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Ovarian cancer surgery march 2012
1.
2. OPTIMAL SURGICAL MANAGEMENT OF
OVARIAN CANCER
March 2012
Prafull Ghatage
Gynecologic Oncologist
Tom Baker Cancer Centre
Calgary, CANADA.
3. Learning objectives
• Pelvic Masses – assessment
• Epidemiology / Etiology
• Recent trends in surgical management
• Recurrent cancer management
• Palliative surgery
4. Approach to Pelvic Mass
Pelvic Mass
Non-gynecologic Gynecologic
Bowel, bladder, kidney
Soft tissues, other Pregnancy Non-Pregnancy
Ovary
Fallopian Tube
Uterus
Benign or Malignant
Benign or Malignant
Benign or Malignant
7. ACOG Guidelines
• Ova 1 assay – Ca125 / Apolipoprotein / B2
microglobulin / Transthyretin / Transferin
• Ca 125
• Abdominal metastasis
• Fixed or nodular pelvic mass
• Family history
8. Serum H4 in Ovarian cancer
• Over-expressed in early ovarian cancer
• Combination of Ca 125 and H4 increases
sensitivity
9. Risk of Malignancy Index
Ultrasound features Risk of Malignancy Score
Multilocular cyst
Solid elements
Bilaterality
Ascites
Intra-abdominal metastasis
Premenopausal
Postmenopausal
Ca125
1= none or 1 abnormality
2= 4 or more abnormalities
1
4
U/ml
Positive predictive Value-80% Specificity 90%
11. Epithelial ovarian cancer - Epidemiology
• 27,000 new cases a year in the US / 2,400 new cases in Canada
– 4% of cancer in women
• 15,000 deaths in the US / 1,500 deaths in Canada
• Rising incidence (now 1/57 ♀) with over 50% > 65 years of age
• 75% Advanced at diagnosis
• Overall Five-year survival: 25–40% overall
– Advanced stage: 30 %
Most will develop recurrent disease and are NOT
curative
14. Age related risk of Ovarian Cancer
20-44 years 7/100,000
45-64 years 27/100,000
65-74 years 70/100,000
> 75 years 145/100,000
15. Ovarian cancer
• 25 % early
• 75 % advanced
5 Year Survival < 40 %
Stage 5 yr survival
IA-B 90%
IC 80%
II-IIIA 55-65%
IIIB-C 30%
IV < 20%
16. Etiology
• cause unknown
• protective factors:
– number of pregnancies
– breast-feeding
– BCP
– tubal ligation – increased protection with
salpingectomy
– hysterectomy
17. Etiology
• risk factors:
– early menarche/late menopause
– ? obesity
– demographic
– age
• family history - 90% sporadic
- 10% hereditary
18. Surveillance for hereditary ovarian cancer
BRCA I and BRCA II
• PV yearly (start 5yrs earlier then youngest relative
diagnosed with ovarian cancer)
• US yearly
• CA125 if > 50 – 9% chance of cancer
if > 100 – 15% chance of cancer
• BCP 50% risk reduction in BRCA mutation carriers
• BSO 90% reduction in risk of ovarian cancer
50% reduction in risk of subsequent breast cancer
• TL 60% risk reduction in BRCA mutation carriers
19. Hereditary ovarian cancer
HNPCC
lifetime risk for developing endometrial
and ovarian cancer is substantially
increased:
• 80% CRC
• 50% endometrial
• 13% stomach
• 12% ovarian
• 4% GU TCC
• 4% brain
• small intestine, liver and biliary tract
NB: if 1 cancer develops, 25% chance of 2nd cancer
20. Surveillance for hereditary ovarian cancer
HNPCC
• screen annually for uterine ca from age 35
• Cox2 inhibitors
• TAH/BSO
22. UKCTOS / PLCO
• 35 surgeries per invasive cancer / 31
surgeries per invasive cancer
• 80% advanced stage
• Screening did NOT change expected stage
distribution from an unscreened
population
Lancet Oncol, 2009
