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Salvage Surgery for Recurrent Nasopharyngeal Carcinoma
Sheng-Po Hao, MD;
Ngan-Ming Tsang, MD, DSc;
Chen-Nen Chang, MD
Arch Otolaryngol Head Neck Surg. 2002;128:63-67.
ABSTRACT
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Objective To evaluate the results of salvage surgery for patients with primary
recurrence of nasopharyngeal carcinoma after radiotherapy.
Design Cohort study.
Setting Academic tertiary referral center.
Patients Eighteen consecutive patients with primary recurrence of nasopharyngeal
carcinoma after radiation failure underwent nasopharyngectomy for cure via
a facial translocation approach from July 1, 1993, to December 31, 1999. Follow-up
ranged from 3 to 71 months. Five patients with skull base invasion required
a combined neurosurgical approach to treatment. Seven patients had additional
postoperative radiotherapy.
Results The actuarial 3-year survival was 57%, while the local control was 78%.
Four of 5 patients who had skull base invasion achieved local control. There
was no surgical mortality, and the morbidity was 22%.
Conclusion Advances in skull base surgery make possible the effective control of
primary recurrence of nasopharyngeal carcinoma, with acceptable mortality
and morbidity.
INTRODUCTION
NASOPHARYNGEAL carcinoma (NPC) is the most common cancer of the head
and neck in the southeastern part of China, Taiwan, Hong Kong, and Singapore.
Nasopharyngeal carcinoma refers to malignant tumor arising from the epithelial
cells lining the nasopharyngeal space. Other malignant tumors, such as glandular
tumors arising from the minor salivary glands or sarcomas and lymphomas, are
not included in the category of NPC. Nasopharyngeal carcinoma is related to
Epstein-Barr virus,1-2 and, contrary
to epithelial tumors from other parts of the upper aerodigestive tract, the
mainstay of NPC treatment is radiotherapy. This is because (1) most NPCs are
undifferentiated or nonkeratinizing carcinomas, which are sensitive to radiotherapy,
and (2) the complexity of the nasopharyngeal anatomy makes radical surgery
difficult. However, in recent years, as we have better understood the anatomy
and spread of nasopharyngeal tumors, and because of the advancements in skull
base surgery, the nasopharynx is no longer considered a no-man's-land. Herein,
we report our experience of salvage surgery for recurrent NPC after radiation
failure at the primary site.
MATERIALS AND METHODS
From July 1, 1993, to December 31, 1999, in the Second Division of Otolaryngology,
Chang Gung Memorial Hospital, Chang Gung University, Taoyua, Taiwan, Republic
of China, we operated on 18 patients in whom local recurrence developed after
radiotherapy for NPC. There were 13 men and 5 women (age range, 30-62 years).
Previously, 17 patients had undergone a single course of radiotherapy with
more than 6600 rad (66 Gy), while 1 patient had undergone a second course
of radiotherapy for his primary recurrence. Four patients had undergone radiotherapy
elsewhere. Our preferred method of preoperative radiologic diagnosis is magnetic
resonance imaging scans; however, early in the study, 2 patients had computed
tomography only.
Preoperatively, the tumors were classified as rT1 (8 patients), rT2b
(1 patient), rT3 (5 patients), and rT4 (4 patients), according to the American
Joint Committee on Cancer staging system.3
The clinical characteristics of the patients are summarized in Table 1. Two patients had previous sinus surgery, including 1 Caldwell-Luc
operation and 1 functional endoscopic sinus surgery. One patient had persistent
cervical metastasis after radiotherapy and underwent modified radical neck
dissection before nasopharyngectomy. Another patient had recurrent neck disease
after completion of nasopharyngectomy for his primary recurrence and subsequently
underwent modified radical neck dissection. The nasopharyngectomies were carried
out via a facial translocation approach. Five patients required a combined
neurosurgical approach (3 subtemporal and 2 subfrontal) and appropriate neurosurgical
resection. Seven patients who had tumor-positive or close surgical resection
margins underwent a second course of radiotherapy postoperatively.
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Table 1. Clinical Characteristics of Patients With Recurrent Nasopharyngeal
Carcinoma at the Primary Site*
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All patients had biopsy-proven primary recurrence. A systemic workup
with chest x-ray, abdominal sonography, and technetium Tc 99m bone scan was
carried out before the operation, and if any of these examinations had positive
findings, the patient entered a second radiotherapy protocol and did not have
surgery. The contraindications for cranial base surgery for recurrent NPC
in our division are (1) extensive intradural invasion, (2) cavernous sinus
involvement, and (3) pharyngobasilar fasciae invasion. We do not consider
bony destruction of the cranial base unresectable.
