10.14639/0392-100X-N1074
Objective. Evaluation of the management and survival in patients treated for temporal bone squamous cell carcinoma (TBSCC) in a tertiary referral centre.Methods. Forty-nine patients underwent primary treatment for TBSCC. Thirty-six patients underwent a lateral temporal bone resection (LTBR) or subtotal temporal bone resection (STBR). Overall survival (OS) and disease-specific survival (DSS) analysis were assessed. Results. Five-year OS of the 49 patients was 39%. Five-year OS of the 36 patients who un- derwent LTBR or STBR was 46%. Tumour-free margins were achieved in all patients with T1 and T2 disease, in 59% patients with T3 tumours and 0% patients with T4 disease. Five- year DSS was 85% for all T1/T2 tumours, 53% for T3 tumours and 0% for T4 tumours. Clear resection margins was the only significant predictor of DSS in our cohort.Conclusions. The mainstay of treatment for TBSCC is temporal bone resection with tu- mour free resection margins, with or without adjuvant radiotherapy. Survival is negatively influenced by non-radical resection. T1 and T2 tumours can be managed safely with LTBR. More advanced disease requires a more extensive resection, with a higher likelihood of non-radical resections and decreased survival rates.
text/xml
1827-675X
1074
en
C. René Leemans
http://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
subtotal temporal bone resection
Surgical treatment for squamous cell carcinoma of the temporal bone: predictors of survival
Text.Serial.Journal
https://www.actaitalica.it/
41
Head and neck
2021-09-14
2020-08-21
2021-09-15
2021-09-15
308-316
1
C. René Leemans
2021/09/14
10.14639/0392-100X-N1074
308
Department of Otolaryngology & Head and Neck Surgery, Amsterdam University Medical Centre, location VU University Medical Centre, Amsterdam, The Netherlands
1827-675X
subtotal temporal bone resection
316
Surgical treatment for squamous cell carcinoma of the temporal bone: predictors of survival
https://www.actaitalica.it/article/download/1074/649
41
ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41:308-316; doi: 10.14639/0392-100X-N1074




Head and neck


Surgical treatment for squamous cell carcinoma
of the temporal bone: predictors of survival
Il trattamento chirurgico del carcinoma a cellule squamose dell’osso temporale:
fattori predittivi di sopravvivenza
Conrad F. Smit1, Niels de Boer1, Birgit I. Lissenberg-Witte2, Paul Merkus1, Erik F. Hensen1,3, C. René Leemans1
1
  Department of Otolaryngology & Head and Neck Surgery, Amsterdam University Medical Centre, location VU University Medical
Centre, Amsterdam, The Netherlands; 2 Department of Epidemiology and Biostatistics, Amsterdam University Medical Centre,
location VU University Medical Centre, Amsterdam, The Netherlands; 3 Department of Otolaryngology & Head and Neck Surgery,
Leiden University Medical Centre, Leiden, The Netherlands


SUMMARY
Objective. Evaluation of the management and survival in patients treated for temporal bone
squamous cell carcinoma (TBSCC) in a tertiary referral centre.
Methods. Forty-nine patients underwent primary treatment for TBSCC. Thirty-six patients
underwent a lateral temporal bone resection (LTBR) or subtotal temporal bone resection
(STBR). Overall survival (OS) and disease-specific survival (DSS) analysis were assessed.
Results. Five-year OS of the 49 patients was 39%. Five-year OS of the 36 patients who un-
derwent LTBR or STBR was 46%. Tumour-free margins were achieved in all patients with
T1 and T2 disease, in 59% patients with T3 tumours and 0% patients with T4 disease. Five-        Received: August 21, 2020
year DSS was 85% for all T1/T2 tumours, 53% for T3 tumours and 0% for T4 tumours.                Accepted: January 30, 2021
Clear resection margins was the only significant predictor of DSS in our cohort.
Conclusions. The mainstay of treatment for TBSCC is temporal bone resection with tu-             Correspondence
mour free resection margins, with or without adjuvant radiotherapy. Survival is negatively       Conrad F. Smit
influenced by non-radical resection. T1 and T2 tumours can be managed safely with LTBR.          Department of Otolaryngology & Head and Neck
More advanced disease requires a more extensive resection, with a higher likelihood of non-      Surgery, Amsterdam University Medical Centre, lo-
                                                                                                 cation VU University Medical Centre, de Boelelaan
radical resections and decreased survival rates.
                                                                                                 1117, 1081 HV Amsterdam, The Netherlands
KEY WORDS: temporal bone carcinoma, squamous cell carcinoma, survival analysis,                  Tel. +31-(0)20-4444444
lateral temporal bone resection, subtotal temporal bone resection                                E-mail: cf.smit@amsterdamumc.nl

