The Sentinel Node Concept in Patients with Cervical Cancer

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The Sentinel Node Concept in Patients with
Cervical Cancer

• -A Multicenter Validation Study-
• of the German

SUBMITTED Hermann Hertel, Christopher
Altgassen, Antje Brandstädt, Christhardt Köhler,
Matthias Dürst and Achim Schneider for the
AGO-study group

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Introduction -sentinel concept in the
surgical treatment of breast cancer
-minimize morbidity -sensitivity
88.6 91.2 -negative
predictive value (NPV) 91.1 95.7
-without compromizing oncological
safetyToday this technique has become method of
choice in the surgical treatment of breast
cancer.
Veronesi et al. N Engl Med 2003349546-553,
Krag et al. N Engl Med 1998339991-995
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Introduction
advantage of sentinel technique -reduction
of negative lymph node dissection -sentinel
lymph nodes predict accurately the negative
status of the remaining regional lymph nodes
Gynecol Oncol update
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Introduction
-cervical cancer metastasize mainly
lymphatic -lymph node status is the most
important prognostic factor -lymphadenect
omy - gold standard If lymph node metastases
are present at the time of primary surgery
5-year survival drops from 85 to 50.
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Introduction
Removal of lymph nodes can lead to -serocele
formation -lymphedema -paraaesthesia -voiding
disorders More than 90 of the removed lymph
nodes are free of metastatic disease. Patients
could be preserved from potential
morbidity. Sentinel concept might be applicable
in cervical cancer.
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prospective studies

• Author Tc/Blue Patients Detection
• (n) ()
• Hauspy et al. 2007 Tc blue 39 98
• Seong et al. 2007 blue 89 57,3
• Schwedinger et al. 2006 blue 47 83
• Vieira et al. 2004 blue 51 62,7
• Yuan et al. 2004 blue 41 75,6
• Niikura et al. 2004 Tc blue 20 90
• Li et al. 2004 Tc 75 96,4
• Rob et al. 2004 blue 100 60-90,5
• Plante et al. 2003 blue /- Tc 70 87-93

Wuppertal 2004
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-evaluation of detection rate and diagnostic
accuracy of sentinel lymph nodes-patients with
cervical cancer-all stages-to predict the
histopathologic pelvic nodal status
Aim
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1998-2006-prospective multi-center cohort
study -Technetium, Patent Blue, or both to
identify sentinel lymph nodes -pelvic (and
para-aortic) node dissection -sentinel nodes
and non-sentinel nodes were histopathologically
examined
The study
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inclusion criteria -histological proven
cervical cancer (all stages), -signed informed
consent, -intension to surgical staging of the
patient, -complete pelvic lymphadenectomy,
exclusion criteria -preoperative detected
metastatic disease, -previous pelvic or
para-aortic lymphdenectomies, -concurrent
adnexal carcinoma, -cervical extension which
made injection in normal cervical tissue
impossible, -neoadjuvant therapy
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primary objective -sentinel lymph node
detection rate -accuracy (sensitivity, negative
predictive value) Hypothesissensitivi
ty 96,5 should be achieved/ 90 clinically
accepted100 sentinel positive patients
necessarytotal sample size depended on
prevalence of positive sentinel nodes and
detection rate
Statistics
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Tracer application
subepithelially
Tc-albumines 60 MBq the day prior
(1ml) Blue dye (Patent Blue) 4 ml
after anesthesia
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surgical procedure
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laparoscopic pelvic lymphadenectomy (left)
N. obturatorius
surgical procedure
N. genito- femoralis
Vasa iliaca externa
M. psoas
laparoscopic paraaortic lymphadenectomy
V. renalis
positive pelvic lymphnode left side
A. mesenterica inferior
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Results
December 1998-October 2006 603 patients
enrolled in 18 centers -excluded 96
patients- (in 64 patients no pelvic sentinel
node was detected) 507 patients for analysis
of accuracy
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n603
-flowchart- disposition of patients
eligible for analysis
n590
n507
n82
n422
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n24!!
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median age 41 years (range 16-79 years)
squamous cell carcinoma 383 patients (75.5)
adenocarcinoma 97 patients (19.1) (5,4
others)FIGO stage -IA1 in 38 patients (7.5),
-IA2 in 42 patients (8.3), -IB1 in 265
patients (52.3), -IB2 in 55 patients (10.8),
-IIA or IIB in 91 patients (17.9), -IIIA to
IVB in 15 patients (3)
Results
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cervical cancer were removed vaginally and
lymph nodes were harvested endocopically in 283
patients (56), open approach was chosen in
224 Patients (44)
Results
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over all detection rate 89,7 (CI95
86.9-92) pelvic 88,6 (CI95
85,8-91,1)Tc alone (n55) 82 detection
ratePatent Blue alone (n195) 82 detection
rateTcPatent Blue (n340) 94 detection rate
(plt0,001)
Results indentification of sentinel lymph nodes
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median number of sentinel lymph
nodespelvic 2 (2-24)paraaortic 1 (1-9)gt5
sentinel nodes identified in 103 patients
(20,3)median number of all lymph
nodespelvic 24 (2-70) n507 patientsparaaortic
13 (1-47) n190 patients
Results indentification of sentinel lymph nodes
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pelvic lymph node metastasis n106
patientssentinel lymph nodes correctly predict
metastatic disease n82 patientsSensitivity
77,4 (CI 68,2-85) (lt90 of
clinically acceptability)NPV 94,3 (CI
83-99,4)
Results accuracy of diagnostic test
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tumor size lower or equal 20mm in 249
patients (45.8) larger than 20mm in 305
patients (47.7) (6,5 no data)overall
detection rate 94 in cancers smaller than 21mm
84 in cancers larger than 20mm (plt0.001).
Results indentification of sentinel lymph nodes
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sensitivity in subgroups of women with tumors
lt21mm 90.9(70,8-98,9), gt21mm 72,7
(61,3-82,3) (p0.091)
Results accuracy of diagnostic test
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tumors lt 21mm NPV99.1 (CI95 96.6 100)
tumors gt20mm NPV88.5 (CI95 82.9
92.8), (plt0.001)
Results accuracy of diagnostic test
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Probability of diagnostic outcome in all
patients flowchart-
100
4 patients!
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Probability of diagnostic outcome in patients
with cervival cancer 20mm -flowchart-
100
1 patient!
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Our data suggest that the sentinel concept is NOT
applicable in patients with cervical cancer.
Sensitivity is to low.
Conclusion
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Using the currently available concept, systematic
lymphadenectomy CAN NOT be omitted!Ultrastaging
of sentinel lymph nodes may have a future role in
addition to systematic lymphadenctomy.HPV-associ
ated markers have the highest potential of
accurate identification of viable tumor cells.
Conclusion
Gynecol Oncol update
Leuven 5. May