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Radiol Oncol 2021; 55(3): 323-332. doi: 10.2478/raon-2021-0012
323
research article
The importance of flaps in reconstruction 
of locoregionally advanced lateral skull-base 
cancer defects: a tertiary otorhinolaryngology 
referral centre experience
Domen Vozel
1,2
, Peter Pukl
1
, Ales Groselj
1,2
, Aleksandar Anicin
1,2
, Primoz Strojan
2,3
, 
Saba Battelino
1,2
1 
Department of Otorhinolaryngology and Cervicofacial Surgery, University Medical Centre Ljubljana, Ljubljana, Slovenia
2 
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
3 
Institute of Oncology Ljubljana, Ljubljana, Slovenia
Radiol Oncol 2021; 55(3): 323-332.
Received 14 January 2021
Accepted 17 February 2021
Correspondence to: Assoc. Prof. Saba Battelino, M.D., Ph.D., Head of Audiology and Otosurgery, Department of Otorhinolaryngology and 
Cervicofacial Surgery, University Medical Centre Ljubljana, Zaloška 2, SI-1000 Ljubljana, Slovenia; E-mail: saba.battelino@kclj.si
Disclosure: No potential conflicts of interest were disclosed.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Background. The aim of the study was to identify the value of extensive resection and reconstruction with flaps in 
the treatment of locoregionally advanced lateral skull-base cancer.
Patients and methods. The retrospective case review of patients with lateral skull-base cancer treated surgically 
with curative intent between 2011 and 2019 at a tertiary otorhinolaryngology referral centre was made. 
Results. Twelve patients with locoregionally advanced cancer were analysed. Lateral temporal bone resection was 
performed in nine (75.0%), partial parotidectomy in six (50.0%), total parotidectomy in one (8.3%), ipsilateral selective 
neck dissection in eight (66.7%) and ipsilateral modified radical neck dissection in one patient (8.3%). The defect was 
reconstructed with anterolateral thigh free flap, radial forearm free flap or pectoralis major myocutaneous flap in two 
patients (17.0%) each. Mean overall survival was 3.1 years (SD = 2.5) and cancer-free survival rate 100%. At the data 
collection cut-off, 83% of analysed patients and 100% of patients with flap reconstruction were alive. 
Conclusions. Favourable local control in lateral skull-base cancer, which mainly involves temporal bone is achieved 
with an extensive locoregional resection followed by free or regional flap reconstruction. Universal cancer registry 
should be considered in centres treating this rare disease to alleviate analysis and multicentric research.
Key words: temporal bone; microsurgery; parotid region; free tissue flaps; neoplasm staging; ear
Introduction
Lateral skull-base cancer, which principally in-
volves temporal bone is a rare pathology with an 
estimated annual incidence of approximately 0.8–6 
per 1 million inhabitants.
1,2
 It presents about 0.2% 
of all head and neck cancers.
3
 Metastatic lesions of 
the lateral skull-base are less frequent than prima-
ry tumours and most commonly originate from the 
breast, pulmonary and renal primaries. 
Previous radiotherapy of skull-base (e.g., due to 
nasopharyngeal cancer), chronic otitis media, hu-
man papillomavirus infection, and chlorinated dis-
infectants are possible risk factors. However, there 
is a lack of scientific evidence.
2,4
 Lateral skull-base 
cancer can arise de-novo or result from a malignant 
transformation of pre-existing benign tumours, 
such as chondroma to chondrosarcoma.
5
Despite the advancement of surgical and non-
surgical treatment modalities, the prognosis re-

