CC BY 4.0 · J Neurol Surg B Skull Base 2023; 84(01): 069-078
DOI: 10.1055/a-1733-2585
Original Article

Surgical Strategy for Squamous Cell Carcinoma of the External Auditory Canal: Management of Locally Advanced Cases with Skull Base Involvement

Seiya Goto
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Kenichiro Iwami
2   Department of Neurosurgery, Aichi Medical University, Aichi, Japan
,
Tadao Yoshida
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Takashi Maruo
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Nobuaki Mukoyama
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Hidenori Tsuzuki
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Sayaka Yokoi
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Akihisa Wada
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Mariko Hiramatsu
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Yuichiro Hayashi
3   Graduate School of Informatics, Nagoya University, Nagoya, Japan
,
Yuzuru Kamei
4   Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Masazumi Fujii
5   Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan
,
Michihiko Sone
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Yasushi Fujimoto
1   Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan
6   Department of Otorhinolaryngology, Head and Neck Surgery, Aichi Medical University, Aichi, Japan
› Author Affiliations
 

Abstract

Objective Surgical indications for advanced-stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) are highly dependent on the skull base surgery team. The aim of this study was to evaluate the surgical outcomes in patients with SCC of the EAC and to clarify the surgical indication of far advanced cases using the T4 subclassification.

Methods Patients with SCC of the EAC who underwent curative treatment from 2002 to 2021 at our hospital were retrospectively reviewed. Clinical and surgical results, including operative data, overall survival (OS), and disease-specific survival (DSS), were analyzed. To clarify the surgical indication for advanced-stage tumors, we proposed the T4 subclassification.

Results In the 46 patients included in the study, 8 patients had T1 tumors, 10 had T2 tumor, 5 had T3 tumors, and 23 had T4 tumors. The 5-year DSS with T1, T2, T3, and T4 tumors were 100, 85.7, 100, and 61.7%, respectively. No prognostic impacts for margin status were found between the 5-year OS and DSS (p = 0.23 and 0.13, respectively). Patients with far-advanced-stage (T4b) tumors were significantly associated with shorter DSS than those with early-stage (T1/T2) and advanced-stage (T3/T4a) tumors (p = 0.007 and 0.03, respectively).

Conclusion The present study focused on patients with SCC of the EAC at a university hospital over a period of 20 years, especially with skull base involvement, and a T4 subclassification was proposed. Complete tumor resection in an en bloc fashion could help achieve a good survival rate even in patients with locally advanced tumors.


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Introduction

Squamous cell carcinoma (SCC) of the external auditory canal (EAC) arises from the external ear and is a quite rare form of head and neck cancer, comprising less than 0.2% of all head and neck tumors.[1] [2] Currently, the modified Pittsburgh classification, which is based on the intraoperative findings and the histopathological assessments, is a commonly used tumor classification for SCC of the EAC.[2] Complete tumor resection with free margins achieved better survival outcomes in patients with early-stage (T1/T2) tumors.[3] However, because of the unique regional anatomy, only few symptoms are experienced in its early stage, such as otorrhea, itching, and swelling of the ear canal, resulting in development of a locally advanced-stage (T3/T4) tumor from the primary tumor.[4] [5] [6] In patients with advanced-stage (T3/T4) tumor, complete tumor resection with free margins is the mainstay of treatment, but is often challenging due to the complicated bony anatomy of the temporal bone and the surrounding crucial organs, including the internal carotid artery, cranial nerves, and brain. A meta-analysis of 274 patients with SCC of the EAC showed that the 5-year overall survival (OS) rates were 72.5 and 35.8% for T3 and T4 tumors, respectively.[7] In particular, the 5-year OS rate for T4 tumors was 29.5 to 46.3%, with a poor prognosis.[8] [9] [10]

Surgery is the mainstay of treatment for patients with SCC of the EAC, and most clinicians agree that, if possible, complete tumor resection in an en bloc fashion should be performed for both early-stage (T1/T2) and advanced-stage (T3/T4) tumors. Craniofacial resection enables us to perform complete en bloc resection of the tumor with tumor-free margins, even for locally advanced skull base malignancies,[11] and thus, could be the first choice of treatment even in patients with locally advanced EAC cancer.[12] Recent studies demonstrated that surgical resection achieved better survival results with a low risk of severe complication in both early[3] and advanced EAC cancers.[12] [13] However, craniofacial resection in temporal bone malignancies requires experienced surgical skills and sufficient anatomical knowledge of the skull base regions. Therefore, surgical indications for advanced-stage SCC of the EAC are highly dependent on the skull base surgery team at each hospital, and it remains challenging to manage the far-advanced cases involving the cochlea, medial wall of the middle ear, or the petrosal apex. Current staging systems, such as the modified Pittsburgh classification, classify the advanced tumors as only T4 tumors and do not discriminate tumors as resectable (in en bloc fashion) or unresectable.[14] In this study, we reviewed our surgical experience in the management of SCC of the EAC in a tertiary hospital with a consistent surgical strategy. The aim of this study was to evaluate the surgical outcomes in patients with SCC of the EAC using several surgical techniques and to clarify the surgical indications of far-advanced cases using the T4 subclassification.


