Transcript Epithelial Ovarian Carcinoma

Epithelial Ovarian Carcinoma
高雄榮總婦產科
劉文雄醫師
Introduction
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Malignant neoplasms of the ovary present an increasing
challenge to the physician. They are the cause of more
deaths than any other female genital tract cancer.
It accounts for 5% of all cancers among women.
In U.S, deaths from this cause occur at a rate of one
every 45 min, and one in every 56 women will develop
this disease.
Classification
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The early development of the ovary may be divided into
four major stages :
 During the first stage, undifferentiated germ cells
(primordial germ cells) become segregated and
migrate from their sites of origin to settle in the genital
ridges.
 The second stage occurs after arrival of the germ cells
in the genital ridges and consists of proliferation of the
coelomic epithelial and the underlying mesenchyme.
 During the third stage, the ovary becomes divided into
a peripheral cortex and a central medulla.
 The fourth stage is characterized by the development
of the cortex and involution of the medulla.
Relative Frequency of Ovarian neoplasms
Type
Coelomic epithelial
Germ cell
Specialized gonadal stroma
Nonspecific mesenchyme
Metastatic tumor
%
50-70
15-20
5-10
5-10
5-10
Classification
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The majority(85 to 90% ) of malignant ovarian
tumors seen in the US are epithelial.
 Serous cystadenocarcinoma :42%
 Mucinous cystadenocarcinoma : 12%
 Endometrioid carcinoam : 15%
 Undifferentiated carcinoma : 17%
 Clear cell carcinoma : 6%
Incidence, Epidemiology, and Etiology
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Approximately 23 % of gynecologic cancers are of
ovarian origin, but 47% of all deaths from cancer of the
female genital tract occur in women who have
gynecologic cancer of ovarian cancer.
Approximately 12 of every 1000 women in the US older
than 40 years will develop ovarian cancer, but only 2 or 3
of the 12 will be cured.
Incidence, Epidemiology, and Etiology
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Malignant germ cell tumors are most commonly seen in
females younger than 20 years, whereas epithelial
cancers of the ovary are primarily seen in women older
than 50 years.
Incidence rate of ovarian cancer related to age :
 40-44 yr : 15.7/100000.
 50-60 yr : 35/100000.
 75-79 yr : 54/100000.
 More than one third of the cases occur in patients 65
yrs or older
Primary ovarian neoplasm related to age
Type
Up to 20 yr
Coelomic epithelium
Germ cell
Specialized gonadal
stroma
Nonspecific mesenchyme
20-50 yr
Over 50 yr
29%
59%
8%
71%
14%
5%
81%
6%
4%
4%
10%
9%
Familial Ovarian Cancer
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Several reports describe families in which girls and
women of the same or succeeding generations develop
similar neoplasms of the ovaries.
Most of these neoplasms were serous carcinomas.
Cancers of the breasts, colon,and other sites were also
found more commonly in female members of these
afflicted families.
NCI studies disclosed the number of relatives with
ovarian cancer was significantly higher ( relative risk :
2.61) than the control.
Familial Ovarian Cancer
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The lifetime risk for ovarian cancer in the population as a
whole is approximately 1.4% ; with one first-degree
relative, it is 5% ; with two or more first-degree relatives,
it rises to 7%.
Among the later group, there is 3% chance of having
hereditary ovarian cancer syndrome; in those families,
the lifetime risk of ovarian cancer is at least 40%.
Firm guidelines for prophylactic oophorectomy have not
been established.
Lifetime probability of ovarian cancer by age in women
with one relative with ovarian cancer
Age(year)
30
35
40
45
50
55
60
Lifetime probability
lifetime probability of
of ovarian Ca (%) ovarian ca with one relative(%)
1.6
1.6
1.6
1.5
1.4
1.3
1.2
5
5
4.8
4.5
4.4
4.1
3.6
Familial Ovarian Cancer
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Three different hereditary syndromes of cancer have been
identified : All three syndrome have a pattern of earlyonset cancer and vertical transmission consistent with
autosomal dominant inheritance.
 The first is a site-specific familial ovarian cancer
syndrome : women are at high risk for the
development of ovarian carcinoma only.