Radiol Oncol 2021; 55(3): 323-332.
Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 324
mains poor since the reported mean overall sur-
vival time does not exceed five years.
6
Classification of lateral skull-base cancer
Lateral skull-base cancer can be classified accord-
ing to the anatomical site into five categories (an 
adaptation of Homer et al.
3
):
– advanced skin cancer of external ear (aEEC); in-
cluding auricle, concha or periauricular skin,
– advanced parotid cancer (aPC),
– infratemporal fossa and temporomandibular 
joint cancer,
– primary external auditory canal cancer (EACC) 
and
– primary middle ear cancer (MEC).
The cancer histological type depends upon 
the abovementioned site.
3
 Regardless the site, the 
squamous cell carcinoma is the most common type 
which accounts for more than 40% of all primary 
lateral skull-base cancers, followed by basal cell 
carcinoma in 10%, adenoid cystic carcinoma in 
8–10% and melanoma is less than 5%.
7
Clinical presentation of lateral skull-base 
cancer
The clinical presentation of lateral skull-base cancer 
is not pathognomonic since it can mimic the chronic 
inflammatory diseases, such as chronic otitis me-
dia, chronic otitis externa, necrotising otitis externa 
or vasculitis (e.g., granulomatosis with polyangii-
tis). For that reason, bloody otorrhoea, hearing loss, 
bleeding, chronic otalgia, facial swelling or palsy 
and mass should be attributed to the lateral skull-
base cancer until proven otherwise. Granulation 
tissue, nonhealing ulcer or erosion should be elu-
cidated by histopathological examination. In case 
of progressive pain in the temporomandibular joint 
area, trismus, facial pain and fullness or subtle mass 
immediately above zygoma, suspicion of infratem-
poral fossa cancer should be raised.
3
Diagnosis of lateral skull-base cancer
Diagnosis of lateral skull-base cancer mainly 
comprises histopathological or cytopathological 
verification, high-resolution computed tomogra-
phy (CT) and magnetic resonance imaging (MRI) 
of skull-base and adjacent structures (i.e. parotid 
region, neck), neck CT or ultrasonography (US) 
and further evaluation of signs of systemic cancer 
spread (e.g., abdominal CT/US, chest CT/x-ray, 
positron emission tomography-CT).
3
The clinical examination and diagnostic proce-
dures enable the assessment of tumour stage ac-
cording to the TNM classification system. Primary 
tumour (T), regional lymph node metastases (N) 
and distant metastases (M) can be assessed accord-
ing to the primary tumour site: e.g. for skin carci-
noma of the head and neck, major salivary glands, 
malignant melanoma of the skin, tumours of bone 
and soft tissue. EACC and MEC deserve particular 
emphasis in T, N and M assessment as the AJCC and 
UICC grading systems do not include these cancer 
types. EACC should be graded with the modified 
Pittsburgh staging system (Table 1)
8,9
, which has the 
highest prognostic accuracy.
10
 This staging system 
should be used in pathological TNM staging also.
11
 
MEC has been graded with many staging systems 
including modified Pittsburgh staging system
18,9
 
and Stell and McCormick grading system.
12
TABLE 1. Modified Pittsburgh staging system
8,9
T assessment
T1
Tumour limited to external auditory canal without 
bony erosion or evidence of soft tissue involvement
T2 
Tumour with limited external auditory canal bone 
erosion (not full thickness) or limited (<0.5 cm) soft-
tissue involvement
T3
Tumour eroding osseous external auditory canal 
(full thickness) with limited (<0.5 cm) soft tissue 
involvement or tumour involving the middle ear 
and/or mastoid
T4
Tumour eroding cochlea, petrous apex, medial wall 
of the middle ear, carotid canal, jugular foramen or 
dura, or with extensive soft tissue involvement (>0.5 
cm) such as involvement of temporomandibular 
joint or styloid process, or evidence of facial paresis
N assessment
N0 No regional lymph node metastasis
N1 Regional lymph node metastasis
M assessment
M0 No distant metastasis
M1 Distant metastasis
Stage group
I T1N0M0
*
II T2N0M0
*
III T3N0M0
‡
, T1N1M0
‡
IV T4N0M0
‡
, T2–4N1M0
‡
, T1–4N0–1M1
†
The TNM assessment is based on the clinical examination and imaging 
findings. This staging system has been applied to assess primary external 
auditory canal cancer and primary middle ear cancer.
1
 Middle ear 
cancer is assessed as at least T3, therefore always locoregionally 
advanced.
T = tumour; N = regional lymph node metastasis; M = distant metastasis; 
*
 = localised cancer; 
‡
 = locoregionally advanced cancer; 
† 
= systemically 
advanced cancer

