Parotid Gland Carcinoma: Surgical Strategy
Based on Local Risk Factors
Francesco Carinci, MD*
Antonio Farina, MD†
Stefano Pelucchi, MD‡
Carlo Calearo, MD‡
Antonio Pastore, MD‡
Ferrarra, Italy
To evaluate the best surgical strategy in cases of
parotid gland carcinoma, local risk factors (T, N,
histology, and treatment) were analyzed in a series
of 134 patients. The efficacy of the facial nerve sac-
rifice in case of macroscopic tumor infiltration was
tested by means of survival analyses (Kaplan-
Meier and Cox algorithms). This study demon-
strated that nerve preservation resulted in a better
prognostic value when compared with resection
only in the group of patients having a T1 or T2. In
patients affected by T3 and T4, the different treat-
ment did not show any difference in survival rate.
In conclusion, the sacrifice of the facial nerve is not
always able to improve the survival rate.
Key Words: Parotid gland, carcinoma, survival, treat-
ment, surgery
P
rimary parotid gland epithelial malignancies
are rare, accounting for approximately 1% to
3% of all head and neck carcinomas.1 The
histological variety of such tumors and their
different natural history can make therapeutic strat-
egy controversial. Appropriate management of pa-
rotid gland carcinoma requires up-to-date informa-
tion regarding prognostic factors able to affect
survival. Among them, the local anatomical extent of
the tumor is one of the most important and is defined
by T and N categories.2
In the present article, we analyzed the local risk
From the *Chair of Maxillofacial Surgery, University of Ferrara,
Ferrara, Italy; †Institute of Histology, University of Bologna, Bo-
logna, Italy; and ‡E.N.T. Clinic, University of Ferrara, Ferrara,
Italy.
Address correspondence to Dr Carinci, E.N.T. Clinic, University
of Ferrara, Arcispedale S. Anna, C.so Giovecca 203, 44100 Ferrara,
Italy. E-mail: crc@unife.it
434
factors (T, N, histology, and treatment) by mean sur-
vival analyses to verify the reliability of different
treatment protocols in cases of parotid gland carci-
noma.
PATIENTS AND METHODS
P reviously, patients, tumor, and treatment were
widely described.3 Briefly, 134 patients with a
histologically proven carcinoma of the parotid gland
were analyzed for follow-up at 60 months. Thirty
(22.4%) had neck nodes and none had evidence of
distant metastases at the time of admission. There
were 71 males (53%) and 63 females (47%). The me-
dian age (minimum–maximum) was 59 (range: 11–
87) years at the time of presentation.
Table 1 shows frequency, number of positive
neck nodes, and breakdown of tumors according to
histological type. Tumors were clinically staged ac-
cording to the 1997 International Union Against Can-
cer Classification (Table 2).
Table 3 shows frequency and modality of tumor
treatment of all 134 patients classified according to
the International Union Against Cancer 1997 stage
grouping. Surgery on T was the principal treatment,
and it was performed in the initial course of the
therapy. Group I is composed of patients who un-
derwent total parotidectomy with preservation of the
facial nerve, whereas Group II is composed of pa-
tients who underwent total parotidectomy with re-
section of the seventh nerve.
Neck dissection was performed in 41 patients, 28
of whom had clinical evidence involvement of lymph
nodes at admission (2 cases of positive neck nodes
did not have neck dissection).
Radiotherapy was delivered to 50 patients with
external beam and the dose was equivalent to 60 to
65 Gy in 6 to 7 weeks. Postoperative radiotherapy
was given not only for positive margins and/or ex-
tracapsular nodal metastases but also for high-grade
malignant tumors.
 PAROTID GLAND CARCINOMA / Carinci et al

Table 1. Frequency and Breakdown of Tumors Table 3. Distribution of the Series by Treatment
According to the Histologic Type Modality and Stage Grouping Calculated Using UICC
1997 Classification
No. of Cases No. (%) of
Histologic Type No. % with Neck Nodes 5-Year Survival No. (%) of
5-Year
Mucoepidermoid Ca. 26 19.4 2 22 (84.6) Therapy I II III IVa IVb Total % Survival
Acinic cell Ca. 17 12.7 3 14 (82.3)
Adenoid cystic Ca. 35 26.1 1 27 (77.1) Group I
Malignant mixed Ca. 9 6.7 2 6 (66.7) TS 17 30 8 2 — 57 42.5 53 (93.0)
Adenocarcinoma 21 15.7 11 9 (42.9) TS + ND 1 — 1 4 — 6 4.5 5 (83.3)
Squamous cell Ca. 19 14.2 10 7 (36.8) TS + RxT — 8 10 3 — 21 15.7 10 (47.6)
Anaplastic Ca. 7 5.2 1 2 (28.6) TS + ND + RxT — — 5 4 1 10 7.5 5 (50)
Group II
TS — — 3 6 — 9 6.7 4 (44.4)
TS + ND 1 — 1 10 — 12 9.0 3 (25)
STATISTICAL ANALYSIS TS + RxT — — 1 5 — 6 4.5 3 (50)
TS + ND + RxT — — 2 10 1 13 9.7 4 (30.7)
Univariate Analysis
Group I: without 7th nerve sacrifice.
Group II: with 7th nerve sacrifice.