 The second is a breast-ovarian cancer syndrome : 50%
risk of ovarian carcinoma if their mothers or sisters
had breast and/ or ovarian carcinoma. The syndrome
have been associated with the BRCA-1 and BRCA-2
gene.
Familial Ovarian Cancer
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The third is the cancer family syndrome in which both
males and females are at increased risk of acquiring
colon cancer, and to a lesser extent other cancers,
including gastric carcinoma, thyroid carcinoma, and
sarcoma.
 Most of the colon cancers are in the proximal colon
and not easily diagnosed.
 Women in these families are at increased risk for
carcinoam of the ovary, endometrium, and breast.
Familial Ovarian Cancer
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Because of the AD inheritance pattern, 50 % risk can be
predicted in all offspring and siblings of inflicted
individuals.
Prophylactic oophorectomy as soon as childbearing is
completed ?
Most of the cancers have been detected in women
between 35 to 45 yrs; thus, if oophorectomy not done,
biannual sonogram with PV plus CA-125 should be
advised.
Even the prophylactic oophorectomy was done; safety?
Familial Ovarian Cancer
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It is important to distinguish women in families with
hereditary ovarian cancer syndromes from those who
have family members with ovarian cancer.
 Thorough medical history : a woman’s family history
of ovarian cancer, breast cancer, endometrial cancer,
and non- polyposis colorectal cancer.
 Determining the age of occurrence of these cancers in
the family members.
 Family pedigree by a physician to identify the AD
inheritance pattern.
Familial Ovarian Cancer
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Suggest for these patients :
 Should be maintain by oral pills until such time that
they desire childbearing.
 Patients less than 35 yrs with a history of hereditary
ovarian cancer syndrome should be monitored with a
PV + sonogram + CA-125 every 6 months.
 At the age of 35, prophylactic oophorectomy may be
elective.
How oral pills use affects the risk of ovarian cancer
Duration of oral No. of women who
pills use
developed ovarian Ca
Never
3-6 months
7-11 months
1-2 years
3-4 years
5-9 years
>10 years
242
26
14
65
40
39
13
Controls
Relative
risk
1532
280
134
602
397
594
328
1.0
0.6
0.7
0.7
0.6
0.4
0.2
Etiology of Ovarian Cancer
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Environmental factors : physical and chemical products
of industry are major causes of epithelial neoplasms.
Theory of “ incessant ovulation” suggests that the
epithelial lining of the ovary may be sensitive to the
constant trauma of ovulation, which in turn can act as a
promoting factor in the carcinogenic process.
Prolonged use of fertility drugs such as Clomid may
increase the risk of borderline and invasive ovarian
cancer.
Etiology of Ovarian Cancer
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Others have suggested that ovarian cancer may be
initiated by a chemical carcinogen via the vagina, uterus,
and fallopian tubes, and the substances promoting cancer
may even be the steroid- rich antral fluid from ruptured
follicles.
Genital exposure to Talc : 42% Vs 28%.
No evidence exists to incriminate viruses in the
development of neoplasms of the human ovary.
Most frequent presenting symptoms of ovarian cancer
Symptom
Relative frequency
Abdominal swelling
Abdominal pain
Dyspepsia
Urinary frequency
Weight change
XXXX
XXX
XX
XX
X
Nonovarian etiology of adnexal mass
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Frequently encountered nonovarian causes of
apparent adnexal masses :
 Diverticulitis.
 TOA.
 Carcinoma of cecum or sigmoid.
 Pelvic kidney.
 Uterine or intraligamentous myomas
Ovarian Cancer Screening
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Periodic pelvic examination, ultrasonography, CA-125.
 10000 PV would be required to pick up one early
ovarian cancer in an asymptomatic patient population.
 CA-125 as a screening technique has not been
rewarding especially in premenopausal women.
 Many conditions of a benign nature as well as most GI
malignancies, may elevated the CA-125.
 Ultrasonography, especially the TVS ( color doppler ).
Scroing System for Ovarian TumorMorphologic Index
DePriest PD, Shenson D, Fried A, Hunter J, Andrews S, Gallion H, et al. A morphology
index based on sonographic findings in ovarian cancer. Gynecol Oncol 1993;51:7-11.