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Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 325
Treatment of lateral skull-base cancer
After the diagnosis has been established, the pa-
tient should be presented at the multidisciplinary 
tumour board to determine the treatment modali-
ties and goals.
3
 In our tertiary referral centre, the 
board, usually consists of an otorhinolaryngologist 
subspecialised in otologic and lateral skull-base 
surgery, otorhinolaryngologist subspecialised in 
head and neck surgery and free flap reconstruc-
tion, radiation oncologist and medical oncologist.
The best prognosis of lateral skull-base cancer is 
achieved with the radical surgical treatment, which 
depends on the tumour’s extent and presence of 
regional lymph node metastasis.
7
 Therefore, it can 
include for an example wide local excision of the 
tumour, temporal bone resection (lateral, subtotal 
or total), parotidectomy (superficial or total), neck 
dissection (selective, modified radical, radical) and 
temporomandibular joint resection. When the his-
topathological examination of the resected speci-
men implies an increased risk of local/regional tu-
mour re-appearance, adjuvant treatment must be 
considered. Other non-surgical treatment modali-
ties (i.e., radiotherapy, systemic therapy), when in-
dicated, can significantly improve the rate of local 
and/or regional control.
7
 
Since the extensive surgery of locoregionally ad-
vanced lateral skull-base cancer results in large tis-
sue defects, the reconstruction should be planned 
immediately. An assortment of free flaps can be 
considered to aid the reconstruction such as radial 
forearm free flap (RFFF), deep inferior epigastric 
perforator flap, latissimus dorsi free flap and ante-
rolateral thigh free flap (ALT).
3
 ALT is considered 
a workhorse in lateral skull-base reconstruction 
since it provides an adequate tissue bulk to fill the 
tissue defect. Additionally, the donor site (i.e., thigh 
wound) can be used to harvest fascia lata to recon-
struct dural defect or statically suspend the oral 
commissure if the facial nerve has been sacrificed. 
Moreover, ALT can be harvested as chimaeric, i.e. 
incorporating the lateral cutaneous femoral nerve, 
which can be used as interposition nerve graft in 
facial nerve reanimation. It is recommended that 
facial nerve reanimation should be initiated at pri-
mary surgery. However, in certain circumstances 
(i.e., peripheral arterial occlusive disease, head and 
neck scarring after the previous radiotherapy) free 
flaps cannot be used or have failed to reconstruct 
the defect.
3
 For that reason, regional flaps such 
as the pectoralis major myocutaneous flap (PM) 
should be harvested.
3,13,14
  
The treatment of lateral-skull base cancer 
should be reserved for highly specialised centres. 
This manuscript aims to provide an experience of 
a single tertiary otorhinolaryngology referral cen-
tre in the treatment of this pathology, emphasising 
the role of regional and free flaps in reconstruction 
after resection of locoregionally advanced lateral 
skull-base cancer.
Patients and methods
The study protocol was approved by the 
Institutional Committee for Medical Ethics and the 
Protocol Review Board (ERIDNPVO-0012/2020, 
29.7.2020). The study was performed according to 
the ethical standards of the responsible institution-
al review board on human experimentation and 
with the Helsinki Declaration. Patients provided 
written, informed consent at the admission.
Patients’ data acquisition
A retrospective case review of patients treated 
at the Institute of Oncology Ljubljana, Slovenia 
and/or Department of Otorhinolaryngology and 
Cervicofacial Surgery, University Medical Centre, 
Ljubljana, Slovenia was performed. Inclusion cri-
teria were:
–  time of cancer diagnosis between the January 
1
st
 2011 and December 31
st
 2019,
–  international classification of diseases, 10
th
 
revision (ICD-10) diagnoses:
•  C07 (lat. neoplasma malignum glandulae 
parotideae), 
•  C30.1 (lat. neoplasma malignum auris mediae), 
•  C41.0 (lat. neoplasma malignum ossium cranii et 
faciei), 
•  C43.2 (lat. melanoma malignum auris et meatus 
acustici externi), 
•  C44.2 (lat. neoplasma malignum cutis auris et 
meatus acustici externi) or 
•  C49.0 (lat. neoplasma malignum textus 
connexivi et mollis capitis, faciei et colli).
–  surgical treatment with curative intent.
The data were collected from the Cancer 
Registry, Slovenia, databases of Department of 
Otorhinolaryngology and Cervicofacial Surgery, 
University Medical Centre Ljubljana, Slovenia and 
Institute of Oncology Ljubljana, Slovenia.

