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Is
Occult Cancer in Lymph Nodes the Achilles Heal of Successful treatment? A
Few Cells May Cast a Long shadow (October 2003)
[The September
Commentary presented data indicating that extended lymphadenectomies find
more metastatic spread in nodes than is found in more limited procedures;
in the August Commentary the possibility that Combidex MR imaging may
lower the threshold for detection of nodal cancer to 5 mm masses. This
article addresses the early application of sentinel lymph node mapping
technique to this problem.]
For more than forty
years clinical researchers of breast cancer have exhaustively studied the
extent of axillary nodal metastases from the primary breast lesion,
correlating their findings with the risk of relapse, and using the
information as the basis of therapeutic decisions. They developed a method
for identifying the sentinel axillary lymph node, the first node in the
nodal chain. As collective experience matured, clinicians have become more
confident that a pathologically negative sentinel node implies with >95%
accuracy that neither macroscopic nor microscopic spread is present in the
unresected remaining nodes. Although it is still controversial as to the
significance of the extreme minimum of cells, i.e. those metastatic cells
only identified by immunocytochemistry or seen only in the nodal sinuses,
none the less, there is agreement that cell clusters as small as 2 mm
adversely affect outcome. This observation has been found to apply to lung
cancer, esophageal cancer and other cancers, and it would be surprising if
prostate cancer was an exception.
The premises of the
following discussion are: 1) in prostate cancer surgery if the node
sampling is limited to only nodes in the obdurator and external iliac
chains, a significant number of positive nodes will be missed; 2) sentinel
lymph node (SLN) mapping with technetium-99m nanoparticles, although in an
early stage of clinical usage, can identify the principle first node in
the draining pathway and guide the surgeon's selection for excision to one
or two significant nodes; 3) by limiting the pathologists' task to
examining only these one or two nodes extensive thin sectioning and
immunohistochemical analyses can be efficiently employed; and 4)
accumulating experimental results will define which patients with
apparently localized disease should be subjected to SLN studies.
Wawroschek and
colleagues in Augsburg, Germany, (Eur Urol.2003 Feb;43(2) 132-6) found
26.8% nodal positivity in 194 patients with apparently clinically
localized prostate cancer by doing an extended lymphadenectomy (LAD).
After retrieving the SLN, which had been identified by Tc-99m, the various
surgeons carried out modified or extended LADs. "At first all patients had
a sampling of the sentinel lymph nodes followed in most cases by a
modified or extended pelvic lymphadenectomy. Step sections, serial
sections and immunohistochemistry (IHC) were analyzed in all SLN and
so-called nonSLN of the first 100 patients. Later serial section and IHC
of non-SLN nodes were left out." They concluded that by examination of
just the obdurator nodes only 44.2% of the total positive nodes would have
been found; the additional inclusion of nodes from around the external
iliac vessel only improved the sensitivity to 65%.
Additional support
for these conclusions comes from a study by Heidenreich, Philipps-University
Marburg, Germany, (J Urol. 2002 Apr;167(4):1681-6) who based his rationale
for extended LAD on the awareness that the prostate's principle lymphatic
drainage is to the internal iliac and the presacral nodes. A total of 103
consecutive men with clinically localized prostate cancer received a
radical prostatectomy and accompanying lymphadenectomy which included
retrieval of nodes from the external and internal iliac, the obdurator,
common iliac, and presacral lymphoid areas. A mean of 28 nodes were
examined per patient and 26.2% were positive. For the 27 patients with
positive nodes one, two and three nodes were positive in 15, 9, and 1
patients, respectively. They compared the surgical complications in their
extended LAD series with 100 patients with RP and standard LAD. "There
were no significant differences in regard to intraoperative or
postoperative complications, lymphocele formation or blood loss between
the two groups." A useful observation was that 95.8% of the patients with
positive nodes had a PSA of >10.5 ng/ml and a Gleason score >
7. Patients with less than those values were therefore identified as a low
risk group where the risk of nodal positivity was 2%. Epstein and Partin
(CANCER, Sept. 1, 2002; p. 1016) reported in a study of 443 patients who
underwent sextant biopy and RP with lymphadenopathy that the risk of nodal
spread was 2.2% in instances wherein none of 6 biopsy cores had a major
Gleason pattern 4 or only < 3 showed any minor pattern 4.
Reports of sentinel
node mapping are just emerging in the literature. The article by
Wawroschek (Urol Int.2003;70(4)303-10) is a good primer. They performed
SLN mapping in 350 patients. The procedure began the day before surgery
with an ultrasound guided transrectal injection of 2-3 ml of 99mTc
radiolabled particles dividing half the volume per lobe.
Lymphoscintography was then performed. At the subsequent operation those
nodes that were identified as SLN by means of intraoperative gamma probe
detection and prior lymphoscintography were removed. After retrieval of
the SLN, a modified or extended LAD was performed. Results: 335 of 350
patients showed at least 1 SLN; 24.7% had lymph nodes metastases, and
there were 2 false negatives.
Bottom Line:
Sentinel lymph node mapping is emerging as a technique to guide
urologists in selecting which node (or nodes) to sample. Also, guidelines
are developing to indicate which patients should undergo SLN testing.
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