Laparoscopic sentinel lymph node biopsy for prostate cancer: the relevance of locations outside the extended dissection area.

Abstract

Objective. To assess the relevance of sentinel lymph nodes (SNs) outside the extended pelvic lymph node dissection area (e-PLND). Patients and Methods. Evaluation of our laparoscopic SN procedures for prostate cancer patients of intermediate prognosis. Retrospective data collection on the exact location of the excised SNs and the pathology results were analyzed. Results and Limitations. Of the 121 patients, 49 had positive lymph nodes. 37 patients (31%) had SNs outside the e-PLND template. Five of these nodes were tumor bearing but only twice exclusively so. Of the 14 patients considered for salvage treatment, 6 were node positive. 7 of these 14 patients (50%) had SNs outside the extended dissection area, yet none of these nodes were tumor positive. Limitations are those of a retrospective study. Conclusions. Laparoscopic SN biopsy may show SNs outside the e-PLND template in 31% of the patients. However, nodes that are exclusively positive in one of these areas are rare. For the dichotomy positive or negative nodes, the locations outside the e-PLND area are not often relevant. Nevertheless, when all positive nodes are to be treated by resection or radiotherapy, these locations are relevant. When considering salvage treatment for prostate cancer, the method is feasible.

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Hindawi Publishing Corporation
Prostate Cancer
Volume 2012, Article ID 751753, 4 pages
doi:10.1155/2012/751753
Clinical Study
LaparoscopicSentinelLymphNodeBiopsy forProstate Cancer:
TheRelevanceof LocationsOutsidetheExtendedDissectionArea
W.Meinhardt,1H.G.vander Poel,1R.A.Vald´ es Olmos,1,2A. Bex,1
O.R.Brouwer,1,2and S.Horenblas1
1Department of Urology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121,
1066 CX Amsterdam, The Netherlands
2Department of Nuclear Medicine, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital,
Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Correspondence should be addressed to W. Meinhardt, w.meinhardt@nki.nl
Received 10 May 2011; Revised 14 June 2011; Accepted 19 July 2011
Academic Editor: Ganesh S. Palapattu
Copyright © 2012 W. Meinhardt et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Objective. To assess the relevance of sentinel lymph nodes (SNs) outside the extended pelvic lymph node dissection area (e-
PLND).PatientsandMethods.EvaluationofourlaparoscopicSNproceduresforprostatecancerpatientsofintermediateprognosis.
Retrospective data collection on the exact location of the excised SNs and the pathology results were analyzed. Results and
Limitations. Of the 121 patients, 49 had positive lymph nodes. 37 patients (31%) had SNs outside the e-PLND template. Five
of these nodes were tumor bearing but only twice exclusively so. Of the 14 patients considered for salvage treatment, 6 were node
positive. 7 of these 14 patients (50%) had SNs outside the extended dissection area, yet none of these nodes were tumor positive.
Limitations are those of a retrospective study. Conclusions. Laparoscopic SN biopsy may show SNs outside the e-PLND template
in 31% of the patients. However, nodes that are exclusively positive in one of these areas are rare. For the dichotomy positive or
negativenodes,thelocationsoutsidethee-PLNDareaarenotoftenrelevant.Nevertheless,whenallpositivenodesaretobetreated
by resection or radiotherapy, these locations are relevant. When considering salvage treatment for prostate cancer, the method is
feasible.
1.Introduction
Sentinel node (SN) biopsy for prostate cancer has been
validated in open surgery, combined with a prostatectomy,
as well as in laparoscopic surgery [1–3].
The SN concept is based on the concept of sequential
metastatic spread, starting with 1 or more nodes on a direct
drainage pathway from the primary tumor site. A negative
tumor status of the SN is equivalent to the absence of
lymphatic involvement. The SN method does not pretend to
identify all tumor-bearing nodes.
Distinguishing the SN from second echelon nodes on
only one preoperative image can be difficult in the pelvic
region, since lymphatic channels are seldom visualized. An
alternative way to make the distinction between the SN
and second echelon nodes is by acquiring several sequential
images and use the order of appearance as a criterion.
Compared to an extended pelvic lymph node dissection
(e-PLND), SN biopsy has the advantage that it enables
identification of SNs outside the e-PLND area [3, 4].
In the present study, our experience with this aspect is
presented.
2.Patients andMethods
2.1. Patients. According to the EAU guidelines, we perform a
laparoscopic SN procedure only in prostate cancer patients
for whom the results will influence treatment decisions
[5]. Patients who opt for external beam radiation therapy
are candidates for a laparoscopic SN biopsy, when their
PSA is >10, Gleason >6 or Stage >T2b. Depending on the
nodal status, we adjust the radiation target volume and
the duration of the hormonal therapy. Other candidates
are patients who had local treatment failure and consider