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Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 326
Patients’ data analysis
Included patients were analysed for the gender, 
age, symptoms at presentation, date of cancer di-
agnosis, ICD-10 diagnosis, histology, clinical and 
pathological TNM stage (utilising the University of 
Pittsburgh TNM staging system (Table 1) for EACC 
and MEC or 8th edition of UICC staging system for 
aEEC and aPC), tumour localisation according to 
the abovementioned classification, preoperative 
head and neck imaging modalities and preopera-
tive pure tone audiometry. Pure tone average was 
calculated for the affected ear (for bone and air 
conduction) as an average of hearing levels of pure 
tone audiometry at speech frequencies (i.e., 500 Hz, 
1000 Hz, 1500 Hz, 2000 Hz, 3000 Hz and 4000 Hz). 
The average air-bone gap was calculated from pure 
tone average for bone and air conduction. 
Moreover, date of surgery, treatment modali-
ties employed (i.e., surgery, radiotherapy, systemic 
ICD = International statistical classification of diseases and related Health problems 10
th
 revision
FIGURE 1. Data acquisition flowchart of patients with lateral skull-base cancer. Data of 177 patients were thoroughly analysed using 
Cancer Registry of the Republic of Slovenia and databases of Department of Otorhinolaryngology and Cervicofacial Surgery, 
University Medical Centre Ljubljana, Slovenia and Institute of Oncology Ljubljana, Slovenia. The majority of excluded patients 
suffered from auricular or parotid cancer without lateral skull-base involvement. Additional analysis was performed on the data of 
locoregionally advanced cancer.

Radiol Oncol 2021; 55(3): 323-332.
Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 327
therapy), residual tumour classification according 
to the UICC staging system (i.e., R0 no residual 
tumour, R1 microscopic residual tumour and R2 
macroscopic residual tumour), and date of the last 
recorded check-up or date and reason of death 
were analysed. Cancer recurrence was defined as 
the re-appearance of cancer in the surgical bed af-
ter the treatment was completed, and cancer was 
considered cured.
Listed data was used to analyse age at the cancer 
diagnosis, age at death, postoperative follow-up 
period and survival. Local control and overall sur-
vival crude rates and estimates using the Kaplan-
Meier method were determined. Patients were con-
sidered cancer-free if there was no cancer recorded 
at five years after the surgery.
Statistical analysis was performed using 
Microsoft Excel for Mac (version 16 and later, 
Microsoft Corporation, Redmond, Washington) 
and SPSS (version 23, IBM Corp., Armonk, New 
York). Basic descriptive statistics were reported 
with means (M) and standard deviations (SD) and 
a p-value (p) below 0.05 was considered statistically 
significant.
Results
Study flowchart, demographics and 
clinical presentation 
Data collection was cut off on September 14
th,
 2020. 
Initially, 177 patients were included in the study. 
Seventeen (10%) patients with lateral skull-base 
cancer were treated with curative intent between 
2011 and 2019, and in 12 of them, the tumour was 
locally advanced (Table 2). 
At the admission, 12 (71%) patients reported 
discharge, 10 (59%) crusting or nonhealing lesion, 
10 (59%) pain, 6 (35%) bleeding, 5 (29%) hearing 
loss and 2 (12%) itching. A patient (6%) with aPC 
extending to the lateral skull-base reported the 
unilateral facial muscle weakness. None reported 
vertigo or other symptoms related to other cranial 
nerves involvement.
Tumour characteristics and localisation
There was no left to right predominance (53% left 
and 47% right). Seven patients (41%) had an aEEC. 
Basal cell carcinoma was present in four (57%) and 
squamous cell carcinoma in three (43%) patients 
(Table 2). 
Six patients (35%) suffered from EACC. The lat-
ter was classified as C44.2 in 100%. The cancer was 
squamous cell carcinoma in three (50%), basal cell 
carcinoma in two (33%) and adenoid cystic carci-
noma in one patient (17%). 
Both (12%) MECs were squamous cell carci-
noma and two (12%) aPCs were mucoepidermoid 
carcinoma (50%) and adenocarcinoma (50%).
Disregarding the tumour localisation squamous 
cell carcinoma was the most common type (8 pa-
tients, 47%), followed by basal cell carcinoma (6 pa-
tients, 35%), and others (adenoid cystic carcinoma 
(6%), mucoepidermoid carcinoma (6%) and adeno-
carcinoma (6%).
Locoregionally advanced lateral skull-
base cancer
In twelve patients (71%), the tumour was lo-
coregionally advanced (i.e., grades III and IV). 
Preoperative skull-base imaging (i.e., CT or MRI) 
was performed in all of them. Pure tone average for 
air and bone conduction and air-bone gap could be 
calculated in eight patients (67%). Average value of 
pure tone average was 69 dB (SD = 39 dB) for air 
conduction, 43 dB (SD = 19 dB) for bone conduction 
and average air-bone gap was 26 dB (SD = 20 dB).
The primary surgery was the only treatment mo-
dality in five patients (42%) patients. Other treat-
ment modalities employed were salvage surgery 
in three (25%) patients (i.e., one after radiotherapy, 
one after radiotherapy and electrochemotherapy, 
FIGURE 2. Barchart of seventeen patients with lateral skull-base cancer treated with 
curative intent between 2011 and 2019.

