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Nasopharyngectomy for Recurrent Nasopharyngeal Cancer
A 2- to 17-Year Follow-up
Willard E. Fee, Jr, MD;
Melinda S. Moir, MD;
Eun Chang Choi, MD;
Don Goffinet, MD
Arch Otolaryngol Head Neck Surg. 2002;128:280-284.
ABSTRACT
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Objective To review the 2- to 17-year outcome of nasopharyngectomy following local
recurrence of nasopharyngeal carcinoma.
Design Retrospective review.
Setting University medical center.
Patients Thirty-seven patients with biopsy-proven recurrent nasopharyngeal cancer
followed up for a minimum of 2 years after transpalatal, transmaxillary, and/or
transcervical resection with and without neck dissection.
Outcome Clinical examination, magnetic resonance imaging, chest x-ray examination,
and liver function tests to determine re-recurrence; unlimited follow-up.
Results With a mean follow-up of 5.4 years, the crude, 5-year, overall, free-of-disease
survival rate was 52%, local control at 5 years was 67%, and the 5-year actuarial
survival rate was 60%. Survival by recurrent T stage (rT) was as follows:
rT1, 73%; rT2, 40%; rT3, 14%; and rT4, 0%. Complications occurred in 54% and
included 1 death from carotid artery injury and 1 patient with permanent pharyngeal
plexus paralysis with resultant dysphagia. The remaining patients had transitory
complications that spontaneously resolved, required further surgery (closure
of palate fistula, debridement, and reapplication of skin graft), or required
further medical therapy.
Conclusions The results of this study are better than most published reports of
additional irradiation for rT1 and rT2 lesions. More recent radiation studies
that use radiosurgery or implants suggest promising early results. A randomized
prospective study comparing surgery with additional irradiation for recurrent
disease at the primary site is warranted.
INTRODUCTION
PATIENTS WITH recurrent nasopharyngeal carcinomas continue to challenge
physicians' creativity and skill. Although there are no great options for
treating metastatic disease, neck dissection is an excellent choice for treating
regional recurrence after radiation therapy (XRT) when the primary site is
controlled. Recurrence at the primary site has usually been treated with a
second course of XRT. Until recently, surgery was considered impossible because
of the inaccessible location of the nasopharynx. Lee et al1
reported that long-term survival after a second course of XRT was less than
30% and was associated with a 26% incidence of complications, including 2%
therapy-related death. Such results prompted us to explore the feasibility
of surgical resection. This report documents our long-term survival results.
MATERIALS AND METHODS
From May 4, 1984, to March 31, 1999, one of the authors (W.E.F.) performed
nasopharyngectomy for recurrent nasopharyngeal carcinoma on 44 patients at
the Stanford University Medical Center. Initially, the first 9 patients had
computed tomographic and magnetic resonance imaging (MRI) scans to localize
tumor; subsequently, MRI scans with gadolinium and fat suppression were used
to stage disease in addition to the clinical examination, chest x-ray examination,
and liver function tests. A retrospective medical record review was performed
by 2 surgeons (M.S.M. and E.C.C.) unassociated with the surgery (to eliminate
any potential bias), paying particular attention to all complications associated
with (but not necessarily due to) the surgical procedure. Follow-up was obtained
from patient medical records either at Stanford or from referring physicians.
The surgical approach was variable, depending on the tumor location,
but included an intraoral, transpalatal, and sublabial transmaxillary approach;
isolation of the internal carotid artery and cranial nerves IX, X, and XII
to the skull base; and modified (sparing cranial nerve XI) or radical neck
dissection as the clinical condition dictated. No transfacial or lateral infratemporal
approaches were used. Since this tumor mimics juvenile angiofibroma in its
location, the surgical approaches are similar with the exception of the need
for isolating the internal carotid artery and performing a neck dissection.
One-centimeter margins were obtained around the tumor and then frozen section
margins were obtained from the patient and submitted for analysis; if the
margins were positive, additional sections were taken, continuing, if possible,
until a negative margin was obtained.
Nasopharyngeal specimens are removed en bloc, although the specimen
will occasionally fragment (<10%) when the primary site is extensively
ulcerated. After resecting the main specimen, the entire anterior wall of
the sphenoid sinus wall is removed, with the sphenoid sinus contents, when
necessary. The remaining sphenoid bone is drilled with a diamond burr, with
care taken to prevent injury to the internal carotid artery and the optic
nerves. Next, the clivus and anterior arch of the atlas and axis are drilled
with a cutting burr followed by the diamond drill for 3 to 5 mm until healthy
bleeding is encountered and all mucosal, ligamentous, and muscular filamentous
attachments to the anterior bone are removed.
