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Vol.2, No.8, 836-841 (20
Copyright © 2010 SciRes. http://www.scirp.org/journalT /
Openly accessible at/HEAL H
Current status of sentinel node biopsy in urological
Alexander Winter1*, Jens Uphoff1, Jens de la Roche2, Friedhelm Wawroschek1
1Department of Urology and Pediatric Urology, Hospital Oldenburg, Oldenburg, Germany; *Corresponding Author:
2Institute of Nuclear Medicine, Hospital Oldenburg, Oldenburg, Germany
Received 26 January 2010; revised 21 February 2010; accepted 23 February 2010.
Like in most other malignancies the lymph node
status is of outstanding prognostic relevance
and an important tool for the determination of
adjuvant strategies for urological tumor entities,
too. Even in the era of PET/CT and MRI with iron
oxid nano-particles the radiological imaging
technology is strongly limited in cases of me-
tastases smaller than 5 mm. Therefore only the
operative lymph node exploration is suitable for
an exact lymph node staging. The dilemma,
however, is that the extended lymphadenectomy
techniques feature a high morbidity and that
any limitation of the dissection area results in a
reduced detection rate of metastases in penile
and prostate cancer. In contrast the sentinel-
guided lymphadenectomy (SLND) offers a short
operation time and a low morbidity without the
risk of a significantly reduced detection of
lymph node positive patients. As a consequence
of many published papers dealing with a few
thousands of patients the European Association
of Urology (EAU) guidelines recommend the
SLND in penile cancer (tumor stages ≥ T1G2)
and as an option in prostate cancer. The latest
studies of bladder, renal cell and testicular
cancer promise the feasibility for these tumor
entities, too. Up to which extend these thera-
peutic concepts are able to replace or at least
complement the default therapeutic procedures
has to be shown in further studies.
Keywords: Sentinel Lymph Node; Lymphadenectomy;
Prostate Cancer; Penile Cancer; Bladder Cancer;
Testicular Cancer; Renal Cell Cancer
The origin of radioguided surgery in urological tumors is
mainly based upon the gained experiences of Cabanas in
penile cancer. Seventeen years after the introduction of
the term “sentinel lymph node” (SLN) in malignant tu-
mors of the parotid gland by Gould , Cabanas postu-
lated a constant anatomically reproducible SLN for the
penile cancer on the base of the classical lymphan-
giography . Subsequent analysis however showed an
individual variability for the SLN of the penile cancer as
well as for other tumors. Based on the use of different
tracers the previously pure anatomical concept changed
towards a functionally defined SLN with an individual
Since the end of the nineties an account of first posi-
tive experience of the gamma-probe guided lymph node
surgery is given in urological malignancies as prostate
and penile cancer. In the new millennium there are also
reports for this method used in urinary bladder carci-
noma, testicular tumour and renal cell carcinoma.
At this juncture it has to be considered that the lymph
node status in urological malignancies has not only a
prognostic value but is also of tremendous therapeutic
relevance. In case of positive lymph nodes an adjuvant
therapy can be planned and the therapy modified respec-
tively. Nevertheless, none of the currently available
methods of radiological imaging (such as computed to-
mography (CT), magnetic resonance imaging (MRI) and
positron emission tomography (PET-CT)) provide a suf-
ficient identification of lymph node (micro-) metastases
( < 5 mm). Even the nano-particle enhanced MRI is not
able to detect micro metastases ( < 2 mm) by force of the
spatial resolution [3,4]. Furthermore, this method is not
available as a routine so far. Presently, only lymph node
dissection or the histological detection of lymph node
metastases is suitable for the exact lymph node staging.
Moreover, it seems that the dissection of lymph node
metastases can enhance the survival at least in cases of
small tumor load.
A. Winter et al. / HEALTH 2 (2010) 836-841
Copyright © 2010 SciRes. http://www.scirp.org/journal/HEALTH/Openly accessible at
2. PENILE CANCER
In penile cancer the presence and the extent of lymph
node metastases is the most important predictor of sur-
vival [5,6]. Patients with negative lymph nodes have an
excellent long-term survival rate (85-90%). If lymph
node metastases are present, the 5-year survival rate
however declines below 30%. Depending on the tumor
grade, the local tumor stage and other risk factors of
metastatic rates are reported which vary from 0% to
50-100% in pT3/pT4-cases [7,8]. But patients with lim-
ited lymph node disease (1-2 nodes involved) can be
healed also by sole surgery treatment . This is juxta-
posed by the high morbidity of the groin dissection and
by a potential over-treatment of up to 80% of the pa-
tients . Because of this the diagnostic evaluation and
the extent of lymph node dissection is controversially
discussed especially in clinical lymph node negative
The procedure of sentinel lymph node biopsy in penile
carcinoma was initially described in 1977 by Cabanas.