                                                                                                 Funding
RIASSUNTO                                                                                        None.
Obiettivo. Valutazione della gestione e sopravvivenza in pazienti trattati per carcinoma a
cellule squamose dell’osso temporale (TBSCC) in un centro di riferimento terziario.              Conflict of interest
Metodi. Quarantanove pazienti sono stati sottoposti a trattamento primario per TBSCC.            The Authors declare no conflict of interest.
Trentasei pazienti sono stati sottoposti a resezione ossea temporale laterale (LTBR) o re-
sezione ossea temporale subtotale (STBR). Sono state eseguite analisi della sopravvivenza          How to cite this article: Smit CF, de Boer N,
globale (OS) e della sopravvivenza specifica per la malattia (DSS).                                Lissenberg-Witte BI, et al. Surgical treatment
Risultati. l’OS a cinque anni di tutti i 49 pazienti è stata del 39%. L’OS a cinque anni di        for squamous cell carcinoma of the tempo-
tutti i 36 pazienti sottoposti a LTBR o STBR è stata del 46%. Margini liberi da tumore sono        ral bone: predictors of survival. Acta Otorhi-
stati raggiunti in tutti i pazienti con malattia T1 e T2, nel 59% dei pazienti con tumori T3 e     nolaryngol Ital 2021;41:308-316. https://doi.
nello 0% pazienti con malattia T4. Il DSS a cinque anni era dell’85% per tutti i tumori T1 /       org/10.14639/0392-100X-N1074
T2, del 53% per i tumori T3 e dello 0% per i tumori T4. I margini di resezione chiari erano
l’unico predittore significativo di sopravvivenza specifica per malattia nella nostra coorte.    © Società Italiana di Otorinolaringoiatria
                                                                                                 e Chirurgia Cervico-Facciale
Conclusioni. Il cardine del trattamento per TBSCC è la resezione dell’osso temporale con
margini di resezione senza tumore, con o senza radioterapia adiuvante. La sopravvivenza
                                                                                                                OPEN ACCESS
è influenzata negativamente dalla resezione irradicale. I tumori T1 e T2 possono essere
gestiti in sicurezza con LTBR. Una malattia più avanzata richiede una resezione più estesa,      This is an open access article distributed in accordance with
                                                                                                 the CC-BY-NC-ND (Creative Commons Attribution-Non-
con una maggiore probabilità di resezioni irradicali e tassi di sopravvivenza ridotti.           Commercial-NoDerivatives 4.0 International) license. The
                                                                                                 article can be used by giving appropriate credit and mentio-
PAROLE CHIAVE: carcinoma osseo temporale, carcinoma a cellule squamose, analisi
                                                                                                 ning the license, but only for non-commercial purposes and
di sopravvivenza, resezione laterale dell’osso temporale, resezione dell’osso temporale          only in the original version. For further information: https://
subtotale                                                                                        creativecommons.org/licenses/by-nc-nd/4.0/deed.en




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                                                     Surgical treatment for squamous cell carcinoma of the temporal bone: predictors of survival




