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Lymphadenectomy in Epithelial Ovarian Cancer
Ginger J. Gardner, MDAssociate Professor, Weill Cornell Medical College
Associate Member, Gynecology ServiceDirector, Survivorship Program
Department of SurgeryMemorial Sloan-Kettering Cancer Center
Ovarian Cancer DebulkingSurgical Outcomes
SuboptimalResidual > 1
cm
OptimalResidual ≤ 1 cm
Complete Gross Resection
No visible residual
CGR = greatest survival advantage
Bristow RE et al, JCO 2002.Elattar A et al, Cochrane Database Syst Rev 2011.
Diaphragm peritonectomy
Splenectomy/distal pancreatectomy
Cul de sac obliteration for recto-sigmoid resection
Photos: Levine DL, et al. Atlas of Procedures in Gynecologic Oncology 2nd Ed., ©Informa, London 2008.
Ovarian Cancer DebulkingIndication for Lymphadenectomy
No LND Bulky LNs Other LNs?
SuboptimalResidual > 1
cm
OptimalResidual ≤ 1 cm
Complete Gross Resection
No visible residual
RCT N=427HR for PFS 0.75 (95%CI 0.59-0.94)No difference in OS(Benedetti-Panici et al, JNCI 2005)
Bulky LNs onlyRetrospective N=966 with CGRHR for OS 0.75 (95%CI 0.60-0.93)Included IIB-IV all grades/histologies(du Bois et al, JCO 2010)
RCT N=61HR for OS 1.23 (95%CI 0.44-3.42)(Saygili et al, JSO 2002)
Objective
To determine if the extent of LND is associated with improved PFS and OS in patients otherwise achieving CGR at primary cytoreductive surgery for advanced stage high grade serous ovarian cancer.
Patient population
Inclusion:• Stage IIIC-IV• Ovarian cancer• Serous histology• Grade 3/high grade• Primary debulking between
10/2001-12/2009• Surgical outcome = CGR
Exclusion:• Neoadjuvant chemotherapy• Loss at follow-up ≤ 30 days• Stage IIIC patients based on
LN metastasis alone
- Extent of LND:
Group A: No LND
Group B: 1-19 LNs removed
Group C: ≥ 20 LNs removed
• Extent of LND:
Definitions
• ASA score: – Surrogate for general state of health (pre-operative)
• HBOC:– Known genetic mutation
or
– Personal/family history highest risk categorya (20-25%)
aACOG Practice Bulletin No. 103, Obstet Gynecol 2009.
Definitions
Definitions• OR Tumor Indexa (score 0-2)
– 1 point for carcinomatosis– 1 point for bulky upper abdominal diseaseb
Score of 0 Score of 1 Score of 2aTanner et al, Gyn Onc 2012 (in press).bZavanovic o, et al, Gyn Onc 2008.
Statistics
• Chi square– Categorical variables
• Kruskal-Wallis– Continuous variables
• Kaplan-Meier survival analysis– Log rank test
• Cox regression multivariate model
Stage IIIC-IV HG serous ovary Ca
385 pts
Primary debulking323 (84%)
Suboptimal66 (20%)
Optimal 257 (80%)
CGR109 (34%)
Neoadjuvant chemo62 (16%)
7 pts IIIC nodal only3 pts loss at follow up
99 patients included
Results – Patient Selection
Patient characteristics by extent of lymphadenectomy
CharacteristicsGroup A
(No LND)N=31
Group B (1-19 LNs)
N=34
Group C (≥ 20 LNs)
N=34P
Age, median [range] 61 [39-80] 57 [30-81] 58 [32-78] 0.148Family history / HBOC 12 (39%) 11 (32%) 12 (35%) 0.866Intraperitoneal chemotherapy 14 (45%) 18(53%) 12 (35%) 0.341FIGO stage IIIC 27 (87%) 26 (77%) 31 (91%) IV 4 (13%) 8( 24%) 3 (9%) 0.219ASA score 1 3 (10%) 3 (9%) 3 (9%) 2 18 (58%) 21 (62%) 24 (71%) 3 10 (32%) 10 (29%) 7 (21%) 0.854