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Materials and Methods

Patients

The clinical charts of patients with SCC of the EAC who underwent curative treatment between 2002 and 2021 at Nagoya University Hospital were retrospectively reviewed. Patients with a different pattern on histological examination; with metastases of the carcinoma to distant areas such as the bone, lungs, and liver; or who refused to receive curative treatment were excluded from the study. Clinical and surgical results, including operative data, overall survival, and disease-specific survival (DSS) were analyzed. This study was approved by the ethics review committee of Nagoya University Hospital (2020–0162) and was performed in accordance with the Helsinki Declaration of 1975 and its amendments.


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Treatment Strategy

The main treatment strategy for SCC of the EAC was complete tumor resection in an en bloc fashion. All patients were preoperatively assessed using thin-slice computed tomography (CT) and other imaging modalities, including magnetic resonance imaging (MRI), ultrasound, and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). In our hospital, CT and MRI were evaluated by two radiologists, who were blinded to the clinical outcomes, and the diagnostic information, such as the invasion pattern in the surrounding tissues, was reported as a diagnostic radiological report. Based on this diagnostic report, tumor and nodal (TN) staging was determined according to the modified Pittsburgh classification.[2] [15] Further, an appropriate surgical procedure was determined based on the preoperative assessment of tumor involvement in the surrounding adjacent tissues.

Surgery was performed by a multidisciplinary skull base surgery team, including the head and neck surgeons, neurosurgeons, and the plastic and reconstructive surgeons. During surgery, to perform accurate tumor resection, a Vector Vision Compact Navigation System (BrainLAB, Munich, Germany) was used to determine the positional relationship between the tumor and surrounding normal tissues.[16] Because of the difficulty in achieving an en bloc resection, patients with involvement of the petrous apex, carotid canal, or jugular foramen were not indicated for surgical resection.

It is recommended that postoperative radiotherapy (a dose of 50–60 Gy at 2 Gy per fraction and 5 fractions per week to the tumor bed) should be administered within 8 weeks of tumor resection, based on the extent of tumor invasion, margin status, and the patient's general condition.[17] Cisplatin-based chemoradiotherapy is recommended as an adjuvant treatment in patients with positive margins or extranodal spread.


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Surgical Techniques with or without Craniotomy

Representative designs of skin incisions and craniotomies for each surgical classification are shown in [Fig. 1]. For the early-stage (T1/T2) tumors, lateral temporal bone resection (LTBR) was generally performed, in which the tumor was resected en bloc with the surrounding normal tissue. This procedure was performed using a tympanic approach, without craniotomy. Sleeve resection was performed only in the selective patients with early-stage T1 tumors. For the locally advanced-stage (T3/T4) tumors, an extended-LTBR (Ex-LTBR) or subtotal temporal bone resection (STBR) was performed. Head and neck surgeons and neurosurgeons performed Ex-LTBR and STBR using intracranial techniques, and the surgical defects of the cranial base were covered using a free flap from the omentum or anterolateral thigh, sometimes with a fascia for closure of the dura by plastic and reconstructive surgeons. Craniofacial resection was not performed in patients with advanced-stage tumors, whose general condition was not suitable for surgery (i.e., worse than performance status of 2, as defined by the Eastern Cooperative Oncology Group).[18]

Zoom Image
Fig. 1 Surgical procedures for squamous cell carcinoma of the external auditory canal. Upper: Representative designs of skin incisions (red line) and craniotomies (black dotted line) of surgical procedures for external auditory canal cancer; sleeve resection, lateral temporal bone resection (LTBR), extended lateral temporal bone resection (Ex-LTBR), and subtotal temporal bone resection (STBR). Lower: Resection line of the intracranial skull base (black dotted line) and surrounding organs, including the temporomandibular joint (TMJ), internal carotid artery (ICA), sigmoid sinus (SS), jugular valve (JV), and semicircular canals (SCs).

Complications were considered if they occurred within 30 days postoperatively and were categorized into three groups, as previously reported: central nervous system (CNS) complications, wound complications, and systemic complications.[11] Cerebrospinal fluid (CSF) leak was classified as a major complication, if it lasted for more than 1 week or required operative intervention. The loss of all or part of the flap used in reconstruction and the need for surgical retreatment were considered the major wound complications.


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Statistical Analysis

OS and DSS were estimated using the Kaplan–Meier analysis, and the differences in survival rates were estimated using the log-rank test for all patients and for those requiring surgery. OS was calculated from the first visit of the patient to the day of death, or to the date of last follow-up. DSS was calculated from the first day of treatment to the day of death from the disease, or the date of last follow-up. Statistical analysis was performed using the EZR software package (version 1.35; Saitama Medical Center, Jichi Medical University, Saitama, Japan), which is a graphical user interface for R (The R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was set at p < 0.05.


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Results

Patient Characteristics

A total of 46 patients (24 men, 22 women; median age at the first visit: 67 years) who underwent curative treatment were investigated ([Table 1]). The median duration of follow-up was 28 months (range: 2–224 months). Based on the T classification, the tumors were in T1 stage in 8 patients, T2 in 10, T3 in 5, and T4 in 23 patients. Fourteen patients received platinum-based combination chemotherapy before treatment. Out of the 46 patients, 30 patients (65%) underwent surgical tumor resection in an en bloc fashion, of which 2 underwent sleeve resection, 13 LTBR, 6 Ex-LTBR, and 9 STBR as a curative treatment. Postoperative radiotherapy was administered to four patients and chemoradiotherapy to two patients. Sixteen patients (35%) underwent nonsurgical treatment, including chemoradiotherapy, radiotherapy, or particle therapy.