The inferior turbinate(s) is helpful to use as a mucosal graft to resurface
the nasopharynx and facilitate cleaning of the resultant cavity. If the surface
area is too great, then a 0.018-in split-thickness skin graft is applied to
the bare bone and secured with antibiotic-impregnated packing, which is held
in place for 5 to 7 days. Unilateral or bilateral tympanostomy tubes are placed
when the eustachian tube(s) is removed.
After removal of the packing, the nasopharynx is irrigated with warm
tap water with added salt and bicarbonate of soda as the patient desires.
Initially, patients are encouraged to irrigate 2 to 4 times per day via the
nose and oral cavity or, as necessary, to decrease crust formation. Some patients
find it helpful to use nasal mucosal emollient (Ponaris; Jamol Laboratories
Inc, Emerson, NJ), topically applied to the nose and nasopharynx via nose
drops, between irrigations. Others find mineral oil, petroleum jelly, or antibiotic
ointment useful. Crusting of the nose and nasopharynx is removed 1 to 2 times
per week for 6 to 12 weeks or until the wound is healed; this activity eliminates
odoriferous breath.
A temporary soft palate obturator is constructed by a skilled prosthodontist
for those patients who require soft palatectomy, and a permanent prosthesis
is usually made 4 to 6 months postoperatively.
RESULTS
No patients were excluded from the study except 5 of the 44 patients
who had minor salivary gland carcinomas. Four of the 5 patients are free of
disease, whereas the fifth patient is alive free of local disease but with
pulmonary metastases. Two patients who had tumor extension into the spinal
canal were also excluded because they were treated for palliation only because
of pain, nasal obstruction, and bleeding; they lived 12 and 80 months, respectively,
after resection, with only the latter patient receiving meaningful palliation.
These 7 patients were excluded from the final analysis, and the remaining
37 patients had typical World Health Organization class I or IIa or IIb nasopharyngeal
carcinoma.
The group consisted of 24 men and 13 women with an average age at the
time of operation of 49 years (range, 28-72 years). Disease was restaged based
on the preoperative evaluation using the AJCC Cancer Staging
Manual (revised 1998). Twenty-two patients were staged as having recurrent
T-stage (rT) 1 disease; 5 patients, rT2; 7 patients, rT3; and 3 patients,
rT4.
In all patients, primary treatment with XRT had failed to control the
neoplasm. The average dose delivered to the nasopharynx was 6800 rad (68 Gy)
(range, 6000-7500 rad [60-75 Gy]). The mean number of fractions was 38 (range,
33-60), and the mean length of treatment was 55 days (range, 30-79 days).
The mean time to recurrence after irradiation was 28.6 months (range, 2-108
months). In 6 patients, a second course of external beam XRT failed before
surgical treatment; 5 (83%) are free of disease more than 5 years after surgery.
Perioperative data are as follows.
Surgical complications occurred in 20 patients (54%), 2 (5%) of which
were considered major. Serious complications included 1 death from an intraoperative
carotid artery injury and a pharyngeal plexus paralysis, resulting in permanent
dysphagia in a second patient.
Transitory complications occurred in 18 patients, including 4 instances
of nerve paresis (1 with Horner syndrome, 1 with marginal mandibular branch
of the facial nerve, and 2 with 9th, 10th, and 12th nerve paresis with resultant
temporary dysphagia). Osteoradionecrosis and skull base osteomyelitis developed
in 6 patients (5 of whom failed 2 courses of XRT), followed by complete recovery
after treatment with prolonged intravenous antibiotics, debridement, and reapplication
of the split-thickness skin graft. Four patients had exposed bone postoperatively,
which was treated with local wound care; a single patient had a complete loss
of the skin graft that closed secondarily. Five patients developed palatal
fistulas, of which 2 required surgical repair, 2 closed spontaneously, and
1 required a palatal obturator. Baroreceptor dysfunction occurred in 1 patient
who had bilateral internal carotid artery isolation that required 2
months of medical therapy (clonidine) to control his hypertension and tachycardia.
Thyroid storm developed in 1 patient intraoperatively, with complete recovery.
One patient who had severe depression preoperatively remained severely depressed
postoperatively, despite intensive treatment. One patient developed pneumonia,
requiring readmission and antibiotics, and 1 patient developed nasopharyngeal
stenosis. Three patients had more than 1 complication.
