Sentinel node biopsy in Low- and Intermediae endometrial cancer Management: The SLIM-study

Cancer of the endometrium has the highest prevalence of all gynecological
cancers in North America and Europe. The incidence is still increasing due to
prolonged life expectancy, changes in reproductive behavior and prevalence of
overweight. Early stage endometrial cancer restricted to the uterus has an
overall survival of 85-90%. The treatment of endometrial cancer is primarily
surgery. However, an ongoing controversy in the management of endometrial
cancer relates to lymphadenectomy. For patients with early stage endometrial
cancer, randomized trials and a meta-analysis have shown that pelvic
lymphadenectomy has no effect on overall or recurrence-free survival. A full
lymphadenectomy can necessitate extensive dissection, which is time-consuming
and involves morbidity. However, the trials on lymphadenectomy in early stage
endometrial cancer did not take into account the contribution of sentinel lymph
node (SLN) biopsy in reducing the risk of surgical complications and improving
staging. Moreover, when lymph node status is unknown, indications for adjuvant
therapies are on pathological features of surgical specimen of the primary
tumor, exposing some patients to overtreatment and undertreatment.
Recently, Ballister showed that SLN biopsy with ultra-staging upstaged 10% of
patients with presumed low-risk and 15% of patients with presumed intermediate
risk.
SLN biopsy might be a good compromise between systemic lymph node dissection
and no node dissection in women with low- or intermediate-risk endometrial
cancer.
SLN biopsy seems a feasible method with a detection of the SLN in about 85%,
and reliable in terms of negative predictive value (97% in the SENTI-ENDO study
by Ballister et al.) and sensitivity (84%) when ultra-staging of SLNs is
implemented.

The SLN biopsy is a well-known technique in the Netherlands as is has been used
for over a decade in vulvar cancer. SLN biopsy in endometrial cancer should
therefore be implemented easily in Dutch centers for gynecological oncology.

1. To assess the feasibility of SLN identification in endometrial cancer.

2. To examine in how many cases SLN biopsy provides results that will tailor
adjuvant treatment

3. To investigate if SLN biopsy in women with low- and intermediate-risk
endometrial cancer will lead to better disease free and overall survival

Our aim is to individualize the care for patients with low-, and
intermediate-risk endometrial cancer. Lymph node-tailored adjuvant treatment
may lead to better recurrence-free and overall survival

142 patients with presumed low- or intermediate risk endometrial cancer will be
included in this pilot.

Low-risk: type 1 endometrial cancer, stage 1A grade 1 or 2
intermediate-risk: type1endometrial cancer stage 1B grade 1 or 2.

To estimate the differentiation grade, every patient will undergo a
pre-operative endometrial biopsy using the pipelle© sampling system. The
pipelle has a sensitivity of 75% for all grades, but a sensitivity of 90% for
diagnosis of either grade 1 or grade 2.

The sentinel node procedure: Four cervical injection of 0.2mL (20 MBq each) of
Technetium-99m-labeled Nanocolloid with patente-blue of ICG will be given with
a 25-gauge spinal needle at 3, and 9 o*clock positions deep and superficial. In
case of subserosal application 2 injections are given subserosal.
Then a pause of 30 minutes is needed for both tracers to find their way through
the lymphatic vessels. In the mean time preparation of the operation will take
place in these 30 minutes.
The SLNs will be localized will be localized using a gamma probe (if
laparoscopic approach the probe is inserted through a 12mm trocar) by selecting
the areas with the highest radioactivity. Furthermore, the patent blue dye will
be traced in the retro-peritoneum. Finally, a hysterectomy and bilateral
salpingo-oophorectomy is performed.

Patients with a positive sentinel node will be upgrade towards a stage 3A
diases and treated accordingly with adjuvant external beam radiotherapy.

prior to the operation 4 cervical injections are needed. In case of subserosal
appilcation 2 injections are given in the uterus subserosal during the
operation. There is a risk of an allergic reaction of 0.6%, mainly pruritis and
oedema, or hypotension (0.5%). These injections are given under anaesthesia
before the start of the surgery.

- The operation procedure is extended wth SLN biopsy. This might give some
extra blood loss and will extend the procedure with approximately 45 minytes.
However, the SLN biopsy is a well-known technique in the Netherlands as it has
been used for over a decade in vulvar cancer. SLN biopsy in endometrial cancer
should therfore be implemented easily.