DR Melsew Abeje from bahir dare university

1. Management of EOC
moderator :Dr Munir(clinical oncologist)
presenter: Dr Melsew A
COR2
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2. outlines of presentation
• case presentation
• clinical manifestation
• diagnosis
• management
• case critics
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3. MRN 555758
• This is a 36 years old female patient presented with lower abdominal pain of
6 months duration.
• She has no cough ,chest pain ,loss of appetite
• She has no abdominal swelling, failure to pass faces and flatus.
• TAH and BSO was done 5 months back at Chorea hospital
•
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4. currently
• SUBJ: no new compliant
P/E
ECOG 1
V/S stable
Abdomen :there is midline scar
GUS:PV:no palpable mas, no discharge
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5. IXS
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6. Cont.…
• CXR :normal
• Post op abdominopelvic u/s :normal
• CBC and OFT:normal
• Ca125=35.1
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7. ASST:High risk stage 1B ovarian ca
• Plan :give adjuvant cisplatin and taxol
• With this plan she has completed 6 cycle of chemotherapy 3 weeks ago and
she has normal mid cycle assessment .
• Currently she is appointed for her 1st follow up
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8. Question???
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9. Clinical manifestations
• Historically, ovarian cancer was called a “silent killer,”
• a woman with early ovarian cancer was believed to have no or minimal symptoms
until she developed metastatic disease at which point abdominal symptoms :
bloating,
distention,
early satiety, loss of appetite, nausea,
 weight loss and pelvic symptoms .
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10. cont..
• In premenopausal women, most of these masses are benign, as ovarian
cancer represents <5% of adnexal neoplasms.
• An adnexal mass in a postmenopausal woman has a higher likelihood of
malignancy, and surgical exploration is often indicated.
• Physical examination findings such as a fixed pelvic mass, palpable upper
abdominal mass, and ascites are highly suggestive of an ovarian malignancy
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11. DIAGNOSTIC WORKUP
• Evaluation of a pelvic mass will be influenced by:
 the patient’s age,
 clinical presentation,
 and imaging features.
• An ovarian mass is more likely to be a malignant:
 neoplasm in the pediatric,
 perimenopausal,
 and postmenopausal age
 benign during the reproductive years
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12. Cont.…
• Ultrasound is often the first, noninvasive step for the evaluation of a pelvic
mass.
• Sonographic characteristics suggestive of malignancy include:
irregular borders with septations, ascites,
 peritoneal masses,
enlarged nodes,
 or matted bowel
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13. Cont.…
• CA125
• B HCG
• AFP
• INHIBIN
• LDH
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14. Principles if pathology report
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15. DIAGNOSIS
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16. SURGICAL STAGING
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17. 1/17/2020 17

18. Management
• Surgery
• Chemotherapy
• Radiotherapy????
•
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19. Surgery
• Surgery is a cornerstone of the diagnosis and treatment of ovarian
carcinoma.
• The surgical goals differ based on the nature and stage of disease.
• The most commonly encountered scenario unfortunately is that of
advanced epithelial ovarian cancer.
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20. PRINCIPLES OF SURGERY
• It is recommended that a gynecologic oncologist perform the appropriate
surgery.
• If clinical judgment indicates that maximum cytoreduction cannot be
achieved, neoadjuvant chemotherapy should be considered.
• Patients who are unable to be optimally debulked using minimally invasive
techniques should be converted to an open procedure.
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21. • An open laparotomy including a vertical midline abdominal incision should
be used in patients with a suspected malignant ovarian/fallopian
tube/primary peritoneal neoplasm in whom a surgical staging procedure, a
primary debulking procedure, an interval debulking procedure, or secondary
cytoreduction is planned.
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22. Operative Reports
• Surgeons should describe the following in the operative report:
Extent of initial disease before debulking pelvis, mid abdomen, or upper
abdomen (cutoffs: pelvic brim to lower ribs).
Amount of residual disease in the same areas after debulking.
Complete or incomplete resection; if incomplete, indicate the size of the
major lesion and total number of lesions.
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23. The rationale for debulking surgery
• Removing large necrotic masses promotes drug delivery to smaller tumors
with good blood supply.
• Removing resistant clones decreases the likelihood of early-onset drug
resistance.
• Tiny implants have a higher growth fraction that should be more
chemosensitive.
• Removing cancer in specific locations, such as tumors causing a bowel
obstruction, improves the patient’s nutritional and immunologic status.
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24. Management of early-Stage Disease(stages I
and II)
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25. Surgery
• At diagnosis, approximately one third of patients with epithelial ovarian cancer have early-stage disease that is confined to
the ovary or pelvis.
• Although the 5-year survival for patients with early-stage ovarian cancer is much better than that for those with advanced
disease, relapse rates ranging from 20% to 30% have been quoted for patients with poor prognostic factors
• Classic clinical and pathologic prognostic factors, such as :
 degree of differentiation,
 FIGO sub stage,
 histologic type,
 dense adhesions, l
 arge-volume ascites
 , rupture before or during surgery, bilaterality, positive peritoneal cytology extra capsular growth, and age of the patient
have been identified as prognostic characteristics.
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26. 1/17/2020 26