Table 1

Characteristics in all 46 patients

Characteristics

No. of patients (%)

Age (y[a])

67 (34–84)

Sex

 Male

24 (52)

 Female

22 (48)

Side

 Right

23 (50)

 Left

23 (50)

T stage according to modified Pittsburg classification

 1

8 (17)

 2

10 (22)

 3

5 (11)

 4

23 (50)

N classification

 Presence

8 (17)

 Absence

38 (83)

Type of treatment

 Surgery

30 (65)

 Sleeve resection

2 (4)

 Lateral temporal bone resection

13 (28)

 Extended lateral temporal bone resection

6 (13)

 Subtotal temporal bone resection

9 (20)

 Radiotherapy

6 (13)

 Chemoradiotherapy

8 (17)

 Particle therapy

2 (4)

a Median (range).


Out of the 16 patients who did not undergo surgery, 4 patients were those with T1 tumors and 12 patients with T4 tumors. The median age of the four patients with T1 tumors was 83 years (range: 79–84 years). They received radiotherapy as an alternative therapy. [Supplemental Table S1] (available in the online version) shows the tumor invasion features in patients with T4 tumors who received surgery (n = 11) and those who did not (n = 12). There was a trend of tumor invasion in the anterior portion of the EAC, such as the TMJ, in patients who underwent surgery for T4 tumors. In patients with T4 tumors, who did not undergo surgery, seven patients (58%) showed tumor invasion in the jugular foramen, five patients (42%) in the sigmoid sinus, and nine patients (75%) in the dura.


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Survival Outcome

In all 46 patients, the 5-year OS and DSS rates were 69.5 and 77.6%, respectively ([Fig. 2]). The 5-year OS rates of patients with T1, T2, T3, and T4 tumors were 83.3, 64.3, 100, and 61.7%, respectively, and the 5-year DSS rates of patients with T1, T2, T3, and T4 tumors were 100, 85.7, 100, and 61.7%, respectively.

Zoom Image
Fig. 2 Kaplan–Meier survival curves based on the modified Pittsburgh classification for overall survival and disease-specific survival in all 46 patients with squamous cell carcinoma of the external auditory canal (DSS, disease-specific survival; OS, overall survival).

Analysis of the 30 surgical patients showed 5-year OS and DSS rates of 85.3 and 92.4%, respectively. Among the 30 surgical patients, the 5-year OS rates of patients with T1, T2, T3, and T4 tumors were 100, 64.3, 100, and 90.0%, respectively; while the 5-year DSS rates of patients with T1, T2, T3, and T4 tumors were 100, 85.7, 100, and 90.0%, respectively ([Supplemental Fig. S1], available in the online version). Out of the 30 patients, 26 showed negative tumor margins, while 4 showed close margins or positive margins. No prognostic impacts of margin status (negative margin vs. positive or close margins) were noticed between the 5-year OS and DSS rates (p = 0.23 and 0.13).


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Operative Results in Surgical Patients

Among the 30 surgical patients, the median operation time for sleeve resection, LTBR, Ex-LTBR, and STBR were 185, 291, 720, and 881 minutes, respectively. The median amount of intraoperative blood loss during sleeve resection, LTBR, Ex-LTBR, and STBR were 38, 60, 822, and 1920 mL, respectively. The mortality rate in the 30 patients was 0%. Nine patients who received Ex-LTBR and STBR developed surgical complications after craniofacial resection, comprising a minor CSF leak in 2 patients (6.7%), a major CSF leak in 2 (6.7%), a minor wound in 5 (16.7%), and a major wound in 1 (3.3%). No other CNS complications, such as brain contusion, cerebral infarction, cerebral hemorrhage, and/or brain abscess, were observed ([Table 2]).

Table 2

Mortality and complications in 30 surgical patients

Type of complications

No. of patients (%)

Mortality rate

0 (0)

Complications

9 (30)

Central nervous system

 Cerebral infraction

0 (0)

 CSF leakage major

2 (7)

 CSF leakage minor

2 (7)

 Meningitis

0 (0)

 Cerebral hemorrhage

0 (0)

Wound

 Major

1 (3)

 Minor

5 (17)

 Flap necrosis

0 (0)

Systemic

 Pneumonia

0 (0)

 Sepsis

2 (7)

Abbreviation: CSF, cerebrospinal fluid.



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Tumor Recurrence in Surgical Patients

Among the 30 surgical patients, 9 patients experienced tumor recurrence ([Table 3]). Four patients experienced local recurrence after surgery, of which two died of the disease. In the three patients with early-stage tumor, two patients had local recurrences at the petrous apex and received chemoradiotherapy. One patient achieved a complete response after salvage radiotherapy, while the other died of the disease. One patient had parotid gland lymph node metastasis, but was rescued by surgical resection. Among the six patients with advanced-stage tumors, two had local recurrences, one had a posterior lymph node metastasis, and three had a distant metastasis in the lung. All patients received adjuvant chemotherapy. Representative CT images of the patients preoperatively, postoperatively, and at the time of recurrence are shown in [Fig. 3].