Scroing System for Ovarian TumorMorphologic Index
Doppler Study
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In Doppler velocimetry, the flow velocity waveform obtained from
a target vessel is evaluated according to standard parameters,
pulsatility index (PI) and resistant index (RI).
The vessels supplying benign ovarian tumors generally were
peripheral in location, had high systolic flow, and a high PI (>1.0)
and RI (>0.4). In contrast, vessels supplying ovarian malignancies
generally had significant diastolic flow, were centrally located, and
had a low PI (<1.0) and RI (<0.4).
It is difficult to clearly identify ovarian malignancies on the basis
of pulsed Doppler findings alone.
CA-125
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An ideal marker should have high sensitivity (few falsenegative results), high specificity (few false-positive
results), and high accuracy. Serum levels of CA 125 are
elevated (>35 u/mL) in approximately 50% of patients
with stage I epithelial ovarian cancer and in more than
90% of those with advanced disease.
Generally, serum CA 125 values rise over time in patients
with ovarian cancer, whereas they remain stable or
decrease in patients with benign ovarian tumors.
Therefore, serial CA 125 determinations at 2 to 4-week
intervals can be helpful in deciding whether a
sonographically confirmed ovarian tumor can be
monitored safely or should be removed surgically.
CA-125
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With advances in molecular technology, a number of
candidate tumor markers for ovarian cancer have been
identified including CA 15.3, CA 72.4, CA 19.9, and
soluble epidermal growth factor.
At present, however, there is little evidence to suggest
that their use in a multimodality screening panel is
superior to CA 125 alone in differentiating benign from
malignant ovarian tumors.
Proteomics
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Proteomic profiling of serum using mass spectroscopy
(surface-enhanced laser desorption and ionization) has
been proposed recently as a method to detect ovarian
cancer.
Basically, a population of proteins can be profiled
according to the size and net electrical charge of the
individual proteins.
The discriminating proteomic pattern formed by a subset
of proteins is defined by peak amplitude at key
mass/charge positions along the spectrum.
Ovarian Cancer Screening
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Improve the effectiveness of ovarian cancer screening
would be to target populations at increased risk of the
development of the disease, such as individuals, with a
positive family history of ovarian cancer.
Another strategy to improve sensitivity and specificity in
screening for ovarian cancer involves the use of multiple
serum tumor markers. Because less than 50% of patients
with stage I ovarian cancer will have an elevated CA-125.
Management Guideline
Non-malignant conditions that may elevate CA125 concentrations

 Nongynecologic
Gynecologic
 Active hepatitis
 Acute PID
 Acute pancreatitis
 Adenomyosis
 Cirrhosis
 Benign ovarian neoplasm
 Congestive heart failure
 Endometriosis
 DM(poor control)
 Functional ovarian cyst
 Diverticulitis
 Meig’s syndrome
 Mesothelioma
 Menstruation
 Nonmalignant ascites
 OHSS
 pericarditis
 Unexplained infertility
 Pneumonia
 Uterine myoma
 Post-op period
 SLE
Pattern of Spread
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Transcelomic : The most common and earliest mode of
dissemination is by exfoliation of cells than implant
along the surfaces of the peritoneal cavity.
Lymphatic : retroperitoneal ( pelvic and paraaortic ) LN
spreading is common in advanced- stage disease. 78%
with stage III disease had positive pelvic LN. And the
rate of the positive paraaortic LNs was 18% in stage I ,
20% in stage II, 42% in stage III, and 67% in stage IV.
Hematogenous : is uncommon at the time of diagnosis,
lungs and liver is the most common sites
Diagnostic Techniques
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Pelvic examination remains the most practical means of
detecting early disease.
Pain is usually a late complication.
Any ovary palpated in a patient 3 or more years after
menopause should raise a high index of suspicious of an
early ovarian neoplasm.
Diagnostic paracentesis is a patients with ascites and a
pelvic-abdominal mass is unnecessary and dangerous.
Diagnostic Techniques
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Ovarian cancer is classically a serosal spreading disease,
and thus all peritoneal surfaces must be carefully
inspected, especially when disease is thought to limited
to the pelvis.
