AC cancer (unsuccessfully in 1 case), in 6 patients with AC cancer up to the midline (unsuccessfully in 1 case), and successfully in 4 patients with AC cancer beyond the midline, whose primary conservative surgical procedures failed. Moreover, radiotherapy was employed in another 2 patients with recurrence (1with AC cancer up to the midline, 1 with AC cancer beyond the midline) with a favorable result in the first patient. The 5-year recurrence-free survival of frontolateral laryngectomy, which was the most com-
0
Surgery Radiotherapy
20 0 4
0
0
I
1
3
2
4
5
veerr Year.
FIGURE 1. Actuarial survival results of total group by T stage.
Treatment of Glottic Cancer Involving AC
FIGURE 3. Recurrence-free survival according to primary treatment.
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September/October 1991
405
Table 2. Surgical local control in 123 patients with glottic cancer involving the AC. No. salvagedINo. attempted T stage
T1a Tlb T2a T2b Total
Subgroup
Excluded
Local control(%)
Total laryng.
38 FL 33 c 28 FL 4 0s 8 FL 3 0s 8 FL 1 0s 123
1 1
35/38 (92%) 27/32 (84.5%) 23/27 (85%) 414 418 (50%) 313 718 (87.5%) 111 1041121 (86%)
212 415 313 -
2
Ultimate local control(5)
Other
38/38 (100%) 31/32 (97%) 26/27 (96%) 414 718 (87.5%) 313 718 (87.5%) 1I1 1161121 (97.5%)
-
-
11/13
FL, frontolateral laryngectomy; C, cordectomy;os, other conservation surgery 'Radiotherapy-salvage.
mon surgical procedure for tumors involving AC, is shown in Figure 4. The data show that this procedure was successfully used in the control of glottic tumors extending into AC, but not in pure AC carcinomas. In fact, 4 of 17 (23.5%)local recurrences were observed within 5 years in the group of patients with pure AC involvement. Moreover, with surgical (2 cases) and radiotherapy (1 case) salvage, the ultimate local control in patients with AC carcinoma first treated with frontolateral laryngectomy was 10 of 11 (91%). The 59 patients treated with radiotherapy are classified, according to tumor extension, as follows: 23 patients with pure AC carcinoma; 28 patients with glottic carcinoma involving AC up to the midline, and 8 patients with glottic carcinoma involving AC beyond the midline. Two disease-free patients died of other causes within 2 years after surgery and were excluded. Control of the primary tumor was achieved in 42 of 57 patients (74%) (Table 3). The 5-year follow-up in this group showed 15 local recurrences (62%within 2 years). In fact, control of the tu-
mor by radiotherapy was achieved in 18 of 22 (82%) patients with pure AC cancer, in 5 of 8 with cancer extending up to the midline, and in 19 of 27 (70%) with cancer extending beyond the midline. Moreover, in 8 of 15 local recurrences a surgical salvage was attempted (7total laryngectomies and 1 conservative laryngectomy with cricohyoidopexy), without success in 2 cases. Thus, the ultimate local control rate of patients initially treated with radiotherapy was 48 of 57 (84%).Seven patients with extensive local recurrences (5 patients) or distant metastases (2 patients) did not consent to any salvage and died of disease. Considering the disease-free rates according to the 3 subgroups mentioned above (Figure 51, it was observed that, at 5 years, local control of the primary tumor by radiotherapy was achieved in 18 of 22 (82%)patients with pure AC, 5 of 8 with glottic cancer extending into the AC up to the midline, and 19 of 27 (70%) with glottic cancer extending into the AC beyond the midline. Radiotherapy seemed to control successfully only pure AC carcinomas. On the other hand, it
Table 3. Radiotherapy-local control in 59 patients with glottic cancer involving the AC. No. salvagedlNo. attempted T stage T1a Tlb T2a T2b Total
Subgroup
Excluded
Local control (%)
Total laryng.
Other
5 RT 39 RT 13 RT 2 RT 59
2 2
415 (80%) 28/37 (76%) 9113 (69%) 112 (50%) 42/57 (74%)
111 414 1I2 617
-
011* 011*
Ultimate local control (%)
5/51 32/37 (86%) 10113 (77%) 112 48/57 (84%)
RT, treated with radiotherapy. 'Surgical salvage with partial /aryngectomy with cficohyioidopexy.
406
Treatment of Glottic Cancer Involving AC
HEAD 8, NECK
SeptemberlOctober 1991
Table 4. Surgical local control in 18 patients with pure AC cancer. No. salvaged/No. attempted T stage
T1 a Tlb T2a
Subgroup
Excluded
1 FL 8 FL 4 0s 3 FL
1 1
2 0s -
T2b Total
18
Local control (%)
Total laryng.
