Update on Sentinel Node Biopsy in Endometrial Cancer: Feasibility, Technique, Impact
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1 Update on Sentinel Node Biopsy in Endometrial Cancer: Feasibility, Technique, Impact Bjørn Hagen, MD, PhD St Olavs Hospital Trondheim University Hospital Trondheim, Norway
2 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
3 Uterine Risk Factors in Apparent Stage 1 Disease Risk Category Histologic Type Substage Grade Low Endometrioid 1A Intermediate Endometrioid Endometrioid 1A 1B High Endometrioid Nonendometrioid 1B Any 3 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
4 Overall Survival, % Overall Survival, Proportion Alive Benedetti Panici P, et al. J Natl Cancer Inst. 2008;100(23): Kitchener et al.. Lancet (2009);373:125 May K, et al. Cochrane Database Syst Rev. 2010;(1):CD
5 Obstet Gynecol. 2014;124(2 Pt 1): Risk of lower limb lymphedema attributable to lymphadenectomy: 23% increased compared to hysterectomy alone Gynecol Oncol. 2015;136(1): «The strongest risk factor for lymphedema is the number of nodes removed at surgery»
6 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
7 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): Leiter U, t al. Lancet Oncol. 2016;17(6): 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): SLN, sentinel lymph node
8 SLN The first node to receive drainage from a primary tumor and the most likely to harbor metastases Allowing selective and limited LN assessment
9 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
10 Abu-Rustum NR, et al. Gynecol Oncol. 2008;111(2 Suppl):S44-S50. Injection of Dye Into the Cervix at 9 and 3 O Clock
11 Drainage Routes After Cervical Injection Abu-Rustum NR. J Natl Compr Canc Netw. 2014;12(2):
12
13 Cave: Iodine allergy, hepatic impairment
14
15 Surgical Algorithm Peritoneal & serosal evaluation & washings Retroperitonal evaluation Excision of all mapped SLN with ultrastaging Any suspicious nodes must be 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):
16 Pancytokeratin Immunohistochemistry HE, 20 X CKAE1/AE3, 20 X
17 Use of a Novel Sentinel Lymph Node Mapping Algorithm Reduces the Need for Pelvic Lymphadenectomy in Low-Grade Endometrial Cancer SLN Mapping With Reflex Frozen Section (FS) Algorithm SLN Mapping With NCCN Algorithm SLN Mapping SLN Mapping TLH/BSO TLH/BSO FS performed ONLY if failed bilateral mapping Side-specific PLND ONLY if high-risk featured on FS Side-specific PLND performed on any side that does not map 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):
18 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 Outcome Reflex Frozen Section SLN Matting Algorithm NCCN SLN Mapping Algorithm % Patients requiring any pelvic LA 7.1% 18.6%.02 % Hemipelvises requiring LA 5.3% 12.4%.01 P Tanner E, et al. Gynecol Oncol. 2017;147(3):
19 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):
20 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% True Positive Nodes True Negative Nodes Positive sentinel lymph node 35 0 Negative sentinel lymph node % of 1098 SLNs were positive vs 1% of 5416 non-slns (P =.0001) Rossi EC, et al. Lancet Oncol. 2017;18(3): Sensitivity and Specificity Data
21 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 imagesuspicious pelvic and low paraaortic nodes All histologies From November 2012 through 2015 Hagen B, et al. Gynecol Oncol. 2016;143(3):
22 ICG Sentinel Lymph Node Detection Rate (n = 108) ICG SLN Detection Number of Patients Percentage Not detected 4 4 Unilateral pelvic detection Bilateral pelvic detection Overall pelvic detection Total Hagen B, et al. Gynecol Oncol. 2016;143(3):
23 Lymph Node Metastases by Node Category (n = 17) Metastatic Node Category Number of Patients Percentage In SLN only Only SLN removed SLN + non-sln removed In SLNs and non-slns 4 24 In non-slns a 1 6 Total a In 1 of 4 patients with negative SLN mapping Hagen B, et al. Gynecol Oncol. 2016;143(3):
24 The Distribution of Risk Categories and Corresponding Rates of Lymph Node Metastatic Disease Risk Category Number of Patients, n (%) Number With LN 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):
25 Adjuvant Chemotherapy by Postoperative Risk Category Risk Category # of Patients Chemotherapy Percentage Low 41 a 3 7% Intermediate 31 a 4 13% High % Total % a 4 low-risk and 4 intermediate-risk patients transferred to high-risk due to LN metastases Hagen B, et al. Gynecol Oncol. 2016;143(3):
26 Disease-Free Survival, % Comparison of Sentinel Lymph Node and a Selective Lymphadenectomy Algorithm in Patients With Endometrioid Endometrial Carcinoma and Limited Myometrial Invasion 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):
27 Progression-Free Survival, Proportion Progression-Free Survival, Proportion SLN vs Standard Lymphadenectomy in High-Risk Endometrial Cancer PFS in Patients Undergoing SLN Mapping vs Standard Lymphadenectomy Carcinosarcoma Serous Carcinoma Months Schiavone MB, et al. Ann Surg Oncol. 2016;23(1): Months Schiavone MB, et al. Ann Surg Oncol. 2017;24(7):
28 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
29 LN Metastatic Node Category by Recurrence- Status LN Met. Category Recurrence-Free Recurrence Total ITC (<0.2 mm) Micro (0.2-2 mm) Macro (>2 mm) Total
30 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
31 Further research needed: Summary Continued The clinical significance of low volume metastasis Long-term morbidity following SLN biopsy
32 Thanks for your attention
33
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