Transcript STAGING - Medical Oncology at University of Toronto

Optimal Surgery for Ovarian and Endometrial
Cancers
Jason Dodge, MD, FRCSC, MEd
May 11th, 2012
Objectives
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 CANCER
Prototype 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 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
Outline
• Optimal surgery for ovarian cancer
–
–
–
–
Diagnosis
Surgical Staging
Debulking
Facilitating optimal treatment
Roles of Primary Surgery in
Ovarian 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:
Staging
Patterns of spread:
• Intraperitoneal
• Local
• Lymphatic
• Hematogenous
Optimal surgical staging procedure must rule
out metastases by all of these routes
Surgery in Ovarian Cancer:
Staging
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
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
13
What stage is this
woman’s ovarian
cancer?
a) 1A
b) 1B
c) 1C
d) 2B
e) 3C
?
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:
Staging
“Stage 1”
patients
who are
not
optimally
staged at
surgery
have a
poorer
survival!
ACTION trial
Trimbos et al., JNCI, 2003
Surgery in Ovarian Cancer:
Staging
No benefit to
adjuvant
chemoRx in
patients who
are optimally
surgically
staged!
ACTION trial
Trimbos et al., JNCI, 2003
Surgery in Ovarian Cancer:
Debulking
• Optimal debulking of metastatic disease associated
with improved survival
– Best predictor of survival in patients with
advanced stage disease
Bristow et al., J Clin Oncol, 2002
– Delay in definitive surgical debulking may be
associated with decreased survival
Bristow & Chi, Gynecol Oncol, 2006
Therapeutic Debulking
Bristow et al., JCO, 2002
Surgery in Ovarian Cancer:
Facilitating 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 trials
Trimbos et al., JNCI, 2003
Surgery in Ovarian Cancer:
Facilitating Optimal Adjuvant Therapy
• Advanced Stage
– Chemotherapy demonstrated to improve overall
Covens et al., CCO Guidelines, 2005
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
Surgery in Ovarian Cancer:
Intraperitoneal Chemotherapy
• Delivery of chemotherapy directly into
peritoneal cavity via implanted catheter
• Most pronounced survival benefit ever
documented in ovarian cancer (17 m)
Armstrong et al., NEJM, 2006
• Only patients optimally debulked at primary
surgery are eligible
Current practice in Ontario…
• Many ovarian cancer surgery cases in
Ontario are not performed optimally
Elit et al., JOGC, 2006
• 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
Role 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, 2006
Giede et al., Gynecol Oncol., 2005
Le et al., JOGC, 2009
Early 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)
Minimal staging
vs comprehensive
staging
Recurrence
OR 2.62
favouring
comprehensive
Le
Saskatchewan
2002
Early stage
Advanced Ovarian Cancer
N
Population
Question
Outcome
Results
Eisenkop 1992
263
Stage
3C & 4
Gyne onc vs non
onc
survival
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
High volume vs
low volume
Survival
Elit 2006
Ontario
35vs 17%
(p<0.0001)
86% vs 70%
21% vs 13%
(p=0.03)
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, 2006
SOGC Guidelines – Le et al., JOGC, 2009
SGO Referral Guidelines, Gynecol Oncol, 2000
ACOG Committee Opinion #280, December, 2002
ENDOMETRIAL CANCER
Prototype 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 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
Endometrial 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:
Staging
Patterns of spread:
• Local
• Lymphatic
• Intraperitoneal
• Hematogenous
Optimal surgical staging procedure must rule
out metastases by all of these routes
Surgery in Endometrial Cancer:
Staging
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 Carcinoma
FIGO 1971
Clinical Staging
FIGO 1988
Surgical Staging
GOG 33, 1987
Surgical staging: Findings
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
DISEASE
Pelvic 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,
1987
Para-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,
1987
2009 FIGO staging (endometrium)
40
Benefits 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
Benefits of Pelvic Lymphadenectomy
• Therapeutic value
– Benefit from chemotherapy +/- RRx
if nodes involved
Randall, 2006
Muggia, 2007
– Avoidance of whole pelvic RRx
PORTEC, EN-5, MRC,
if staging negative
GOG 99, NRH
– ? Independent survival benefit
MRC, Italian trial vs.
Kilgore, Fanning, Orr,
Para-aortic lymphadenectomy
• Higher potential for morbidity
• Prolonged operative time
• Most cases (98%) can be predicted based
GOG 33, 1987
on:
– +ve pelvic nodes, OR
– +ve adnexa, OR
– +ve cervix
• Potential benefit small
Faught, 1994
GOG LAP-2,2006
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
GI injury
GU injury
1%
2%
0.5%
Vascular injury
4%
Ileus
10%
Thrombosis
2%
Fistula
1%
Death
0.5%
Perspective from Other Pelvic
Cancers
• 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
Endometrial Cancer in Toronto
• NOT ROUTINE
• SELECTIVE SAMPLING (suspicious
nodes)
• 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!
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.”