Table 3

Characteristics for patients with a recurrent tumor after surgery

Case

Age (y)

Sex

T stage

Progress

Surgery

Margin status

Follow-up (mo)

Recurrent area

Outcome

1

65

M

2

Partial bone erosion

LTBR

Negative

16

Local

DOD

2

63

M

2

Partial bone erosion

LTBR

Negative

87

Local

NED

3

66

M

3

Eroding the osseous EAC

LTBR

Close

38

Local

AWD

4

73

M

1

Limited to the EAC

LTBR

Negative

73

Regional

NED

5

57

F

4

Eroding the medial wall of middle ear

STBR

Close

72

Distant

AWD

6

60

F

4

Involvement of TMJ and dura

Ex-LTBR

Negative

27

Distant

AWD

7

54

M

4

Involvement of dura

STBR

Positive

12

Local

DOD

8

72

F

4

Extensive (>0.5 cm) soft-tissue involvement

Ex-LTBR

Negative

37

Distant

NED

9

49

F

4

Involvement of styloid process

STBR

Positive

29

Regional

AWD

Abbreviations: AWD, alive with disease; DOD, dead of disease; EAC, external auditory canal; Ex-LTBR, extended lateral temporal bone resection; F, female; LTBR, lateral temporal bone resection; M, male; NED, no evidence of disease; STBR, subtotal temporal bone resection; TMJ, temporomandibular joint.


Zoom Image
Fig. 3 Representative computed tomography images of the three surgical patients: preoperative, postoperative, and at the time of recurrence.

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Surgical Indications and T4 subclassification for Locally Advanced Stage

To clarify the surgical indications for patients with locally advanced-stage tumor, an analysis was performed later. Considering the difficulty in achieving an en bloc resection and subsequent severe central complications arising in the far-advanced-stage tumors, we divided the T4 stage of tumor into T4a (resectable; tumor eroding the cochlea, medial wall of the middle ear, with extensive [> 0.5 cm] soft-tissue involvement, or evidence of facial paresis) and T4b (unresectable; tumor eroding the petrous apex, carotid canal, jugular foramen, or dura) subtypes, based on the diagnostic radiological report. According to the surgical procedures performed with or without craniotomy, EAC cancer can be classified as follows: early-stage (T1//T2), advanced-stage (T3/T4a), and far-advanced-stage (T4b) tumors.

The survival outcomes with OS in 46 patients with early-stage (T1/T2), advanced-stage (T3/T4a), and far-advanced-stage (T4b) tumors are shown in [Fig. 4]. According to our T4 subclassification, 23 patients with T4 tumor were divided into T4a (10 patients) and T4b (13 patients). Patients with a far-advanced-stage (T4b) tumor were significantly associated with shorter OS than those with early-stage (T1/T2) and advanced-stage (T3/T4a) tumors (3-year OS: 50.3 vs. 84.6 and 84.6%, p = 0.02 and 0.03, respectively), and shorter DSS (3-year DSS: 50.3 vs. 92.3 and 84.6%, p = 0.007 and 0.03, respectively).

Zoom Image
Fig. 4 Kaplan–Meier survival curves based on the T4 subclassification of early-stage (T1/T2), advanced-stage (T3/T4a), and far advanced-stage (T4b) tumors for overall survival and disease-specific survival in all 46 patients with squamous cell carcinoma of the external auditory canal (DSS, disease-specific survival; OS, overall survival).

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Discussion

Surgical tumor resection with free margins is considered the most favorable treatment in patients with SCC of the EAC,[2] [8] [13] [19] which poses the following clinical question: is the tumor in the locally advanced stage resectable or not? The cancer staging system is considered representative of tumor prognosis in most of the solid tumors. Currently, several tumor-staging classifications have been proposed for EAC cancer, including the original Pittsburgh classification,[15] the modified Pittsburgh classification,[2] the staging system proposed by Stell and McCormick,[20] or the American Joint Committee on Cancer (AJCC) staging system (8th edition).[21] Generally, the TNM classification using the AJCC 8th edition is used for head and neck cancer, in which EAC cancer is categorized in the section of ear skin cancer. However, due to the rarity of EAC cancer and the anatomical differences from other skin cancers, T-classification using the AJCC 8th edition does not reflect the clinical survival outcome. In this study, we developed a modified Pittsburgh classification to clarify surgical indications in patients with SCC of the EAC, in which the patients with T4 tumors were divided into two groups as follows: T4a (resectable) and T4b (unresectable) tumors. Using our T4 subclassification, SCC of the EAC could be classified as early-stage (T1/T2), advanced-stage (T3/T4a), and far-advanced-stage (T4b) tumors. Better survival outcomes were obtained in patients with early-stage (T1/T2) and advanced-stage (T3/T4a) tumors, with a 3-year OS of 84.6 and 84.6%, respectively, compared with 50.3% with far-advanced-stage (T4b) tumors. Our surgical strategy for patients with SCC of the EAC is shown in [Fig. 5]. We initially considered the tumor invading the dura as “resectable” and removed the tumor with dural invasion in an en bloc fashion. However, the clinical outcomes in patients with dural invasion were generally poor, and the survival results were not satisfactory. Several authors have discussed the prognostic impact of dural invasion in patients with SCC of the EAC. A recent study of patients with T4 tumors in the temporal bone demonstrated that the invasion of the dura in the posterior fossa could be considered an independent prognostic factor in multivariate analysis.[22] Although we technically excised the tumor with dural invasion, we consider the tumor with dural invasion as “unresectable.” At present, the tumors with dural invasion are thought to be T4b tumors in our hospital.

Zoom Image
Fig. 5 Surgical strategy for squamous cell carcinoma of the external auditory canal based on the T4 subclassification, in which T4 disease is divided into resectable cases (T4a) and unresectable cases (T4b). (EAC, external auditory canal; Ex-LTBR, extended lateral temporal bone resection; LTBR, lateral temporal bone resection; STBR, subtotal temporal bone resection.)

