Update on Sentinel Node Biopsy in

Endometrial Cancer: Feasibility, Technique,

Impact

Bjørn Hagen, MD, PhD

St Olavs Hospital
Trondheim University Hospital
Trondheim, Norway
 Endometrial Cancer (EC)
• The most common gynecologic cancer in
industrialized countries
• >90% of cases are in women aged >50 years
• 80% of cases diagnosed in stage 1
 Uterine Risk Factors in Apparent Stage 1 Disease

Risk Category Histologic Type Substage Grade

Low Endometrioid 1A 1+2
Endometrioid 1A 3
Intermediate
Endometrioid 1B 1+2

Endometrioid 1B 3
High
Nonendometrioid Any Any

However, lymph node (LN) status is a better predictor of recurrence than

uterine factors
LN assessment included in EC staging since 1988 but still
controversial
 Overall Survival,
Proportion Alive
Overall Survival, %

Benedetti Panici P, et al.

Kitchener et al..
J Natl Cancer Inst.
Lancet (2009);373:125
2008;100(23):1707-1716.

May K, et al. Cochrane Database Syst Rev. 2010;(1):CD0077585.

Obstet Gynecol. 2014;124(2 Pt 1):307-315.

Risk of lower limb lymphedema attributable to lymphadenectomy:

23% increased compared to hysterectomy alone

Gynecol Oncol. 2015;136(1):87-93.

«The strongest risk factor for lymphedema is the number of nodes removed at surgery»
 At Least 5 Lymph Node Assessment
Strategies in Endometrial Cancer
• No lymphadenectomy (LA) for any patient
• Selected LN sampling in all or some patients
• Comprehensive (pelvic + paraaortic) LA based on risk
factors, refrain from LA in low-risk patients
• Comprehensive LA in all patients
• SLN detection—a middle ground providing the needed
prognostic and treatment-influencing information while
limiting morbidity from the procedure and allowing LN
assessment in all patients, potentially preventing both
under-treatment and over-treatment
 SLN in Breast Cancer and Melanoma
4 prospective randomized trials:
• No survival advantage from performing completion LA in
patients with SLN metastasis
‒ Melanoma Morton DL, et al. N Engl J Med. 2006;355(13):1307-1317. Leiter U, t al. Lancet Oncol. 2016;17(6):757-767.
‒ Breast cancer Krag et al. Lancet Oncol 2010;11:927, Giuliano et al. JAMA 2011;305:569

Randomized trial in breast cancer:

• Significant (two-thirds) reduction of lymphedema with SLN
compared to conventional axillary LA
Mansel RE, et al. J Natl Cancer Inst. 2006;98(9):599-609.

SLN, sentinel lymph node

 SLN
The first node to receive drainage from a
primary tumor and the most likely to harbor metastases

Allowing selective and limited LN assessment

 SLN Technique Issues
• Injection
‒ Cervical
‒ Fundal—laparoscopic
‒ Intrauterine—hysteroscopic
• Tracer
‒ Blue dye—naked eye
‒ Technetium-99—radioactivity
‒ Indocyanine green (ICG)—near-infrared fluorescence
• Surgical algorithm
‒ Triage of mapping failure
‒ Extended pathology
 Injection of Dye Into the
Cervix at 9 and 3 O’Clock

Abu-Rustum NR, et al. Gynecol Oncol. 2008;111(2 Suppl):S44-S50.

 Drainage Routes After Cervical Injection

Abu-Rustum NR. J Natl Compr Canc Netw. 2014;12(2):288-296.

Cave: Iodine allergy, hepatic impairment
 Surgical Algorithm
Peritoneal & serosal evaluation & washings

Retroperitonal evaluation
Excision of all mapped SLN Any suspicious nodes must be
with ultrastaging removed regardless of mapping

If there is no mapping on a hemipelvis,

a side-specific LND is performed
Paraaortic LND‒
at attending discretion

LND, lymph node dissection

Barlin JN, et al. Gynecol Oncol. 2012;125(3):531-535.
Pancytokeratin Immunohistochemistry

HE, 20 X CKAE1/AE3, 20 X
Use of a Novel Sentinel Lymph Node Mapping Algorithm Reduces the
Need for Pelvic Lymphadenectomy in Low-Grade Endometrial Cancer
SLN Mapping With Reflex SLN Mapping With
Frozen Section (FS) Algorithm NCCN Algorithm

SLN Mapping SLN Mapping

TLH/BSO TLH/BSO

FS performed ONLY if
failed bilateral mapping
Side-specific PLND
performed on any side
Side-specific PLND that does not map
ONLY if high-risk
featured on FS

FS high-risk features (Mayo criteria): Size >2 cm, outer half (1B), grade 3/LVSI
LVSI, lymphovascular space invasion; NCCN, National Comprehensive Cancer Network; PLND, pelvic LND; TLH/BSO, total abdominal hysterectomy and bilateral salpingo oophorectomy
Tanner E, et al. Gynecol Oncol. 2017;147(3):535-540.
Use of a Novel Sentinel Lymph Node Mapping Algorithm Reduces the
Need for Pelvic Lymphadenectomy in Low-Grade Endometrial Cancer

Lymphadenectomy Rates With Reflex Frozen Section SLN Algorithm

vs NCCN SLN Mapping Algorithm

Reflex Frozen Section SLN NCCN SLN Mapping

Outcome Matting Algorithm Algorithm P
% Patients requiring any pelvic LA 7.1% 18.6% .02
% Hemipelvises requiring LA 5.3% 12.4% .01

Tanner E, et al. Gynecol Oncol. 2017;147(3):535-540.