Based on the classical lymphangiography he postulated
the existence of a static, anatomically reproducible SLN
located medial of the V. saphena magna at the orifice of
the V. femoralis. The individual variability of the SLN-
location even in the penile cancer was documented in
subsequent examinations; they showed a high false
negative rate (9-50%) . In spite of a negative biopsy
of the “Cabanas-lymph-node” courses with an extended
lymphogenic dissemination were seen . This failure
resulted in the fact that the SLN-concept in penile cancer
was shelved for two decades. Not until perennial posi-
tive experiences were achieved in the SLN-diagnostic in
the malignant melanoma and breast cancer a renaissance
occurred for the sentinel-concept in penile cancer. The
method is based on the detection of the individual lymph
node which is the first drainage node. Thereby a step-
wise and orderly progression of lymphogenous metas-
tatic spread from the primarily involved node (the senti-
nel node) to secondary lymph nodes is assumed.
In analogous manner to the technique in the malignant
melanoma a peritumoral intracutaneous injection is
made with 99mTc-nanocolloid (approx. 80 MBq). The
time of the injection varies from 1 day to 4 hours 
before surgery. On the following day an intraoperative
SLN-detection is performed with the aid of a gamma-
probe. The sole SLN-representation by dint of patent
blue is not favoured anymore, but sometimes it is in-
jected in addition shortly before surgery. In case of posi-
tive lymph nodes on either frozen section or definitive
histology, a conventional inguinal lymphadenectomy is
performed. Different centres have concentrated on this
method. The indication for SLND in penile cancer was
The group from the Netherlands Cancer Institute ini-
tially reported a high false-negative rate of 17-22% [13,
14]. However the SLND was performed here as sole
intervention even in locally advanced states ( > T2) and
only in the case of positive SLN it was combined with
an inguinal lymphadenectomy. Thereby it has to be con-
sidered that the value of the lymphatic scintigraphy in
clinically suspicious lymph nodes could be limited be-
cause of possible existing tumor blockade of the lym-
phatic drainage . The rate of wrong negative find-
ings could be reduced later to 4.8% by technical modifi-
cations . Then routinely preoperative ultrasound-
guided fine needle aspiration cytology was done on sus-
picious nodes. A surgical exploration was supplemented
on scintigraphically non-visualised but operative palpa-
ble nodes . Furthermore a histo-pathologically re-
processing of the removed lymph node was intensified
with serial sections and immuno-histochemistry.
Our own findings of the first 11 patients who received
a SLND in penile cancer showed so far no wrong nega-
tive findings. This group included patients with pT1G2
(n = 4)-pT3G2 (n = 7) tumors. The fraction of the lymph
node positive patients in the advanced states (> T2, 6 of
7 cases) was noticeably higher than in the Amsterdam
workgroup. In 5 out of these 6 men only the SLN were
affected. The patients with the pT1G2 tumours showed
no positive lymph node. Here, the patients with an ad-
vanced state had an inguinal LA in addition to the SLND
Meanwhile the SLN biopsy in penile cancer has been
validated in further centres. The guidelines of the Euro-
pean Association of Urology (EAU) recommend this
technique for penile cancer in patients with intermediate
risk disease (≥ T1G2) when there are no palpable lymph
nodes existent. A modified or radical lymph node dissec-
tion should be done if there are negative prognostic fac-
tors (nodular growth, vascular invasion) or positive SLN
biopsy . Also, the findings in an actual study with
900 patients with T1G2 tumours militate in favour of
this approach. The rate of LN-positive patients was in
total 13% or 9% for non-palpable LN. The SLN-biopsy
was approved as a suitable minimal invasive staging
However, in cases of macrometastases the tracer
might not be reliable stored with the consequence of
false negative results. Furthermore in secondary surgery
after the resection of the primary tumour the injection of
the tracer could not be done effectively peritumoral so
that the real way of the lymphatic drainage may not be
3. PROSTATE CANCER
Lymph node staging in prostate cancer has a significant
A. Winter et al. / HEALTH 2 (2010) 836-841
Copyright © 2010 SciRes. http://www.scirp.org/journalT /Openly accessible at/HEALH
clinical importance. The risk of progression can be cal-
culated and appropriate adjuvant therapy can be planned.