Introduction                                                       Table I. Characteristics of patients treated for temporal bone squamous cell
                                                                   carcinoma.
Squamous cell carcinoma of the temporal bone (TBSCC) is                                                       Patients (n)    Percentage (%)
rare. The reported annual incidence of squamous cell carci-         Gender
noma (SCC) of the external auditory canal (EAC) and mid-               Male                                      28                57%
dle ear is 1-6:1,000,000 people, which accounts for 0.2%
                                                                       Female                                    21                43%
of all head and neck tumours 1-9. SCC accounts for 60-80%
                                                                    Size of tumour (T)
of all primary malignancies of the temporal bone 1-9. The
                                                                       T1                                        17                34%
presenting symptoms of TBSCC can be similar to those of
                                                                       T2                                        5                 10%
chronic suppurative or external otitis, which often leads to
initial misdiagnosis and diagnostic delay.                             T3                                        19                38%
There is no consensus on the management of malignant tu-               T4                                        9                 18%
mours of the EAC and temporal bone. Lateral (LTBR) or               Primary site
subtotal temporal bone resections (STBR) are commonly                  EAC                                       42                84%
used, depending on the extent of the tumour. Due to lack               Middle ear                                3                 6%
of comparable studies, the role of parotidectomy, neck dis-            Mastoid                                   5                 10%
section, condylectomy and adjuvant radiotherapy remains             Lymph node metastases (N)
unclear 2-11.                                                          N0                                        41                82%
The published survival rates of temporal bone resection                N+                                        9                 18%
(TBR) for tumours limited to the EAC (T1/T2) are good               Distant metastases (M)
(80-100%). The reported survival rates of advanced stage               M0                                        50              100.0%
disease (T3-T4) are generally much worse (0-60%) 2-11.                 M+                                         0               0.0%
Reports on outcomes of primary radiotherapy for T1/T2               Squamous differentiation
tumours are inconsistent, but survival rates after radiother-          I (well)                                  14                28%
apy (43-83%) appear to be inferior to adequate LTBR with
                                                                       II (moderate)                             26                52%
clear surgical margins (80-100%) 2-11.
                                                                       III (poorly)                              8                 16%
The primary purpose of this retrospective study is to evalu-
                                                                       Unknown                                   2                  4%
ate the management and outcomes of patients treated for
TBSCC with curative intent from 1975 to 2018 in our ter-
tiary referral centre. The secondary purpose is to identify
predictors of outcome of TBR by using regression analyses.         Arriaga et al., and later modified by the Pittsburgh group in
                                                                   2000 (PITT2000) (Tab. III) 1,12.
                                                                   Ethical considerations: approval by the institutional Medical
Patients and methods                                               Ethics Committee (OHRP IRB00002991 FWA00017598)
All patients treated with curative intent for primary TBSCC        was obtained.
between 1975 and 2018 were evaluated. We excluded all
non-squamous histologies and tumours arising from the              Surgery
parotid, pinna or peri-auricular skin. Patients who received       T1 and T2 tumours are managed by LTBR, comprising en
surgery or radiotherapy prior to referral were also exclud-        bloc resection of the entire bony EAC, tympanic membrane,
ed. Medical charts were reviewed and the following data            malleus and incus. The facial nerve, stapes and promontory
were collected: gender, age, localization and site of origin,      form the medial limit of the LTBR 3,5,13.
pre-operative facial nerve function, histological differen-        Over the last decades, our surgical strategy for more ad-
tiation grade, treatment modalities, microscopic resection         vanced tumours involving the middle ear and mastoid (T3/
margins, histological demonstration of parotid involve-            T4) consisted of either a LTBR followed by piecemeal re-
ment, metastases, follow-up and outcomes. Patient char-            section of the tumour from the middle ear by local excision
acteristics and treatment-related data are shown in Tables         and (mainly) drilling (extended LTBR), or a subtotal tem-
I and II. All preoperative computed tomography (CT) and            poral bone resection (STBR). STBR has been our approach
from 1985 magnetic resonance imaging (MRI) scans were              for these tumours during the last 15 years and usually in-
also collected and systematically reviewed by three authors        cludes a temporal craniotomy with middle fossa approach
(CFS, NBO, and EFH). Preoperative CT and MRI findings              to achieve en bloc resection of the EAC, mastoid bone,
(if available) were used to stage all tumours according to         middle ear, facial nerve and otic capsule 3,5,13.
the Pittsburgh classification system, originally proposed by       The incisions and soft tissue management depend on the



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C.F. Smit et al.