Other
Ultimate local control (%)
-
-
111
517 (71.5%)
212
-
414 1/3
-
-
011
1 */1*
717 414 213
-
-
-
212 -
213
1 *I1
111
212 -
13/17(76.5%)
1611 7 (94%)
FL, fronfolateral laryngectomy; 0s. other conservation surgery. 'Surgical salvage with partial laryngectomy with cricohyioidopexy
should be noted that in the 4 cases in which a local recurrence was seen, it was not possible to attempt any surgical salvage. In contrast, surgical salvage was attempted in 2 of 3 patients with glottic cancer extending into the AC up to the midline and in 6 of 8 patients with glottic cancer extending into the AC beyond the midline, whose primary radiotherapy failed. Local- regional disease control by surgical salvage was achieved in 6 of 8 (75%) patients. Moreover, the low number of patients with glottic cancer extending into the AC up to the midline (only 8) makes impossible any comparative analysis with surgery or with other reports. CONCLUSION
Involvement of the AC as a primary event or as a complication of unilateral or bilateral vocal cord cancer has been extensively studied.'-7sf0 Tumor at this site is very close to the thyroid cartilage being separated from it only by a fibrous structure (AC tendom and/or " X space).
The exact pretreatment evaluation of AC tumors, particularly with regard to deep infiltration, is very difficult even with direct laryngoscopy and also with TC and Furthermore, the treatment method of choice (radiotherapy or conservation surgery) for these particular cancers has long been discussed. The literature with regard to radiotherapy varies widely as to local-regional control rates ranging from 61% to 93% in patients primarily treated with radi~therapy."-~' This is evident in the review presented in Table 7 of previously published series of glottic carcinomas involving the AC treated by radi~therapy."-~' Although heterogeneity in the stage, extent, and modality of treatment of tumors among these series exists, our local control rate in T1 and T2 lesions is not very dissimilar from the overall local control of the all cases reported (76% vs 80% in T1 and 67% vs 70% in T2 cancers, respectively). Furthermore, the analysis of several reports evidences that the involvement of the AC was a
Table 5. Surgical local control in 75 patients with glottic cancer extending into the AC up to the midline. No. salvaged/No. attempted T stage
Total laryng.
Other
-
33/35(94%)
1 *I1* -
-
27/32 (84.5%) 212
1 I1 415
213
1
-
-
19/20 (95%)
-
-
-
415
-
-
313 111 313
1
66/74(89%)
516
Excluded
35 FL 33 c
Tlb T2a
2 FL
T2b
5 FL
Total
75
Tl a
Ultimate local control (%)
Local control (%)
Subgroup
111
l'll*
72/74(97%)
FL, fronfolateral laryngectomy; C, cordectomy. 'Radiotherapy-salvage.
Treatment of Glottic Cancer Involving AC
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September/October 1991
407
Table 6. Surgical local control in 30 patients with glottic cancer extending into the AC beyond the midline. ~
~
~~~
T stage T1a Tlb T2a T2b Total
Subgroup
Excluded
Local control (%)
2 FL 20 FL 3 FL 1 0s 3 FL 1 0s 30
-
112 18/20 (90%) 113 111 313 1I1 25/30 (83%)
-
No. salvage1 No. attempts
Total laryng.1 Other
Ultimate local control (%)
111 111 212
-
011"
-
-
-
-
-
011*
2/2 .I9120 (95%) 313 1I1 313 111 29/30 (97%)
-
414
FL, frontolateral laryngectomy; 0s. other conservation surgery. 'Radiotherapy- salvage.
cause of increased local recurrence in glottic cancer.11,14i16,20i22*24i30i32 Therefore, recently many a ~ t h o r s have ~ ~ - suggested ~~ a primary surgical approach for the treatment of AC lesions, employing various conservative procedures as partial fronto-anterior laryngectomy, partial frontolateral laryngectomy, hemilaryngectomy,14 and others. Laser surgery has also been suggested in the treatment of such cancers, but there is no ~ ~ > the ~~ agreement concerning its r e s ~ l t s .Thus, problem remains open. We have analyzed our experience in the treatment of 182 patients with glottic carcinoma involving AC (41 pure AC carcinomas and 141 extending from 1vocal cord). In contrast with almost all the above-mentioned reports, in our series we considered 3 different modalities of neoplastic involvement of AC (pure AC cancers, AC cancers involving 1 or both cords) and not only T l b but also T2 glottic tumors extending into the AC . Our overall results evidence a higher rate of local control of neoplastic disease with surgical
Dure AC glonlc up to AC glonlc beyond AC
I:
.
,
.
,
,
,
.
0
pure AC glonic , beyond , AC
,
0
0
0
3
2 Years
FIGURE 4. Recurrence-free survival after frontolateral laryngectomy by the modalities of AC involvement.