Radiol Oncol 2021; 55(3): 323-332.
Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 328
one after surgery and radiotherapy) and postoper-
ative radiotherapy in four patients (33%) (Table 2). 
None received postoperative chemotherapy.
Wide local excision only was performed in two 
(16.7%), mastoidectomy in one (8.3%) and lateral 
temporal bone resection with obliteration in nine 
patients (75%). Additional partial parotidectomy 
was performed in six (50%), total parotidectomy in 
one (8.3%), ipsilateral selective neck dissection of 
regions II–IV in eight (66.7%) and ipsilateral modi-
fied radical neck dissection including resection 
of the sternocleidomastoid muscle in one patient 
(8.3%). 
The post-resection lateral skull-base defect was 
reconstructed with primary closure in five (41.7%) 
and flap in six (50%) patients with locoregionally 
advanced cancer. The wound was left to heal by 
secondary intention in one (8.3%) patient with 
T1N1M0 (stage III) EACC. 
Reconstruction with ALT (Figure 3), RFFF 
(Figure 4) and PM (Figure 5) was performed in two 
patients each. There was no flap failure. In five pa-
tients (83%) with flap reconstruction, the resection 
was R0. Postoperative photon radiotherapy with a 
dose of 60 Gy and 64 Gy in 2 Gy daily fractions was 
performed in two patients, including the one with 
R1 resection.
Local control and survival after 
locoregionally advanced lateral skull-
base cancer resection
The mean follow-up time (i.e., the mean overall 
survival time) of twelve patients after locoregion-
TABLE 2. Dataset of patients with lateral skull-base cancer treated between 2011 and 2019
Age Year Site ICD-10 HP
Clinical TNM staging
Preoperative 
imaging
PTA
Treatment 
modalities
Otosurgical 
resection
Parotidectomy
Neck 
dissection
TMJ 
resection
Reconstruction RTC Survival
cT cN cM Grade
80
M
2012 aEEC
R
C44.2 SCC cT4
*
cN1
*
cM0
*
IV
P
CT
SB, 
US
N
yes SURG RT WLE partial iSND none PM R1 8.1
79
M
2014 EACC
R
C44.2 BCC cT1
P
cN0
P
cM0
P
I
P
CT
SB
none SURG WLE none none yes skin graft R0 6.9
52
M
2014 EACC
L
C44.2 SCC cT4
P
cN0
P
cM0
P
IV
P
MRI
SB
, CT
SB
, US
N
yes SURG LTBR partial iSND none primary closure R0 5.7
90
F
2015 EACC
L
C44.2 SCC T3
P
cN0
P
cM0
P
III
P
CT
SB
, US
N
yes SURG LTBR none none none primary closure R0 5.5
59
M
2017 EACC
L
C44.2 ACC cT4
P
cN0
P
cM0
P
IV
P
MRI
SB
, CT
SB
, US
N
yes SURG RT LTBR partial iSND none primary closure R1 5.2
50
M
2017 EACC
L
C44.2 BCC cT
 P
cN0
P
cM0
P
I
P
MRI
SB
none ECT»SURG WLE partial none none primary closure R0 4.5
85
F
2017 aEEC
R
C44.2 BCC cT2
*
cN0
*
cM0
*
II
*
US
N
none SURG WLE none none none primary closure R0
2.9
(†88)
75
M
2018 aEEC
L
C44.2 BCC cT1
*
cN0
*
cM0
*
I
*
none none SURG WLE none none none skin graft R0
2.8
(†78)
79
M
2018 MEC
R
C30.1 SCC cT3
P
cN0
P
cM0
P
III
P
MRI
SB
, CT
SB
, MRI
N
yes SURG LTBR none none none primary closure R1
0.4
(†80)
67
M
2018 aEEC
R
C44.2 BCC cT4a
*
cN0
*
cM0
*
IVa
*
MRI
SB
, CT
SB
yes SURG LTBR
+
partial iSND none RFFF R0 2.3
66
F
2019 EACC
L
C44.2 SCC cT1
P
cN1
P
cM0
P
III
P
MRI
SB, 
CT
SB
yes SURG WLE none iSND none
secondary 
intention
R0 2.0
76
M
2019 aEEC
R
C44.2 SCC cT3
*
cN0
*
cM0
*
III
*
MRI
SB
, CT
SB
yes RT»SURG LTBR
+
partial iSND none PM R0 2.4
85
M
2012 MEC
R
C30.1 SCC cT3
P
cN0
P
cM0
P
III
P
CT
SB
, US
N
yes SURG RT LTBR none none none primary closure R0
0.5
(†85)
73
F
2014 aEEC
L
C44.2 BCC cT4a
*
cN0
*
cM0
*
IVa
*
MRI
SB
, CT
SB
, US
N
yes RT»ECT»SURG LTBR
+
partial iSND none RFFF R0 1.6
58
F
2014 aPC
R
C07 MC cT4a
**
cN0
**
cM0
**
IVa
**
MRI
SB
, CT
SB
yes SURGRT»SURG LTBR
+
performed 
previously
iSND none ALT R0 0.6
85
F
2015 aPC
R
C07 AC cT4a
*
cN2b
*
cM0
*
IVa
*
CT
SB
yes SURGRT MWLE total iMRND none ALT R0 0.3
84
M
2017 aEEC
L
C44.2 SCC cT2
*
cN0
*
cM0
*
II* US
N
none SURG RT WLE partial iSND none
secondary 
intention
R0 0.8
Locoregionally advanced cancer is shown in bold. Age and survival are depicted in years
AC = adenocarcinoma; ACC = adenoid cystic carcinoma; aEEC = advanced skin cancer of external ear (including auricle, concha or periauricular skin); Age = age at 
the time of cancer diagnosis; ALT = anterolateral thigh free flap; aPC = advanced parotid cancer; BCC = basal cell carcinoma; CT
SB
 = skull-base computed tomography; 
EACC = primary external auditory canal cancer; ECT = electrochemotherapy; ECT»SURG = ECT was performed with primary curative intent and surgery as salvage; 
F
 = female; 
HP = histopathological diagnosis; ICD-10 = international classification of diseases, 10
th
 revision; iMRND = ipsilateral modified radical neck dissection; iSND = ipsilateral selective neck 
dissection; 
L 
= left; LTBR = lateral temporal bone resection; LTBR
+
 = lateral temporal bone resection with wide local excision; 
M
 = male; MWLE = mastoidectomy with wide local 
excision; MC = mucoepidermoid carcinoma; MEC = primary middle ear cancer; MRI
N
 = neck magnetic resonance imaging; MRI
SB
 = skull-base MRI; 
P 
= modified Pittsburgh staging 
system; PM = pectoralis major myocutaneous flap; PTA = pure tone audiometry performed prior surgery; 
R
 = right; R0 = no residual tumour; R1 = microscopic residual tumour; 
RFFF = radial forearm free flap; RT = radiotherapy; RTC = residual tumour classification according to the UICC staging system; SCC = squamous cell carcinoma; 
SURG = surgery; SURG RT = combined surgery and postoperative radiotherapy; TMJ = temporomandibular joint; US
N
 = neck ultrasound; WLE = wide local excision; Year = year of 
cancer diagnosis; 
*
 = Union for International Cancer Control (UICC) staging system for skin carcinoma of the head and neck 
**
 = UICC staging system for major salivary glands; 
† with a number = an age at death