27. 1/17/2020 27

28. Surgery
• Comprehensive surgical staging should be performed in all women with
apparent early-stage disease to confirm that the cancer is confined to the
adnexa.
• Fertility-sparing surgery with unilateral salpingo-oophorectomy may be
considered in a small subset of women with stage IA disease if the
contralateral ovary is normal in appearance.
• In addition to abdominal exploration and full surgical staging, endometrial
biopsy should be considered to sample the endometrium.
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29. Satoh et al
• A multi-institutional
• Retrospective
• On Stage I EOC treated with fertility-sparing surgery
• The objective of this study was to assess clinical outcomes and fertility in
patients treated conservatively for unilateral stage I invasive EOC.
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30. Satoh et al
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211 patients with
unilateral stage I EOC
N=21
group III: stage IA and
clear cell histology grade
3 , stage
IC and clear cell
histology, or stage IC and
G3
N=108
Group I: stage IA
and
favorable histology
N=82
group II: stage IA and
clear cell histology, or
stage IC and
favorable histology;
Pepts OS,RFS
Median duration of follow-up was 78
months

31. 1/17/2020 31

32. 1/17/2020 32

33. CONCLUSION
• Our data confirm that fertility-sparing surgery is a safe treatment for stage
IA patients with favorable histology and suggest that stage IA patients with
clear cell histology and stage IC patients with favorable histology can be
candidates for fertility-sparing surgery followed by adjuvant chemotherapy
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34. Do early ovarian ca need adjuvant chemo??
• Early studies by GOG and others have identified a small subgroup of patients with
well- to moderately differentiated :
(grade 1 or 2) stage IA and IB tumors who have a low risk of relapse and may not
require adjuvant therapy.
The NCCN guidelines state that women with early-stage (FIGO IA or IB) grade 1
endometrioid carcinoma of the ovary may be treated with surgical resection and
observation with expected 5-year survival rates on the order of 90%.
 If observation is considered for women with early-stage grade 2 disease, full
surgical staging should be performed
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35. 5 year survival in ovarian ca
• Recently published data from the SEER Program of the NCI indicate t
• FIGO stage I and low grade= 92.3%.
• FIGO stage II=71.7%.
• FIGO stage III, the 5-year relative survival rate is only 27.4%.
• FIGO stage IA or IB grade 3, stage IC any grade, all clear cell carcinoma,
and completely resected stage II)=75%
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36. NEJM 1990
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92 patients
with grade 1
and 2 stage
1A and 1B
PEPTS
5Y DFS
OS
48
patients
recieve
44
patients
observat
ion
Melphal
an
5y DFS
91%
OS
98%
5Y
DFS.
98%
OS
94%
P
=0.43

37. TRIAL 2 NEJM 1990
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141 Patients
with stage 1A
and 1B high
grade
5y DFS
OS
68 patients
receive
melphalan
73 patient
to
observation
melphalan
5Y DFS
80%
OS
80%
5Y DFS
80.5%
OS
78%
P=0.48