S urvival curves were calculated according to the

product-limit method (Kaplan-Maier algo-
rithm).4 Time zero was defined as the date of the
TS = surgery on T; ND = neck dissection; RxT = radiotherapy.

patient’s initial diagnosis. Patients who are still alive
were included in the total number at risk for death
only up to the time of their last follow-up. Therefore,
survival rate only changed when death occurred.
The calculated survival curve was the “most likely”
estimate (“maximum likelihood” estimate) of the
true survival curve. Log-rank test was used to ex-
plore differences among the survival curves strati-
fied for the variable of interest.
confidence bounds were calculated. Confidence
bounds do not have to include the value “1”.5
If a positive and significant odds ratio was ob-
served for the independent variables, then an appro-
priate number of categories was generated in appro-
priate dummy variables to better explore the
association with the dependent variable (death). Un-
der this assumption, the lower category of indepen-
dent variable was considered as reference level.

Multivariate Analysis RESULTS

Cox regression analysis was then applied to deter-
mine the single contribution of covariates on survival
rate according to Group I and Group II. Cox regres-
T he crude survival rate was 64.9% after a follow-
up of 5 years, irrespective of the extent of the
tumor, the histological type, and the treatment.
sion analysis compares survival data while taking The proportion of patients surviving 5 years af-
into account the statistical value of independent vari- ter time of diagnosis according to T1, T2, T3, and T4
ables such as age and gender on whether an event categories were 95%, 88.4%, 55.6%, and 34.1%, re-
(i.e., death) is likely occur. If the associated probabil- spectively.
ity was less than 5% (P < 0.05), the difference was The 5-year survival rates into the groups strati-
considered statistically significant. In the process of fied according to histological type are reported in
doing the regression analysis, odds ratios and 95% Table 1.
The 5-year survival by N stage was N0 72.1%,
N1 50%, N2 25%, and N3 0%, respectively.
Table 2. Distribution of the Series by T and N
The survival curve of treatment modalities was
According to 1997 UICC T Classifications
developed dividing patients into two groups (Fig 1).
No. (%) 5-Year The first group (Group I) comprised patients treated
T N0 N1 N2 N3 Tot % Survival by total parotidectomy with conservation of the fa-
cial nerve. The second (Group II) was patients
T1 19 1 — — 20 14.9 19 (95.0)
T2 38 5 — — 43 32.1 38 (88.4)
treated by total parotidectomy with resection of the
T3 23 2 2 — 27 20.2 15 (55.6)
seventh nerve. The 5-year survival rates by groups
T4 24 12 6 2 44 32.8 15 (34.1) were 77.7% and 35%, respectively. These data reflect
not only differences in treatment modalities, but also

435
THE JOURNAL OF CRANIOFACIAL SURGERY / VOLUME 12, NUMBER 5 September 2001

resection (odds ratio 12.8) only in patients having a

low T. In the group having a high T, the treatment
does not reach any statistical value in defining the
prognosis.

