Keywords
carcinoma - squamous cell/surgery - mouth neoplasms/therapy - neck dissection/methods
- neoplasm recurrence, local - survival rate
Introduction
Oral cancer is among the commonest cancers in some parts of South Asia.[1]
[2] Over 95% of oral cancers are squamous cell carcinomas (SCCs).[3] The estimated incidence of cervical metastasis in this group is of up to 40%.[4] Multiple studies have shown that the presence of neck metastasis is the most important
prognostic factor in the management of oral cancers.[5]
[6] The presence of neck metastasis reduces the survival by up to 50%.[7]
[8] Therefore, neck dissection is considered a standard of care in the treatment of
oral cancers. However, morbidity associated with neck dissection remains a challenge.[9]
[10] Currently, by consensus, supraomohyoid neck dissection (SND), as well for node negative
oral SCC. However, the role of selective neck dissection in clinically palpable nodes
is controversial, as many surgeons still recommend comprehensive neck dissection in
patients with node-positive disease.[11]
[12]
In the past 2 decades, many clinicians have explored the role of selective neck dissection
in node-positive SCC. In the beginning of the present century, Loree et al[13] showed that the overall regional control rates with selective neck dissection were
88 versus 71% for pathologically negative versus positive-node neck disease, respectively.
Two recent review articles on the same subject have also concluded that SND can be
an adequate substitute for comprehensive neck dissection (CND) without compromising
oncological efficacy.[14]
[15] Interestingly, studies have also shown that < 50% of the clinically palpable nodes
turn positive pathologically.[16] The reason for this lymphadenopathy can be superimposed infection at the cancer
site or tuberculosis (TB) lymphadenitis, especially in the regions where TB is endemic.[17] Based on these observations, a recent article from the All India Institute of Medical
Sciences has also proposed that comprehensive neck dissection in all clinically palpable
oral cancers may not be warranted.[16]
Despite the changing trends toward performing selective neck dissection internationally,
the practice is still different in our part of the world. Most of our local surgeons
still recommend comprehensive neck dissection as the standard of care for node-positive
SCC, with specific reference to studies by Ehsan ul Haq et al.[18] and Shaikh et al.[19] There is severe scarcity of local published literature available on the subject
of selective neck dissection in node-positive oral cancers. Therefore, the role of
selective neck dissection in node-positive neck needs to be explored in our set of
patients.
Based on this background, we intend to evaluate the role of selective neck dissection
in clinically positive oral SCC, and to compare it with node-negative oral cancers
in terms of regional control and disease-free survival.
Material and Methods
First, approval of the study was obtained from the Ethics Review Committee of the
hospital (approval form no 36). A review of the prospectively collected oral cancer
database of the Department of Otolaryngology Head and Neck Surgery at a tertiary care
hospital was performed. All patients who underwent selective neck dissection for SCC
involving the oral cavity and lip between April 2006 and July 2015 were reviewed.
The medical records of these patients were also reviewed to confirm findings of the
database. Only patients with primary SCC of the lip or of the oral cavity were included.
Non-SCC cancers, patients who underwent resection of nonlymphatic structures such
as the sternocleidomastoid muscle (SCM), the spinal accessory nerve (XI Nerve), the
internal jugular vein (IJV), or the skin, and patients who underwent comprehensive
neck dissection (that is, radical or modified radical neck dissection) and/or preoperative
chemoradiation were excluded from the study.
Selective neck dissection for SCC of the oral cavity or of the lip involves the systematic
and comprehensive removal of lymph nodes and lymphatic-bearing tissue from neck levels
I, II, III and/or IV.[20]
[21] Nonlymphatic structures such as the SCM, the XI nerve, and the IJV are preserved.
The extent of SND in the present study corresponded to this definition.
All patients were divided into two groups, one with clinically node-negative and the
other clinically node-positive, irrespective of the site and stage of the primary
site. Both groups underwent selective neck dissection and postoperative radiotherapy,
except for those in early T stage with pathologically N0 disease. All patients were
regularly followed-up in the ear, nose, and throat (ENT) clinic. Data was prospectively
collected by a dedicated research officer either face to face in the clinic, or by
telephonic interviewing of the patients.