Obstet Gyecol, 2009
23. Role of Surgery
• Diagnosis
• Early disease – comprehensive staging
• Advanced disease – primary
cytoreduction
• Secondary cytoreduction
• Palliative Surgery
24. Surgery for Early Ovarian Cancer
• includes pelvic nodes, para-aortic nodes,
infracolic omentectomy, multiple biopsies
• Appendectomy in all mucinous tumors. Consider
also in all epithelial tumors if suspicious of
disease
30 % of patients upstaged – hence impact
on survival
25. Staging procedure if fertility sparing required
• Preserve contralateral ovary and uterus
• Comprehensive staging – infracolic omentectomy,
pelvic nodes, para-aortic nodes, peritoneal biopsies
still required
26. Upstaging of a clinical Stage I cancer
• Positive cytology 20%
• Omentum 6%
• Diaphragm 15%
• Peritoneal biopsies 13%
• Para-aortic nodes 14%
• Pelvic nodes 6%
JB Trimblos, Int J gyne cancer,2000
32. Ovarian Cancer: Staging by Surgical
Specialty
Evaluation of completeness of surgical staging
Nearly half of women with early ovarian cancer were inadequately staged by general Ob/
Gyns or General Surgeons
Surgeon Complete Staging
Gyn/Onc 97%
Ob/Gyn 52%
Surgeon 35%
Source: McGowen et al. Ob/Gyn 1985.Junor et al,BJOG 1999
33. Case Presentation
• 70 year old
• 6 month history of
– increased abdominal
girth
– weakness
– weight loss
• ascites
• complex pelvic mass
40. Survival
influenced by:
• stage
• grade
• histologic type
• completeness of cytoreduction
other favourable prognostic factors:
• younger age
• good performance status
• smaller disease volume prior to any surgical
cytoreduction
• absence of ascites
41. Theoretical Benefits of Cytoreductive
Surgery for Advanced Otaviran Carcinoma
• Removal of large bulky tumors with poor blood
supply
• Improved sensitivity of residual masses to
postoperative chemotherapy
• Greater likelihood of tumor eradication before
chemoresistance develops
42. cytoreductive surgery is critical
Cytoreduction 5 yr OS
micro residual 60 – 75 %
macro residual
< 2cm 40%
> 2cm 15%
43. Cytoreductive Surgery meta-analysis
• each 10 % increase in maximal
cytoreduction associated with
4.1% increase in median survival
time
• gyn oncologists – OR – 25%
reduction in death compared to
generalists in advanced cancers
( P = 0.005 )
44. Bristol et al. J Clin Oncol 2002
Meta-Analysis (N=6,885)
50. Is Less Than 1 cm Residual the Best Cutoff
Point for Optimal Cytoreduction?
As data accumulates, it is becoming
increasingly clear that even among
optimally resected patients, extended
survival rates are associated with debulking
of all visible disease
Median progression-free survival:
- No gross residual: 22 months
- Gross 0.1-1.0 cm: 12 months
- Gross > 1.0 cm: 6 months
Bristow and Montz. Gynecol Oncol 2001
51. Median Survival by Residual Disease
Chi DS et al. Gynecol Oncol 2006
Residual Disease No. Patients Median Survival
No gross 57 81 months
Gross <0.5 cm 51 56 months
Gross 0.5 – 1.0 cm 92 47 months
Gross 1 – 2 cm 53 31 months
Gross > 2 cm 172 34 months
55. Randomised EORTC-GCG / NCIC-CTG
trial on NACT + IDS versus PDS
Study conduct
• Between September 1998 and December 2006, 718
patients were randomised in 60 institutions (range: 1
– 125 patients).
• 498 events were needed to perform the final
analysis, and were reached in August 2008
• Median follow-up was 4.8 years.
