Ann Surg Oncol (2010) 17:3287–3293

DOI 10.1245/s10434-010-1137-6

ORIGINAL ARTICLE – ENDOCRINE TUMORS

Prophylactic Central Neck Dissection and Local Recurrence

in Papillary Thyroid Cancer: A Meta-analysis
Tarek Zetoune, MD1, Xavier Keutgen, MD1, Daniel Buitrago, MD1, Hasan Aldailami1, Huibo Shao, MS2,
Madhu Mazumdar, PhD2, Thomas J. Fahey III, MD1, and Rasa Zarnegar, MD1

1
Department of Surgery, Weill Cornell Medical College, New York, NY; 2Department of Public Health, Weill Cornell
Medical College, New York, NY

ABSTRACT However, the available studies have substantial limitations

Background. The effectiveness of prophylactic central and a prospective multicenter study to determine the
neck dissection (pCND) in the treatment of patients with indications for pCND is warranted.
papillary thyroid carcinoma (PTC) to prevent local recur-
rence is controversial. We performed a meta-analysis to
assess the effect of pCND on local recurrence in PTC.
Papillary thyroid carcinoma (PTC) is the most common
Methods. Exhaustive search of online search engines
thyroid malignancy, accounting for 80% of all thyroid
identified five retrospective studies that compared the local
cancers. Although the incidence of PTC in the United States
recurrence rates of PTC in patients without clinically
has increased in recent years and has reached over 37,000
detectable nodal disease in patients undergoing thyroidec-
cases annually, its prognosis remains good and survival
tomy ? pCND (group A) to those undergoing
rates exceed 90% at 10 years.1 Despite these excellent
thyroidectomy alone (group B). A meta-analysis was per-
outcomes, recurrence remains an important issue and
formed by the fixed effects method. Recurrence was
accounts for an increase in morbidity in PTC patients.2,3 A
documented by imaging, thyroglobulin detection, or reop-
total of 15% to 30% of patients with PTC experience
eration. Location of recurrence was identified in either the
recurrence after successful thyroidectomy due to lymph
central or lateral neck compartment.
node metastasis.2–5 Furthermore, in some groups, a recent
Results. A total of 1264 patients were included, 396 in
study found that survival correlates with recurrence.6
group A and 868 in group B. Follow-up ranged from
Older patients, patients with more aggressive histological
6 months to 27 years. The overall recurrence rate was
subtypes, and patients with extrathyroidal extension have a
2.02% in group A versus 3.92% in group B (odds ratio
higher risk of recurrence.7–10 It is well established that in
[OR] = 1.05, 95% confidence interval [95% CI] 0.48–
patients with local recurrence, surgery remains the first line
2.31). The recurrence rate in the central neck compartment
of treatment but is associated with a higher risk of compli-
in group A was 1.86% compared to 1.68% in group B
cations. To improve staging, as well as to avoid
(OR = 1.31, 95% CI 0.44–3.91). The recurrence rate in the
complications related to reoperation in the thyroid bed, some
lateral neck compartment in group A was 3.73% compared
surgeons advocate routine prophylactic central lymph node
to 3.79% in group B (OR = 1.21, 95% CI 0.52–2.75).
dissection (pCND). This implies central neck dissection
There was no statistically significant difference in the OR
(CND) without evidence of suspicious lymph node clinically
in the local recurrence between the two groups.
or on imaging. However, pCND in itself is not without risk; it
Conclusions. This meta-analysis indicates that pCND
has been associated with a marked increase in postoperative
does not greatly reduce local recurrence in thyroid cancer.
hypocalcemia and recurrent laryngeal nerve injury when
compared with total thyroidectomy alone.11,12
Ó Society of Surgical Oncology 2010 We hypothesize that prophylactic central neck dissec-
First Received: 7 March 2010; tion (pCND) decreases recurrence in the central lymph
Published Online: 2 July 2010 node basin in patients with PTC. This meta-analysis aims
R. Zarnegar, MD to determine whether the current literature supports the role
e-mail: raz2002@med.cornell.edu of pCND in the management of patients with PTC. We
3288
aimed to evaluate overall nodal recurrence and to evaluate