Table II. Characteristics of patients treated with temporal bone resection.
 Patient Gender Age Site Side               T      Resec- Paroti-         Neck   Post Resection   Parotid  pN                                 Recur-       FU- Outcome
                                          stage      tion    dectomy dissection op. RT margins involvement                                    rence       months
 1             F       68     EAC      L       1        LTBR          -             -            +           -               -          0                    18        DOC
 2             F       45     EAC      R       1        LTBR          -             -            +           -               -          0                    58        DOC
 3             M       57     EAC      L       1        LTBR          -             +            -           -               -          0                    36        NED
 4             M       84     EAC      R       1        LTBR          -             -            +           -               -          0                   169        NED
 5a            F       48     EAC      L       1        LTBR          +             +            +           -               -         0                    172        NED
 5b            F       52     EAC      R       1        LTBR          +             +            +           -               -         0                    123        NED
 6             M       63     EAC      L       1        LTBR          +             -            +           -               -         0                    193        NED
 7             M       62     EAC      R       1       STBR           +             -            -           -               -         0                      5        DOD
 8             F       73     EAC      R       2        LTBR          +             +            +           -               -         1      LR + N         10        DOD
 9             M       78     EAC      L       2        LTBR          +             +            +           -               -         0                     29        DOC
 10            M       81     EAC      R       2        LTBR          +             +            +           -               -         1                     55        NED
 11            M       70     EAC      L       2        LTBR          +             -            +           -               -         0                    167        NED
 12            M       79     EAC      R       2       STBR           +             -            +           -               -         0                    152        NED
 13            F       69     EAC      R       3       eLTBR          +             +            +           +               +         2b     LR + N          6        DOD
 14            F       85     EAC      L       3       eLTBR          +             +            +           +               -         0      LR + N          9        DOD
 15            F       74     EAC      L       3        LTBR          +             +            +           -               -         0                     39        NED
 16            F       56     EAC      R       3        LTBR          +             +            +           -               -         1                     81        NED
 17            F       78     EAC      R       3       eLTBR          +             +            +           -               -         2b                   110        NED
 18            M       82     EAC      R       3       STBR           +             -            -           -               -         0                     3         DOD
 19            F       78     EAC      R       3       STBR           +             +            +           -               +         2b        N          10         DOD
 20            M       44     EAC      R       3       STBR           +             +            +           -               -         0         LR         12         DOD
 21            M       54     EAC      R       3       STBR           +             +            +           +               +         2b        LR         22         DOD
 22            F       37     EAC      L       3       STBR           +             +            +           -               -         0         LR         23         DOD
 23            M       58     MB       L       3       STBR           +             +            +           +               -         0         LR         31         DOD
 24            M       90     EAC      R       3       STBR           +             -            +           -               -         0                     62        DOC
 25            M       68     EAC      R       3       STBR           +             -            +           -               -         0                    175        NED
 26            M       47     EAC      R       3       STBR           +             +            +           +               -         2b                   204        NED
 27            M       79     ME       L       3       STBR           +             -            +           +               -         0                    205        NED
 28            M       52     EAC      R       3       STBR           +             +            +           +               -         0                    219        NED
 29            F       29     EAC      L       3       STBR           +             +            -           -               -         0                    355        NED
 30            F       75     EAC      L       4       eLTBR          +             +            +           +               +         1      LR + N          9        DOD
 31            F       48     EAC      R       4       eLTBR          +             +            +           +               +         0      LR + N         34        DOD
 32            F       71     EAC      L       4       STBR           +             +            +           +               -         0        RD           9         DOD
 33            F       69     ME       R       4       STBR           +             +            +           +               -         0      LR + N        12         DOD
 34            M       78     EAC      L       4       STBR           +             +            +           +               +         0        LR          14         DOD
 35            M       55     MB       R       4       STBR           +             +            +           +               -         0                    32         DOC
 36            F       71     MB       R       4       STBR           +             +            +           +               -         0                    33         NED
F: female; M: male; EAC: external auditory canal; ME: middle ear; MB: mastoid bone; LTBR: lateral temporal bone resection; eLTBR: extended lateral temporal bone resection;
STBR: subtotal temporal bone resection; LR: locoregional; N: nodal disease; RD: residual disease; FU-time: follow-up (months); NED: no evidence of disease; DOD: dead of disease;
DOC: dead other cause.



planned management of the pinna, parotid and neck. Pro-                                    subtotal temporal bone resections. Our policy towards elec-
phylactic superficial parotidectomy is performed in tu-                                    tive neck dissection has changed somewhat over time. It
mours of the anterior wall of the external auditory canal.                                 was not standard in the beginning of the series and changed
Total parotidectomy is performed in tumours growing be-                                    thereafter from more comprehensive to selective dissection.
yond the anterior wall of the external auditory canal and in                               If the pinna is preserved, a circumferential incision in the



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                                                                             Surgical treatment for squamous cell carcinoma of the temporal bone: predictors of survival




Table III. Modified Pittsburgh classification system.
 T status                        Description
 T1                                   Tumour limited to the external auditory canal without bony erosion or evidence of soft tissue involvement
 T2                                   Tumour with limited external auditory canal bony erosion (not full thickness), or limited (< 0.5 cm) soft tissue involvement
 T3                                   Tumour eroding the osseous auditory canal (full thickness) with limited (< 0.5 cm) soft tissue involvement, or tumour involving
                                      the middle ear and/or mastoid
 T4                                   Tumour eroding the cochlea, petrous apex, medial wall of middle ear, carotid canal, jugular foramen or dura, or with extensive
                                      (> 0.5 cm) soft tissue involvement, such as involvement of temporomandibular joint or styloid process, or evidence of facial
                                      paresis
 N status                             Lymph node involvement is a poor prognostic sign; any node involvement should automatically be considered as advanced
                                      stage, i.e. T1N1 = stage III and T2, 3, 4 N1 = stage IV
 M status                             Distant metastases indicate a very poor prognosis and should be considered as stage IV disease
In the absence of metastatic lymph nodes or distant metastases, T status of the tumour defines clinical stage.