Washing cytology : 1. subdiaphragm, bil . 2. Paracolic
gutter, bil. 3. Cul-de-sac .
Care should be taken to visualize and palpate all
peritoneal surfaces including the underside of the
daiphragm, the surface of the liver and the small and
large bowel mesentary.
Complete Workup For Ovarian Cancer
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Careful history
Physical examination
Pelvic examination and Pap’s smear
Proctosigmoidoscopy, where indicated
CBC and urinalysis
Blood chemistries, including CA-125
Chest film, IVP, Barium enema, or CT scan
Pelvic sonogram.
Surgical Therapy in Ovarian Cancer
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Peritoneal cytologic examination
Determination of extent of disease
 Pelvis
 Peritoneal surface
 Diaphragms
 Omentum
 Lymph node
Removal of all tumor possible
Guidelines For Staging in Epithelial Ovarian
Cancer
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4 peritoneal washings ( diaphragm, bil paracolic gutter and
cul-de-sac ).
Careful inspection and palpation of all peritoneal surfaces
Biopsy of smear from undersurface of bil diaphragm.
Biopsy of all suspicious lesions .
Infracolic omentectomy.
Biopsy or resection of any adhesions
Random biopsy of normal peritoneum of bladder reflection
cul-de-sac, Rt and Lt paracolic gutters and both pelvic side
walls.
Selected lymphadenectomy of pelvic and para-aortic nodes.
ATH,BSO, and excision of all masses where prudent
Stage and 5-year Survival
Stage Ia
Stage Ib
Stage Ic
Stage IIa
Stage IIb
Stage IIc
Stage IIIa
Stage IIIb
Stage IIIc
Stage IV
Overall
84%
79%
73%
65%
54%
61%
52%
29%
18%
14%
31%
Early-Stage Ovarian Cancer
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Early-stage ovarian cancer: I-IIa
The primary treatment for early stage epithelial ovarian
cancer is surgical, that is, a ATH+BSO+ complete
surgical staging. (24% will be upstaging to stage III)
Based on the prognostic variables, early stage epithelial
ovarian cancer can be subdivided into low-risk and highrisk disease.
The uterus and the contralateral ovary can be preserved
in women with stage IA , low-risk disease who wish to
preserve fertility. Zanetta et al. BJOG,1997; Favalli et al. Int J Gyn
Cancer, 2001
Prognostic Variables in Early-stage
Epithelial Ovarian Cancer
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Low risk
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Low grade
Non-clear cell histologic
type
Intact capsule
No surface excrescences
No ascites
Negative peritoneal
washing
Unruptured or
intraoperative rupture
No dense adhesion
Diploid tumor
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High risk
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High grade
Clear cell type
Tumor growth through
capsule
Surface excrescences
Ascites
Malignant cells in fluid
Preoperative rupture
Dense adhesion
Aneuploid tumor
Early-Stage Low-Risk Ovarian Cancer
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Stage IA, IB, Grade 1 and 2.
GOG randomized trial of observation versus melphalan
in this group of patients and the 5-year survival for each
group were 94% and 96%.
No further adjuvant treatment is needed for such patients.
Early-Stage High-Risk Ovarian Cancer
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In patients whose disease is high risk ( e.g., more poorly
differentiated or in whom there are malignant cells either
in ascitic fluid or in peritoneal washings ) . Additional
therapy in indicated.
Treatment options include chemotherapy or wholeabdominal radiation
Randomized Trials in Stage I Epithelial Ovarian Cancer
( since 1995)
Author
Young et al
GOG7601
GOG7602
Bolis et al.
Stages
Treatment
Best Arm
81
141
47
104
I(Low)
I(High), II
I(Low)
I(High)
Observation Vs. Melphalan
P32 Vs melphalan
Observation Vs cisplatinx6
P32 Vs cisplatinx6
Young et al.
205
GOG95
Trope et al
134
Closed/maturing
GOG172
331
I(High), II
Cisplatin75mg/m2/ cyclo
750mg/m2 Vs P32
Carboplatin vs. observation
NP
NP
NP
Cisplatin
79 Vs 69%
Cis/cyclo
77 Vs 66%
NP
Ongoing Trial
GOG175
Patients
I(High)
I(High), II
Taxol 175 mg/m2/ carbo
AUC 7.5 (3 vs 6 courses)
I(high), II
Taxol 175mg/m2/carbo AUC
6 followed by observation vs.
