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Cancer of the Nasal Cavity
Survival and Factors Influencing Prognosis
Neil Bhattacharyya, MD
Arch Otolaryngol Head Neck Surg. 2002;128:1079-1083.
ABSTRACT
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Objective To determine overall survival and prognostic factors for cancer of the
nasal cavity.
Design Cross-sectional analysis of a national cancer database.
Methods All cases of nasal cavity cancer were extracted from the Surveillance,
Epidemiology and End Results database for 1988 through 1998. Cases with distant
metastatic disease were excluded. Tumor histologic types, TNM staging, and
pathological features were computed. Kaplan-Meier and Cox proportional hazards
analyses were conducted to determine factors influencing overall survival.
Results A total of 981 cases were identified, with 3.5% presenting with distant
metastatic disease. After exclusion of missing variables, 783 cases were analyzed,
with a mean patient age of 63.8 years. Squamous cell carcinoma was the most
common tumor histologic type (49.3%), followed by esthesioneuroblastoma (13.2%).
More than half of the cases presented with early (T1) primary site disease,
and only 5% had positive nodal disease at presentation. Overall mean (median)
survival was 76 (81) months, with an overall 5-year survival rate of 56.7%.
On multivariate analysis, male sex, increasing age, T stage, N stage, and
poorer tumor grade independently adversely affected survival (P<.05). Radiotherapy was administered in 50.5% of patients and also
independently predicted poorer survival (P = .03).
The mean (median) survival for squamous cell carcinoma was 79 (84) months;
only melanoma showed a statistically significantly poorer mean survival of
40 (30) months when compared with other tumors (P<.001).
Conclusions Age, sex, and staging variables have a significant prognostic impact
in nasal cavity cancer. Melanomas of the nasal cavity manifest very poor survival.
INTRODUCTION
CANCER OF the nasal cavity proper is an uncommon clinical entity. Overall,
sinus and nasal malignancies account for 3% of upper aerodigestive tract malignancies,
and nasal cavity cancers themselves account for only a fraction of these tumors.1 Symptoms of nasal cavity cancer are also common manifestations
of many other more prevalent diagnoses, such as chronic rhinitis or sinusitis,
and therefore the diagnosis is often only secondarily suspected.2
Risk factors for nasal cavity cancer include exposure to wood dust, nickel,
and chemical solvents.3 Cigarette smoking has
also been strongly implicated.4
Given the rarity of the lesion, determination of survival and factors
affecting survival is often limited by sample sizes. Furthermore, analysis
is often confounded by the fact that many different histologic types may be
encountered in nasal cavity cancer, and, to date, an approved staging system
has not been accepted for carcinoma of the nasal cavity.5
To better understand the clinical behavior of nasal cavity cancer, a national
cancer database was used to determine staging, overall prognosis, and factors
affecting survival.
METHODS
The Surveillance, Epidemiology, and End Results6
database for the period 1988 through 1998 was examined. All cases of nasal
cavity malignancy were extracted from this database (International
Classification of Oncologic Diseases7
tumor code C30.0). Fields extracted from the database included standard demographic
information (age, sex, and year of diagnosis) as well as tumor-dependent variables
including histologic type of tumor, tumor grade, extent of disease, type of
surgery performed, and type of radiotherapy delivered. Survival time and vital
status were also extracted. The tumor histologic types were segregated into
1 of 8 broader histologic categories based on the International
Classification of Oncologic Diseases7
(Table 1). Tumor staging was determined
from extent of disease variables (Table
2). When tumor size, nodal disease, or metastasis could not be appropriately
determined, the data were coded as "missing." Cases for which tumor stage
was indeterminate or in situ were excluded from the database. In addition,
patients in whom distant metastatic disease was identified (M1) were eliminated
from the database, as these patients were unlikely to be treated with curative
intent.