lateral EAC skin is performed and the external meatus is                                     (median, stratified in two age categories: ≤ 68 years and
closed as a blind sac to prevent tumour spillage. If the pinna                               ≥ 69 years), gender, T-stage (stratified in three categories:
is affected, it is completely or partially resected in continu-                              T1/T2, T3, T4), histological differentiation grade, neck dis-
ity with the temporal bone and parotidectomy specimen. In                                    section, parotidectomy, condylectomy, post-operative ra-
all cases the surgical defect is closed using a fat graft, vas-                              diotherapy, resection margins and pN-status.
cularised soft tissue transposition or a free vascularised flap
reconstruction. Tumours with carotid artery encasement,                                      Results
intracerebral infiltration and petrous apex involvement are
deemed not suitable for surgery with curative intent. Tu-                                    A total of 49 patients (with 50 tumours) who received cura-
mour-free resection margins cannot safely be achieved in                                     tive treatment for primary TBSCC were identified. Twenty-
these tumours and total temporal bone resection seems to                                     eight patients (57%) were men, and 21 (43%) were women.
be of no benefit 3-5,13,14.                                                                  The site of origin was the EAC for 42 tumours (84%), mid-
                                                                                             dle ear (ME) for 3 tumours (6%) and mastoid for 5 tumours
Statistical analysis                                                                         (10%). Thirteen tumours were classified as T1, 9 tumours
Kaplan-Meier curves for overall survival (OS) and disease-                                   as T2, 19 tumours as T3 and 9 tumours as T4. Two patients
specific survival (DSS) were plotted and hazard ratios (HR)                                  presented with facial paralysis and were thus staged as T4.
with corresponding 95% confidence intervals (CI) were                                        Nine patients presented with positive neck nodes on clini-
obtained with Cox regression models using Stata/SE (ver-                                     cal examination, CT and/or MRI. More than 50% of all
sion 14.1 for Windows; StataCorp LP, College Station, TX,                                    tumours showed a moderate squamous differentiation
USA). P values < 0.05 were considered statistically signifi-                                 (Tab. I).
cant, and p values < 0.1 were considered to indicate a trend.                                Four patients were treated with primary radiotherapy (RT)
All 36 patients who underwent temporal bone resection                                        because of a contraindication for major surgery; i.e. exten-
entered the OS analysis. Patient 5 with bilateral tumours                                    sive comorbidity or an explicit desire for non-surgical treat-
participated in the OS analysis only with the first diagnosed                                ment. Nine patients, treated in the earlier part of the series,
tumour (patient 5a). For DSS, however, both tumours (pa-                                     were treated with a local resection (pinna amputation with
tient 5a and 5b) entered the analysis individually.                                          sleeve resection and/or modified radical mastoidectomy)
Two patients (patient 7 and 18) died from early postop-                                      combined with radiotherapy. Two patients were lost to fol-
erative complications related to the surgery and their gen-                                  low-up after less than 5 years, and were censored after their
eral condition. We expected that these two patients would                                    last known contact date.
strongly affect our analyses and – at the same time – the                                    A total of 37 tumours (36 patients) were treated by TBR
cause of death in these patients was not associated with the                                 (Tab. II). These resections include 18 (extended) lateral
disease-specific risk factors that were evaluated. Therefore,                                temporal bone resections (17 patients) and 19 en-bloc sub-
we performed an additional regression analysis for DSS,                                      total temporal bone resections. One patient (patient 5a)
excluding these two patients.                                                                developed a SCC of the EAC after a disease-free interval
Potential factors that could influence OS or DSS of patients                                 of four years following treatment for a T1 SCC of the con-
who underwent temporal bone resection were individually                                      tralateral EAC (patient 5b). This patient therefore had un-
analysed using the log-rank test. These factors were age                                     dergone bilateral LTBR.



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C.F. Smit et al.