the location of this recurrence—central versus lateral
lymph nodes—in patients with PTC who undergo thy-
roidectomy with pCND versus thyroidectomy alone.
METHODS
Search Strategy
Three authors independently performed a systematic
search of the databases PubMed, Ovidsp, and Cochrane, to
identify studies published in the English language through
July 2009. The Internet was also searched separately,
looking for articles that compared lymph node recurrence
rates in PTC patients after treatment with thyroidectomy
alone versus thyroidectomy with pCND. The search crite-
rion included the combination of the following terms: (1)
papillary thyroid carcinoma, (2) prophylactic central neck
dissection or prophylactic level 6 neck dissection or pro-
phylactic level VI neck dissection, (3) total thyroidectomy
or total thyroidectomy alone, and (4) recurrence or local
recurrence. All potentially relevant articles were then
retrieved through the consensus of the investigators. The
corresponding reference lists were reviewed to identify
additional relevant articles.
Selection of the Studies
Eligible studies fulfilled the following inclusion criteria:
(1) retrospective or prospective studies, (2) patients with
papillary thyroid cancer, (3) no evidence of lymph node
metastasis clinically by imaging or intraoperatively, (4)
study with two arms comparing thyroidectomy with pCND
(with or without modified neck dissection) (group A) to
thyroidectomy alone (group B), and (5) recurrence data
obtained primarily from authors. Studies with either thy-
roidectomy or thyroidectomy with pCND alone, presence
of nodal metastasis, and lack of recurrence data were
excluded. Study titles, abstracts, and full text were inde-
pendently reviewed by three investigators to assess their
appropriateness. The results were compared, and dis-
agreements were resolved by consensus. Full text of the
studies was evaluated according to the inclusion criteria. If
necessary, authors of publications in which the data we
wished to analyze were not clear were contacted by e-mail
for clarification of data and for additional information.
Data Abstract
The following information was extracted from each
article: type of study, first authorship, country of origin,
year of publication, method of preoperative diagnosis, total
T. Zetoune et al.
number of patients, number of patients in group A and
group B, number of patients receiving radioactive iodine
(RAI) treatment, follow-up period, number of nodal
recurrence, site of recurrence, number of patients who had
recurrences in either/both central and lateral lymph nodes,
and number of patients in each group who had transient or
permanent recurrent laryngeal nerve injury and transient or
permanent hypoparathyroidism.
Statistical Analysis
Recurrence rate in central lymph nodes and lateral
lymph nodes, together and individually, in the respective
study arms were estimated as a pooled odds ratio (OR) with
a 95% confidence interval (95% CI) by the fixed effects
method. Statistical heterogeneity was assessed by v2 test
and P value. Statistical publication bias was estimated by
both Begg’s and Egger’s tests.13 This study had the
approval of the institutional review board of the New York
Presbyterian–Weill Cornell Medical Center.
RESULTS
Eligible Articles
The literature review identified 165 abstract that were
potentially relevant to the study (Fig. 1). A total of 128
articles were excluded, either because other types of thy-
roid cancer were studied or because only one arm was
included in the study. The full text of the remaining 37
articles was reviewed. Of these, 32 were excluded for lack
of recurrence data or identification of positive lymph nodes
Abstract from 165
publications were screened
128 Articles were excluded for the
following reasons:
• Either thyroidectomy or thyroidectomy
with CND.
• Other type of thyroid tumors.
Full text from 37 potentially
relevant articles were
32 Articles were excluded for the
following reasons:
• No recurrent data.
• Lymph nodes were identified by
pre-operative clinical exam and imaging.
5 articles were finally
included in the study
FIG. 1 Flow chart of studies retrieved and studies excluded, with
specification of reasons
Prophylactic Central Neck Dissection 3289