38. EORTC action trial
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448 patients
Stage 1A and
1B grade 2 and
3
224
patients
reciev
chemo
224 patients
obserbation
PETS
OS
RFS
Platiniu
m based
chemo
40Europea
n centers
OS
85%
RFS
79.5
OS
80%
RFS
69%
P=0.009

39. • Women with FIGO IA grade 2 and 3 diseases, all stages IC-IIA, or any clear
cell histology were eligible for the trial.
• recurrence-free survival, but not overall survival, was significantly improved
in the chemotherapy group
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40. 1/17/2020 40

41. Advanced-Stage Disease
• Surgical Considerations:
Optimal or complete cytoreduction is one of the most important prognostic
factors for survival in patients with advanced-stage ovarian cancer.
Cytoreductive surgery in advanced-stage disease may improve the patient’s
disease-related symptoms such as abdominal pain and early satiety and allow
for the ability to maintain nutritional status.
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42. • The definition of “optimal cytoreduction” continues to evolve.
• Since 1986, the Gynecologic Oncology Group (GOG) has defined optimal
cytoreduction as leaving residual disease less than 1 cm in maximum tumor
diameter .
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43. 1/17/2020 43

44. 1/17/2020 44

45. Gynecol
Oncol 2006;
• Objectives: to determine the survival impact of adding extensive upper
abdominal surgical cytoreduction to standard surgical techniques for
advanced ovarian cancer
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46. • Methods: the records of all patients with stages IIIC–IV epithelial ovarian cancer who underwent
primary surgery at our institution from 1998 to 2003 were reviewed.
• The cohort was divided into 3 groups:
 Group 1 patients required extensive upper abdominal surgery, such as diaphragm
peritonectomy/resection, resection of parenchymal liver or porta hepatis disease and/or
splenectomy with or without distal pancreatectomy, to achieve optimal cytoreduction (residual
disease ≤1 cm).
 Group 2 patients were optimally cytoreduced by standard surgical techniques, including
hysterectomy, oophorectomy, omentectomy, and bowel resection.
 Group 3 patients were suboptimally cytoreduced. Primary outcome measures were response to
primary chemotherapy, progression-free survival, and overall survival
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47. Gynecol
Oncol 2006
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262 patient
Stage 3c-4
G1
57
patients;
G2
122
patients;
G3
83
patients.
PETS
PFS
OS
CHEMO
RESPONS
OS
84 M
PFS
24 M
R
82%
OS
84M
PFS
23M
R
78%
R
57%
OS
38
M
PFS
11M

48. Conclusions
• Patients requiring extensive upper abdominal procedures to achieve optimal
cytoreduction demonstrated a similar initial response, progression-free
survival, and overall survival to patients optimally cytoreduced by standard
surgical techniques.
• The presence of bulky upper abdominal disease alone did not appear to
indicate poor tumor biology.
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49. 1/17/2020 49

50. Second-look laparotomy
• was introduced to assess the extent of residual disease following
cytoreductive surgery and adjuvant chemotherapy.
• Up to 20% to 50% of patients may have residual disease after adjuvant
therapy that was not detected on physical examination or by CA-125 levels or
imaging.
• Although SLL demonstrated the prognostic importance of a pathologic
remission, it was not found to have a therapeutic benefit in a GOG trial of
800 patients.
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51. NEJ M 351;24
1/17/2020 51
424 patients
After 10 surg>1cm
residual
PETS
OS
PFS216 eligible
patients receive
2^CYRS
208 to receive
chemotherapy alone.
Goal
To see effect of 2^
Cytoreductive surgMedian OS
36.2 month
PFS
12.5 M
median
35.7 month
PFS
12.7 M
P=0.54

52. Neoadjuvant Chemotherapy
• Patients in whom malnutrition is significant or the metastatic disease process
appears unrespectable may be treated with neoadjuvant chemotherapy
followed by interval cytoreduction and postoperative chemotherapy.
• However, there has been significant movement in considering neoadjuvant
chemotherapy for women who are candidates for even primary debulking
surgery.
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53. NEJM 363;10 NEJM.org september 2, 2010
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670Stage IIIC or IV
patients Underwent
randomization336 Were
assigned to
primary surgery
PETS
OS
PFS
334 Were assigned to
neoadjuvant
chemotherapyTo see the role of
neoadjuvant chemo
medianOS
29 months
PFS
12 months
Median OS
30 months
PFS
12 months

