Paraaortic Lymphadenectomy in Endometrial Cancer

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Paraaortic Lymphadenectomy in Endometrial Cancer

• A Mariani, KC Podratz
• Mayo Clinic Rochester - MN

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Thank you

• Karl C Podratz, MD, PhD

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Plan of the Talk

• Introduction
• Preliminary Data of Mayo Clinic Prospective Study
• Frequently Asked Questions on Paraaortic
  Lymphadenectomy
• Conclusions

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Endometrial CancerEstimated New Cases-2007
Disease Sites New Cases
11,150
Cervix
Corpus
39,080
Ovary
22,430
Vulva
3,490
Other
2,140
78,290
Jemal et al CA 2007
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Endometrial CancerEstimated Cancer Deaths 2007
Site of Disease
Died of Disease
Cervix
3,670
Corpus
7,400
Ovary
15,280
Vulva
880
Other
790
28,020
Jemal et al CA 2007
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Endometrial CancerAnnual Incidence Cases and
Deaths
Estimate ACS
Cases
Year
Died of Ca
35,000
2,900
1987
39,080
7,400
2007
CA 1987 CA 2007 increase 12 increase 155
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RETROSPECTIVE ANALYSIS MAYO 1984-1996
DATA GENERATED 29 PEER-REVIEWED PUBS ON
ENDOMETRIAL CANCER
PROSPECTIVE STUDY 2004-2006
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Prospective AnalysisCriteria for Staging
Patients(Based on Intraoperative Pathologic
Evaluation)
No SURGICAL STAGING
SURGICAL STAGING

• Endometrioid
• Myometrial Invasion lt 50
• Grade 1 or 2
• Tumor Diameter 2 cm
• No macroscopic evidence of extrauterine tumor

• All the others

When all the criteria are present
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Preliminary Data of Prospective Study

• 422 patients with endometrial cancer had
  hysterectomy during 36 months (2004-06)

Mayo Clinic 2007
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Need for Surgical Staging by Protocol Criteria
422 EndoCa Patients
112 (27) No Need LND
310 (73) Need LND
22 (20) had LND
90 (80) No LND
281 (91) had LND
29 (9) No LND
91 feasibility of LND
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Preliminary Data of Prospective Study

• By protocol lymphadenectomy is NOT necessary in
  112 (27) patients

NO LND
27
LND
Mayo Clinic 2007
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Preliminary Data of Prospective Study

• 63 of 281 (22) patients who had lymphadenectomy
  had positive nodes

22
LN
LN-
Mayo Clinic 2007
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Preliminary Data of Prospective Study (sites of
positive nodes)
n57
PA
9 (16)
19 (33)
P
PPA
29 (51)
2004-06
PA LN
67
Mayo Clinic 2007
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Patterns of Lymphatic Spread
39 pts PA
Negative Common Iliac 25/35 (71) PA
Mayo Clinic 2007
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Frequently Asked Questions on Paraaortic
Lymphadenectomy in Endometrial Cancer
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Question 1What are the Consequences of not
Accurately Knowing Paraaortic Lymph Node Status?
Diagnostic Role
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Endometrial Cancer Patient

• 61 y-o, G3P3, grade 1 endometrioid endometrial
  cancer at biopsy. BMI 34
• At community hospital VHBSO. No frozen section
• Definitive path report G2 endometrioid EndoCa,
  with 55 myometrial invasion, LVI

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Mayo Clinic Risk Calculator for Lymph Node
Invasion in Endometrial Cancer
Risk For LN Invasion
38.7 (95 CI 29.1 - 66.0)
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What to Do ?
39 Risk of LN Invasion Unstaged Patient
Pelvic RT
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Decision for Pelvic RT in an Unstaged Patient
Undertreatment 67 of pts with LN but with tumor
in the PA
If not adequately staged
Pelvic RT For a 39 risk
Overtreatment 61 with LN-
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Decision for Pelvic RT in an Unstaged Patient
Correct treatment in 13 of Pts
If not adequately staged
Pelvic RT For a 39 risk
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Question 2Which Patients Can Potentially
Benefit of Paraaortic Lymphadenectomy ?
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Risk Factors for Lymph Node Invasion in
Endometrial Cancer (GOG 33)
Traditional risk factors for PA LND invasion (GOG
33) gross pelvic LND involvement, gross
adnexal invasion, Invasion of the outer third of
the myometrium
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Preliminary Findings on Low Risk Patients from
the Prospective Study (n266)Paraaortic Lymph
Node Invasion
Mayo Clinic 2007
M2
M3
M1
Endometrioid G1-2 M1 TD 2 cm
38
7
0
G1
27 of pts
29
0
7
G2
G3
19
43
12
73 of pts
M1 lt 33 M2 33-66 M3 gt 66
Still waiting for path review
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Isolated Paraaortic
2 isolated PA
Mariani 2004
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Mayo Clinic 2007
Preliminary Findings on Low Risk Patients from
the Prospective Study (n218)ISOLATED Paraaortic
Lymph Node Invasion (i.e. negative pelvic lymph
nodes)
M2
M3
M1
Endometrioid G1-2 M1 TD 2 cm
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0
0
G1
27 of pts
0
0
2
0
G2
G3
2
6
21
2
73 of pts
n 14
M1 lt 33 M2 33-66 M3 gt 66
Still waiting for path review
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High Risk Subgroup for Paraaortic
Lymphadenectomy(conservative approach for simple
minded surgeons)
M2
M3
M1
38 (33)
7 (0)
0 (0)
G1
0 (0)
7 (2)
29 (0)
G2
12 (2)
G3
43 (21)
19 (6)
M1 lt 33 M2 33-66 M3 gt 66
(In parentheses are isolated PA rates)
Theoretically, can do only pelvic LND and
frozen section of nodes
Mayo Clinic 2007
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Question 3How Extensive Should Paraaortic
Lymphadenectomy Be?
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Patterns of Lymphatic Spread
Tumor above IMA
20/26 (77) of PA have tumor above IMA
12/20 (60) skipping of nodes below IMA
Mayo Clinic 2007
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Question 4Safety of Paraaortic Lymphadenectomy
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Characteristics of Patients and Surgical Morbidity
Hospital Stay (Days)
5.6 0.2
3.8 0.4
0.0002
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Complications of Laparotomic Pelvic and
Paraaortic Lymphadenectomy Mayo Clinic