Mean 8.1 years, median 6.0 years (for both groups); range 1–27

T ? pCND thyroidectomy with prophylactic central neck dissection, T thyroidectomy alone, RAI radioactive iodine, TT total thyroidectomy, ST subtotal thyroidectomy, MND modified neck
pre- or intraoperatively. Overall, five studies describing a

Median 68 months (for both groups); range 6–332 months

total of 1264 patients met our inclusion criteria. All studies

Mean 52 months (for both groups); range 12–69 months

Mean 61.6 months (T ? pCND); range 13–144 months

were retrospective and were published between 2002 and
2008.

Study Characteristics

recorded Mean 53 months (T); range 12–132 months

A total of 1264 patients with PTC were identified in the

Median of 70 months (T ? pCND)

five studies. The diagnosis of PTC was based on the
pathological report. One out of five studies had prophy-

Median of 24.5 months (T)

lactic lateral neck dissection together with pCND.14 Two
out of five studies performed either a total thyroidectomy
or less than total thyroidectomy (lobectomy and subtotal

Follow-up period
thyroidectomy) with or without a central neck dissec-
tion.14,15 Three of the five studies performed total
thyroidectomies in all their patients.16–18 Three out of five

years
studies treated their patients with RAI therapy; however,
two of the five studies did not mention use of or RAI

recorded
dosage postoperatively (Table 1). The follow-up period
ranged 6 months to 27 years. This was based on the range

90%
RAI

Not

TT ? ST ? lobectomy TT ? ST ? lobectomy Not

of follow-up provided by four studies as well as the median

All
All
follow-up time from one study (Table 1).
Of the 1264 patients, 396 (31.3%) had undergone thy-
roidectomy ? pCND and 868 (68.7%) had undergone

TT or lobectomy
thyroidectomy alone. Eight (2%) of 396 patients in the
thyroidectomy ? pCND group compared to 34 (3.9%) of
868 patients in the thyroidectomy group had lymph node
recurrences (Table 2).
TT
TT

TT
T

Four of the five studies differentiated between the cen-

tral and lateral site of lymph node recurrence, comprising a
TABLE 1 Data extracted from published studies of papillary thyroid carcinoma

total of 874 patients (81.6%). A total of 161 patients TT or lobectomy

(18.4%) had thyroidectomy ? pCND and 713 had thy-

roidectomy alone. Three (1.9%) of 161 patients in the
thyroidectomy ? pCND group experienced recurrence in
TT
TT

TT

the central lymph node basin, compared to 12 (1.7%) of

713 with thyroidectomy alone. Recurrence in the lateral
lymph node basin occurred in 6 (3.7%) of 161 patients in
pCND ? MND

the thyroidectomy ? pCND group compared to 27 (3.8%)

of 713 patients in the thyroidectomy-alone group
T ? pCND

pCND or

(Table 2).
pCND
pCND

pCND
Switzerland pCND

Two studies evaluated the complication rate of thyroid-

ectomy ? pCND compared to thyroidectomy alone.16,17
The rate of transient recurrent laryngeal nerve injury was
Australia
Country

1.8% to 5.4% in the thyroidectomy ? pCND group

France
Korea

Japan

compared to 1% to 1.3% in the thyroidectomy-alone group.

This did not reach statistical significance in either study.
The rate of permanent recurrent laryngeal nerve injury
Sywak et al.17 (2006)

Bardet et al.18 (2008)

Wada et al.14 (2002)

Gemsenjager et al.15

ranged between 0% to 3.6% in the thyroidectomy ? pCND

Roh et al.16 (2007)

group compared to 1% to 2.7% in the thyroidectomy-alone

group. This was not statistically significant. The rate of
dissection

transient hypoparathyroidism ranged between 18% and

(2003)
Study

44% in the thyroidectomy ? pCND group compared to 8%

and 14% in the thyroidectomy-alone group (P \ 0.02).
 3290

TABLE 2 Recurrence data of published studies of papillary thyroid carcinoma

Study Total no. Group Patients No. of patients R%b No. of patients Group No. of CNRc CNR%d LNR LNR%e
of patients (%) with LNRa in studies that patients regardless regardless
mention site of of LNRa of CNR
recurrence

