optimal surgery for ovarian and endometrial cancers jason dodge, md, frcsc, med may 11 th, 2012

Optimal Surgery for Ovarian and Endometrial Optimal Surgery for Ovarian and Endometrial CancersCancers

Jason Dodge, MD, FRCSC, MEdMay 11th, 2012

ObjectivesObjectives

At the end of this session, participants will be able to…

• list the rationales for the surgical management of endometrial and ovarian cancers

• recognize the optimal components of surgical staging for both endometrial and ovarian cancers

• understand the importance of surgical staging for endometrial and ovarian cancer in determining prognosis and the role(s) for adjuvant therapy

• identify the importance of surgical debulking for ovarian cancer

OVARIAN CANCEROVARIAN CANCER

Prototype CasePrototype Case

• 52 y.o. G3P3 post-menopausal woman

• Healthy, asymptomatic

• 7-8 cm pelvic mass on routine exam

• U/S – 7.5 cm multiloculated, solid/cystic mass arising within right ovary

• CA-125 – 25

• Booked for surgery by community gynaecologist

Prototype CasePrototype Case

• TAH-BSO through lower transverse incision

• Solid/cystic ovarian mass resected intact

• No other abnormalities identified in OR note

• Final pathology:– Grade 2 serous carcinoma of ovary– Negative uterus and contralateral adnexa

What stage is this woman’s ovarian cancer?

a) 1A

b) 1B

c) 1C

d) 2B

e) 3C

What is the risk this woman has (undetected) metastatic disease?

a) <1%

b) 10%

c) 30%

d) 50%

e) 80%Young et al., JAMA, 1983

What is the best approach to her management at this point?

a) Observation

b) Refer back to local gynaecologist for repeat surgery for optimal surgical staging

c) Refer to Gynaecologic oncologist for repeat surgery for optimal surgical staging

d) Adjuvant chemotherapy (Carbo/Taxol IV)

e) Other

OutlineOutline

• Optimal surgery for ovarian cancer– Diagnosis– Surgical Staging– Debulking– Facilitating optimal treatment

Roles of Primary Surgery in Roles of Primary Surgery in Ovarian CancerOvarian Cancer

• Diagnosis (final)• Staging (SURGICAL, NOT CT!)• Therapy

– Palliation of symptoms– Removal of cancer (debulking)

• Facilitating optimal adjuvant therapy– Prognosis of individual patient– Risks/benefits of adjuvant therapy

Surgery in Ovarian Cancer:Surgery in Ovarian Cancer:StagingStaging

Patterns of spread:• Intraperitoneal• Local• Lymphatic• Hematogenous

Optimal surgical staging procedure must rule out metastases by all of these routes

Surgery in Ovarian Cancer:Surgery in Ovarian Cancer:StagingStaging

Components of optimal surgical staging:• Peritoneal washings• Inspection and palpation of abdominal and

pelvic organs and peritoneal surfaces– biopsy of all suspicious lesions

• BSO (+/- TAH)• Omentectomy• Pelvic & para-aortic lymphadenectomies• Multiple peritoneal biopsies

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FIGO staging (ovary)FIGO staging (ovary)

• I – confined to ovary/ies– A (single ovary)– B (bilateral ovaries)– C (positive washings, surface disease, ruptured)

• II – confined to pelvis– A (fallopian tube or uterine extension)– B (other pelvic metastases)– C (pelvic involvement with +washings or tumour rupture)

• III – abdominal/pelvic cavity extension or nodes +ve– A (microscopic only)– B (<2 cm nodule(s))– C (>2cm nodule(s) or retroperitoneal lymph nodes involved)

• IV – positive pleural effusion, parenchymal liver or other distant metastases

What stage is this woman’s ovarian cancer?

a) 1A

b) 1B

c) 1C

d) 2B

e) 3C

?

KEY MESSAGE!KEY MESSAGE!