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Table 1. Tumor Histologic Findings and Survival for Nasal Cavity Cancer*
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Table 2. Staging Definitions for Nasal Cavity Malignancy
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The data were then imported into SPSS version 10.0 software (SPSS Inc,
Chicago, Ill) for subsequent processing. Standard descriptive statistics were
computed for the variables under consideration. Kaplan-Meier survival analysis
was conducted for the entire cohort. The potential effect of clinical variables
on survival was determined by means of a Cox proportional hazards model. All
variables were entered simultaneously in the multivariate model. For the purposes
of the proportional hazards analysis, missing values were recoded to the mean
value for the same variable. P values less than .05
were considered statistically significant. Hazard ratios and 95% confidence
intervals were computed for variables with a statistically significant impact
on overall survival.
RESULTS
A total of 981 cases of cancer of the nasal cavity were identified in
the Surveillance, Epidemiology, and End Results database. At presentation,
34 patients (3.5%) had evidence of distant metastatic disease. For 164 patients,
T stage was in situ or could not be determined, and they were dropped from
subsequent analysis. Thus, 783 cases were included in the survival analysis.
Of the patients, 55.6% were male, with a mean age of 63.8 years. The incidences
for the various tumor histopathologic types are listed in Table 1. The distributions of T stage, N stage, and tumor grade
are presented in Table 3. For
patients alive at the end of the period, the mean follow-up was 45.9 months.
For the overall cohort, the mean (median) survival was 76 (81) months. Overall
5-year survival was 56.7% (Figure 1).
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Table 3. TNM and Grade Classification and Survival for Nasal Cavity
Cancer*
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Figure 1. Overall survival for the entire
cohort.
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Survival variables according to T stage, N stage, and tumor grade are
tabulated in Table 3. On univariate
analysis, T stage, N stage, and tumor grade each statistically significantly
influenced survival (P<.001). Survival curves
according to these variables are depicted in Figure 2, Figure 3, and Figure 4. Radiotherapy was administered to
50.5% of patients. Mean (median) survival for patients receiving radiotherapy
was 69 (58) months vs 86 (94) months for those patients who did not receive
radiotherapy. This difference in survival was significant (P<.001). When stratified according to T stage, differences in survival
with and without radiotherapy were not significant for T1, T3, and T4 lesions.
T2 lesions fared worse if they required radiotherapy (P<.001; Figure 5). Given
the negative association between radiotherapy and survival identified for
T2 lesions, further subgroup analysis was conducted. The distribution of histologic
types within the T2 group did not differ significantly from that of the overall
cohort. Eighty-eight percent (56/64) of patients in this group also underwent
cancer-directed surgery. This limits a potential bias against radiotherapy
by diminishing the chance that these patients simply underwent biopsy and
then were treated with curative radiotherapy alone.
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Figure 2. Overall Kaplan-Meier survival
according to T stage.
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Figure 3. Overall survival according to
nodal stage.
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Figure 4. Overall survival according to
tumor grade.
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Figure 5. Survival for T2 lesions with (XRT+)
and without (XRT-) radiotherapy.
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Results of the Cox proportional hazards analysis are tabulated in Table 4. On multivariate analysis, increasing
age, male sex, increasing T stage, increasing N stage, and increasing tumor
grade each significantly reduced survival for nasal cavity cancer. Also, radiotherapy
was associated with a significant reduction in overall survival. Among tumor
histologic types, only malignant melanoma was associated with a statistically
significant decrease in survival. Hazard ratios and 95% confidence intervals
are also listed in Table 4.