The cutoff point for study data was May 31, 2001. Statistical analysis
was carried out using commercially available software (SPSS version 7.5; SPSS
Inc, Chicago, Ill). The actuarial overall survival and local tumor control
were calculated by the Kaplan-Meier method.
RESULTS
Of the 18 patients, 15 had negative margins, while 3 had microresidual
diseases. There was no surgical mortality, and the morbidity was 22% (4/18),
including cerebrospinal fluid rhinorrhea in 1 patient, flap necrosis in 1,
osteoradionecrosis (ORN) of the translocated facial bone graft in 1, and mild
epiphora in 1 (Table 1). The patient
who had postoperative cerebrospinal fluid rhinorrhea died of brain involvement
3 months after surgery. The patient with ORN was treated with 3 successive
sequestrectomies and hyperbaric oxygen therapy and ultimately required a free
flap to resolve the problem. The patient with flap necrosis underwent several
debridements, and the oropharyngeal wound healed with a secondary intention.
However, she died of massive bleeding from carotid artery blowout 15 months
after surgery.
The 18 patients were followed up for 3 to 71 months (Table 1). To date, 3 patients have died of local disease (including
2 with microresidual disease), 2 have died of nodal metastases (1 neck and
1 axilla), 1 has died of distant metastasis, and 1 has died of massive bleeding
(Table 1). The actuarial 3-year
survival was 57% (Figure 1), while
the local control was 78% (Figure 2). The survival rates of the patients according to rT stage are summarized in Table 2.
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Figure 1. Actuarial survival of patients
who underwent nasopharyngectomy for primary recurrence of nasopharyngeal carcinoma.
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Figure 2. Actuarial control of disease in
the nasopharynx after resection.
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Table 2. Two-Year Survival According to rT Stage
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Five patients who had skull base or intracranial extension needed a
combined neurosurgical resection; 1 died of local recurrence in the brain
and 1 died of axillary nodal metastases. Four (80%) of the 5 patients had
local control.
Of the 18 patients, 16 had undifferentiated carcinomas (World Health
Organization type 3), and 2 had keratinizing squamous cell carcinomas (World
Health Organization type 1). In 3 patients, no cancer was found in the surgical
specimens, although preoperative biopsies had demonstrated recurrent cancer.
COMMENT
The mainstay of NPC treatment is radiotherapy, as most NPCs are undifferentiated
or nonkeratinizing carcinomas, which are radiosensitive. Nasopharyngeal carcinoma,
compared with other epithelial cancers of the upper aerodigestive tract, has
a high incidence of distant metastasis. However, locoregional failure is still
the main cause of death. For example, in our tumor registry, 1002 (35%) of
2860 registered patients with NPC died of local disease or local recurrence,
despite radical radiotherapy.4
Although the incidence of local persistent or recurrent disease has
decreased following introduction of concurrent chemoradiotherapy,5 such occurrences lead patients to a dismal prognosis.
Treatment of primary recurrence can be accomplished by additional external
beam radiotherapy or by skull base surgery. Reirradiation of the primary recurrence
of NPC has been reported,6-9
but it was accompanied by significant morbidity caused by complications such
as severe xerostomia, trismus, deafness, and neurological sequelae.8-9 Other pitfalls include the complications
of ORN following reirradiation.10-11
The patient may experience foul odor, severe pain, and massive bleeding. Furthermore,
it cannot be assumed that NPC cells surviving the first course of radiotherapy
will respond to further radiotherapy.
The surgical approach to the nasopharynx has been the focus of interest
since the development of skull base surgery. Fisch12
used an infratemporal fossa approach to resect nasopharyngeal tumors. However,
in this lateral approach, mastoidectomy must be accomplished before attacking
the nasopharynx. Transpalatal approaches have been favored by Fee13 and Hsu14 and their
colleagues; however, only small mucosal tumors in the central roof of the
nasopharynx are suitable for this approach. A mandibular swing approach attacks
the tumor from below, but we have found the exposure of the skull base to
be limited with this approach, especially when the tumor has invaded the foramen
ovale or touched the pterygoid plate base. Nevertheless, it has been claimed
that this method offers control of the ascending internal carotid artery and
allows resection of the tumor in the parapharyngeal space medial to the artery.14 Wei et al,15 from
Hong Kong, used the maxillary swing approach to resect these difficult tumors.