LTBR was performed for seven T1 tumours (88%) and                 disease. All patients with histological evidence of parotid
four T2 tumours (80%). Five T3 tumours (29%) and two              involvement developed locoregional recurrence and died
T4 tumours (29%) were treated with a LTBR followed by             within three years after treatment. No patients in our cohort
exenteration of infra- and supra-labyrinthine air cells and       developed distant metastases.
resection of tumour from the middle ear, mastoid and dura
(extended LTBR). Each LTBR resulted in macroscopically-           Survival analysis
free resection margins.                                           Five-year OS for all 49 patients was 39%. Five-year OS of
Nineteen patients were treated with STBR, these included          the 36 patients treated with temporal bone resection was
one T1 tumour, one T2 tumour, 12 T3 tumours and 5 T4              46%. Five-year OS of 13 patients treated with local resec-
tumours. The patients who underwent STBR for T1/T2                tion (LR) or primary radiotherapy (RT) was 17% (Fig. 1).
disease would nowadays be planned for a LTBR proce-               DSS for the 36 patients (37 tumours) who were treated
dure. In one patient (with T4 disease) we failed to achieve       with temporal bone resection was 59% (Fig. 2). Two pa-
macroscopically-free resection margins with STBR due to           tients with T1/T2 disease died of disease-specific causes.
intracranial and intracerebral infiltration. In 9 patients with   One with T1 disease developed postoperative endocarditis
STBR, positive resection margins were found on histologi-
cal examination.
A form of selective neck dissection (24 cases) or modified
radical neck dissection (2 cases) was performed in 70%
of the procedures. Partial parotidectomy was performed
in 25/37 (68%) cases, total parotidectomy in 8/37 (22%)
cases, and in four cases (11%) no parotidectomy was per-
formed.
Fractionated postoperative radiotherapy (Intensity Modu-
lated RT from 2003 onwards), 50-60 Gy over 6 weeks, di-
rected at the primary tumour and to the neck in case of
positive nodes, was given to 33/37 patients (89%). Two
patients (patient 7 and 18) died shortly after STBR due to
treatment related complications. Two patients (patient 3
and 29) did not receive postoperative radiotherapy for un-
known reasons.
Histopathological examination showed tumour-free (R0)
resection margins in 23/37 temporal bone resection speci-         Figure 1. Overall survival of all 49 patients treated with curative intent,
mens (62%), tumour positive (R1) margins were found in            grouped by their treatment.
14/37 patients (38%), in one of these patients macroscopic
radical resection could not be achieved (R2). A radical re-
section was achieved in all 13 T1 and T2 tumours, in 10 of
17 (59%) T3 tumours and in none of 7 T4 tumours.
Multiple ipsilateral lymph node metastases were found in
nine patients with clinically positive neck disease. Histo-
logical evidence of extra nodal spread was found in the
neck dissection specimens of five patients (patients 10, 14,
16, 32 and 33). No occult lymph node metastases were en-
countered in patients with a cN0 neck. Parotid involvement
was found in six cases; local tumour infiltration in four pa-
rotid specimens and parotid lymph node metastases were
found in 3 patients.
Local or neck recurrence occurred in 12 of 37 (32%) resec-
tions (36 patients). In 8 of 12 (67%) patients locoregional
recurrence was seen after failure to achieve macroscopi-
cally-free resection margins with temporal bone resection.        Figure 2. Disease-specific survival per temporal bone resection and all 37
All 12 patients with recurrent or residual disease died of        cases.



312
                                                                   Surgical treatment for squamous cell carcinoma of the temporal bone: predictors of survival