Categorical variables are analyzed as proportions and compared between groups with
the chi-squared test. Continuous variables are analyzed as means with standard deviations
(SDs). Both groups were analyzed separately in terms of disease-specific survival
and regional recurrence/residual rates with Kaplan Meier curves.
Results
A total of 124 patients were retrieved from our database. On review of their medical
records, 13 patients were excluded because of the exclusion criteria outlined above.
A total of 111 patients were analyzed; 70 patients belonged to the clinically node-negative
group and 40 patients belonged to the clinically node-positive group. Their mean age
was 47 (SD: 11.97) years old. Eighty-five (76.6%) patients were male and 26 (23.4%)
were females. Our mean follow-up period was 16.62 months (SD: 17.03), ranging from
1 to 78 months. All patients underwent selective neck dissection along with resection
of the primary tumor. The mean total number of lymph nodes dissected in our patients
was 34.75 (SD: 15.12). All patients beyond stage I disease were advised to undergo
postoperative radiotherapy. Eight patients from the node-negative group and two from
the node-positive group did not receive radiation. Distributions of different variables
in both groups are shown in [Table 1].
Table 1
Demographics and other variables from node-negative and node-positive groups
|
Variable
|
Node-negative
|
Node-positive
|
|
Total patients
|
71
|
40
|
|
Age (years old)[*]
|
49 (25–85)
|
43.70 (22–64)
|
|
Male
|
55 (77.5%)
|
30 (75%)
|
|
Female
|
16 (22.5%)
|
10 (25%)
|
|
Total number of nodes[*]
|
35
|
34.3
|
|
Follow-up (months) (SD)[*]
|
16.21 (14.48)
|
17.35 (21)
|
|
RTx Dose#
|
66 Gy
|
66 Gy
|
Abbreviations: RTx, Radiation therapy; SD, standard deviation.
* mean, # Mode.
The most common primary site was the buccal mucosa (56.7%), followed by the tongue
(25.2%). The different subsites and their association with node-negative and node-positive
groups is depicted in [Table 2]. In both groups, the buccal mucosa remains the most common site, followed by the
tongue. Most of the patients in the present study had stage IV disease, mainly because
of their T Stage. The distribution of T stage in our patients is shown in [Fig. 1]. Both in the node-negative and in the node-positive group, T4 remains the most common
stage, followed by T2 and T3, respectively. Further details are shown in [Table 3]. Thus, the majority of our patients had locally advance disease.
Table 2
Oral cavity subsite distribution among node-positive and node-negative groups
|
Node Status
|
Lip
|
Buccal mucosa
|
Oral tongue
|
Hard palate
|
Lower alveolus
|
Floor of mouth
|
Retromolar trigone
|
Total
|
|
Node-negative
|
3 (4.22%)
|
38 (53.5%)
|
21 (29.6%)
|
3 (4.22%)
|
2 (2.8%)
|
1 (1.4%)
|
3 (4.22%)
|
71 (100%)
|
|
Node-positive
|
1 (2.5%)
|
26 (65%)
|
6 (15%)
|
1 (2.5%)
|
4 (10%)
|
0 (0%)
|
2 (5%)
|
40 (100%)
|
Fig. 1 Tumor (T) staging of the patients.
Table 3
Tumor stage distribution among node-positive and node-negative groups
|
Tumor stage
|
Node-negative
|
Node-positive
|
|
T1
|
13 (18.3%)
|
4 (10%)
|
|
T2
|
21 (29.6%)
|
5 (12.5%)
|
|
T3
|
9 (12.7%)
|
9 (22.5%)
|
|
T4
|
28 (39.4%)
|
22 (55%)
|
|
Total
|
71 (100%)
|
40 (100%)
|
All patients, irrespective of the primary site, were treated with resection of the
primary tumor with grossly negative margins, selective neck dissection, and reconstruction
of the defect with microvascular free flap, if required. A total of 101 out of 111
(91%) patients received adjuvant postoperative radiation.
The statistics related to the clinical and pathologic nodal staging of our patients
is shown in [Table 4]. A graphical presentation of the statistics is shown in [Fig. 2]. One very important finding is the conversion rates of clinical versus pathological
staging. Twenty-one out of the 71 (29.5%) patients of the clinically node-negative
group turned out to be positive for cervical metastasis on histopathology. Most of
the clinically missed nodal metastasis staging was N2b. Fifteen out of 40 clinically
node-positive patients were pathologically N0. This conversion is of high statistical
significance, with p value< 0.001, as shown in [Table 4].
