JOURNAL TRANSCRIPT
Sentinel Lymph Node in Endometrial Cancer Reem Abdallah, MD American University of Beirut Medical Center
No disclosures
Percent of Cases by Stage 8%
Localized (confined to primary site)
4%
21% 67%
Regional (spread to regional LN) Distant (metastatic)
5-year Relative Survival 100 80 60 40 20 0
http://seer.cancer.gov/statfacts/html/corp.html (Accessed on January 31, 2016).
95,3 68,2 48,5 16,9
LN status: Prognostic value, guide adjuvant trt Role of Lymphadenectomy controversial Systematic LND not widely adopted around 30% Selective, systematic, none.
No LND 65% Low-risk Pelvic LN mets 9% ASTEC trial, Panici et al: no therapeutic benefit Morbidity of comprehensive LND
Selective Risk of nodal mets size, DOI, grade, LVSI As low as 2% in low risk and Up to 35% in high-risk
Comprehensive FS variable accuracy 25% with preop grade 1 will be upgraded on final path Avoid unnecessary adj trt Therapeutic value? SEPAL study, Chan 2006 SEER
Risk of nodal mets size, DOI, grade, LVSI As low as 2% in low risk and Up to 35% in high-risk FS variable accuracy 25% with preop grade 1 will be upgraded on final path Understaging vs overtrt
Understaging vs overtrt SLN mid option Node most likely to harbor mets SLN endometrial ca first introduced by Burke,1996 Advantages: avoid unecessary extensive LND of neg LN, associated morbidity, guide the need of adjuvant trt, detecting micromets, ultrastaging prognostic significance?
No RCT re role of SLNB, no long-term survival data
Common Lymphatic Drainage
3% 36% 30%
8%
23%
Classical mapping
Techniques Radioactive tracer +/- Green or blue dye Sites of injection: Cervical (combined superficial (submucosal, 1–3 mm) and deep (stroma, 1–2cm))
Fundal subserosal Peritumoral hysteroscopic Courtesy of Abu-Rustum NR, Levine DA, Barakat RR, eds. Atlas of Procedures in Gynecologic Oncology, 3rd ed. London: Informa Healthcare; 2013. c2013, Memorial Sloan-Kettering Cancer Center.
Cervical
Subserosal fundal
Peritumoral
Pros
1. Main lymphatic drainage: parametria 2. Easy, accessible 3. Rarely distorted
1. Better reflection of PA drainage (Detection of PASLN: 39% But Isolated PALN mets in literature 100 cases had detection rate >80%
Cervical
Subserosal fundal
Peritumoral
Pros
1. Main lymphatic drainage: parametria 2. Easy, accessible 3. Rarely distorted
1. Better reflection of PA drainage (Detection of PASLN: 39%)
Cons
1. Low PA detection (Superficial injection: DR 2%, Deep: DR 17%)
1. Not reflective of main lymphatic drainage 2. Rarely infiltrating fundal serosa
1. More complicated 2. Disseminating malignant cells through tubes?
Detection Rates
80-100%
45-75% One study 92%: 8 sites
70-100%
Isolated PALN mets in literature 100 cases had detection rate >80% Most recent studies, DR >92%
Metaanalysis (26 studies, 1101 SLN procedures) Mean SLN detected
2.6 (1-4.7)
Bilaterality of SLN
61% (20%-81%)
Detection Rate
78% (95% CI=73%--84%)
Sensitivity
93% (95% CI=85%–100%)
False Negative Rate
7% (0-14%)
Pericervical injection
Increase in detection rate (p 0.031)
Hysteroscopic only injection Decrease in detection rate (p 0.045) Subserosal only injection
Decrease in sensitivity (p 0.049)
Kang S, Yoo HJ, Hwang JH, et al. Sentinel lymph node biopsy in endometrial cancer: meta-analysis of 26 studies. Gynecol Oncol 2011;123:522–527
Metaanalysis Studies>30pts SLN procedures
1572
Bilaterality of SLN (Range)
52% (19%-100%)
Detection Rate (Range)
83% (62%-100%)
Sensitivity (Range)
81% (43%-100%)
Algorithm Sensitivity
95% (83%-100%)
Pericervical injection DR
62%-100%
Corporeal injection DR
73%-95%
DR in studies >100 pts
>80%
Cormier et al. Sentinel lymph node procedure in endometrial cancer: A systematic review and proposal for standardization of future research. Gynecol Oncol 2015 Aug;138(2):478-85.
