EURURO Vol. 71 No. 4

597 692

1. Introduction
According to European Association of Urology guidelines,
the risk of nodal metastases in prostate cancer (PCa) is
20–45% if any biopsy core has predominant Gleason
4 pattern or more than three cores have any Gleason
4 pattern. For detection of lymph node (LN) metastases via
imaging, the sensitivity of abdominal computed tomogra-
phy (CT) and multiparametric magnetic resonance imaging
(mpMRI) is <40% In addition, 11C- or 18F- choline- and
68Ga–prostate-specific membrane antigen (PSMA) positron
emission tomography (PET)/CT provide low estimated
sensitivity of 49–66% in detection of LN metastases before
treatment of PCa . For this reason, patients with
intermediate- and high-risk disease with a risk of nodal
metastases > 5% (Briganti nomogram or Memorial Sloan
Kettering Cancer Center nomogram), extended pelvic
lymph node dissection (ePLND) is the preferred staging
tool . Unfortunately, ePLND is also associated with
intraoperative and postoperative complications .
Advantages of targeted dissection of tumor-associated
LNs include tailoring of the surgical procedure to the
individual patient, with potentially more accurate staging
and lower morbidity . For malignancies such as breast
cancer, penile cancer, and melanoma, sentinel node biopsy
(SNB) has become routine for nodal staging as it helps in
distinguishing patients who need extensive nodal dissec-
tion from those who would not gain an oncologic benefit
from such dissection. SNB in PCa is still considered
experimental, as the lymphatic drainage for the prostate
gland is highly variable and complex. Knowledge about
lymphatic drainage is crucial for detection of sites of LN
metastases. There are four pelvic lymphatic drainage
pathways known for PCa. The main route of drainage is
the lateral route to the medial chain of the external iliac
nodal group (ie, obturator nodes), spreading from there to
the middle and lateral chains of the external iliac nodes. The
second route of drainage is the internal iliac route, via LNs
positioned along the visceral branches of the internal iliac
vessels. Some lymphatic drainage occurs along an anterior
route, via LNs located anterior to the urinary bladder. The
last possible drainage pathway is a presacral route anterior
to the sacrum, coccyx, and perirectal lymphatic plexus,
subsequently ascending to the lateral sacral nodes and
those at the sacral promontory (ie, medial chain of common
iliac nodes) .
Since 1999, when the first SNB for PCa was performed by
Wawroschek et al , various techniques have been
developed to identify SN in PCa. A separate review
performed by our team revealed significant heterogeneity
of definitions regarding SN, radiotracers, size and radioac-
tivity dose of the tracer, tracer administration, use of
preoperative imaging, and intraoperative detection of SNs
. So far, there is no consensus on the definition and
optimal SN technique, or on the diagnostic role of SN in PCa
patients.
The aim of this systematic review was to assess the
diagnostic accuracy of SNB in PCa as reported in the
literature. The results will be used to develop consensus
statements on how to optimally perform SNB in PCa in order
to guide clinical practice and further research.
2. Evidence acquisition
2.1. Search strategy
The protocol for the review has been published elsewhere
). We used standard methods recom-
mended by the Cochrane Methods Group for Systematic
Review of Screening and Diagnostic Tests , Preferred
Reporting Items for Systematic Reviews (PRISMA) , and
Standards for Reporting Diagnostic Accuracy Studies
(STARD) . Databases including Medline, Embase, and
the Cochrane Central Register of Controlled Trials were
searched systematically from January 1, 1999 to May 31,
2016. The search was complemented by additional sources
including reference lists from the studies included. Only
English language articles were included. The search terms
were prostatic neoplasms, prostate , carcinoma, sentinel lymph
node biopsy, and lymph node excision/dissection . The full
search strategy is outlined in the Supplementary material.
All abstracts and full-text articles were independently
screened by two reviewers (EW and CA). Disagreement was
resolved by discussion or with an independent arbiter
(HvdP or TBL). Exclusion criteria were animal studies,
reviews, historical overviews, editorials, SNB in other
cancers, analysis of SNB techniques in different types of
cancer, studies on the effectiveness of SPECT/CT and/or
radiotherapy treatment without obtaining pathology, and
studies with ten or fewer patients.
2.2. Study types
All retrospective and prospective studies on SNB in PCa with
PLND as reference standard were included. We excluded
studies without a reference standard (ie, when only SNB
was done) or when PLND was performed after frozen
sections obtained from SNs were positive. Conference
abstracts were also included.
2.3. Type of intervention (index test and reference standard)
For inclusion, studies had to assess SNB as the index test
using PLND as the reference standard, with positive or
negative nodal disease as determined by histopathologic
examination. To maintain external validity, any form of
PLND, including limited, standard, extended, or super-
extended PLND, was included. The ePLND template was
defined as removal of nodes from the obturator fossa,
internal, and external iliac vessels up to the ureteric
crossing. All definitions, routes, and approaches for SNB
were included. The procedure could be performed via an
open operation, laparoscopic approach, or with robot
assistance. Treatment of the primary tumor was either
radical prostatectomy or radiotherapy. For SNB, tracers
were administered into the prostate via the transrectal
or transperineal route under ultrasound guidance and
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