Table 4
Nodal staging and conversion of nodal staging patients
|
N Stage
|
Clinical
|
Pathological
|
|
N0
|
72(64.9%)
|
65(58.6%)
|
|
N1
|
28 (25.2%)
|
15 (13.5%)
|
|
N2a
|
06 (5.4%)
|
02 (1.8%)
|
|
N2b
|
05 (4.5%)
|
27 (24.3%)
|
|
N2c
|
0
|
02 (1.8%)
|
|
N3
|
0
|
0
|
Fig. 2 Nodal (N) staging of the patients.
All patients had no evidence of distant metastasis prior to treatment. The main outcome
measures of our patients were disease-specific survival and regional control rates.
Additionally,, distant survival rates were also calculated. Disease-specific survival
in the node-negative group was 84.5 compared with 82.5% in the node-positive group
(p = 0.703). Seven out of 40 patients in the node-positive group expired because of
the disease, 2 of whom were pathologically N0, and rest were N2. The earliest dip
in the graph is at 2 months, because of 2 patients, both belonging to N1 stage clinically.
This is shown as a Kaplan-Myer depiction of survival in [Fig. 3].
Fig. 3 Comparison of disease specific survival in node positive and node negative group.
The regional control rate was of 94.4% in the node-negative group versus 95% in the
node-positive group. In total, 6 patients developed neck disease; 3 of them presented
with residual disease (that is, disease coming back within 6 months of surgery), while
3 presented with recurrence (that is, after 6 months of surgery). Interestingly, 4
of them were from the node-negative group and all presented residual disease, except
for one who presented with recurrence at 1 year postoperatively. The cases in the
node-positive group presented with recurrences at 7 and 57 months (postoperatively),
respectively. The second case also had second primary SCC. The statistical difference
of both groups in this regard is also insignificant (p = 0.47 not significant [NS]). The comparison of outcomes in both groups along with
distant metastasis is shown in [Table 5]. Further description as Kaplan Myer graphs are shown in [Figs. 3] and [4].
Table 5
Outcome measures of the two groups
|
Clinical node status
|
Disease-specific survival (%)
|
Regional control (%)
|
Distant metastasis (%)
|
|
Node-negative
|
84.50
|
94.40
|
2.80
|
|
Node-positive
|
82.50
|
95
|
10
|
Fig. 4 Comparison of regional recurrence in node positive and node negative group.
Discussion
In summary, disease-specific survival and regional control rates were statistically
similar both in the node-positive and in the node-negative groups. Another important
finding of the present study is the significant conversion rates of clinical nodal
staging versus pathological staging. This shows that clinical staging alone is not
sufficient to decide the type of neck dissection. Therefore, instead of exposing the
patients to radical surgeries, we should look into other aspects of cancer biology
to optimize the quality of life (QOL) of our patients, without negatively impacting
the oncological outcome.
Neck dissection still remains the most important part of oral cancer treatment. Since
its introduction in the literature by Crile,[22] the extent of neck dissection has been the subject of significant debate and discussion.
Over the past 3 decades, there has been a significant increase in the amount of literature
supporting conservative or selective neck dissection. The concept of selective neck
dissection first came from the studies done by Shah et al. when the mapping of lymphatic
spread was shown from different subsites of the head and neck. Shah et al. demonstrated
in their remarkable study of 501 oral SCC patients that level IV metastasis only occurs
in ∼ 15% of patients with oral SCC and in < 4% of patients on level V.[21] He also concluded that level V metastasis is almost always associated with metastasis
at other levels. Other researchers have also supported the finding that that skip
metastasis to level IV and V is rare.[16]
[23] In general, it is recommended to include all those levels in nodal dissection, in
which the chances of occult metastasis are > 20%.[24]
[25] Therefore, elective neck dissection in clinically node-negative disease requires
minimum clearance from level I to III.
Controversy prevails in the proper surgical management of the node-positive patient.
As discussed above, many institutions, especially in our part of the world, are still
performing comprehensive or modified versus radical neck dissection. This is despite
the plethora of literature over the past few decades that have supported the less
morbid selective neck dissection, which is still an oncologically sound operation.