This approach is ideal for tumors confined to the mucosal surface of the nasopharynx
or tumors with paranasopharyngeal space invasion.15-16
In our study, a facial translocation approach was used exclusively,17 and this approach can be combined with neurosurgical
craniotomy for tumors with skull base invasion.18
In the facial translocation approach, the facial osteotomy can be localized
based on the location of the tumor. If the tumor is confined to the nasopharynx
or has paranasal extension, a nasoorbitomaxillary osteotomy will suffice,
and the infraorbital neurovascular bundle can be preserved. However, when
the tumor has invaded the parapharyngeal space, a larger facial osteotomy,
optionally including part of the zygoma, is created to remove the tumor.
If the tumor has invaded the pterygoid plate base, a combined preauricular
infratemporal subtemporal approach is used.19
This approach offers superior and lateral approaches to the nasopharyngeal
and parapharyngeal space. After temporal craniotomy, the temporal lobe is
retracted to expose the temporal base. The foramen ovale can be decompressed,
and the transverse portion of the petrous internal carotid artery lying behind
the foramen ovale is located and protected. The tumor can then be removed
from the superior, lateral, and anterior directions. However, it is difficult
to differentiate bony invasion by cancer from ORN intraoperatively.20 Confirmation of clear margins of skull base bone
requires histopathological analysis. After the tumor is resected, the temporalis
muscle is split and its anterior half is transposed to fill the defect, covering
the exposed subtemporal dura and separating the neurocranium from the underlying
upper aerodigestive tract. Anterior craniofacial resection is carried out
if NPC involves the cribriform plate or the planum sphenoidale.
TUMOR EXTENSION
The nasopharynx lies deep and central in the skull. Its roof is the
undersurface of the sphenoid sinus floor. The posterior wall is separated
from the basiocciput and clivus by the pharyngobasilar fasciae. The lateral
wall of the nasopharynx consists of the torus tubarius, surrounded by the
superior constrictor muscle, and is pierced by the sinus of Morgagni, in which
pass the eustachian tube and tensor veli palatini muscle. The nasopharynx
communicates freely with the posterior nasal choanae. Nasopharyngeal carcinoma
is notorious for submucosal extension. It commonly resides in the Rosenmüller
fossa and may extend laterally through the sinus of Morgagni to invade the
parapharyngeal space. Skull base extension by destruction of the pterygoid
base is common, and the tumor may extend superiorly to involve the cavernous
sinus or go laterally to involve the foramen ovale. The pharyngobasilar fasciae
are tough fasciae and can be a strong barrier against tumor. In rare instances,
NPC may invade these fasciae to involve the clivus.
With understanding of the anatomy of the nasopharynx and the natural
extension of NPC, nasopharyngectomy can be accomplished by removing most of
the nasopharyngeal mucosa, the ipsilateral torus tubarius, and the medial
pterygoid plate and its base by a nasoorbitomaxillary osteotomy. Further lateral
extension necessitates a combined subtemporal approach. In our study, anterior
craniofacial resection via a subfrontal approach was carried out in patients
with anterior cranial base tumors. The posterior half of the nasal septum
was commonly removed to gain access to the contralateral Rosenmüller
fossa. Currently, the contraindications in our division for salvage surgery
for NPC are (1) extensive indurated invasion, (2) cavernous sinus involvement,
and (3) pharyngobasilar fasciae invasion. Preoperatively, magnetic resonance
imaging scans are the imaging methods of choice to define the local extension
of the primary recurrence,21 which is important
for surgical planning. Magnetic resonance imaging scans are also valuable
in differentiating sinus invasion by cancer from obstructing sinusitis. Its
excellent soft tissue resolution also reveals cavernous sinus or foramen ovale
involvement. Based on our experience with the first 2 patients in this series,
computed tomographic scans are no longer used to define skull base extensions.