Radiol Oncol 2021; 55(3): 323-332.
Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 329
ally advanced lateral skull-base cancer resection 
was 2.9 years (SD = 2.6 years, range: 0.3 years – 8.1 
years). At the data collection cut-off date, ten of 
these patients (83%) were alive and had no can-
cer recurrence (Table 2) (Figure 6A). Two patients 
(27%) died, but no recurrence was detected. One 
patient died with MEC since the resection was R1, 
and the patient did not receive planned postop-
erative radiotherapy due to generalised weakness. 
One patient after R0 resection of MEC died due to 
comorbidities. The survival was 100% in patients 
treated with flap reconstruction and 67% in pa-
tients treated with other reconstruction modalities 
(Figure 6B).
A B
FIGURE 3. 85-year old female with locoregionally advanced parotid adenocarcinoma (i.e., parotid metastasis after incomplete 
temporal skin adenocarcinoma cancer resection) extending to the right external auditory canal and lateral skull-base. The 
resection margin is outlined (A). Primary surgery involving mastoidectomy with wide local excision, total parotidectomy, modified 
radical neck dissection, temporary tracheostomy, static suspension of oral commissure with fascia lata and anterolateral thigh free 
flap reconstruction were performed (B).
FIGURE 4. 73-year old female with locoregionally advanced external ear basal cell carcinoma extending to the left lateral skull-
base. The resection margin is outlined (A). Salvage surgery (i.e., after primary radical radiotherapy and electrochemotherapy) 
involving lateral temporal bone resection with fat obliteration, with wide local excision, partial parotidectomy, ipsilateral selective 
neck dissection (B) and radial forearm free flap reconstruction (C) were performed.
A B C