What is the risk this woman has (undetected) metastatic disease?

a) <1%

b) 10%

c) 30%

d) 50%

e) 80%Young et al., JAMA, 1983

Surgery in Ovarian Cancer:Surgery in Ovarian Cancer:StagingStaging

“Stage 1” patients who are not optimally staged at surgery have a poorer survival!

ACTION trialTrimbos et al., JNCI, 2003

Surgery in Ovarian Cancer:Surgery in Ovarian Cancer:StagingStaging

No benefit to adjuvant chemoRx in patients who are optimally surgically staged!

ACTION trialTrimbos et al., JNCI, 2003

Surgery in Ovarian Cancer:Surgery in Ovarian Cancer:DebulkingDebulking

• Optimal debulking of metastatic disease associated with improved survival– Best predictor of survival in patients with

advanced stage disease

– Delay in definitive surgical debulking may be associated with decreased survival

Bristow et al., J Clin Oncol, 2002

Bristow & Chi, Gynecol Oncol, 2006

Therapeutic DebulkingTherapeutic Debulking

Bristow et al., JCO, 2002

Surgery in Ovarian Cancer:Surgery in Ovarian Cancer:Facilitating Optimal Adjuvant TherapyFacilitating Optimal Adjuvant Therapy

• “Stage I”– If optimally staged, evidence suggests that

chemotherapy may not be useful in improving survival

– If not optimally staged, chemotherapy indicated to improve survival rates (because significant number have undiagnosed advanced staged disease)

ICON1/ACTION trialsTrimbos et al., JNCI, 2003

Surgery in Ovarian Cancer:Surgery in Ovarian Cancer:Facilitating Optimal Adjuvant TherapyFacilitating Optimal Adjuvant Therapy

• Advanced Stage– Chemotherapy demonstrated to improve overall

survival– Recent acceptance of intraperitoneal

chemotherapy as ideal mode of therapy for women with optimally debulked disease after primary surgery

• Optimal debulking <1 cm residual

• Insertion of IP catheter at primary surgery

Armstrong et al., NEJM, 2006

Covens et al., CCO Guidelines, 2005

Surgery in Ovarian Cancer:Surgery in Ovarian Cancer:Intraperitoneal ChemotherapyIntraperitoneal Chemotherapy

• Delivery of chemotherapy directly into peritoneal cavity via implanted catheter

• Most pronounced survival benefit ever documented in ovarian cancer (17 m)

• Only patients optimally debulked at primary surgery are eligible

Armstrong et al., NEJM, 2006

Current practice in Ontario…Current practice in Ontario…

• Many ovarian cancer surgery cases in Ontario are not performed optimally

• Many women with high pre-operative likelihood of ovarian cancer in Ontario would not be referred to a gynaecologic oncologist prior to surgery

Dodge, JOGC, 2007

Elit et al., JOGC, 2006

Role of Gyn Oncology ReferralRole of Gyn Oncology Referral

• Women with ovarian cancer who have primary surgery performed by a gynaecologic oncologist [at a tertiary centre] have a better outcome (survival)– More likely to be optimally staged– More likely to be optimally debulked– More likely to receive optimal adjuvant therapy

Elit et al., JOGC, 2006Giede et al., Gynecol Oncol., 2005

Le et al., JOGC, 2009

Early Stage Ovarian CancerEarly Stage Ovarian Cancer

N Population Question Measurement Results

Puls

Texas

1997

54 Stage 1 Gyne onc vs community gyne

6 yr survival 90% vs 68%

( p=0.04)

Mayer

Conneticut

1992

87 Stage 1 & 2 Gyne onc vs

non onc

5 yr survival 83% vs 76% (p<0.05)

Grossi

2002

156 Gyne onc vs

non onc

Staging lap adequate

47% vs 15%

(p< 0.001)

Le

Saskatchewan

2002

Early stage Minimal staging vs comprehensive staging

Recurrence OR 2.62 favouring

comprehensive

Advanced Ovarian CancerAdvanced Ovarian Cancer

N Population Question Outcome Results

Eisenkop 1992 263 Stage

3C & 4

Gyne onc vs non onc

survival 35vs 17%

(p<0.0001)