54. 1/17/2020 54

55. EORTC 55971 trial
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670 stage IIIC or
IV patients
336patient receive
primary surgery
334 patients receive
neoadjuvant chemo
Pepts
5year survival
To see goal of
neoadjuvant
chemo

56. 1/17/2020 56

57. conclusion
• In the EORTC trial, patients with stage IVB disease and bulky tumors had
better 5-year survival rates with neoadjuvant therapy,
• whereas those with stage IIIC and less bulky tumors had a greater survival
benefit with upfront surgery.
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58. 1/17/2020 58

59. Chemotherapy for Advanced-Stage Disease
• Platinum agents are the most active class of compounds in the adjuvant
treatment for ovarian cancer.
• Before 1980, alkylating-based regimens such as cyclophosphamide and
doxorubicin were used with clinical response rates of15% to 20%. GOG 47
demonstrated an improvement in clinical complete response rates (51% vs.
26%) and progression-free survival (13 vs. 8 months) with the addition of
cisplatin to cyclophosphamide and doxorubicin.
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60. 1/17/2020 60

61. 1/17/2020 61

62. Role of intraperitoneal chemotherapy
• The peritoneal cavity is the principal site of disease in ovarian cancer.
• Although the intensity of intravenous chemotherapy is limited mainly by
myelotoxicity, several active drugs can be administered directly into the
peritoneal cavity.
• The rationale for intraperitoneal therapy in ovarian cancer is that the
peritoneum, the predominant site of tumor, receives sustained exposure to
high concentrations of antitumor agents while normal tissues, such as the
bone marrow, are relatively spared.
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63. NEJM354;1 www.nejm.org january 5, 2006
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429stage 3c-4
Patients
214 Assigned to
intraperitoneal
therapy
215 Assigned to
intravenous
therapy
Median OS
65.6 months
Median PFS
18.3 months
Pepts
OS
PFS
Ppfs=0.05
Intraperitoneal
Cisplatin and IV
Paclitaxel
Median PFS
23.8 months
Median OS
49.7 months
Pos=0.
03

64. conclusions
• As compared with intravenous paclitaxel plus cisplatin, intravenous paclitaxel
plus intraperitoneal cisplatin improves survival in patients with optimally
debulked stage III ovarian cancer
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65. Management of recurrent Ovarian Cancer
• Women in clinical remission following initial adjuvant treatment for ovarian
cancer may be followed with a combination of physical examination, serial
CA-125 levels, and/or abdominal and pelvic CT.
• Detection of early relapse by a rising CA-125 is fairly specific, although the
lead time between biochemical and clinical progression may be up to 6
months.
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66. Cont.…
• Recurrent ovarian cancer is incurable.
• Chemotherapy is indicated to control disease-related symptoms.
• The benefit from chemotherapy in these patients depends on the platinum free
interval.
• Patients with platinum-resistant disease (a relapse <6 months)
• Patients with platinum semi-sensitive relapse (6-12months )have a response rate of
30% to second-line platinum treatment.
• In patients with platinum-sensitive relapse (>12months) the response rate to
platinum is 60–70%.
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67. Platinum resistant OC
• In the absence of a new therapeutic study, most patients with platinum-
resistant disease are treated with single agents such as pegylated liposomal
doxorubicin (PLD) or topotecan and other agents.
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68. OCEANS trial
• a randomized, placebo -controlled, phase 3 trial
• evaluating the efficacy and safety of bevacizumab combined with
gemcitabine + carboplatin for patients with platinum-sensitive recurrent
ovarian cancer .
• PEPTS, PFS,OS with GC + bevacizumab compared with GC + PL.
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69. OCEANS trial
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484 recurrent
platinum sensitive
patients
recurring>6mo242patients receive
GC+bevaccizumabe 242 patients receive GC+PL
PEPTS
OS
PFS
Median OS
33.6 months
DPFS
12.4 months
Median OS
32.9 months
DPFS
8.4 months
. Median follow-up
for OS was
58.2 months
Pos=0.65
Ppfs
<0.001