Algorithm Peritoneal and serosal evaluation and washings Retroperitoneal evaluation • Excision of all mapped SLNs with ultrastaging • Any suspicious nodes must be removed regardless of mapping • If no mapping on a hemi-pelvis, side-specific LND • Para-aortic LND at the physician’s discretion Barlin JN, Khoury-Collado F, Kim CH, et al. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecol Oncol 2012;125:533
SLN alone
Algorithm
Sensitivity
85.1%
98.1%
Negative Predictive Value
98.1%
99.8%
False Negative Rate
14.9%
1.9%
Barlin JN, Khoury-Collado F, Kim CH, et al. The importance of applying a sentinel lymph node mapping algorithm in endometrial cancer staging: beyond removal of blue nodes. Gynecol Oncol 2012;125:533
Author Barlin Ballester How Niikura Torné Sawicki Vidal Delaloye Solima Lopez-de la Manzanara
N 498 125 100 100 74 70 66 60 59 50
Bats Lopes Holloway Mais Mucke Total
43 40 35 34 31
1385
Algorithm Overall false false Algorithm negative rate negative rate Overall (%) (%) sensitivity (%) sensitivity (%) 13 (7/54) 2 (1/54) 85 98 15 (3/20) 5 (1/20) 84 95 27 (3/11) 9 (1/11) 73 91 17 (3/18) 6 (1/18) 83 94 8 (1/13) 8 (1/13) 92 92 50 (1/2) 0 (0/2) 50 100 57 (4/7) 14 (1/7) 43 86 11 (1/9) 0 (0/9) 89 100 10 (1/10) 0 (0/10) 90 100 0 (0/3) 0 (0/3) 100 100 20 (2/10) 55 (6/11) 10 (1/10) 50 (3/6) 17 (1/6) 19 (37/190)
0 (0/10) 9 (1/11) 10 (1/10) 17 (1/6) 0 (0/6) (9/190)
5
80 45 90 50 83 81
100 91 90 83 100
95
Cormier et al. Sentinel lymph node procedure in endometrial cancer: A systematic review and proposal for standardization of future research. Gynecol Oncol 2015 Aug;138(2):478-85.
Dual Labelling Standard has been: Isotope+Blue Dye Detection rates: 80-100% Bilateral detection: 40-80% Combination was not shown to be significantly higher in metaanalysis
Radiolabeled Colloid-Tc99 Short Protocol: 0.2-1 mCi, 2-4 hrs preop Long Protocol: 2-4 mCi, 20-24 hrs preop Maximum accumulation in SLN: 1.5hrs Lymphoscintigram (2 hrs after injection, then every 30 min to detect SLN) Gamma probes
LSG- Long vs Short Protocol Whole (N=118)
Short (N=44)
Long (n=66)
P
Detection Rate
88 (74.6%)
30 (68.2%)
53 (80.3%)
0.22
Bilateral detection
44 (37.3%)
12 (27.3%)
29 (43.9%)
0.29
0 10 (22.7%)
8 (12.1%) 23 (34.8%)
0.02 0.25
Paraaortic SLN Common iliac SLN Preop LSG
Intraop
Median number of SLN detected per patient
2
1
2
0.02
Number of SLN detected
227
67
146
0.02
Detection Rate
102 (86.4%)
36 (81.8%)
59 (89.4%)
0.62
Bilateral detection
62 (52.5%)
21 (47.4%)
36 (54.5%)
0.89
1 (2.3%) 12 (27.3%)
2 (3%) 16 (24.2%)
1 0.81
92
184
0.5
Paraaortic SLN Common iliac SLN Number of SLN detected
302
Frati et al. Contribution of Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Women with Early Stage Endometrial Cancer: Results of the SENTI-ENDO Study. Ann Surg Oncol (2015) 22:1980–1986