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2Prostate Cancer
Figure 1: Combined intraoperative surgical guidance using the
portable gamma camera and the laparoscopic gamma probe. On
the screen, the iodine seed on the tip of the probe is represented by
a circle, before (left) and after (right) excision of an SN.
salvage treatment of the prostate, since positive nodes make
us refrain from salvage prostate treatment.
2.2. Preoperative Imaging. Fifteen minutes after transrec-
tal injection of 99mTechnetium-nanocolloid (Amersham
Cygne, Eindhoven, The Netherlands) into both lobes of
the prostate, guided by ultrasound, the first static planar
lymphoscintigraphic image is acquired. This is repeated after
2 hours, and by comparing the 2 images, the distinction can
be made between SNs and second-echelon nodes. The first
lymph nodes in each station appearing on early planar imag-
ing were considered to be the SNs. Nodes appearing later in
thesamestationsorcraniallytothepreviouslyidentifiedSNs
were considered to be second-echelon nodes. In addition,
SPECT/CT (Symbia T, Siemens, Erlangen, Germany) was
performed at 2 hours after injection. After image fusion,
SNs were anatomically localized. If the SPECT/CT showed
more lymph nodes compared to the planar images, the same
criteriatodistinguishfirstfromsecondechelonwereapplied.
2.3. Surgical Procedure. A laparoscopic gamma probe (Euro-
Probe, Euro medical Instruments, London, UK) was used to
acoustically localize radioactive nodes during the operation.
After the first 40 patients we refined the method by the
use of a portable gamma camera (Sentinella, Oncovision,
Valencia, Spain) [6] (Figure 1). The portable gamma camera
can visualize the radioactive hotspots on screen and can be
used to guide the gamma probe in the direction of the SN
by placing a radioactive iodine seed on the tip of the gamma
probe, which can be depicted separately on screen (Figure 1).
In addition, if the gamma camera showed residual focal
radioactivity after the removal of an SN at the same location,
it was considered as another possible SN and was also
removed.Exvivo, theremoved tissuewasalsoexamined with
the gamma probe to confirm the excised SN is radioactive
and to separate the radioactive SNs from adjacent tissue.
In case of unilateral nonvisualization of SNs at preopera-
tive imaging, a lymph-node dissection comprising the region
Table 1: Location and pathology results of SNs outside the
extended resection area. No = 37 patients (of the 121).
Location
Number
of patients
9
8
7
6
4
1
Tumor
bearing
1
1
0
1
1
0
Was it the only positive
node retrieved?
Yes
No
Presacral
Cloquet’s node
Inguinal
Para-aortic
Abdominal wall
Pararectal
Behind the common
iliac artery
Lateral to the external
iliac artery
No
No
10
11Yes
around the bifurcation of the common iliac artery, including
nodes of the common iliac, the internal iliac, the external
iliac, and the obturator regions was performed on that side.
The rationale for this is the possibility of nonvisualization in
case of major tumor involvement of a lymph node, leading
to rerouting of the 99mTechnetium-nanocolloid containing
lymphatic.
In the first 35 patients, a confirmatory laparoscopic e-
PLND was performed in order to evaluate the reliability of
our SN method. The areas resected were around the external
iliac artery and vein, the common iliac up to the crossing of
the ureter, the internal iliac just passed the superior vesical
artery, and the obturator fossa. This series has been reported
before and showed no false-negative results [2].
After the first 35 patients, we abandoned the confirma-
tory e-PLND, since we considered our SN method to be
reliable.
3.Results
Between December 2005 and October 2010, 121 patients
were treated. Of these 121 patients, 49 (40%) were node
positive. In 37 patients (31%), SNs were identified and
excised outside the e-PLND template, at the following
locations: presacral, Cloquet’s node, inguinal, para-aortic,
abdominal wall, pararectal, behind the common iliac artery,
and lateral to the external iliac artery. In five patients, these
nodesweretumorpositive(10%ofthenodepositivepatients
and 4% of all patients). However, in merely two cases,
this node was the only positive node retrieved from those
patients. SN results are listed in Table 1.
In case of unilateral nonvisualization of SNs, a dissection
on that side revealed positive lymph nodes in 4 of 12 cases.
Characteristics of patients considered for salvage treat-
ment in case of a prostate cancer recurrence are shown in
Table 2. 6 of the 14 patients were node positive. In 7 of these
14 patients, we retrieved nodes outside the extended dissec-
tion area; however, none of these nodes were tumor positive.
So, although in salvage candidates the occurrence of SNs
outside the extended template is higher (50% versus 28%),
harvesting these nodes did not result in change of treatment.