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Table 4. Results of Cox Regression Analysis for Survival Outcome*
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COMMENT
Cancer of the nasal cavity proper is an uncommon entity. Because it
is so uncommon, several problems arise when attempts are made to determine
its clinical behavior. First, tumors of the nasal cavity proper have historically
often been rolled into case series of paranasal sinus carcinoma, making determination
of survival indistinct for cancer of the nasal cavity proper. Survival analysis
is also hampered by the fact that many different cancer histologic types may
be encountered in the nasal cavity.8 The lack
of a universally accepted staging system for malignant tumors of the nasal
cavity leads to additional difficulties when survival results are compared
across various studies.5 Likewise, significant
variations in treatment exist in the literature, with some authors recommending
radiotherapy primarily for these tumors, other authors recommending combination
therapy, while still others recommend radical surgery.9-11
The goal of the present study, which used data from a national cancer database,
was to examine enough cases in a short period to provide sample sizes large
enough to undergo multivariate analysis with respect to histologic type, staging,
and other clinical variables, in hopes of overcoming some of these difficulties.
Squamous cell carcinoma was by far the most common malignant tumor of
the nasal cavity proper, accounting for almost 50% of cases, in keeping with
other institutional series of nasal cavity cancer.9
In a dual-institutional series of 32 patients with squamous cell carcinoma
of the nasal cavity, Fornelli et al5 identified
an absolute 2-year survival of 69% and an overall 5-year survival of 50%.
Recurrence was common, occurring in 56% of patients, with most (13 of 18 cases)
being regional recurrences. They found that multiple subsite involvement within
the nasal cavity predicted poorer survival. Interestingly, patients with known
occupational risk factors for cancer of the nasal cavity did not demonstrate
more advanced disease at presentation or higher recurrence rates. Our 5-year
survival for squamous cell carcinoma of the nasal cavity approximating 60%
reinforces the survival results reported in the literature.5
Adenoid cystic carcinoma also exhibited a similar 5-year survival of
59.1%, in keeping with the results of others.12
However, survival for adenoid cystic carcinoma of the nasal cavity is probably
better assessed by 10-year survival rates, since patients may live significant
periods with locally recurrent but slowly progressive disease. Our data also
reinforce the data of Lund et al,12 who found
that chondrosarcoma and esthesioneuroblastoma tended to exhibit more favorable
survival than other histologic types within the nasal cavity and paranasal
sinuses. Among the histologic types encountered, melanoma was clearly found
to manifest the poorest survival, demonstrating a survival of only 22% at
5 years. Melanoma of the sinonasal cavity has previously been found to carry
a very poor prognosis, with other authors reporting 5-year survival rates
ranging from 19% to 31%.13-15
Sinonasal undifferentiated carcinoma also exhibited a relatively poorer survival
than other lesions, although this difference was not statistically significant
on multivariate analysis. Other authors have previously commented on the relatively
aggressive nature of sinonasal undifferentiated carcinoma, with very poor
3-year survival rates despite aggressive multimodality therapy.16
Comparing survival and treatment results from various authors for cancer
of the nasal cavity is difficult primarily because of the lack of a uniformly
accepted staging system. The staging system used in the present study did
effectively segregate patients into distinct clinical groups that had notably
different survivals (Figure 2).
Therefore, the T-stage designations proposed in Table 2 deserve further prospective study. As this was a retrospective
analysis based on a national database, I cannot recommend this as a primary
site staging system until it is validated by further prospective evaluation.
Not surprisingly, a more advanced T stage predicted significantly poorer survival,
on both univariate and multivariate analysis. Although advances in craniofacial
resection and reconstructive techniques have made almost every cancer of the
nasal cavity "resectable," involvement of the eye and anterior cranial fossa
remain clinically important negative prognostic factors.12
These data clearly indicate that cervical node involvement at the time
of presentation predicts poorer survival in nasal cavity cancer. Given that
the hazard ratio was highest for nodal involvement among the variables studied,
this is a very significant prognostic factor. Since nodal involvement has
such a pronounced impact, treatment of positive cervical disease should be
aggressive. However, in the case of necks with N0 disease, treatment of the
ipsilateral lymphatic drainage basins has been the subject of some controversy.
Netterville et al17 found that regional metastasis
from midface carcinomas may arise in a delayed fashion. Therefore, at the
very least, these patients merit careful extended follow-up.