408
treatment than with irradiation (86%vs 74%) (p < 0.05). These data are more significant if we consider the results of salvage after local failures. In 16 of 17 patients with local recurrence after conservative surgery, a surgical (14 cases) or radiotherapy (2 cases) salvage was possible with an ultimate local control of 97.5% (118 of 121). In 15 patients with local recurrence after irradiation only 7 could be surgically retreated, but 2 died of the disease. Therefore, our patients with a local recurrence have been more successfully treated when surgery was the initial therapeutic approach, rather than radiotherapy. Moreover, in patients with pure AC lesions, the local control rate was superior by radiotherapy (82% vs 76.5%). These data could be explained considering that in head and neck cancers one of the major advantages of irradiation compared with surgery is the ability to cover potential subclinical avenues of spread with less m~rbidity.~' It has been reported that tumors of the vocal cord spreading to the AC almost always involve
Treatment of Glottic Cancer Involving AC
0
1
3
2
4
5
YMrl
FIGURE 5. Recurrence-free survival after radiotherapy by the modalities of AC involvement.
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SeptemberlOctober 1991
Table 7. Review of previously published series of glottic cancer extending into the AC treated with radiotherapy. Author Oloffson et al.” Horiot et a1.12 Fletcher et aI.l3 Sessions et a1.14 Ennuyer and Bataini15 Sung et a1.16 Mills” Harwood et al.” Woodhouse et al.” Chacko et aL20 Dickens et Mantravadi et aL2* Mittal et aLz3 Olszewski et al.24 Amornmarn et al.25 Karim et aLZ6 Mendenhall et al.27 Schwaibold et aL2’ Teshima et al.” Fernberg et aL3’ Lusinchi et aL3’ Total
No. of Datients
T staae
% Local control
57 36 28 39 31 20
T l b + T2 Tlb Tlb T2 Tlb Tlb
80 (45/57) 91 (33/36) 85 (24/28) 71 (28139) 61 (19/31) 80 (16/20)
20 16 50 45
Tlb Tlb Tlb Tlb
32 16 20 31 21 58 35 34 45 31 13 13 9 22
Tlb Tlb T2 Tlb T2 Tlb Tlb Tlb T2 Tlb Tlb Tlb Tlb Tlb
70 (14/20) 75 (12/16) 82 (41/50) 80 (36/45) 64 (16/25) 87.5 (28/32) 81 (13/16) 55 (11/20) 71 (22131) 69 (16/21) 79 (46158) 74 (26/35) 91 (31/34) 75 (34/45) 93 (29/31) 84 (11/13) 84 (1 1/13) 66 (619) 80 (17/22)
597 150
Tlb T2
80 (480/597) 70 (105/150)
this structure superficially, whereas cancer growths in the midline larynx frequently show a deep infiltration.2i6 Therefore, radiotherapy could give better results in the treatment of infiltrative lesions, often not correctly assessed and staged by the two-dimensional picture given by laryngos~opy.~.~~ In pure AC cancers, these data are more significant, due to the well-distinguished modality of local recurrence linked to primary treatment. Generally, when irradiation is unsuccessful in treating a primary lesion, the disease almost always recurs at the site of the original lesion; disease recurring at the margins of the primary lesion is uncommon. Surgical recurrences usually
develop at the margins of the resection. These elements indicate that the surgical salvage of irradiation failure is usually more likely to succeed than the salvage of a surgical failure by surgery, radiotherapy, or both.38 On the contrary, in AC cancers a central recurrence is far worse than a recurrence at the margins of the surgical resection: in the midline larynx, a recurrent tumor is difficult to distinguish and the diagnosis of recurrence is often delayed, with less success in surgical salvage, because of an easy anterior extralaryngeal spreading through the thyroid cartilage. Considering the different conservative surgical techniques, our experience confirms that the treatment of choice for cancers involving the AC is frontolateral laryngectomy, as evidenced above by rates of local control. Regarding tumor extension, the results of local failures after frontolateral laryngectomy need to be analyzed. When a tumor involved the AC from an adjacent true vocal cord, this conservative technique successfully controlled the disease (but if the tumor did not cross the midline, the rate of local control was obviously similar for frontolateral laryngectomy and cordectomy). On the contrary, pure AC carcinoma treated with frontolateral laryngectomy had a high rate of local recurrence (34%), but the successful surgical salvage (ultimate local control rate of 97.5%%) enabled us to avoid the use of primary demolitive laryngeal surgery and radiotherapy in these patients. Because of the different clinical behavior of pure AC cancer, a very strict control for patients with pure AC carcinoma primarily treated with frontolateral laryngectomy is recommended. In our study we also found that glottic AC cancers (usually all staged as Tlb), in relation to the different involvement of the AC, have a variable behavior and prognosis. Therefore, we emphasize the need to define universally the AC region and, in staging laryngeal glottic tumors, to consider separately its different modalities of involvement in well-distinguished T categories with a possibly better therapeutic approach.
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Treatment of Glottic Cancer Involving AC
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Treatment of Glottic Cancer Involving AC
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