Eight patients who had positive surgical margins received postoperative
XRT, 3 with intracavitary cesium implants, 3 with stereotactic radiosurgery,
1 with external beam irradiation (photons), and 1 with heavy particle (proton)
irradiation. Only 2 of those patients (1 undergoing stereotactic radiosurgery
and 1 undergoing proton irradiation) survived 5 years or longer free of disease.
The 1 patient who received a second course of external beam XRT died from
airway obstruction secondary to supraglottic edema but was free of disease
at autopsy. The remainder recurred locally and these patients eventually died
from disease.
Patients were followed up for a minimum of 2 to 17 years (mean, 5.4
years; median, 5.2 years) or until death. The survival following nasopharyngectomy
is given in Table 1 and actuarial
survival in Figure 1. Thirty-three
patients have 5 or more years of follow-up; 52% have no evidence of disease.
The pattern of recurrence following nasopharyngectomy is given in Table 2, with a local control rate of 67%
at 5 or more years. Patient survival free of disease and local control rates,
respectively, are as follows: rT1, 73% and 77%; rT2, 40% and 40%; rT3, 14%
and 57%; and rT4, 0% and 0%. The apparent disparity in those patients with
rT3 tumors (survival vs local control) is attributable to death caused by
distant metastases. In those patients who developed postoperative recurrences,
the mean time for diagnosis of recurrent disease was 8 months (median, 6 months;
range, 1-31 months) and to death was 19 months (median, 17 months; range,
3-38 months).
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Actuarial survival of patients (n = 37) with resected recurrent nasopharyngeal
carcinoma following nasopharyngectomy.
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Table 2. Patterns of Recurrence Following Nasopharyngectomy
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COMMENT
Sooy2 was one of the earliest Americans
to recommend electrodesiccation of recurrent nasopharyngeal tumor followed
by additional XRT. Fisch3 was the earliest
to recommend surgical resection for either recurrent or "persistent" disease.
In 1988, Fee et al4 and Tu et al5
reported their experience with surgical resection on a small series of patients
(n = 9) using a transpalatal approach; in both studies, 44% of patients were
alive free of disease. Table 3
gives the results of other surgical studies for recurrent disease. Wei et
al6 described the maxillary swing approach
to the nasopharynx in 1991, with a reported 40% actuarial tumor control at
3 years in 18 patients. By 2000,7 they
reported a 43% actuarial tumor control at 2 years in 45 patients who
had recurrent nasopharyngeal cancer. With a mean follow-up of 4.5 years, Morton
et al8 reported a 71% crude survival rate in
7 patients, 6 of whom had rT1 disease, who underwent a transpalatal, transmandibular,
or transcervical approach. Hsu et al9 described
24 patients treated by a transpalatal, transmaxillary, or transmandibular
approach, with 46% surviving free of disease 8 to 50 months after surgery
(median, 18 months). King et al10 reported
on 31 patients, 29 of whom had rT1 or rT2 disease. The overall survival rate
was 47%, with 43% having tumor control and a 42% actuarial 5-year survival.
Finally, To et al11 described 15 patients with
a facial degloving approach assisted with a stereotactic navigation guidance
system; no follow-up data were provided.
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Table 3. Surgical Resection Results
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All of these surgical articles (including this one) demonstrate that
recurrent nasopharyngeal carcinoma can be resected through a variety and combination
of approaches with acceptable outcome and morbidity statistics. Unlike the
study by King et al,10 our study showed little
benefit with the addition of postoperative supplemental XRT. With the exception
of the transpalatal and the facial degloving approach, all of the other surgical
approaches produced significant trismus and/or an undesirable facial scar.
The wise surgeon will tailor the operation to the areas involved by tumor
and not try to make the tumor resection fit a standard operative approach.
For an individual patient, a combination of approaches may be necessary, similar
to patients who undergo resection for angiofibroma.
Resurfacing exposed bone with a skin or mucosal graft is a quick and
simple solution to a difficult problem. The take rates of these grafts vary
from 0% to 100% and average about 70%. For those patients who have had 2 courses
of XRT, use of skin or mucosal grafts is not adequate, as demonstrated by
5 of the 6 patients who developed a low-grade osteomyelitis of the skull base.
Using flaps such as a radial forearm free flap or temporalis fascia flap will
be problematic in anchoring the flap in position, because there is no soft
tissue remaining on the lateral or posterior walls of the nasopharynx. The
best method of reconstruction of this defect has yet to be determined.