56. Neo-adjuvant Chemotherapy in advanced
ovarian cancer
Ovarian tubal or peritonal cancer
FIGO stage IIIC and IV (n = 720)
Randomisation
Upfront Debulking Surgery Neoadjuvant chemotherapy
3 x Platinum based CT 3 x Platinum based CT
Interval debulking
(not obligatory)
Interval debulking
If no PD
> 3 x Platinum based CT > 3 x Platinum based CT
Primary Endpoint : Survival
Secondary endpoints: Progression Free Survival, Quality of Life, Complications
57. Randomised EORTC-GCG/NCIC-CTG trial on
NACT + IDS versus PDS < 1 cm residual per country (PP1)
Total PDS
( n = 329)
NACT -> IDS
(n = 339) *
Belgium (n = 133) 83% 72% 94%
Argentina (n = 48) 71% 68% 74%
The Netherlands (n = 104) 59% 40% 77%
Sweden (n = 23) 59% 40% 75%
Norway (n = 82) 55% 35% 73%
Italy ( n=38) 52% 40% 64%
Spain (n = 62) 49% 44% 58%
UK (n = 101) 47% 37% 63%
Canada (n = 84) 44% 29% 59%
58. Randomised EORTC-GCG/NCIC-CTG trial on
NACT + IDS versus PDS
Surgical findings and results (PP1)
PDS
(n = 329)
NACT -> IDS
(n = 339)*
Metastases before > 2cm 95% 68%
Metastases before > 10cm 62% 27%
No residual after surgery 21% 53%
< 1cm after surgery 46% 82%
* % calculated on the 306 patients who underwent IDS
59. Randomised EORTC-GCG/NCIC-CTG trial on
NACT + IDS versus PDS
Surgical characteristics (PP1)
PDS
(n = 329)
NACT -> IDS
(n = 339)*
Postoperative mortality
(< 28 days)
2.7% 0.6%
Postoperative sepsis 8% 2%
Fistula (bowel/GU) 1,2% / 0,3% 0,3% / 0,6%
Operative time (minutes) 180 180
Red blood cell transfusion 51% 53%
Hemorhage Grade 3/4 7% 1%
Venous Gr ¾ 2.4% 0,3%
* % calculated on the 306 patients who underwent IDS
62. Gynecologic Cancer Intergroup - 2010
• Surgical staging should be mandatory
and be performed by a gynecologic
oncologist
• The term optimal cytoreduction should
be reserved for those with no
macroscopic residual disease
• Delayed primary surgery following
neoadjuvant chemotherapy is an option
for selected patients with stage IIIC and
IV ovarian cancer
63. Advantages of neoadjuvant chemotherapy followed
by IDS
• Decrease in morbidity and mortality
• Advantage in advanced cancer
65. Secondary Cytoreductive Surgery in
Patientss With Platinum-Sensitive
Disease
Chi DS, et al. Cancer. 2006;106:1933-1939.
DFI Single Site Multiple Sites:
No Carcinomatosis
Carcinomatosis
6-12 mos Offer SC Consider SC No SC
12-30 mos Offer SC Offer SC Consider SC
> 30 mos Offer SC Offer SC Offer SC
66.
Harter
P,
et
al.
Ann
Surg
Oncol.
2006;13:1702-‐1710
Combina@on
of
PS,
early
FIGO
stage
ini@ally
or
no
residual
tumor
aHer
first
surgery,
and
absence
of
ascites
could
predict
complete
resec@on
in
79%
of
pts
DESKTOP-OVAR: Predictors of Successful
Surgery (= Complete Resection)
Multivariate Analysis
Pre-Op Variable OR 95% CI P Value
PS (ECOG 0vs > 0) 2.65 1.56-4.52 < .001
Residual disease 1st surgery (0 vs > 0) 2.46 1.45-4.20 < .001
Or initial FIGO stage (I/II vs III/IV) 1.87 1.04-3.37 .036
No ascites (cutoff 500 mL) 5.08 1.97-13.16 < .001
68. A
randomized
trial
evalua@ng
cytoreduc@ve
surgery
in
pts
with
pla@num-‐sensi@ve
recurrent
ovarian
cancer
Pla@num-‐sensi@ve
recurrent
cancer
of
the
ovaries,
fallopian
tubes,
or
peritoneum
PFI
>
6
mos
No
previous
chemotherapy
for
this
1st
relapse
Complete
resec@on
seems
feasible
and
posi@ve
AGO
score:
§
ECOG
PS
0
§
No
ascites
>
500
mL
§
Previous
complete
debulking
or
ini@al
FIGO
I/II
(if
data
available)
R
A
N
D
O
M
I
Z
E
Cytoreduc@ve
surgery
Pla@num-‐based
chemotherapy*
recommended
*
No
surgery
AGO-OVAR DESKTOP III
70. Role of Secondary Cytoreduction
Gynecologic Cancer Intergroup
Consensus Conference
2010
• Surgery appropriate in select patients
• No level I evidence of benefit
• However, it may be of benefit if optimal
cytoreduction
74. Surgery to relieve bowel obstruction
Only useful if a mass is causing the
obstruction. Usually the obstruction is
due to a tumor ileus
75. Options for bowel obstruction due to a mass
• Bowel resection with anastamosis
• Bypass surgery
• Colostomy / mucous fistula
• Ileostomy / mucous fistula
76. Conclusions
• Early clinical stage- 30% upstaged
• Advanced stage- cytoreduction critical
for better survival
• Role for neoadjuvant chemotherapy in
advanced cancer
• Role for secondary cytoreduction in
select patients
• Role for palliative surgery
