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