Radiol Oncol 2021; 55(3): 323-332.
Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 330
Discussion
Our study presents 17 patients treated surgically 
with curative intent in 9 years at Slovenia’s two 
main healthcare centres dealing with surgical and 
non-surgical head and neck cancer treatment. As 
many as 12 patients (71%) had locoregionally ad-
vanced disease at the time of surgery.
The percentage (10%) of patients included in the 
final analysis (17 patients) among initially collected 
data (177 patients) confirms that the lateral skull-
base cancer is a rare entity, and data acquisition is 
arduous. The main reason is that this cancer can be 
classified under various ICD-10 diagnoses. Middle 
ear cancer is the only lateral skull-base cancer with 
a universal ICD-10 code (C30.1). Our study pre-
sents only the minority of lateral skull-base can-
cer; therefore, other ICD-10 diagnoses should be 
included. Despite the efforts, the list of included 
diagnoses in our study is possibly not exhaustive, 
and some cases with lateral skull-base involvement 
may have been diagnosed under other diagnoses 
(i.e., C44.3). As already proposed
1,3
, the establish-
ment of the universal lateral skull-base cancer 
registry should be encouraged, which would over-
come obstacles in prospective data analysis and 
alleviate multicentric research in this rare type of 
cancer. 
Male predominance (65%) and discharge as the 
most common initial symptom (71%) in our group 
are consistent with the literature. Nevertheless, the 
average age at the cancer diagnosis (M = 74 SD = 
13) was higher in our study.
6
Set of histopathological types recorded in our 
patients are consistent with the literature which 
reports the predominance of squamous cell carci-
noma.
6
 Nonetheless, its predominance over other 
cancer types is not as significant as reported in 
other studies.
1
 This is perchance due to the pre-
dominance (57%) of basal cell carcinoma classified 
as aEEC, which present the majority (41%) of cases 
in our study.
A B C
FIGURE 5. 76-year old male with locoregionally advanced external ear squamous cell carcinoma extending to the right lateral skull-base. The resection 
margin is outlined (A). Salvage surgery (i.e., after primary radical radiotherapy) involving lateral temporal bone resection with wide local excision, partial 
parotidectomy, ipsilateral selective neck dissection and pectoralis major myocutaneous flap reconstruction (due to recipient vessel insufficiency) were 
performed (B, C).