• Symptomatic Lymphedema 6
• Postoperative Ileus (gt 7 days) 5
• Thromboembolic Events 7
• Symptomatic/Infected Lymphocele 7
• Mean Length of Hospital Stay 5.6 0.2 days

Mayo Clinic 2007
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E Leblanc Extraperitoneal Laparoscopic
Paraaortic Lymphadenectomy
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Question 5Is Paraaortic Lymphadenectomy
Therapeutic?
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Therapeutic benefit of Paraaortic Lymphadenectomy
(Retrospective Study)
Mayo Clinic 2000
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Unresolved Issues

• Reliability of Intraoperative Frozen Section on
  Pelvic Node Status (G3 M1)
• Possibility of Performing Postoperative
  Extended-Field RT when Positive Pelvic LN and
  Unknown Paraaortic LN Status (45 efficacy ?)
• Role of Chemotherapy ?

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TAKE HOME MESSAGES OF PARAAORTIC LYMPHADENECTOMY

• Importance of Surgical Staging for Avoiding
  Under- and Over-treatment
• No Need for Lymphadenectomy in Low Risk Subgroup
  G1-2 and M1
• Need for Both Pelvic and Paraaortic
  Lymphadenectomy in Patients at Risk of Lymph Node
  Invasion (G3 or M2)
• When Paraaortic Lymphadenectomy is Performed,
  Always Extend It to Lymph Nodes above the IMA
  (77)

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TAKE HOME MESSAGES OF PARAAORTIC LYMPHADENECTOMY
5) Morbidity of Paraaortic Lymphadenectomy and
Possible Role of Laparoscopic Retroperitoneal
Paraaortic Lymphadenectomy 6) Potential
Therapeutic Role in Patients with Positive Lymph
Nodes
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Acknowledgments
Prof Eric Leblanc

• CR Stanhope
• TO Wilson
• SC Dowdy
• MB Jones

• KC Podratz
• WA Cliby
• BS Gostout

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Lymph Node Distribution in Endometrial
Cancer Patients with Positive Lymph Nodes
n25
n32
PA
3 (12)
PA
6 (19)
P
7 (28)
P
12 (37)
15 (60)
P / PA
P / PA
14 (44)
Endometrioid
Non-endometrioid
PA in 72
PA in 63
Or mucinous Undifferentiated, Serous, Clear
Cells
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Management of Endometrial Cancer At Mayo Clinic
LND 74 ERT 16
No LND / No RT
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58
16
LND but No RT
LNDRT
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AddendumIf Not Using Surgical Staging
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Risk Factors in Unstaged Patients From Mayo Clinic
M 50 is a risk factor for hematogenous dissem
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Risk Factors in Unstaged Patients From Mayo Clinic
Hemato Diss
4
28
lt 0.01
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Endometrial Cancer After Inadequate Surgical
Staging
Endometrioid, Mucinous or Adenosquamous
with Unknown Pelvic and Paraaortic Node Status
Tumor diameter 2 cm Myometrial
invasionlt50 Grade 1-2 No LVI
Stage IIA, IIB
Stage IA, IB, IC
Yes
No
No Adjuvant therapy
Vaginal Brachytherapy External Pelvic and
Paraaortic Radiotherapy OR Surgical
Re-staging Note 1 Add Chemotherapy if LVI or
Myometrial Invasion 50
External Pelvic and Paraaortic Radiotherapy
OR Surgical Re-staging If Tumor diameter gt 2 cm
and either one of the following Myometrial
Invasion 50, LVI, Grade 3 Note 1 If Grade 3
or LVI Add Vaginal Brachytherapy Note 2 If
Myometrial Invasion 66 or LVI Add Chemotherapy