In case of positive lymph node findings, common stan-
dards demand the renunciation of local curative therapy
(such as radical prostatectomy or radiotherapy) and
hormonal deprivation. Another opportunity is the modi-
fication of the treatment volume in radiotherapy to opti-
mize pelvic irradiation. The RTOG 94-13 trial has pro-
vided evidence that patients with high-risk prostate can-
cer benefit from additional irradiation of the pelvic
nodes. Another study also showed an excellent long-term
outcome for node-positive patients treated with radical
surgery plus adjuvant pelvic irradiation .
But none of the currently available radiological imag-
ing (computed tomography (CT), magnetic resonance
imaging (MRI), positron emission tomography (PET) or
PET/CT) provide sufficient identification of lymph node
(micro-) metastases (< 5 mm). Nanoparticle enhanced
MRI is also constrained by its spatial resolution (> 2 mm)
 and not yet been approved for routine diagnostics.
Therefore only the histological detection is presently
suitable for exact lymph node staging. Pelvic lymph
node dissection (PLND) is considered the gold standard
to identify lymph node metastases in prostate cancer.
Multiple surveillances in the primary situation possibly
argue for a therapeutic benefit of the PLND respectively
the excision of lymph node metastases. A progression-
free survival up to 70% after 10 years could be noticed
in LN-positive patients [21-23]. Furthermore, our own
first experiences in the secondary lymph node surgery
show the possibility to influence the course of the dis-
ease or enable a curative approach. 3 out of 6 patients
achieved a complete PSA-remission after secondary ex-
cision of a single lymph node metastasis detected via
PET/CT and they stayed free of a relapse so far (fol-
low-up: mean 29.7, range 24-41 months) .
The first studies about prostate lymph scintigraphy in
humans were published at the end of the seventies [25-
27]. The examinations were aimed at proving the former
challenged existence of the intraprostatic lymph system
and thereby demonstrating the regional lymph drainage
area. Although both principally succeeded, this tech-
nique was not further developed for years because of the
lack of clinical consequences that could be drawn from
the proof or absence of the lymph drainage area.
Because of the immense therapeutic consequences
mentioned before, the high expenditure of time and the
increased complication rate of the extended PLND and
of the low detection rate of the so-called modified PLND,
an Augsburg workgroup 1998 started to transfer tech-
niques and concepts of the SLN-identification in other
tumour entities to the prostate cancer [28,29].
The technique differs not insubstantially from those in
other tumor entities. In breast cancer and malignant
melanoma , a well-directed peritumoral injection is
only placed to observe the lymphatic drainage of the
tumor. In prostate cancer it is unknown from which part
of the organ the metastatic spread originates. Therefore,
the aim of prostate lymph scintigraphy must be the im-
aging of all primary draining lymph nodes of the pros-
tate, under which the SLN of cancer also exist. Further-
more, only the use of highly sensitive and well shielded
probe systems is promising because of the comparatively
high background activity of the bone marrow and of the
closeness of the SLN in the iliaca interna area to the
place of injection. The preoperative lymph scintigraphy
is only of limited importance because the lymph chan-
nels could mostly not be represented, the time of the
lymph drainage varies not insubstantially and the opera-
tive probe measurement often demonstrates more radio-
active lymph nodes than described preoperatively.
In the biggest Augsburg patient-collective (2020 cases)
analysed so far, in 98% of the cases at least 1 SLN could
be operatively detected. Positive lymph nodes were
found in 16.7% of the patients. For lymph node positive
men who had either a standard or extended lymphaden-
ectomy in addition to a SLND the false-negative rate
could be calculated, resulting in false-negative findings
in 11 out of 187 patients (6%) . As in penile cancer,
reasons for false negative results could be macrometas-
tases due to obstructed lymphatic vessels, a previously
done transurethral resection of the prostate and also a
neoadjuvant hormonal therapy leading to shrunken
Earlier studies could already show that even patients
with a comparatively good vantage point exhibited un-
expectedly often positive lymph nodes . Here the
SLN were often located in the iliaca interna region and
so beyond the region of standard lymphadenectomy.
This was further proven by others in series of extended
lymph dissections . More than 60% of lymph node
positive patients would have falsely been classified as
pN0 stage if only a standard PLND had been undertaken
. Meanwhile, the feasibility with comparable values
in sensitivity and localisation of the SLN or metastases
could be reproduced by different workgroups [34-37].