The survival results for re-irradiation are given in Table 4. Wang12 reported a 5-year
actuarial survival rate of 38% for 32 patients with rT1 and rT2 disease and
15% for 6 patients with rT3 and rT4 disease. Pryzant et al13
demonstrated a 5-year actuarial local control rate of 35% and an overall survival
rate of 21%; those with rT1 or rT2 tumors had a survival rate of 32% vs 9%
for those with rT3 or rT4 tumors. This study also showed a 5-year local control
rate of 67% in 9 patients who underwent external beam irradiation (2000-3000
rad [20-30 Gy]), followed by 4000 to 5000 rad (40-50 Gy) by intracavitary
cesium. The study by Hwang et al14 of 74 patients
showed a 5- and 10-year actuarial survival rate of 37% and 18%, respectively,
suggesting that long-term follow-up is needed in this disease.
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Table 4. Studies of Re-irradiation*
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The report by Lee et al1 of 706 patients
treated for recurrences represents the world's largest series to date and
is precisely detailed. They readily admit that the data are old, because they
represent patients treated from 1976 to 1985, but much worthwhile information
can be obtained. Lee and coauthors reported survival rates of 27% for patients
with rT1 disease, 17% for patients with rT2 disease, and 4% for patients with
rT3 or rT4 disease. The report by Teo et al15
of a later period demonstrated a 5-year overall survival rate of 7.6% and
a 5-year local control rate of 15.2% with significant complications. Teo et
al15 reported survival rates of 26% for patients
with rT1 disease, 8% for patients with rT2 disease, and 3% for patients with
rT3 disease. They compared their statistics of additional irradiation of 103
patients with 20 patients (70% of whom received postoperative irradiation)
who underwent nasopharyngectomy; those undergoing nasopharyngectomy had a
statistically significant better survival than those who received high-dose
additional irradiation for rT1 and rT2 lesions; it is noteworthy that the
survival curves get very close at 4 years; therefore, this difference
may be only an early advantage. Nonetheless, they concluded that for the "suitably
chosen patient, nasopharyngectomy is preferred to re-irradiation mainly with
external beam to high dose."
Chua et al16 analyzed 212 patients treated
between 1984 and 1995. The 5-year overall survival rates were 57% for patients
with rT1 and rT2 disease, 42% for patients with rT3 disease, and 17% for patients
with rT4 disease. Unfortunately, this study combined patients with persistent
and recurrent disease even though it is well known that patients with persistent
disease do better than those with locally recurrent disease, as documented
by a study from the same institution.17 Kwong
et al17 demonstrated a 5-year overall survival
rate of 53.6% and a local control rate of 63% in patients undergoing gold-grain
implantation for rT1 lesions. Although this result is not as satisfactory
as the 73% reported in this article, it is definitely an improvement from
prior XRT articles. Chua et al18 described
10 patients with locally persistent or recurrent nasopharyngeal carcinomas
treated by stereotactic radiosurgery. Although the median follow-up of 10
months was short, the overall response rate was excellent at 60%, and complications
were said to be minimal. Orecchia et al19 treated
13 patients with hypofractionated stereotactic radiotherapy (2400 rad [24
Gy] in 2 or 4 fractions) with a 3-year overall survival of 31%, and no severe
acute or late complications were seen.
CONCLUSIONS
Surgical resection offers an advantage over additional irradiation for
rT1 and rT2 tumors, but newer modalities of XRT offer great promise. Although
not supported by data from this study, patients with rT3 tumors should be
treated either with surgery plus postoperative XRT or with XRT alone. Since
many of these patients with rT3 disease develop distant metastases, consideration
should be given to administering chemotherapy. Surgery would not seem to benefit
patients with rT4 tumors, except for palliation. A randomized prospective
trial comparing surgery to external beam irradiation plus implant or stereotactic
radiosurgery should be performed in countries where the disease is endemic,
paying particular attention to 2- to 5-year rates of complications.
AUTHOR INFORMATION
Accepted for publication October 2, 2001.
This study was presented at the annual meeting of the American Head
and Neck Society, Palm Desert, Calif, May 14, 2001.
Corresponding author and reprints: Willard E. Fee, MD, Stanford University
Medical School, Stanford, CA 94305-5328 (e-mail: wfee{at}stanford.edu).
From the Division of Otolaryngology/Head and Neck Surgery (Drs Fee,
Moir, and Choi) and Department of Radiation Oncology (Dr Goffinet), Stanford
University, Stanford, Calif. Dr Choi is now with the Department of Otolaryngology,
Yonsei University, Seoul, Korea.
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