Roh et al.16,f 113 T ? pCND 40 (35.4%) 0 0.0 113 T ? pCND 40 0 0.0 0 0.0
T alone 73 (64.6%) 3 4.1 T alone 73 3 4.1 2 2.7
17
Sywak et al. 447 T ? pCND 56 (12.5%) 2 3.6 447 T ? pCND 56 0 0.0 2 3.6
T alone 391 (87.5%) 22 5.6 T alone 391 7 1.8 17 4.3
Bardet et al.18 197 T ? pCND 36 (18.3%) 4 11.1 197 T ? pCND 36 2 5.6 4 11.1
T alone 161 (81.7%) 6 3.7 T alone 161 2 1.2 6 3.7
Gemsenjager et al.15 117 T ? pCND 29 (24.8%) 1 3.4 117 T ? pCND 29 1 3.4 0 0.0
T alone 88 (75.2%) 2 2.3 T alone 88 0 0.0 2 2.3
14
Wada et al. 390 T ? pCND 235 (60.3%) 1 0.4 Not recorded Not recorded Not recorded
T alone 155 (39.7%) 1 0.6
Total 1264 T ? pCND 396 (31.3%) 8 2 874 T ? pCND 161 3 1.9 6 3.7
T alone 868 (68.7%) 34 3.9 T alone 713 12 1.7 27 3.8
T thyroidectomy alone, pCND prophylactic central neck dissection
a
LNR lymph node recurrence
b
R% recurrence percentage
c
CNR central neck recurrence
d
CNR% central nodal recurrence percentage
e
LNR% lateral nodal recurrence percentage
f
Recurrence data were obtained primarily from the author (unpublished data)
T. Zetoune et al.
Prophylactic Central Neck Dissection
However, the rate of permanent hypoparathyroidism was
0% to 0.27% in the thyroidectomy ? pCND group com-
pared to 1% to 1.8% in the thyroidectomy-alone group,
which is not statistically significant.
Results of Statistical Analysis
Figure 2 presents a Begg’s funnel plot, which provides
no evidence of publication bias. Begg’s test (Pr [ z =
0.462) and Egger’s test (P [ t = 0.420) showed no sta-
tistical publication bias. Also, there was no heterogeneity
between the thyroidectomy ? pCND group when com-
pared to the thyroidectomy-alone group with v2 = 4.36
(P = 0.359). The OR for the recurrence rate between
thyroidectomy ? pCND and thyroidectomy alone was 1.05
(95% CI 0.48–2.31), with no significant difference evident
between the two groups in terms of overall recurrence
(Table 3a).
Studies were evaluated for location of recurrence. Four
of the five studies defined the location of recurrence. Of
note, the study of Wada et al., which was the only study
that performed prophylactic modified lateral dissections,
did not define the location of recurrence and was excluded
from this analysis.14
For central lymph node recurrence, we found no visual
or statistical publication bias by Begg’s test
(Pr [ z = 0.734) and Egger’s test (P [ t = 0.419). There
was no heterogeneity with v2 = 4.69 (P = 0.196). The OR
comparing lymph node recurrence was 1.31 (95% CI 0.44–
3.91), indicating no statistical significance (Table 3b).
For lateral lymph node recurrence, we found no was no
visual or statistical publication bias by Begg’s test
(Pr [ z = 0.734) and Egger’s test (P [ t = 0.343). There
was no heterogeneity, with v2 equal to 3.20 (P = 0.362).
The OR comparing the recurrence between these groups
Log OR
4
2 to correlate with disease recurrence, we were surprised to
0
-2
-4 0 .5 1 1.5
Standard Error: Log.OR
FIG. 2 Begg’s funnel plot with pseudo 95% confidence limits of the
5 included studies
3291
was 1.21 (95% CI 0.52–2.85), which was not statistically
significant (Table 3c).
DISCUSSION
This study shows no statistically significant difference in
the overall lymph node recurrence when comparing thy-
roidectomy with pCND with thyroidectomy alone in
patients with PTC. Subgroup analysis also showed no
statistically significant difference in central and lateral
lymph node recurrence when comparing patients who
underwent a thyroidectomy with pCND and thyroidectomy
alone. This is in contrast to what we expected to find.
Although the recurrence rates in our meta-analysis were
slightly higher in the thyroidectomy-alone group (3.9%)
compared to the thyroidectomy with pCND group (2%),
the confidence interval of the OR was not statistically
significant.
Therefore, when comparing patients who underwent
thyroidectomy alone compared to the patients who under-
went thyroidectomy ? pCND, the balance between the
benefits and risks favors thyroidectomy alone. This is due to
the increased morbidity associated with pCND.12,16,17,19
Documented complications include temporary hypo-
parathyroidism (up to 44% of cases), permanent hypopara-
thyroidism (up to 4%), transient recurrent laryngeal nerve
injury (7.3%), and permanent recurrent laryngeal nerve
injury (3.6%).12,16–21 Other studies have shown a marked
increased rate of hypoparathyroidism in patients undergoing
bilateral CND as compared to unilateral CND, with no
marked difference in rates of undetectable thyroglobulin
levels, recurrence, or mortality.22–24 In this meta-analysis,
only two studies documented this potential complica-
tion.16,17 However, thyroidectomy with pCND was not
associated with a higher rate of complications when com-
pared to thyroidectomy alone.
Even though our support for thyroidectomy with pCND
is based on the evidence that cervical lymph node metas-
tases is common (20% to 50%) and on the high incidence
of occult nodal metastasis in PTC, which has been shown
find that the addition of pCND did not greatly decrease the
recurrence.25,26 However, there are several important lim-
itations to our meta-analysis. First, two of the studies did
not mention the use of RAI therapy postoperatively, which
can influence nodal recurrence.14,15 Second, the extent of
pCND may have been inadequate in some patients in two
of the studies in terms of ipsilateral or contralateral
side.17,18 Third, the extent of thyroidectomy differed in two
of the studies; some patients underwent subtotal thyroid-
ectomies or lobectomies.14,15 Fourth, estimating the time to
recurrence was difficult because these data were not
3292 T. Zetoune et al.