CharacteristicsGroup A (No LND)
N=31
Group B (1-19 LNs)
N=34
Group C (≥ 20 LNs)
N=34P
Procedures performed Liver resection 3 (10%) 5 (15%) 4 (12%) 0.822 Splenectomy 7 (23%) 7 (21%) 4 (12%) 0.478 Diaphragm peritonectomy 13 (42%) 20 (59%) 14 (41%) 0.262 Any bowel surgery 19 (61%) 21 (62%) 17 (50%) 0.544 Supradiaphragmatic LND 0 6 (18%) 1 (3%) 0.011OR Tumor Index score 0 7 (23%) 11 (32%) 14 (41%) 1 13 (42%) 10 (29%) 6 (18%) 2 11 (36%) 13 (38%) 14 (41%) 0.273
Surgical characteristics by extent of lymphadenectomy
Study population99 pts
Clinically suspicious LNs44 pts
LN metastases34 pts (77%)
Clinically normal LNs55 pts
LN metastases16 pts (29%)
Results – LN status among all pts
All patients with LND68 pts
Clinically suspicious LNs44 pts
LN metastases34 pts (77%)
Clinically normal LNs24 pts
LN metastases16 pts (67%)
Results – LN status among pts with LND
LN status by extent of LND (among 68 pts with “any” LND)
Extent of LND No metastatic LN ≥ 1 metastatic LN p
Group B (1-19 LNs) 12 (35%) 22 (65%)
Group C (≥ 20 LNs) 6 (18%) 28 (82%) 0.099
VariableProgression free survival
Median (95% CI) p
Overall survival
Median (95% CI) p
HBOC
Positive 28.6 (23.8-33.4) 102.6 (---)
Negative 23.4 (18.4-28.4) 0.129 57.9 (44.7-71.1) 0.047
Stage
IIIC 26.1 (21.7-30.5) 78.8 (52.0-105.6)
IV 17.2 (7.3-21.7) 0.140 38.0 (26.2-49.8) 0.002
OR tumor index
0 50.5 (19.7-81.3) 92.4 (82.6-102.2)
1 24.2 (20.5-27.9) 58.5 (52.9-64.1)
2 19.3 (13.6-25.0) 0.001 46.6 (34.3-58.9) 0.007
ASA score
1 29.0 (27.0-31.0) Not Reached
2 24.2 (22.0-26.4) 63.9 (37.8-90.0)
3 21.0 (14.1-27.9) 0.878 56.7 (31.1-82.3) 0.0499
Univariate survival analysis
VariableProgression free survival
Median (95% CI) p
Overall survival Median (95% CI) p
Metastatic LN
Yes 23.4 (16.2-30.6) 63.9 (38.5-89.3)
No 25.1 (19.5-30.7) 0.447 92.4 (47.5-137.3) 0.647
Type of LND
Group A 23.1 (15.5-30.7) 58.5 (41.5-75.5)
Group B 23.6 (20.7-26.5) 56.7 (35.5-77.9)
Group C 28.6 (19.4-37.8) 0.610 87.0 (63.6-110.4) 0.428
IP chemotherapy
Yes 26.1 (20.4-31.8) Not Reached
No 19.3 (11.8-26.8) 0.296 57.9 (44.5-71.3) 0.053
Univariate survival analysis
Survival curves
A: No LNDB: 1-19LNsC: ≥ 20 LNs
A: No LNDB: 1-19LNsC: ≥ 20 LNs
p=0.610 p=0.428
Progression Free Survival Overall Survival
VariableProgression free survival
Hazard Ratio (95% CI) p
Overall survival Hazard Ratio (95% CI) p
HBOC (pos vs. neg) 0.54 (0.32-0.92) 0.023 0.41 (0.19-0.89) 0.024
Stage (IIIC vs. IV) 0.90 (0.43-1.85) 0.766 0.36 (0.17-0.78) 0.009
OR tumor index
0 Ref. level 0.001 Ref. level 0.013
1 2.47 (1.30-4.72) 1.60 (0.70-3.64)
2 4.06 (1.86-7.30) 3.31 (1.46-7.49)
ASA score
1 Ref. level 0.946 Ref. level 0.113
2 1.11 (0.50-2.50) 1.18 (0.35-4.00)
3 1.03 (0.43-2.51) 2.35 (0.66-8.36)
Multivariate survival analysis
Conclusions
• LNs harbor disease– 77% of pts with suspicious LNs -> metastases – 67% of pts with normal LNs -> metastases
Conclusions
• Among patients with stage IIIC-IV high grade serous ovarian ca achieving CGR at primary debulking:
– HBOC, stage, and OR tumor index are strong prognostic factors
– Extent of LND was not associated with PFS or OS• Selection bias?• Sample size?• Lymphadenectomy In Ovarian Neoplasms (LIONS) trial