In patients with far-advanced-stage (T4b) tumors, other treatment modalities such as radiotherapy or proton/heavy-ion therapy are recommended, instead of surgical resection. Concomitant chemoradiotherapy with a combination of cisplatin, 5-fluorouracil, and docetaxel can be considered an effective alternative for surgical treatment and achieved a 5-year OS rate of 56% in 34 patients with unresectable T4 tumors,[23] which might be classified as T4b tumors in our T4 subclassification. Considering the difficulty in achieving an en bloc resection, highly invasive surgery, and severe perioperative complications due to the sacrifice of the carotid artery, sigmoid sinus, or brain, we do not recommend extensive curative surgery in patients with far-advanced-stage (T4b) tumor, which invades the petrous apex, carotid canal, jugular foramen, or dura.

To achieve a safe surgical margin in EAC cancer, an appropriate surgical strategy based on preoperative imaging should be determined by a multidisciplinary skull base surgery team, including head and neck surgeons, neurosurgeons, and plastic and reconstructive surgeons. The key to select an appropriate surgical procedure is dependent on whether the intracranial approach is needed or not. We demonstrated four types of surgical procedures for EAC cancer, as shown in [Fig. 1]. Sleeve resection is a surgical technique that allows removal of the tumor with the surrounding tissue, and this technique is only performed for T1 tumors without bone invasion. LTBR is commonly used for T1 and T2 tumors, in which the cancer is resected with the surrounding external bone. Using LTBR, most T1 and T2 tumors were resected with acceptable survival results.[3] [24] These procedures do not require the intracranial approach and are considered relatively safe.[24] Alternatively, a more aggressive surgical approach is needed for locally advanced cases, such as T3 or T4a tumors. Ex-LTBR was performed for locally advanced tumors with involvement of the mastoid bone or temporomandibular joint, in which the tumor was resected in an en bloc fashion by using both intra- and extracranial approaches. Despite the relatively longer operative time and intraoperative blood loss during surgery, Ex-LTBR allows removal of the tumor with the surrounding tissue, including the temporomandibular joint and the mastoid bone, to achieve tumor-free margins. Due to the complexity of the temporal bone, an en bloc resection with tumor-free margins is not easy for locally advanced-stage tumors such as T4 tumors. STBR is feasible and useful as a curative surgical method, especially for T4a tumors. Matoba et al also reported the effectiveness and safety of STBR, although STBR is a difficult surgical procedure and may lead to severe perioperative complications such as hemorrhages or meningitis.[12] Total temporal bone resection was previously performed, but has not been currently performed for locally advanced cases because of the risk of severe complications and the difficulty in performing an en bloc resection.[5] [25] Considering the surgical impact of craniofacial resection in both the physical and psychological aspects of the patients with advanced-stage tumors, surgeons should carefully determine the surgical indication according to the patient's condition, age, and comorbidity in clinical settings.

Surgical margin status is thought to be an important prognostic factor in SCC of the EAC.[19] [25] Although in this study, no prognostic impact for margin status was found between the 5-year OS and DSS (p = 0.23 and 0.13), 4 (13%) of the 30 surgical patients showed close or positive margins on pathological assessment of resected tumor specimens. To achieve complete en bloc resection of the tumor, accurate preoperative evaluation of tumor invasion based on CT and MRI and careful discussion among a multidisciplinary skull base surgery team are essential. A recent surgical virtual simulation using patient's original CT images is very helpful for bone resection and tissue reconstruction in extended craniofacial resection in the head and neck cancer,[17] [26] enabling surgeons to understand the complicated skull base anatomy and to teach the surgical technique to young surgeons.

In our study, 20% of patients received adjuvant radiation or chemoradiation. Previous studies have shown that aggressive primary surgical treatment with postoperative radiotherapy offers the greatest chance of cure for SCC of the temporal bone.[27] However, Lobo et al showed that no difference in survival outcome was found between the group treated with surgery plus adjuvant radiotherapy and the group treated only with surgery in stages III and IV.[28] Currently, it remains controversial whether postoperative radiotherapy is recommended for SCC of the EAC.[29] Most importantly, it is essential to determine whether complete tumor resection with free tumor margins is achieved on the resected tumor specimen after surgery. Therefore, pathologists and head and neck surgeons should closely discuss the patient's history and tumor invasion pattern and point out the location closest to the tumor after surgery. Postoperative radiotherapy should be considered an adjuvant therapy when a safe tumor margin is not obtained.

Extended surgical resection is highly invasive for patients because of the high amount of blood loss and the long operation time, which often results in prolonged complications including hearing loss, facial paralysis, and cosmetic deformities. The indirect negative effect of psychiatric disorders, such as depression, on the outcome of head and neck cancer treatment is also well known.[30] In particular, for malignant skull base tumors, early psychiatric intervention is essential to improve the health-related quality of life at preoperative and follow-up periods.[31] A multidisciplinary approach with a skull base surgery team and a liaison consultation team is essential for locally advanced EAC cancer patients. Early psychiatric interventions can be life-saving during the pre- and postoperative periods.

The main limitation of this study was that a relatively small number of EAC cancer patients were selected from a single center based on the retrospective results. Therefore, the results need to be confirmed in a larger sample size, selected from multiple centers.


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Conclusion

The present study focused on patients with SCC of the EAC at a university hospital over a period of 20 years, especially with skull base involvement, and a T4 subclassification was proposed. Complete tumor resection in an en bloc fashion could help achieve a good survival rate even in patients with locally advanced tumors.