resulting in sepsis, and the other patient with T2 disease                       mours) confirmed the statistical significance of resection
developed locoregional recurrence (Fig. 3).                                      margins (HR 4.5, 95% CI 1.4-14.9, p = 0.006) and clinical
Univariate survival analyses were performed on the 36                            T-status (HR 6.0, 95% CI 0.74-49.0, and HR 12.6, 95% CI
patients who were treated with LTBR or STBR (Tab. IV).                           1.5-10.9), respectively (p = 0.019) (Tab. IV).
This group consisted of 19 men and 17 women. Median age                          For overall survival, no significant predictors were found,
at presentation was 69 years (range 29 to 90 years). Follow-                     and only a trend for histological differentiation grade
up time ranged from 3 to 355 months (median 34).                                 (p = 0.099).
Disease-specific analysis revealed that patients with clear
resection margins had significantly better outcomes than                         Discussion
those with positive resection margins (HR 2.9, 95% CI
1.04-8.3, p = 0.032) (Fig. 4). None of the other variables                       The primary goal of curative treatment of a temporal bone
tested was statistically significant, although patients with                     malignancy is to eradicate disease by surgical resection with
T1/T2 disease showed a trend towards better outcomes than                        tumour-free resection margins. En bloc LTBR for tumours
T3 or T4 patients (HR 3.4, 95% CI 0.72-16.0, and HR 6.0,                         limited to the EAC (T1 and T2), and en bloc STBR for tu-
95% CI 1.2-31.3, respectively, p = 0.064).                                       mours extending to middle ear or mastoid (T3 and T4) are
Additional disease-specific analysis in 35 patients (36 tu-                      the most suited surgical techniques to obtain clear resection
                                                                                 margins with acceptable morbidity 2-11,13. In extensive T3 and
                                                                                 T4 tumours it is technically difficult to achieve tumour-free
                                                                                 surgical margins and the nature of the resection technique
                                                                                 (with otologic burrs) might sometimes hamper the accuracy
                                                                                 of histopathological evaluation of resection margins. Both
                                                                                 false positive and false negative resection margins may oc-
                                                                                 cur. This provides a rationale for postoperative radiotherapy
                                                                                 in all T3 and T4 tumours 1-9,13-16. The role of adjuvant radio-
                                                                                 therapy for small tumours remains unclear 1-9,15,16.
                                                                                 To create a homologous series we used strict inclusion
                                                                                 criteria for our study, including only primary TBSCC and
                                                                                 tumours arising from the bony ear canal. Therefore, all tu-
                                                                                 mours originating from the external ear (pinna), cartilagi-
                                                                                 nous framework, peri-auricular skin and parotid gland were
                                                                                 excluded. We retrospectively staged all tumours uniformly,
                                                                                 according to the modified University of Pittsburgh grad-
                                                                                 ing system, using clinical data and the available imaging
Figure 3. Disease-specific survival by clinical T stage.
                                                                                 studies. Our study confirms the significant role of clinical T
                                                                                 stage (PITT2000) and clear resection margins on survival
                                                                                 in SCC of the temporal bone (p = 0.006; Tab. IV) 10,17.
                                                                                 Several authors have agreed that sleeve resection and mas-
                                                                                 toidectomy will unintentionally compromise resection
                                                                                 margins for all stages of TBSCC and consequently increase
                                                                                 the risk of developing recurrent disease with a fatal progno-
                                                                                 sis 8,9,18. The present study shows that radical tumour resec-
                                                                                 tion can be achieved with the LTBR technique in 100% of
                                                                                 T1 and T2 tumours, and we have found 85% DSS for T1
                                                                                 and T2 tumours treated with LTBR (Fig. 3). In our study,
                                                                                 7 patients with a T4 tumour were treated with curative in-
                                                                                 tent. We did not achieve radical resection in any and de-
                                                                                 spite postoperative radiotherapy 6 of 7 patients died within
                                                                                 three years, while one had no evidence of disease after 33
                                                                                 months. Other studies have described successful and cura-
                                                                                 tive treatment of T4 tumours with (e)LTBR or STBR and
Figure 4. Disease-specific survival for clear and positive resection margins.    adjuvant radiotherapy 4,18-21. There is much debate about the



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Table IV. Survival analyses of patients treated with temporal bone resection.
 Variable                                  OS (n = 37)                                                DSS (n = 37)                                         DSS (n = 35)
                                     p-value                 HR [95% CI]                  p-value                HR [95% CI]                   p-value              HR [95% CI]
 Age                                   0.43                                                 0.25                                                 0.21
 Sex                                   0.22                                                 0.24                                                 0.07
    Male                                                                                                                                                                 1.0
    Female                                                                                                                                                         2.8 [0.86-9.2]
 cT-status                             0.12                                                 0.06                                                 0.02
    T1/T2                                                                                                             1.0                                                1.0
    T3                                                                                                         3.4 [0.72 - 16.0]                                   6.0 [0.74-49.0]
    T4                                                                                                          6.0 [1.2 - 31.3]                                   12.6 [1.5-109]
 Neck dissection                       0.34                                                 0.14                                                 0.01
 Parotidectomy                         0.67                                                 0.13                                                 0.16
 Condylectomy                          0.58                                                 0.53                                                 0.68
 Post-operative                        0.73                                                 0.39                                                 0.31
 radiotherapy
 Histological                          0.10                                                 0.43                                                 0.41
 differentiation
    Well                                                         1.0
    Moderate                                               2.0 [0.72-5.7]
    Poor                                                   0.37 [0.04-3.2]
 Resection margins                     0.11                                                 0.03                                                 0.01
    Clear                                                                                                             1.0                                                1.0
    Positive                                                                                                    2.9 [1.04-8.3]                                     4.5 [1.4-14.9]
 pN-status                             0.68                                                 0.31                                                 0.17
CI: confidence interval; cT-status: clinical T status; DSS: disease specific survival; HR: hazard ratio; OS: overall survival; pN-status: pathological N status.