Carney 2002 848 All Utah Gyne onc vs non onc

5 yr survival 26 vs 15 mos

(p<.01)

Junor 1999 1866 All Scotland Gyne onc vs non onc

Survival 25 % death reduction

Tingulstad 2003 38 All stages Gyne onc vs non onc

Survival 21 vs 12 mos

(p=0.01)

Engelen 2006 512 All stages Gyne onc vs non onc

Survival

Stages 1-2

Stages 3-4

86% vs 70%

21% vs 13% (p=0.03)

Elit 2006 Ontario High volume vs low volume

Survival Higher volume better

outcome

• “Women with a high likelihood of having ovarian cancer should ideally be referred to a gynaecologic oncologist preoperatively to facilitate optimal surgery for ovarian cancer.”

CCO Quality Indicators - Gagliardi et al., Gynecol Oncol, 2006SOGC Guidelines – Le et al., JOGC, 2009

SGO Referral Guidelines, Gynecol Oncol, 2000 ACOG Committee Opinion #280, December, 2002

ENDOMETRIAL CANCERENDOMETRIAL CANCER

Prototype CasePrototype Case

• 61 y.o. G0P0 post-menopausal woman

• Healthy, bleeding x few weeks

• No abnormality detected on routine exam

• Endometrial biopsy reveals grade 3 endometrioid adenocarcinoma of uterus

• Booked for surgery by community gynaecologist

Prototype CasePrototype Case

• TAH-BSO through lower transverse incision

• No other abnormalities identified in OR note

• Final pathology:– Serous carcinoma of uterus– No myometrial invasion, no LVSI/CLS– Negative cervix and adnexa

What is the risk this woman has (undetected) metastatic disease?

a) <1%

b) 10%

c) 25%

d) 50%

e) 80%

What is the next best step in her management?

a) Observation

b) Refer to Gynaecologic oncologist for repeat surgery for optimal surgical staging

c) Adjuvant chemotherapy (Carbo/Taxol IV)

d) Adjuvant radiotherapy

e) Other

Roles of Primary Surgery in Roles of Primary Surgery in Endometrial CancerEndometrial Cancer

• Diagnosis (final)• Staging (SURGICAL, NOT CT!)• Therapy

– Palliation of symptoms– Removal of cancer (debulking)

• Facilitating optimal adjuvant therapy– Prognosis of individual patient– Risks/benefits of adjuvant therapy

Surgery in Endometrial Cancer:Surgery in Endometrial Cancer:StagingStaging

Patterns of spread:• Local• Lymphatic• Intraperitoneal• Hematogenous

Optimal surgical staging procedure must rule out metastases by all of these routes

Surgery in Endometrial Cancer:Surgery in Endometrial Cancer:StagingStaging

Components of optimal surgical staging:• Peritoneal washings• Inspection and palpation of abdominal and

pelvic organs and peritoneal surfaces– biopsy of all suspicious lesions

• BSO (+/- TH)• “extended” surgical staging

– Omentectomy and peritoneal biopsies– Pelvic & para-aortic lymphadenectomies

Staging for Endometrial CarcinomaStaging for Endometrial Carcinoma

FIGO 1971

Clinical StagingFIGO 1988

Surgical Staging

GOG 33, 1987GOG 33, 1987

Surgical staging: FindingsSurgical staging: Findings

GOG 33 (n=621) – “clinical stage I”GOG 33 (n=621) – “clinical stage I”

• exploratory laparotomy, TAH-BSO, pelvic & para-aortic nodes, peritoneal washings– positive peritoneal washings 12%– positive adnexa 5%– positive pelvic nodes 9%– positive aortic nodes 6%– intraperitoneal disease 6%