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Prostate Cancer3
Table 2: Characteristics of 14 patients with a recurrence in the prostate and the outcome of the SN procedure. None of the nodes outside
the extended dissection area was tumor positive.
Age
Previous treatment and
time passed
External beam, 9y
Brachy therapy, 8y
External beam, 5y
External beam, 8y
Brachy therapy, 6y
PSA at time of
recurrence
2.2
17
4.0
4.8
2.1
Gleason score
Outcome
+: tumor bearing nodes
−
−
−
+
−
−
+
+
+
−
+
Location outside of
extended dissection area
−
Para-aortic
−
−
−
Abdominal wall, near
umbilical ligament
Inguinal node (negative)
−
Para-aortic (negative)
inguinal
Para-aortic (negative)
Abd. Wall, next to
umbilical ligament
53y
68y
68y
70y
63y
7
7
6
8
6
65yBrachy therapy, 7y117
73y
64y
61y
62y
69y
Brachy therapy, 2y
External beam, 3y
External beam, 5y
HIFU, 2y
External beam, 3y
21
7
12.7
30
3.8
6
7
8
8
7
63y HIFU, 1y5.46
−
−
+
71y
61y
External beam, 6y
Brachy therapy, 5y
1.7
2.1
7
9
4.Discussion
By comparing the early and late static planar images,
we make the distinction between SNs and second-echelon
nodes. If this distinction is not made, we agree with
Weckermann that it is better to avoid the term SN biopsy but
use “radio guided surgery” instead [7]. The SN technique is
designed to individualize the diagnostics and the therapeutic
decisions. Pooling these data to draw conclusions on what an
extended dissection area might be, or which area should be
radiated, results in unpractical large areas [8].
The original application of the SN concept in melanoma
and penile cancer often shows 1 or 2 lymphatic vessels
leading to SNs [9, 10]. In the pelvic region, this is seldomly
the case. Results of a recent study in bladder carcinoma
illustrate this. Only the healthy side of the bladder was
injected with tracer and crossing to the contralateral side
was often found even to contralateral tumor bearing nodes
[11]. In the pelvis, it is more appropriate to consider the
lymphatics as a reticulum with only a few valves.
Blockage of the lymph flow by tumor in the node may
lead to nonvisualization and rerouting and even retrograde
lymph flow of the 99mTechnetium-nanocolloid containing
lymphatic flow. This concept has been visualized with
SPECT/CT [12]. In our patients, it is illustrated by the fact
that in the case of nonvisualization on one particular side,
positive nodes on that side were found in a third of those
cases.
The appearance of radioactive nodes in the abdominal
wall near the umbilical ligament, of pararectal nodes, of
direct drainage to Cloquet’s nodes and even to inguinal
nodes may be explained by the above-named mechanisms.
Tumor-positive nodes of prostate cancer in the inguinal
region have been reported before by others. This may also
be explained by leakage of the tracer during the injection,
transrectally near the linea dentata. However, inguinal nodes
have been reported without any transrectal injections [13,
14]. This leakage may also explain the drainage to pararectal
nodes, which is often reported but hazardous to dissect
laparoscopically.
Radioactive lymphnodes are regularly identified outside
the extended resection area more cranially and around the
aortaandthevenacava.Thismaybeexplainedbytheregular
lymph flow, and often these nodes might well be second-
echelon nodes. In older studies, the presacral area is already
included in the regular drainage regions of the prostate [15].
However, laparoscopic excision of these nodes may also be
challenging.
Salvage treatment of the prostate may result in serious
complications. Identifying even micrometastases is impor-
tant, since the balance between the potential benefits and
risks for this type of treatment is different. We only consider
salvage prostate treatment when the prostate is the only
tumor-bearing site. As lymph node micrometastases cannot
be accurately visualized using current imaging modalities,
removal of lymph nodes for microscopic investigation is still
indicated [16]. The usual parameters to stratify patients in
riskgroupsdonotapplytopatientswitharecurrenceintheir
prostate, as illustrated by our high percentage of positive
nodes in this group.
5.Conclusions
In prostate carcinoma, the laparoscopic SN technique identi-
fied positive lymph nodes outside the e-PLND area in 31%
of the cases. They were the only site of tumor bearing
nodes in 4% of the patients with positive nodes. For diag-
nostic purposes only, this vmakes these locations less

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4Prostate Cancer
relevant. However, for dissection or radiation of lymph
nodes with curative intent, these locations are relevant, since
they contained tumor in 10% of node positive patients.
When considering salvage treatment for prostate cancer, the
method is feasible, and in almost half of these patients, the
results have led to a change in therapeutic decisions.
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