Based on this data, since 2009 even the guidelines of
EAU find only methods of histological detection of
lymph node metastases with high sensitivity such as
sentinel lymph node dissection or extended pelvic lymph
node dissection suitable for lymph node staging in pros-
4. BLADDER CANCER
In patients with muscle-invasive bladder cancer the most
important prognostic factor is the lymph node status
together with the tumor stage. However, here as well the
A. Winter et al. / HEALTH 2 (2010) 836-841
Copyright © 2010 SciRes. http://www.scirp.org/journal/HEALTH/
Openly accessible at
extent or the amount of the lymph nodes that should be
removed is discussed. Therefore it seems to be reason-
able to verify the SLN-conception even for bladder can-
cer. In these tumor entities it is less the fact of minimiz-
ing the postoperative morbidity, which is comparatively
low in the scope of the radical cystectomy, but more the
fact of improving diagnostics and therapy in cases of
positive lymph nodes.
The first publication concerning bladder cancer was
released by a Swedish workgroup in the year 2001 .
SLN were detected in 85% (11/13) of the patients. Mean-
while, the biggest experience could show Liedberg et al.
with an examination of 75 patients . In 65 cases
(87%) at least 1 SLN could be detected. 26 out of 32
lymph node positive patients had positive SLN. For this
reason, 6 patients (19%) were false negative, whereas 5
of these cases showed macro metastases. In addition, the
SLN-technique was verified in animal experiment in real
time with near-infrared fluorescent albumin .
One problem in using this method in bladder cancer is
the injection of the tracer in multifocal or huge tumors.
An exact peritumoral injection of the tracer is impossible
in these cases. Moreover, macro metastases could be a
limitation, because they could block the lymphatic drain-
age and so impede an accumulation of the tracer.
5. TESTICULAR CANCER
In 2002, the first two studies were published [41,42]
which verified the sentinel-concept in the stage I in tes-
ticular cancer. The aim of the technique in this case is to
avoid a potentially dispensable adjuvant chemo- or radio-
therapy with a minimal invasive intervention. Both work
groups achieved a high presentation rate of the retrop-
eritoneal situated SLN after intratesticular peritumoural
injection. The Japanese workgroup managed to do the
radio guided laparoscopic dissection of SLN in 21 out of
22 patients (95%) after injection of (99m) Technetium-
labelled phytate one day preoperative . Furthermore,
a laparoscopic gamma probe was combined with the use
of a portable gamma camera to improve the localization
of the SLN .
6. RENAL CELL CANCER
The indication and extension of lymph node dissection
in renal cell cancer is discussed controversially. On the
one hand, studies had shown that patients do not benefit
from a lymph node dissection complementary to the
radical nephrectomy . On the other hand, an im-
provement of survival could be observed in patients with
lymph node metastases which received an immunother-
apy postoperatively .
The feasibility of SLNE in animal model could be
shown by the use of blue dye and (99 m) Technetium
. The purpose was also to increase the detection rate
of LN metastases in due consideration of the variable
lymphatic drain of the kidney. Furthermore, data con-
cerning the use of the sentinel technique on 2 patients
has been published so far . Para aortal SLN could be
PLND is presently indispensable for an exact lymph
node staging in urological malignancies due to the inade-
quancy of preoperative imaging for the identification of
lymph node micro-metastases. The SLND offers a good
compromise between high sensitivity and low complica-
tion rate in contrast to the extended lymphadenectomy
In penile cancer indication and necessity of an addi-
tional inguinal LA were handled differentially depending
on the tumor stage. The EAU guidelines for the diagnos-
tic and therapy of penile cancer recommend this proce-
dure for patients with intermediate risk disease (≥ T1G2)
when no palpable lymph nodes are existent.
The radio guided PLND in the clinically localized
prostate cancer prove the existence of lymph node me-
tastases substantially more often and earlier than previ-
ously assumed. These were often mistaken because in a
high percentage they occur in lymph drainage areas that
were spared by limited LA-techniques. Because ex-
tended PLND, which capture these lymph drainage areas
(iliaca interna region, presacral, pararectal, paravesical)
are elaborate and accompanied with a higher morbidity,
the gamma probe guided PLND lends itself to solve this
problem. It provides the possibility to capture lymph
node positive patients with minimal complications and
with a high reliability.
The latest studies show for bladder cancer, renal cell
cancer and testicular cancer that the feasibility for these
tumor entities is probably given, too. To which extend
these therapeutic concepts are able to replace or at least
complement the default therapeutic procedures has to be
shown in further studies.
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