• 22% ADVANCED STAGE DISEASE22% ADVANCED STAGE DISEASE

Pelvic lymph node metastasesPelvic lymph node metastases

Grade 1 Grade 2 Grade 3 TOTAL

None 0% 3% 0% 1%

Inner 1/3 3% 5% 9% 5%

Mid 1/3 0% 9% 4% 6%

Outer 1/3 11% 19% 34% 25%

TOTAL 3% 9% 18% 9%

GOG 33, 1987GOG 33, 1987

Para-aortic lymph node metastasesPara-aortic lymph node metastases

Grade 1 Grade 2 Grade 3 TOTAL

None 0% 3% 0% 1%

Inner 1/3 1% 4% 4% 3%

Mid 1/3 5% 0% 0% 1%

Outer 1/3 6% 14% 23% 17%

TOTAL 2% 5% 11% 6%

GOG 33, 1987GOG 33, 1987

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2009 FIGO staging (endometrium)2009 FIGO staging (endometrium)

Benefits of Pelvic LymphadenectomyBenefits of Pelvic Lymphadenectomy

• Documentation of true nodal status (prognostic)– usually only microscopic involvement (~90%)– worse prognosis when +ve (50-70% 5-yr OS

with Rx) Randall, 2006

Muggia, 2007

Randall, 2006

Muggia, 2007

Benefits of Pelvic LymphadenectomyBenefits of Pelvic Lymphadenectomy

• Therapeutic value– Benefit from chemotherapy +/- RRx

if nodes involved

– Avoidance of whole pelvic RRx if staging negative

– ? Independent survival benefitMRC, Italian trial vs.

Kilgore, Fanning, Orr,

MRC, Italian trial vs.

Kilgore, Fanning, Orr,

Randall, 2006

Muggia, 2007

Randall, 2006

Muggia, 2007

PORTEC, EN-5, MRC, GOG 99, NRH

PORTEC, EN-5, MRC, GOG 99, NRH

Para-aortic lymphadenectomyPara-aortic lymphadenectomy

• Higher potential for morbidity

• Prolonged operative time

• Most cases (98%) can be predicted based on:– +ve pelvic nodes, OR– +ve adnexa, OR– +ve cervix

• Potential benefit small Faught, 1994Faught, 1994

GOG 33, 1987GOG 33, 1987

What are the risks?What are the risks?• Improved with training (Gyn

Onc)

• These risks not solely due to nodes

• Much of this risk related to para-aortic node dissection

• Much improved with laparoscopy (Lap-2)

Blood loss > 1 litre

1%

GI injury 2%

GU injury 0.5%

Vascular injury 4%

Ileus 10%

Thrombosis 2%

Fistula 1%

Death 0.5%

GOG LAP-2,2006GOG LAP-2,2006

Perspective from Other Pelvic Perspective from Other Pelvic CancersCancers

• Adjuvant chemotherapy proven survival benefit in node-positive colorectal cancer

mesorectal excision (node dissection)• Adjuvant chemotherapy proven survival

benefit in node-positive cervical cancer• Risk of pelvic node metastases in cervical

cancer managed surgically at PMH:

5%

Current Use of Lymphadenectomy for Current Use of Lymphadenectomy for Endometrial Cancer in TorontoEndometrial Cancer in Toronto

• NOT ROUTINE

• SELECTIVE SAMPLINGSELECTIVE SAMPLING (suspicious

nodes)

• STAGING (not completely uniform)STAGING (not completely uniform)

– Grade 2,3 endometrioid

– Stage IC (with >50% myometrial invasion)

– High risk histologic subtype without obvious

extra-uterine disease

KEY MESSAGE!KEY MESSAGE!

What is the risk this woman has (undetected) metastatic disease?

a) <1%

b) 10%

c) 30%

d) 50%

e) 80%

• “Every woman with (endometrial) cancer deserves

individualized management that maximizes her

prognosis and minimizes her morbidity.”

• “Documentation of disease extent via surgical

staging allows optimal tailoring of adjuvant

therapy to an individual patient’s risks.”