Sentinel Lymph Node Assessment in Endometrial Cancer:
A Systematic Review and Meta-Analysis
• 55 studies – 4915 women

• Overall SLN mapping rate 81%

• Bilateral pelvic mapping rate 50%

• Cervical injection and ICG tracer increased bilateral

pelvic mapping

• 96% sensitivity to detect lymph node metastases

Bodurtha Smith AJ, et al. Am J Obstet Gynecol. 2017;216(5):459-476.

A Comparison of Sentinel Lymph Node Biopsy to Lymphadenectomy
for Endometrial Cancer Staging (FIRES Trial): A Multicentre,
Prospective, Cohort Study
• Robotic platform cervical ICG injection, 10 centers, 18 surgeons, SLN mapping followed by
completion lymph LA, clinical stage 1, any histology, IHC ultrastaging of H-E negative SLNs
• 385 patients enrolled between Aug 2012 and Oct 2015, 340 underwent SLN + LA
(+ paraaortic in 58%)
• SLN mapping: Total 86%, bilateral 52%, paraaortic 23%, isolated paraaortic <1%
• 41 (12%) with LN metastases:
36 with SLN mapping: 35 SLN+, 1 SLN‒/non-SLN+; sensitivity 97.2%, NPV 99.6%
Sensitivity and Specificity Data
True Positive Nodes True Negative Nodes
Positive sentinel lymph node 35 0
Negative sentinel lymph node 1 257

• 5 % of 1098 SLNs were positive vs 1% of 5416 non-SLNs (P = .0001)

Rossi EC, et al. Lancet Oncol. 2017;18(3):384-392.
Indocyanine Green Fluorescence Imaging of Lymph Nodes During Robotic-
Assisted Laparoscopic Operation for Endometrial Cancer. A Prospective
Validation Study Using a Sentinel Lymph Node Surgical Algorithm

• 108 consecutive patients with uterine size ≤8 cm and

disease apparently restricted to the uterus except image-
suspicious pelvic and low paraaortic nodes
• All histologies
• From November 2012 through 2015

Hagen B, et al. Gynecol Oncol. 2016;143(3):479-483.

ICG Sentinel Lymph Node Detection Rate (n = 108)

ICG SLN Detection Number of Patients Percentage

Not detected 4 4

Unilateral pelvic detection 20 18

Bilateral pelvic detection 84 78

Overall pelvic detection 104 96

Total 108 100

Hagen B, et al. Gynecol Oncol. 2016;143(3):479-483.

Lymph Node Metastases by Node Category (n = 17)

Metastatic Node Category Number of Patients Percentage

In SLN only
Only SLN removed 4 24
SLN + non-SLN removed 8 47
In SLNs and non-SLNs 4 24

In non-SLNsa 1 6
Total 17 100

aIn 1 of 4 patients with negative SLN mapping

Hagen B, et al. Gynecol Oncol. 2016;143(3):479-483.
The Distribution of Risk Categories and Corresponding
Rates of Lymph Node Metastatic Disease
Number With LN
Risk Category Number of Patients, n (%) Metastases, n (%)
Low 45 (42) 4 (9)

Intermediate 35 (32) 4 (11)

High 28 (26) 9 (32)

Total 108 (100) 17 (16)

Hagen B, et al. Gynecol Oncol. 2016;143(3):479-483.

Adjuvant Chemotherapy by Postoperative Risk Category

Risk Category # of Patients Chemotherapy Percentage

Low 41a 3 7%

Intermediate 31a 4 13%

High 36 30 83%

Total 108 37 34%

a4 low-risk and 4 intermediate-risk patients transferred to high-risk due to LN metastases

Hagen B, et al. Gynecol Oncol. 2016;143(3):479-483.
 Comparison of Sentinel Lymph Node and a Selective
Lymphadenectomy Algorithm in Patients With Endometrioid
Endometrial Carcinoma and Limited Myometrial Invasion
Disease-Free Survival

Disease-Free Survival, %

14 recurrences within 3 years in the LND cohort

19 recurrences within 3 years in the SLN cohort
Log-rank P value = .35

Years Following Surgery

Eriksson AG, et al. Gynecol Oncol. 2016;140(3):394-399.

 SLN vs Standard Lymphadenectomy in
High-Risk Endometrial Cancer
PFS in Patients Undergoing SLN Mapping vs Standard Lymphadenectomy

Carcinosarcoma Serous Carcinoma

Progression-Free Survival, Proportion

Progression-Free Survival, Proportion

Months Months

Schiavone MB, et al. Ann Surg Oncol. 2016;23(1):196-202. Schiavone MB, et al. Ann Surg Oncol. 2017;24(7):1965-1971.
 By November 2017:
4 Recurrences, 96.3% Recurrence-Free Survival

• Time to recurrence: Range 9 months - 20 months

• Location: 2 retroperitoneal (nodal), 1 nodal + distant, 1 distant
• All 4 were LN positive
• All 4 were uterine high-risk (2 endometrioid grade 3, 2 serous)
• 3 of 4 had >50% infiltration depth
• 3 of 4 were LVSI positive
• 3 received adjuvant chemotherapy, 1 refused chemotherapy
LN Metastatic Node Category by Recurrence-
Status
LN Met. Category Recurrence-Free Recurrence Total
ITC (<0.2 mm) 2 0 2

Micro (0.2 - 2 mm) 2 2 4

Macro (>2 mm) 9 2 11

Total 13 4 17
 Summary SLN in Endometrial Cancer
• For diagnostic/staging purpose: SLN biopsy can be
considered a standard-of-care approach for all risk
categories
• Cervical injection and the use ICG improve overall and
bilateral pelvic SLN mapping
• Surgical algorithm nessessary to adjust for mapping
failure
• Reassuring survival data so far
 Summary Continued
• Further research needed:
– The clinical significance of low volume metastasis
– Long-term morbidity following SLN biopsy
Thanks for your attention