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Conflict of Interest

None declared.

Acknowledgments

The authors would like to thank Editage ( www.editage.com ) for the English language review.

Author Contributions

S.G. and N.N. designed the study, analyzed the results, and drafted the manuscript. Data collection was performed by all the authors. M.S. and Y.F. supervised the study and assisted in preparation of the manuscript. All authors reviewed and approved the final version of the manuscript.


Supplementary Material

  • References

  • 1 Barrs DM. Temporal bone carcinoma. Otolaryngol Clin North Am 2001; 34 (06) 1197-1218 , x
  • 2 Moody SA, Hirsch BE, Myers EN. Squamous cell carcinoma of the external auditory canal: an evaluation of a staging system. Am J Otol 2000; 21 (04) 582-588
  • 3 Shinomiya H, Uehara N, Teshima M, Kakigi A, Otsuki N, Nibu KI. Clinical management for T1 and T2 external auditory canal cancer. Auris Nasus Larynx 2019; 46 (05) 785-789
  • 4 Allanson BM, Low TH, Clark JR, Gupta R. Squamous cell carcinoma of the external auditory canal and temporal bone: an update. Head Neck Pathol 2018; 12 (03) 407-418
  • 5 Lovin BD, Gidley PW. Squamous cell carcinoma of the temporal bone: a current review. Laryngoscope Investig Otolaryngol 2019; 4 (06) 684-692
  • 6 Lechner M, Sutton L, Murkin C. et al. Squamous cell cancer of the temporal bone: a review of the literature. Eur Arch Otorhinolaryngol 2021; 278 (07) 2225-2228
  • 7 Takenaka Y, Cho H, Nakahara S, Yamamoto Y, Yasui T, Inohara H. Chemoradiation therapy for squamous cell carcinoma of the external auditory canal: a meta-analysis. Head Neck 2015; 37 (07) 1073-1080
  • 8 Yin M, Ishikawa K, Honda K. et al. Analysis of 95 cases of squamous cell carcinoma of the external and middle ear. Auris Nasus Larynx 2006; 33 (03) 251-257
  • 9 Morita S, Mizumachi T, Nakamaru Y. et al. Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer. Int J Clin Oncol 2018; 23 (06) 1029-1037
  • 10 Pfreundner L, Schwager K, Willner J. et al. Carcinoma of the external auditory canal and middle ear. Int J Radiat Oncol Biol Phys 1999; 44 (04) 777-788
  • 11 Nishio N, Fujimoto Y, Fujii M. et al. Craniofacial resection for T4 maxillary sinus carcinoma: managing cases with involvement of the skull base. Otolaryngol Head Neck Surg 2015; 153 (02) 231-238
  • 12 Matoba T, Hanai N, Suzuki H. et al. Treatment and outcomes of carcinoma of the external and middle ear: the validity of en bloc resection for advanced tumor. Neurol Med Chir (Tokyo) 2018; 58 (01) 32-38
  • 13 Komune N, Noda T, Kogo R. et al. Primary advanced squamous cell carcinoma of the temporal bone: a single-center clinical study. Laryngoscope 2021; 131 (02) E583-E589
  • 14 Nabuurs CH, Kievit W, Labbé N. et al. Evaluation of the modified Pittsburgh classification for predicting the disease-free survival outcome of squamous cell carcinoma of the external auditory canal. Head Neck 2020; 42 (12) 3609-3622
  • 15 Arriaga M, Curtin H, Takahashi H, Hirsch BE, Kamerer DB. Staging proposal for external auditory meatus carcinoma based on preoperative clinical examination and computed tomography findings. Ann Otol Rhinol Laryngol 1990; 99 (9, Pt 1): 714-721
  • 16 Ito E, Fujii M, Hayashi Y. et al. Magnetically guided 3-dimensional virtual neuronavigation for neuroendoscopic surgery: technique and clinical experience. Neurosurgery 2010;66(6, Suppl Operative):342–353, discussion 353
  • 17 Nishio N, Fujii M, Hayashi Y. et al. Preoperative surgical simulation and validation of the line of resection in anterolateral craniofacial resection of advanced sinonasal sinus carcinoma. Head Neck 2017; 39 (03) 512-519
  • 18 Oken MM, Creech RH, Tormey DC. et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5 (06) 649-655
  • 19 Omura G, Ando M, Saito Y. et al. Survival impact of local extension sites in surgically treated patients with temporal bone squamous cell carcinoma. Int J Clin Oncol 2017; 22 (03) 431-437
  • 20 Stell PM, McCormick MS. Carcinoma of the external auditory meatus and middle ear. Prognostic factors and a suggested staging system. J Laryngol Otol 1985; 99 (09) 847-850
  • 21 Amin MB, Edge SB, Greene FL. et al. AJCC Cancer Staging Manual. 8th ed.. New York, NY: Springer; 2017
  • 22 Komune N, Miyazaki M, Sato K. et al. Prognostic impact of tumor extension in patients with advanced temporal bone squamous cell carcinoma. Front Oncol 2020; 10 (08) 1229
  • 23 Shinomiya H, Hasegawa S, Yamashita D. et al. Concomitant chemoradiotherapy for advanced squamous cell carcinoma of the temporal bone. Head Neck 2016; 38 (Suppl. 01) E949-E953
  • 24 Moore MG, Deschler DG, McKenna MJ, Varvares MA, Lin DT. Management outcomes following lateral temporal bone resection for ear and temporal bone malignancies. Otolaryngol Head Neck Surg 2007; 137 (06) 893-898
  • 25 Bacciu A, Clemente IA, Piccirillo E, Ferrari S, Sanna M. Guidelines for treating temporal bone carcinoma based on long-term outcomes. Otol Neurotol 2013; 34 (05) 898-907
  • 26 Yokoi S, Nishio N, Fujimoto Y. et al. Feasibility of virtual surgical simulation in the head and neck region for soft tissue reconstruction using free flap: a comparison of preoperative and postoperative volume measurement. Int J Oral Maxillofac Surg 2021; 50 (03) 316-322
  • 27 Moffat DA, Wagstaff SA, Hardy DG. The outcome of radical surgery and postoperative radiotherapy for squamous carcinoma of the temporal bone. Laryngoscope 2005; 115 (02) 341-347
  • 28 Lobo D, Llorente JL, Suárez C. Squamous cell carcinoma of the external auditory canal. Skull Base 2008; 18 (03) 167-172
  • 29 Nam GS, Moon IS, Kim JH, Kim SH, Choi JY, Son EJ. Prognostic factors affecting surgical outcomes in squamous cell carcinoma of external auditory canal. Clin Exp Otorhinolaryngol 2018; 11 (04) 259-266
  • 30 Adachi Y, Kimura H, Sato N. et al. Preoperative level of depression is a predictor of postoperative levels of depression in patients with head and neck cancer. Jpn J Clin Oncol 2014; 44 (04) 311-317
  • 31 Mukoyama N, Nishio N, Kimura H. et al. Prospective evaluation of health-related quality of life in patients undergoing anterolateral craniofacial resection with orbital exenteration. J Neurol Surg B Skull Base 2020; 81 (05) 585-593