DISCUSSION

I t has been known for a long time that seventh

nerve involvement is an extremely important
prognostic factor for survival, because very few pa-
tients presenting with facial paralysis survive their
disease.6–12 Biorklund and Eneroth6 reported a study
of 378 malignant parotid tumors in which they found
100% mortality in patients with facial nerve paraly-
sis. The same result was observed by Pedersen et
al.10 We also have previously reported a worse prog-
nosis in cases of facial palsy.8,13 In our series, only
36.6% (15/41) of the patients with involvement of the
facial nerve are still alive at 5 years. This risk factor
has been recognized by the International Union
Against Cancer, which in the last classification has
classified all the cases with seventh nerve involve-
Fig 1 Survival rate calculated according to treatment mo- ment as T4.2
dalities. ␹2 = 29.93, P < 0.0001, with 1 df, log-rank test. As previously reported,3 histological tumor type
is another relevant prognostic factor, above all in
terms of different biological behavior.6,9–11,14 Al-
the status of the disease. In fact, in Group I, 12 of 94 though there is no absolute agreement between the
(12.8%) patients were T4, and 14 of 94 (14.9%) pa- various authors, it is evident that there are different
tients were stage IV, whereas in Group II, T4 and “degrees” of malignancy. In this light, anaplastic
stage IV were both 32 of 40 (80%). squamous cell carcinoma and high grade mucoepi-
All the variables considered (T, N, histological dermoid have the worst prognosis, whereas low
type, and Group) in univariate survival analysis grade mucoepidermoid and acinic cell carcinoma
yielded a significant P value. have the best.6,11 Furthermore, for same carcinoma,
A Cox analysis was performed using the Group such as acinic cell carcinoma and above all adenoid
(I versus II) as predictors of survival adjusted for T, cystic carcinoma, it is essential to have a very long
N, histological type, age, and gender of the patients. follow-up (10–15 years) to correctly estimate the sur-
To better show the effect of the therapy in the pres- vival because they maintain their potential malig-
ence of lower T (T1 and T2) and higher T (T3 and T4), nancy for a long period.6,9 Finally, the grading is of
two different Cox models were used (Models 1 and paramount importance in determining prognosis for
2), splitting the series according to low and high T some histological types, such as the mucoepidermoid
(Table 4). As shown, the preservation of the facial carcinoma and adenoid cystic carcinoma.6,9–11 In our
nerve has a better prognosis when compared with series, we have found differences in the rate of me-
tastases and in survival according to the histological
type (Table 1). Moreover, we previously demon-
Table 4. Cox Regression Analyses for T Adjusted
strated3 that the histological type is one of the stron-
for Therapy
ger axes in determining the prognosis of the patients,
Covariate Odds Ratio 95% Bounds P-Value only second to the T category.
Cervical lymph nodes are a statistically signifi-
Model 1
cant predictor of survival, as well as in other head
T1 vs. T2 2.73 0.27–26.85 NS
and neck oncological regions.15,16 In our series, glob-
Therapy 12.89 1.24–132.52 0.0323
Model 2
al survival is 72.1% (75/104) and 40% (12/30) in case
T3 vs. T4 2.52 1.64–3.87 <0.001
of N0 and N1–3, respectively. The rate of regional
Therapy 1.57 0.79–3.15 NS metastases is different according to the different his-
tological types (Table 1), as found also by Spiro et

436

al.11 Although in case of positive neck nodes neck
dissection (with or without radiotherapy) is manda-
tory, the best protocol in patients with N0 is still
under debate.9,11,17 Spiro et al.11 and Kane et al.9 rec-
ommended performing neck dissection in almost ev-
ery case. In our patients with negative lateral lymph
nodes, the survival rate at 5 years is 85.9% (55/64) in
“wait and see,” 50% (5/10) in patients treated with
neck dissection, 48.1% (13/27) in patients treated
with radiotherapy, and 66.7% (2/3) in patients
treated with both neck dissection and radiotherapy.
This result also reflects the T status because the per-
centage of T4 is 12.5% (8/64), 70% (7/10), 29.6%
(8/27), and 33.3% (1/3), respectively. From these
data we infer that the best strategy could be “wait
and see” (or radiotherapy) in case of T1–2 of low
grade (or high grade) carcinomas, whereas neck dis-
section (with or without radiotherapy) remains the
best option in case of T3–4.
Different treatment strategies for parotid gland
surgery (preservation versus resection of the seventh
nerve) have been proposed. Biorklund and Eneroth6
recommended performing a total parotidectomy and
sacrificing the facial nerve in all of the histological
types but highly differentiated mucoepidermoid car-
cinoma and acinic cell carcinoma. Conversely, Frank-
enthaler et al.7 have obtained good results preserving
the seventh nerve when it is not incorporated in tu-
mor. Our results are shown in Table 3 and Figure 1.
Group I showed a significantly higher survival rate
when compared with Group II. This, according to
our analysis that yielded a significant odds ratio for
the T, would be related to the different rate of T4
patients (12 of 94 cases or 12.8% versus 32 of 40 or
80%) into Group I and II, respectively. Because of a
good correlation between the T and survival, we be-
lieve that it is correct to perform a total parotidecto-
my with preservation of the facial nerve when there
is no clinical or macroscopic evidence of invasion of
the nerve. Finally, in agreement with other au-
thors,6,7,9,10 radiotherapy has been used as an adju-
vant for surgery not only for positive margins
and/or extracapsular nodal metastases but also for
high grade malignant tumors, because we thought
that it decreases local recurrence and distant me-
tastases. As shown in Table 3, in case of advanced
disease (as in Group II, which is mainly composed of
PAROTID GLAND CARCINOMA / Carinci et al
stage III and IV), the 5-year survival rate for com-
bined treatment protocols (surgery plus radio-
therapy) produces a better result than surgery on T
alone (3 of 6 versus 4 of 9), even if the comparison of
the two proportions is not statistically significant.
Thus, we conclude that multimodality treatment
protocols are indicated in advanced cases.
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