NEW ORLEANSA prospective study in colorectal cancer patients
has found that sentinel lymph node (SLN) mapping correctly predicts
the presence or absence of nodal metastases, with a very low
incidence of skip metastases (disease in a non-SLN), as it does in
melanoma and breast cancer.
At the Society of Surgical Oncology Cancer Symposium, Michigan State
University researchers presented data on 168 consecutive colorectal
cancer patients who underwent SLN mapping (see Figures 1 and 2).
Exclusive sampling of the sentinel nodes correctly predicted the
presence or absence of lymph node metastasis in 96% of the cases,
reported Sukamal Saha, MD, assistant professor of surgery and
anatomy, McLaren Regional Medical Center, Flint, Michigan.
Multiple studies have shown that up to 30% of stage I and II
colorectal cancer patients will develop metastatic disease within 5
years of diagnosis. We believe this is largely due to pathologic
under-staging of nodal micrometastases, Dr. Saha said.
Furthermore, he said, studies have shown that about 70% of involved
lymph nodes are under 5 mm in size, and it is possible that a cursory
examination of the lymph nodes may indeed miss small metastases.
If we can identify the first few nodes where most of the
metastatic disease could lodge, he said, then, with
careful pathological examination using microsection-ing, H&E
[hematoxylin and eosin] staining, immunohistochemical staining, and
PCR techniques, we may enhance the diagnosis of micrometastatic
disease and give adjuvant therapy to these upstaged patients.
In the study, SLNs were sectioned at intervals of 20 to 40 microns at
10 levels and stained with H&E, then immuno-histochemically
stained for cytokeratin and carcinoembryonic antigen (CEA). In
addition, standard pathological examination of the remaining
non-sentinel lymph nodes also was done.
To assure that any increased detection of micrometastases in the SLNs
was not due solely to this increased sampling, all initially negative
non-SLNs in the first 25 patients were also sectioned at 10 levels.
The SLN was identified in 164 of 168 patients (98%); one, two, or
three sentinel lymph nodes were found in 160 patients, or more than
95%. A total of 300 SLNs were identified out of 2,504 total lymph nodes.
Negative Predictive Value
In 98 patients (60%), the SLNs were negative for metastatic disease.
In 91 of these patients (93%), all non-SLNs were negative as well.
The negative predictive value, therefore, was 93%, Dr. Saha reported.
In 7 of these 98 patients with negative SLNs, other non-SLNs were
positive, yielding a skip metastases rate of about 7%. But we
presented consecutive patients, and we did not discard patients for
any reason, Dr. Saha pointed out. Now, we know more about
the limitations of this method, and which patients would not benefit.
If we exclude patients who would not undergo this procedure in normal
clinical practice, our skip metastases rate is closer to 4%.
In 59 patients, SLNs were positive for metastatic disease; 28 (17%)
of these patients had additional non-SLNs that were positive. In 31
patients (19%), SLNs were the only nodes positive for metastatic
disease, he said.
Most important, Dr. Saha said, in 28 of these 31 patients,
micrometastatic disease was identified in only one, two, or three
microsections of the 10 that were taken of a single sentinel lymph
node. In 10 patients, this was discovered only by
immunohistochemistry, as H&E was negative.
Such micrometastatic disease in 6- to 7-mm nodes could have
been missed by standard pathologic examination, he said.
In the first 25 patients with negative SLNs, in whom all initially
negative non-SLNs were sectioned at 10 levels, fewer than 1% of nodes
were positive for metastatic disease. Similar studies were carried
out in the first 82 consecutive patients, and again, when the SLN was
negative, the incidence of finding metastatic disease in non-SLNs was
only 1%, he emphasized.
By this mapping technique, more than one third of patients
categorized as clinical stage I or pathologic stage I were upstaged
to stage III disease.
A Short Learning Curve
Dr. Saha concluded, This is a viable technique with a short
learning curve and minimal side effects. Its accuracy in identifying
metastatic disease is 93%. It definitely allows the pathologist to
focus attention only on one to four sentinel nodes.
Examination of only 12% of the nodes [the SLNs in this series] would
have given the correct diagnosis in most patients, he said, allowing
the pathologist to avoid examining 88% of the lymph nodes.
The main point is that when the SLNs are negative, the chance
of missing cancer in the non-sentinel nodes is less than
1%, Dr. Saha continued. From a pathological point of
view, you should bet on the sentinel nodes. The accuracy of your
diagnosispresence or absence of metastasesis 96%.
Alfred Cohen, MD, chief of colorectal surgery, Memorial
Sloan-Kettering Cancer Center, said that he remains concerned about
the skip metastases rate, but called the presentation
important and said he has been encouraging Dr. Saha to
work with the American College of Surgeons Oncology Group on this project.