Address for correspondence

Naoki Nishio, MD, PhD
Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine
65, Tsurumai-cho, Showa-ku, Nagoya 466-8550
Japan   

Publication History

Received: 27 August 2021

Accepted: 04 January 2022

Accepted Manuscript online:
07 January 2022

Article published online:
04 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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Rüdigerstraße 14, 70469 Stuttgart, Germany

  • References

  • 1 Barrs DM. Temporal bone carcinoma. Otolaryngol Clin North Am 2001; 34 (06) 1197-1218 , x
  • 2 Moody SA, Hirsch BE, Myers EN. Squamous cell carcinoma of the external auditory canal: an evaluation of a staging system. Am J Otol 2000; 21 (04) 582-588
  • 3 Shinomiya H, Uehara N, Teshima M, Kakigi A, Otsuki N, Nibu KI. Clinical management for T1 and T2 external auditory canal cancer. Auris Nasus Larynx 2019; 46 (05) 785-789
  • 4 Allanson BM, Low TH, Clark JR, Gupta R. Squamous cell carcinoma of the external auditory canal and temporal bone: an update. Head Neck Pathol 2018; 12 (03) 407-418
  • 5 Lovin BD, Gidley PW. Squamous cell carcinoma of the temporal bone: a current review. Laryngoscope Investig Otolaryngol 2019; 4 (06) 684-692
  • 6 Lechner M, Sutton L, Murkin C. et al. Squamous cell cancer of the temporal bone: a review of the literature. Eur Arch Otorhinolaryngol 2021; 278 (07) 2225-2228
  • 7 Takenaka Y, Cho H, Nakahara S, Yamamoto Y, Yasui T, Inohara H. Chemoradiation therapy for squamous cell carcinoma of the external auditory canal: a meta-analysis. Head Neck 2015; 37 (07) 1073-1080
  • 8 Yin M, Ishikawa K, Honda K. et al. Analysis of 95 cases of squamous cell carcinoma of the external and middle ear. Auris Nasus Larynx 2006; 33 (03) 251-257
  • 9 Morita S, Mizumachi T, Nakamaru Y. et al. Comparison of the University of Pittsburgh staging system and the eighth edition of the American Joint Committee on Cancer TNM classification for the prognostic evaluation of external auditory canal cancer. Int J Clin Oncol 2018; 23 (06) 1029-1037
  • 10 Pfreundner L, Schwager K, Willner J. et al. Carcinoma of the external auditory canal and middle ear. Int J Radiat Oncol Biol Phys 1999; 44 (04) 777-788
  • 11 Nishio N, Fujimoto Y, Fujii M. et al. Craniofacial resection for T4 maxillary sinus carcinoma: managing cases with involvement of the skull base. Otolaryngol Head Neck Surg 2015; 153 (02) 231-238
  • 12 Matoba T, Hanai N, Suzuki H. et al. Treatment and outcomes of carcinoma of the external and middle ear: the validity of en bloc resection for advanced tumor. Neurol Med Chir (Tokyo) 2018; 58 (01) 32-38
  • 13 Komune N, Noda T, Kogo R. et al. Primary advanced squamous cell carcinoma of the temporal bone: a single-center clinical study. Laryngoscope 2021; 131 (02) E583-E589
  • 14 Nabuurs CH, Kievit W, Labbé N. et al. Evaluation of the modified Pittsburgh classification for predicting the disease-free survival outcome of squamous cell carcinoma of the external auditory canal. Head Neck 2020; 42 (12) 3609-3622
  • 15 Arriaga M, Curtin H, Takahashi H, Hirsch BE, Kamerer DB. Staging proposal for external auditory meatus carcinoma based on preoperative clinical examination and computed tomography findings. Ann Otol Rhinol Laryngol 1990; 99 (9, Pt 1): 714-721
  • 16 Ito E, Fujii M, Hayashi Y. et al. Magnetically guided 3-dimensional virtual neuronavigation for neuroendoscopic surgery: technique and clinical experience. Neurosurgery 2010;66(6, Suppl Operative):342–353, discussion 353
  • 17 Nishio N, Fujii M, Hayashi Y. et al. Preoperative surgical simulation and validation of the line of resection in anterolateral craniofacial resection of advanced sinonasal sinus carcinoma. Head Neck 2017; 39 (03) 512-519
  • 18 Oken MM, Creech RH, Tormey DC. et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982; 5 (06) 649-655
  • 19 Omura G, Ando M, Saito Y. et al. Survival impact of local extension sites in surgically treated patients with temporal bone squamous cell carcinoma. Int J Clin Oncol 2017; 22 (03) 431-437