Mclean et al. published a systematic review on prophylactic level V dissection in
node-positive mucosal head and neck SCC. They have shown that, irrespective of the
site, the incidence of occult metastasis is not > 2.56%. On this basis, they have
concluded that elective dissection of level V in absence of clinical involvement may
be an extra morbidity for the patient.[26]
Recently, a study from the Shuakat Khanum memorial hospital has shown that SND can
provide similar results in node-positive disease, if combined with postoperative radiotherapy.[27] These results from South Asia match with the ones published by many authors in the
European and American literature over the last 2 to 3 decades.
It is also debated in the literature whether the regional control of the disease in
oral cancers after SND is due to radiation therapy or to chemoradiation therapy.[28] However, in a systematic review published in 2018 Rodrigo et al have concluded that
adjuvant chemoradiation is elemental in achieving regional control after SND.[15] As the National Comprehensive Cancer Network (NCCN) recommends radiation therapy
in every node-positive oral cancer,[29] this would also be an argument against performing a more radical neck dissection
surgery. The main concern in performing a comprehensive neck dissection is the increased
incidence of multiple complications and of sequelae, as described in the literature,
for radical and modified radical neck dissection, such as damage to the spinal accessory
nerve, to the phrenic nerve, to the brachial plexus, and to the thoracic duct. Comparatively,
complication rates are much lower in selective neck dissection, as opposed to comprehensive
neck dissection. Apart from complications, comprehensive neck dissections usually
lead to neck and upper limb dysfunction despite sparing the spinal accessory nerve,
mainly because of its excessive manipulation.[30]
The results of our study strongly support the notion that selective neck dissection
can provide very good oncologic outcomes in most of the cases of oral SCC. Although
our study is retrospective, all of our data bank was prospectively collected with
a dedicated team continuously following patients from the initial evaluation to the
most recent follow-up visit. We only evaluated lip and oral cancer patients undergoing
selective neck dissection to minimize the bias, as different sites of the head and
neck have different routes of spread. Another strong point of our study is that the
results are from a single surgeon. The most significant limitations of the present
study were that selective neck dissection was not compared with comprehensive neck
dissection and that the mean follow-up was of < 2 years. Furthermore, around 5% of
patients were lost to follow up and level of neck recurrence was not recorded in the
data. The importance of the level of recurrence is obvious, as it can show the exact
relation with the inclusion of different levels in neck dissection.
The results of our study are also consistent with the international literature. We
have compared our outcomes – regional control and disease specific survival – in [Tables 6] and [7]
[31]
[32]
[33]
Table 6
Regional control rates after selective neck dissection in node-positive and node-negative
groups
|
Authors
|
Node-negative (%)
|
Node-positive (%)
|
Follow-up (months)
|
|
Loree et al.[13]
|
88
|
71
|
24 (min)
|
|
Chepeha et al.[33]
|
84.6
|
92.3
|
24.5#
|
|
Iqbal et al.[27]
|
91.1
|
86.9
|
29>
|
|
Shimura et al.[11]
|
——
|
94
|
42 (min)
|
|
Our Results
|
94.4
|
95
|
16.62#
|
*Regional control in node-negative was not described in the present study, # mean
follow-up, > median follow-up, (min) minimum follow-up.
Table 7
Disease-specific survival after SND in node-positive oral squamous cell carcinoma
|
Author
|
DSS (%)
|
Follow-up period
|
|
Shah et al.[32]
|
68.8[>]
|
40.8*
|
|
Shin et al.[28]
|
70
|
47 months*
|
|
Feng et al.[33]
|
52.8
|
68 months#
|
|
Shimura et al.[11]
|
61
|
42 (min)
|
|
Our Results
|
82.5
|
16.62*
|
Abbreviation: DSS, disease-specific survival.
> actuarial survival, * mean follow up, # median follow up, (min) minimum follow up.
Conclusion
Selective neck dissection in neck node-positive oral SCC has similar regional control
rates when compared with node-negative neck SCC. The difference in disease-specific
survival between the two groups is also not significant. Furthermore, the study also
reveals a high conversion rate of clinical node-negative to pathological node-positive.
Therefore, we suggest that selective neck dissection can provide results comparable
to those of node-negative patients in oral SCC. Therefore, we suggest that SND should
be performed in all early node-positive patients, followed by postoperative radiation.