70. Cont.…
• In the OCEANS trial, the addition of bevacizumab to
carboplatin/gemcitabine chemotherapy resulted in improved progression-
free survival (median 12.4 vs. 8.4 months) in women with platinum-sensitive
recurrent disease.
• In the final survival analysis, there was not a significant increase in overall
survival with the addition of bevacizumab when compared to chemotherapy
alone (33.6 vs. 32.9 months).
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71. 1/17/2020 71

72. CALYPSO trial
• Pegylated Liposomal Doxorubicin and Carboplatin Compared With
Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian
Cancer in Late Relapse
• randomized, multicenter, phase III noninferiority trial
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73. CALYPSO trial
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976 patients
Assigned CD
(n = 467) Assigned CP
(n = 509)
PFS
11.3 months
OS
immat
ure PFS
9.4 months
OS
immature
Pepts
PFS,OS
median follow-up of 22
months
P=0.005

74. 1/17/2020 74

75. • Patients who experience relapse >12 months after primary platinum-based
therapy have platinum-sensitive disease.
• The therapeutic landscape for these patients is dominated by reinduction of
platinum-based chemotherapy
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76. PARP INHIBITORS
• About 15% of epithelial ovarian cancers are deficient in homologous
recombination repair, owing to mutations in BRCA1/2.
• In up to 50% of patients with high-grade serous tumors, the tumor cells
may be deficient in homologous recombination as a result of germ line or
somatically acquired BRCA1/2 mutations, epigenetic inactivation of BRCA1,
or defects in the homologous recombination pathway that are independent
of BRCA1/2.
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77. Olaparib
• Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in
germline BRCA1 and BRCA2 (BRCA1/2) –associated breast and ovarian
cancers.
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78. NEJM
• a randomized, double-blind, placebo-controlled, phase 2 study to evaluate
maintenance treatment with olaparib in patients with platinum-sensitive,
relapsed, high-grade serous ovarian cancer who had received two or more
platinum based regimens and had had a partial or complete response to their
most recent platinum-based regimen.
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79. NEJM
•
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265 patients
136 were assigned to
the olaparib
129 to the placebo
group
MedianPF
S
8.4month
s
medianPFS
4.8 months
P<0.001
Pepts
PFS
82 investigational
sites in 16 countries

80. 1/17/2020 80

81. Cont.…
• In the platinum sensitive setting, olaparib maintenance therapy resulted in
progression-free survival benefit of 8.4 months compared to 4.8 months
with placebo for women with relapsed ovarian cancer, although an overall
survival benefit was not observed.
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82. Niraparib Maintenance Therapy in Platinum
Sensitive, Recurrent Ovarian Cancer
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83. NEJM.org on October 8, 2016.
• In this randomized, double-blind, phase 3 trial,
• patients were categorized according to the presence or absence of a germline
BRCA mutation (gBRCA cohort and
• non-gBRCA cohort) and the type of non-gBRCA mutation and were
randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo
once daily. The primary end point was progression-free survival
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84. NEJM.org on October 8, 2016.
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553 enrolled patients
203 patients BRCAM
350 Patients non
BRCA
372 patients receive
Niraparib 300mg po
daily
181 patients receive
placebo
Pepts
PFS
138 patient
BRCA
116 patient
snon BRCA
65 patient
BRCA234 patients non
BRCA
Median
PFS
21
months
Median
PFS
12.9
months
Median PFS
5.5months
Median PFS
3.8 months
P<0.001

85. • Maintenance niraparib resulted in a significant improvement in progression-
free survival, with the greatest benefit among patients with germline BRCA
mutations.
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86. Case critics
• Right risk assessment
• Chemotherapy options??
• Preop investigation should be collected
• Operation report should be attached with referral
• Right decision on adjuvant treatment
• 3 vs 6 cycle CT???
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87. References
• Edward Perez 7th edition
• DaVita 11th edition
• NCCN 2019
• GOOGLE
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