  • 20 Stell PM, McCormick MS. Carcinoma of the external auditory meatus and middle ear. Prognostic factors and a suggested staging system. J Laryngol Otol 1985; 99 (09) 847-850
  • 21 Amin MB, Edge SB, Greene FL. et al. AJCC Cancer Staging Manual. 8th ed.. New York, NY: Springer; 2017
  • 22 Komune N, Miyazaki M, Sato K. et al. Prognostic impact of tumor extension in patients with advanced temporal bone squamous cell carcinoma. Front Oncol 2020; 10 (08) 1229
  • 23 Shinomiya H, Hasegawa S, Yamashita D. et al. Concomitant chemoradiotherapy for advanced squamous cell carcinoma of the temporal bone. Head Neck 2016; 38 (Suppl. 01) E949-E953
  • 24 Moore MG, Deschler DG, McKenna MJ, Varvares MA, Lin DT. Management outcomes following lateral temporal bone resection for ear and temporal bone malignancies. Otolaryngol Head Neck Surg 2007; 137 (06) 893-898
  • 25 Bacciu A, Clemente IA, Piccirillo E, Ferrari S, Sanna M. Guidelines for treating temporal bone carcinoma based on long-term outcomes. Otol Neurotol 2013; 34 (05) 898-907
  • 26 Yokoi S, Nishio N, Fujimoto Y. et al. Feasibility of virtual surgical simulation in the head and neck region for soft tissue reconstruction using free flap: a comparison of preoperative and postoperative volume measurement. Int J Oral Maxillofac Surg 2021; 50 (03) 316-322
  • 27 Moffat DA, Wagstaff SA, Hardy DG. The outcome of radical surgery and postoperative radiotherapy for squamous carcinoma of the temporal bone. Laryngoscope 2005; 115 (02) 341-347
  • 28 Lobo D, Llorente JL, Suárez C. Squamous cell carcinoma of the external auditory canal. Skull Base 2008; 18 (03) 167-172
  • 29 Nam GS, Moon IS, Kim JH, Kim SH, Choi JY, Son EJ. Prognostic factors affecting surgical outcomes in squamous cell carcinoma of external auditory canal. Clin Exp Otorhinolaryngol 2018; 11 (04) 259-266
  • 30 Adachi Y, Kimura H, Sato N. et al. Preoperative level of depression is a predictor of postoperative levels of depression in patients with head and neck cancer. Jpn J Clin Oncol 2014; 44 (04) 311-317
  • 31 Mukoyama N, Nishio N, Kimura H. et al. Prospective evaluation of health-related quality of life in patients undergoing anterolateral craniofacial resection with orbital exenteration. J Neurol Surg B Skull Base 2020; 81 (05) 585-593

Zoom Image
Fig. 1 Surgical procedures for squamous cell carcinoma of the external auditory canal. Upper: Representative designs of skin incisions (red line) and craniotomies (black dotted line) of surgical procedures for external auditory canal cancer; sleeve resection, lateral temporal bone resection (LTBR), extended lateral temporal bone resection (Ex-LTBR), and subtotal temporal bone resection (STBR). Lower: Resection line of the intracranial skull base (black dotted line) and surrounding organs, including the temporomandibular joint (TMJ), internal carotid artery (ICA), sigmoid sinus (SS), jugular valve (JV), and semicircular canals (SCs).
Zoom Image
Fig. 2 Kaplan–Meier survival curves based on the modified Pittsburgh classification for overall survival and disease-specific survival in all 46 patients with squamous cell carcinoma of the external auditory canal (DSS, disease-specific survival; OS, overall survival).
Zoom Image
Fig. 3 Representative computed tomography images of the three surgical patients: preoperative, postoperative, and at the time of recurrence.
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Fig. 4 Kaplan–Meier survival curves based on the T4 subclassification of early-stage (T1/T2), advanced-stage (T3/T4a), and far advanced-stage (T4b) tumors for overall survival and disease-specific survival in all 46 patients with squamous cell carcinoma of the external auditory canal (DSS, disease-specific survival; OS, overall survival).
Zoom Image
Fig. 5 Surgical strategy for squamous cell carcinoma of the external auditory canal based on the T4 subclassification, in which T4 disease is divided into resectable cases (T4a) and unresectable cases (T4b). (EAC, external auditory canal; Ex-LTBR, extended lateral temporal bone resection; LTBR, lateral temporal bone resection; STBR, subtotal temporal bone resection.)