indications for parotidectomy and (selective) neck dissec-                                         of the neck and parotid gland. Comprehensive preoperative
tion in early stage temporal bone tumours with a clinically                                        evaluation of the neck may help prevent unnecessary pro-
N0 neck. The parotid gland contains the first echelon lymph                                        phylactic neck dissection and parotidectomy in an N0 neck.
nodes of the EAC, but the incidence of parotid metastases                                          Neither procedure has been shown to increase 5-year sur-
from TBSCC remains unclear 4,10,22-24. In our cohort, both                                         vival when performed as prophylaxis 4-6,17,23,24. In contrast
parotid involvement due to direct infiltration or to lymph                                         with the studies by Morris et al. and Masterson et al., we
node metastasis was found only in advanced stages; T3                                              did not find a significant effect of nodal disease on survival
(n = 3) or T4 (n = 3), and all 6 patients with parotid involve-                                    in our analysis 15,25.
ment died within 3 years after surgery.                                                            In 2005, Moffat et al. advocated temporomandibular joint
We encountered no occult metastases in patients with a                                             excision for all temporal bone resections 16. There are no
cN0 neck, but neck recurrence occurred in 3 patients with a                                        statistical data on the benefits of condylectomy on survival,
negative neck after non-radical resection of the primary tu-                                       although the morbidity of condylectomy as an additional
mour. In a study by Zanoletti and Danesi, occult neck me-                                          step in TBR is significant 16,25,26. We reserve this additional
tastases were found in 7% (3/45) of patients who received                                          procedure for tumours located in the anterior part of the
neck dissection in addition to surgical treatment for SCC of                                       EAC or for tumour invasion in the TMJ capsule.
the temporal bone 22. Mazzoni et al. found a total of 27%                                          Due to its relative rarity, it is difficult to compare treatment
nodal metastases, with a total of 17% occult metastases in                                         strategies and outcomes of TBSCC in the literature. More-
clinically N0 necks 11. The likelihood of encountering oc-                                         over, insights into state-of-the-art diagnosis and extent of
cult neck metastases in a resection specimen also depends                                          surgical therapy have evolved over time.
on the quality of the preoperative evaluation of the neck.                                         A nationwide study by Nabuurs et al. evaluated the modi-
In our institute, all patients with TBSCC undergo CT scan,                                         fied Pittsburgh classification and deemed it acceptable.
MRI and ultrasound guided fine needle aspiration cytology                                          However, for T4 tumours they suggest a revised classifi-



314
                                                     Surgical treatment for squamous cell carcinoma of the temporal bone: predictors of survival




cation with other predictive factors such as surgical mar-         al is negatively influenced by non-radical resection. For T1
gins 27.                                                           and T2 tumours, LTBR is the treatment of choice with good
Zanoletti et al. also suggest a prognosis scoring system for       results. More advanced disease requires a more extensive
T4 tumours, including dural involvement and histological           temporal bone resection, with a higher likelihood of non-
grade as negative prognosticators. In addition, the site of        radical resection and decreased survival. The prognosis of
tumour origin and direction of tumour extension seem to            patients with advanced disease is poor. To improve prog-
play a role, as T3 and T4 tumours growing from the exter-          nosis in these patients more research is needed with larger
nal auditory canal into the mastoid and petrous bone seem          groups of patients, taking into account histological grade,
to have worse prognosis than T3 and T4 tumours originat-           dural involvement, site of tumour origin and direction of
ing from the anterior wall of the canal extending into the         tumour extension. Because of the rarity of the disease, this
parotid space 28 .                                                 can only be achieved with multicentre studies.
In our study, a homogeneous series of patients with pri-
mary squamous cell carcinoma of the temporal bone with             Ethical approval
curative intent was included. Because of the rarity of the
disease, the number of patients is limited even in a tertiary      Ethical approval was waived by the local Ethical Com-
referral centre and with a selection period spanning over          mittee of the VU University Medical Center Amsterdam
four decades. As for radiological staging, MRI scanning            IRB00002991 FWA00017598.
was introduced in 1985 in our centre and the quality of im-
aging techniques has improved over time. As a result, the          References
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