Radiol Oncol 2021; 55(3): 323-332.
Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 331
The study focused on analysing surgically 
treated locoregionally advanced lateral skull-base 
cancer (i.e., TNM grades III and IV), which pre-
sented the vast majority of all cancers (71%). These 
patients suffered from a severe mixed (i.e., senso-
rineural and conductive) hearing loss according to 
the hearing level measurements. Mostly, the exten-
sive radical surgery was performed such as lateral 
temporal bone resection with obliteration (66.7%), 
ipsilateral neck dissection (66.7% selective, 8.7% 
modified radical) and parotidectomy (50% partial, 
8.3% total). In all patients with locoregionally ad-
vanced skin cancer of external ear (3 patients) and 
parotid cancers (2 patients), the extensive radical 
resection including skin prompted the tissue de-
fect reconstruction with a major regional or free 
flap. Combination of extensive radical resection 
and flap reconstruction proved efficient since all 
of these patients are still alive. According to our 
experiences, ALT, RFFF, and PM can be harvested 
simultaneously while performing the lateral skull-
base resection, which shortens surgery time but re-
quires two surgical teams. None of our ALT, RFFF 
and PM failed, despite postoperative radiotherapy 
in 2 of these patients, consistent with the litera-
ture.
15
 Primary closure was the reconstruction of 
choice after resection of EACC or MEC since there 
was no large skin defect (i.e., blind sac external au-
ditory canal closure and no pinna amputation). 
Results show that our patients’ local control and 
survival with locoregionally advanced cancer were 
high, especially in patients treated with flap recon-
struction (Figure 6). The cancer-free survival rate of 
100% was calculated on only four patients since oth-
ers were not followed-up for at least five years. 83% 
of alive patients at data collection cut-off confirms 
the favourable treatment outcome. This percentage 
is higher than the information collected in the perti-
nent literature (58.7%), although our patients were 
considerably older than in other reports.
1
 
Our study has certain limitations inherent to 
other retrospective studies. The calculation of the 
annual incidence of lateral skull-base cancer in 
our country could not be performed since the data 
involve only patients treated in a single tertiary 
otorhinolaryngology referral centre. Moreover, 
our study does not present patients treated with 
non-surgical modalities only. Namely, for a com-
prehensive overview of the field, it would be es-
sential to consider other treatment modalities such 
as primary radio(chemo)therapy
3
 and also electro-
chemotherapy.
16
Conclusions
Extensive radical resection of the tumour, adjacent 
tissues and structures of lateral skull-base should 
FIGURE 6. Kaplan-Meier analysis of overall survival of 12 patients with locoregionally advanced lateral skull-base cancer treated 
surgically with curative intent. (A) Kaplan-Meier analysis of 12 patients regardless of the reconstruction modality. Cumulative survival 
remained at 83% after six months. (B) Kaplan-Meyer analysis of 6 patients treated with flap reconstruction and six patients with other 
reconstruction modalities. Cumulative survival remained at 67% after six months.
A B

Radiol Oncol 2021; 55(3): 323-332.
Vozel D et al. / Locoregionally advanced lateral skull-base cancer treatment 332
be planned in locoregionally advanced skin cancer 
of external ear and locoregionally advanced parot-
id cancer. The tissue defect should be reconstruct-
ed with tissue flap; therefore, otorhinolaryngolo-
gist treating this cancer should be experienced in 
free and regional flap elevation such as ALT, RFFF 
and PM. This surgical approach enables a high sur-
vival rate. 
In locoregionally advanced primary external 
auditory canal cancer, the high survival rate is al-
lowed with lateral temporal bone resection, oblite-
ration and blind sac external auditory canal closure 
without amputation of the pinna, which offers the 
best chances for durable local control.
MEC is always locoregionally advanced if modi-
fied Pittsburgh staging system is applied, and the 
risk of tumour re-appearance is high despite exten-
sive surgery and adjuvant treatment.
Collaboration within otorhinolaryngology sub-
specialists and oncologists is vital to treat lateral 
skull-base cancer. It is imperative to establish uni-
versal lateral skull-base cancer registry in tertiary 
healthcare centres involved in treating this disease.
Acknowledgements
To Tina Žagar and Aleš Matos for data collection 
and distribution. The study was financially sup-
ported by the Slovenian Research Agency (pro-
gramme no. P3-0307).
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