Tumor grade was found to have a significant prognostic impact on both
univariate and multivariate analysis. The influence of tumor grade is well
established for esthesioneuroblastoma, with more poorly differentiated lesions
faring far worse overall.18 Up to this point,
tumor grade in nasal cavity cancer has received relatively little attention
in the literature. Our data clearly show that tumor grade exerts a significant
influence on survival both on univariate and multivariate analysis (Table 3 and Table 4). More undifferentiated carcinomas exhibited substantially
poorer survivals while histologic type and staging factors were controlled
for on multivariate analysis. Further study of tumor grade may be appropriate
for carcinoma of the nasal cavity, as it may help select subgroups of patients
with given histologic types that are likely to do poorly without aggressive
therapy.
Recent advances in radiotherapy have allowed the delivery of higher
doses of external beam radiation and particle radiation to the nasal cavity
and paranasal sinuses, while sparing critical structures such as the globe
and optic chiasm.19-20 Some centers
have reported successful treatment of nasal cavity cancer with radiotherapy
alone.9 Whether to use radiotherapy as a primary
treatment modality or as an adjunct to surgery depends on the histologic type
of the lesion, the initial tumor extent, and the status of postoperative margins.
In certain histologic types, such as esthesioneuroblastoma, radiotherapy offers
a significant survival benefit, especially for more advanced lesions.21 Unfortunately, risk to the globe and vision is often
the rate-limiting step in radiotherapy for these cancers.9
Somewhat surprising were the survival trends for patients who receive
radiotherapy. On univariate analysis, radiotherapy was found to be associated
with poorer survival rather than improved survival for the overall cohort.
On stratified analysis according to T stage, the use of radiotherapy was found
to exert a negative prognostic influence on survival only for T2 lesions;
survival for other T stages was not significantly influenced by radiotherapy.
On multivariate analysis, radiotherapy was found to be an independent predictor
of poorer survival (hazard ratio, 1.35). Since the multivariate analysis controls
for tumor histologic type and primary site stage, radiotherapy does seem to
influence prognosis negatively. The reasons for this are unclear, and this
deserves further study.
Although the current method provides a large sample size with a wide
variety of tumor histologic types and stages accrued in a relatively short
period with good follow-up, it has several limitations. As this is a national
cancer database, the analysis is dependent on the accuracy of recorded information,
especially information concerning extent of disease. Although data are entered
by trained personnel, variations in diagnostic evaluation such as use of computed
tomography and/or magnetic resonance imaging and other factors may alter the
staging for a given patient. However, since the tumor registry spans multiple
regions and institutions, systematic biases in staging or treatment should
be limited. One significant drawback of the database is that no information
is available with respect to the status of surgical margins. Surgical margins
are widely believed to be a significant prognostic factor in head and neck
cancer. However, the interpretations of surgical margins at the skull base
and within the nasal cavity are fraught with difficulties. Analysis of bone
margins is complex, and the intricate 3-dimensional nature of the nasal cavity
and adjoining structures makes margin interpretation even more difficult.
I believe that these disadvantages of the Surveillance, Epidemiology, and
End Results database are offset by the advantages afforded by larger sample
size and the diversity of the patient population studied.
CONCLUSIONS
Prognosis in cancer of the nasal cavity is determined by multiple factors
including T stage, N stage, tumor grade, and tumor histologic type as well
as age and sex. All of these factors need to be considered when treatment
modalities and prognosis are determined for patients with newly diagnosed
cancer of the nasal cavity. Further study will be required to determine whether
the staging system used herein will prove valuable in prognostication and
evaluation of various treatment modalities in the future.
AUTHOR INFORMATION
Accepted for publication March 5, 2002.
Corresponding author: Neil Bhattacharyya, MD, Division of Otolaryngology,
333 Longwood Ave, Boston, MA 02115.
From the Division of Otolaryngology, Brigham and Women's Hospital,
Department of Otology and Laryngology, Harvard Medical School, Boston, Mass.
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