TABLE 3 Statistical analysis comparing total thyroidectomy with pCND and thyroidectomy alone for (a) overall nodal recurrence, (b) central
recurrence, (c) lateral recurrence only

(a) Overall nodal recurrencea

Study T ? pCND T alone Weight (%) OR Fixed 95% CI Forest plot: OR, fixed 95% CI
Total (n) Overall Total (n) Overall
recurrence (n) recurrence (n)

Roh et al.16 40 0 73 3 20.74 0.25 0.01–4.94

Sywak et al.17 56 2 391 22 44.72 0.62 0.14–2.72
Bardet et al.18 36 4 161 6 16.4 3.23 0.86–12.10
Gemsenjager et al.15 29 1 88 2 8.05 1.54 0.13–17.58
Wada et al.14 235 1 155 1 10.09 0.66 0.040–10.60
Total 396 8 868 34 1.05 0.48–2.32

(b) Central recurrenceb

Study T ? pCND T alone Weight (%) OR Fixed 95% CI Forest plot: OR, fixed 95% CI
Total (n) CNB Total (n) CNB
recurrence (n) recurrence (n)

Roh et al.16 40 0 73 3 46.67 0.25 0.013–4.94

Sywak et al.17 56 0 391 7 35.73 0.45 0.026–8.05
Bardet et al.18 36 2 161 2 13.07 4.68 0.64–34.37
Gemsenjager et al.15 29 1 88 0 4.53 9.32 0.37–235.11
Total 161 3 713 12 1.31 0.44–3.91

(c) Lateral recurrencec

Study T ? pCND T alone Weight (%) OR Fixed 95% CI Forest plot: OR, fixed 95% CI
Total (n) LNB Total (n) LNB
recurrence (n) recurrence (n)

Roh et al.16 40 0 73 2 19.42 0.35 0.017–7.54

17
Sywak et al. 56 2 391 17 45.3 0.82 0.18–3.63
Bardet et al.18 36 4 161 6 21.61 3.21 0.86–12.02
Gemsenjager et al.15 29 0 88 2 13.67 0.59 0.027–12.57
Total 161 6 713 27 1.21 0.52–2.85

T ? pCND thyroidectomy with prophylactic central neck dissection, pCND prophylactic central neck dissection, T thyroidectomy alone, 95% CI
95% confidence interval, CNB central nodal basin, LNB lateral nodal basin recurrence. Overall recurrence includes central ? lateral node
a
Heterogeneity v2 = 4.36 (d.f = 4) P = 0.359; Test of OR = 1: z = 0.12, P = 0.906
b
Heterogeneity v2 = 4.69 (d.f = 3) P = 0.196; Test of OR = 1: z = 0.49, P = 0.626
c
Heterogeneity v2 = 3.20 (d.f = 3) P = 0.362; Test of OR = 1: z = 0.44, P = 0.661

mentioned in all of the studies. Furthermore, in one study,
two of the four recurrences in the group of thyroidectomy
with pCND occurred within 9 months.18 In another study,
the authors mentioned that both recurrences (2 of 56)
occurred at an ‘‘early’’ point of follow-up, and thus it is
uncertain whether these tumors were in fact recurrences or
whether they represented persistent disease.17 Finally, all
of the studies were retrospective in nature. These limita-
tions in the previously published data could potentially
affect the analysis of nodal recurrence in both groups.
In conclusion, although this meta-analysis could not find
any statistical difference in lymph node recurrence when
comparing the addition of a pCND to thyroidectomy versus
thyroidectomy alone for patients with PTC, the use of
Prophylactic Central Neck Dissection
pCND remains controversial. This is due to the substantial
limitations of published retrospective studies. Given the
potential increase in surgical risk of pCNDs, pCND should
probably only be performed by experienced surgeons. To
resolve the role of pCND in the management of papillary
thyroid cancer, a large prospective standardized study is
warranted to properly assess the risks and benefits of pro-
phylactic CND.
ACKNOWLEDGMENT We thank Jong-Lyel Roh, MD, PhD, for
sending data and providing help. There was no commercial interest of
any of the authors or external financial support for this study.
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