LSG
Preop LSG
Intraop
Short (N=44)
Long (n=66)
P
Paraaortic SLN Common iliac SLN
0 10 (22.7%)
8 (12.1%) 23 (34.8%)
0.02 0.25
Number of SLN detected
67
146
0.02
Number of PA SLN detected
0
14 (9.5%)
0.12
6.5%
Number of common SLN iliac detected
18 (27%)
34 (23%)
0.12
31%
Paraaortic SLN Common iliac SLN
1 (2.3%) 12 (27.3%)
2 (3%) 16 (24.2%)
1 0.81
Number of SLN detected
92
184
0.5
Number of PA SLN detected
3 (3.3%)
4 (2.2%)
0.3
Number of common SLN iliac detected
13 (14.1%)
23 (12.5%)
0.55
7%
3%
2.5% 15.5%
Frati et al. Contribution of Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Women with Early Stage Endometrial Cancer: Results of the SENTI-ENDO Study. Ann Surg Oncol (2015) 22:1980–1986
Colored Dye Isosulfan blue 1% (Lymphazurin), Methylene blue 1%, Patent blue 2.5% Under anesthesia in the OR 2-4 ml Slowly, 5-10 sec/quadrant Time to reach LN: 5 min Median stain time in the SLN: 21 min Allergic reactions < 5%
Indocyanine Green (ICG) Near-infrared fluorescence imaging 2-4 ml Main contraindication: iodine allergy DR in literature: 85-100% Bilateral mapping: 65-85% vs Blue dye: Higher overall detection rate (87% vs 71%; p = 0.005) Higher bilateral detection (65% vs 43%; p = 0.002) In particular, obese
vs Tc99: Similar overall (87% vs 88%, p = 0.83) and bilateral (65% vs 71%,p = 0.36) detection
Combination ICG+Tc99 probably yields the best results
Pathology H&E If neg, Ultrastaging: Two 5 μm sections, at each of two levels 50 μm apart from each paraffin block H&E and IHC 4 slides/block +3-7% micromets Kim CH, Soslow RA, Park KJ, et al. Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrialcancer staging. Int J Gynecol Cancer 2013;23:968;
Terminology
Definition
Significance
Macromets
tumor clusters >2 mm
Positive
Micromets
tumor clusters 0.2-2 mm
Positive
Isolated tumor cells
single tumor cells or clusters ≤0.2 mm
Positive value and trt still controversial
Isolated cytokeratinpositive “cells” only
Rare isolated cytokeratin-positive cells not identified on corresponding H&Estained sections or do not demonstrate morphologic features of invasive ca
Negative
DMI
Grade 1
Grade 2
Grade 3
Total
No Invasion
MM 1 ITC 1 n = 165
MM 0 ITC 0 n = 39
MM 0 ITC 0 n = 38
2/242 =
< 50% invasion
MM 2 ITC 4 n = 80
MM 0 ITC 4 n = 62
MM 0 ITC 6 n = 56
16/198 = 8.0%
≥ 50% invasion
MM 0 ITC 2 n = 16
MM 0 ITC 0 n = 15
MM 1 ITC 2 n = 37
5/68 = 7.4%
Total
10/261= 3.8%
4/116= 3.4%
9/131 = 6.9%
0.8%
23/508 =
4.5%
Maybe omit ultrastaging if no myometrial invasion
Kim CH, Soslow RA, Park KJ, et al. Pathologic ultrastaging improves micrometastasis detection in sentinel lymph nodes during endometrialcancer staging. Int J Gynecol Cancer 2013;23:968;
No MI
DMI