En bloc resection of NPC is not always possible, and, as with other
difficult lesions of the skull base, the resection is often completed piece
by piece. However, if the tumor is confined to the nasopharynx, en bloc resection
can be easily accomplished by fracturing down the sphenoid sinus floor, cutting
the eustachian tube, removing the medial pterygoid plate, and stripping the
tumor off the posterior pharyngobasilar fasciae. The resulting nude surface
of the nasopharyngeal space is left to reepithelialization, which takes about
3 months. During this time, diligent endoscopic cleansing and local hygiene
maintenance are crucial.
COMPLICATIONS
Four patients had postoperative complications, including 1 cerebrospinal
fluid rhinorrhea, 1 flap necrosis, 1 ORN of the translocated facial bone,
and 1 mild epiphora. In the patient with ORN, a free facial bone graft technique
via a facial translocation approach was used. Despite diligent sequestrectomies
and hyperbaric oxygen therapy, the ORN persisted and the patient required
a free flap to obliterate the paranasal cavity, thereby resolving the ORN.
Based on our experience with this patient, we now use the vascularized facial
bone graft technique exclusively in facial translocation for patients who
have had previous radiotherapy.22
In the immediate postoperative period, patients may experience crust
formation and accumulation in the hollow paranasal and nasopharyngeal cavities.
Regular self-cleansing and irrigation with warm isotonic sodium chloride solution
are important to improve the condition.
Fee et al13 described 9 patients with
primary recurrence of NPC; 7 were treated for cure and 2 for palliation. Five
of the 7 lived free of disease for 6 to 48 months. The authors concluded that
surgery produced results as good as those of reirradiation, if not better.
In a follow-up study, Fee and colleagues23
reported that long-term survival (>3 years) after surgical resection for recurrent
NPC was possible; however, salvage surgery had only slightly better results
than reirradiation. Wei et al16 described 26
patients who underwent maxillary swing approaches to their nasopharyngeal
or paranasopharyngeal tumors, 18 of which were recurrent NPC. At 3
years after salvage surgery, 9 were alive without disease, and the actuarial
local control of recurrent NPC was 42%. Hsu et al14
described 24 patients with primary recurrence of NPC, in whom various surgical
approaches were used based on the location and invasion of NPC. In their series,
14 patients (58%) survived after surgery during a median 18 months of follow-up.
The authors postulated that cranial nerve invasion was a surgical contraindication
but that salvage surgery otherwise was a reasonable alternative to reirradiation.
King et al24 recently described 31 patients
with primary recurrence of NPC, among whom 7 had cervical metastases in addition
to their primary recurrences, requiring nasopharyngectomy and neck dissection.
In their series, 9 patients had tumor-positive margins, and there was no significant
difference in disease-free survival between them and patients with clear surgical
margins. The actuarial 5-year overall survival was 47%, and the authors concluded
that postoperative radiotherapy significantly enhanced survival and tumor
control.
In our series, the actuarial 3-year survival of 57% and local control
of 78% compared favorably with those of the other series. Postoperative radiotherapy
was administered in only 7 patients (39%) who had tumor-positive or close
surgical resection margins. Furthermore, we conclude that intracranial invasion
is resectable. Superior dissection around the sphenoid sinus and pterygoid
base and lateral dissection around the foramen ovale through a combined anterior
facial and superior neurosurgical approach are crucial to control primary
recurrence of NPC with skull base invasion. In our series, we achieved local
control in 4 of 5 patients with skull base or intracranial involvement. With
the concerted efforts of radiologists, radiation oncologists, head and neck
surgeons, and neurosurgeons, nasopharyngectomy can be a safe and oncologically
sound approach to treatment of primary recurrence of NPC. Further effort should
be directed to early detection of local recurrence by molecular biology techniques.
AUTHOR INFORMATION
Accepted for publication August 24, 2001.
Presented at the Fifth International Conference on Head and Neck Cancer,
San Francisco, Calif, July 30, 2000.
Corresponding author and reprints: Sheng-Po Hao, MD, Department of
Otolaryngology, Head & Neck Oncology (II), Chang Gung Memorial Hospital,
Chang Gung University, 5 Fu-Hsing St, Kuei Shan, 333, Taoyua, Taiwan, Republic
of China (e-mail: shengpo{at}adm.cgmh.org.tw).
From the Departments of Otolaryngology (Dr Hao), Radiation Oncology
(Dr Tsang), and Neurosurgery (Dr Chang), and Head & Neck Oncology (II)
(Drs Hao and Tsang), Chang Gung Memorial Hospital, Chang Gung University,
Taoyua, Taiwan, Republic of China.
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