Taxol 40mg/m2/weeklyx26wks
Early-Stage High-Risk Ovarian Cancer
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Patients with high-risk stage I epithelial ovarian cancer
be given adjuvant chemotherapy. The type depends on
the patient’s overall health and status.
Treatment with carboplatin and Taxol chemotherapy for 3
to 6 cycles seem desirable in most patients, whereas a
short course of a single agent, either carboplatin or Taxol,
may be preferable for older women.
Advanced-Stage Ovarian Cancer
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After the introduction of cisplatin in the latter half of the
1970s, platinum-based combination chemotherapy
became the most frequently used regimen in USA.
Taxol become available in the 1980s, and this drug was
incorporated into the combination chemotherapy in the
1990s.
Cisplatin Combination Chemotherapy
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Combination chemotherapy has been shown to be
superior to single-agent therapy.
After cisplatin became available for the treatment of
ovarian cancer showed that cisplatin was better than an
alkylating agent , cyclophosphamide, as a single agent.
Several studies recommended the platinum-based
chemotherapy were shown to be superior.
Most studies using the PC or PAC regimen, disclosed the
same survival rates.
Taxol-based Combination Chemotherapy
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The next major advance in the treatment of advanced
stage disease was the incorporation of taxol into the
chemotherapeutic regimen.
Several prospective randomized trial with taxol-based
arms have defined the current recommended protocol in
advanced epithelial ovarian cancer.
Based on the GOG111,1996 and OV10,1998 studies,
Taxol should be included in the primary treatment of all
women with advanced-stage epithelial ovarian cancer
Platinum and Taxol Chemotherapy randomized Trials
in Advanced-Stage epithelial Ovarian Cancer
Author
McGuire
Year
1996
Group
GOG 111
Status
Subopt
Stuart
1998
Opt/Subopt
Muggia
1997
EORTC
OV10
GOG132
Ozols
1999
GOG158
Opt
Bois
1999
AGO
Opt/subopt
Albert
1996
GOG104
Opt
Markman 1998
GOG114
Opt
Subopt
Drugs/doses
T:135(3)/cis75
vs ctx750/cis75
T:175/cis75
vs ctx750/cis75
Cis100 vs T200(24)
vs cis75/T135(24)
Carbo7.5/T175(3)
vs cis75/T135(24)
Carbo6/T185(3)
vs cis75/T185(3)
Ipcis100/ctx750
vs Iv cis75/ctx750
Carbox2-9/Ip cis100
/T135(24) vs Iv cis
75/T135(24)
Best
Taxol/cis
Taxol/cis
Taxol/cis
Taxol/carbo
Taxol/carbo
Ip cis/ctx
Ip cis/carbo
/ Taxol
Platinum and Taxol Chemotherapy randomized Trials
in Advanced-Stage epithelial Ovarian Cancer-Ongoing
Author
Harper
Group(Protocol)
ICON3
Status
Opt/Subopt
GOG162
Subopt
GOG172
Opt
Drugs/Doses/(hrs)
T135(24)/cis75 vs
Carbo vs cis/ctx/doxo
T135(24)/cis75 vs
T120(96)/cis75
Iv T135(24)/Ipcis100
(D2)/Ip T60(D8) vs
Iv T135(24)/Iv cis75
Chemotherapeutic Recommendation in
Advanced Ovarian Cancer
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Combination chemotherapy with carboplatin and Taxol.
The recommended doses and schedule are carboplatin
( AUC 5 to 6) and Taxol 175 mg/m2(3hrs) Q3W for 6
cycles.
In patients who cannot tolerate the combination, singleagent carboplatin (AUC 5 to 6 ) can be given.
In those who have a hypersensitivity to Taxol, an
alternative active drug can be substituted ( e.g.,
cyclophosphamide or topotecan).
In patients who cannot tolerate IV chemotherapy, an oral
alkylating agent can be substituted.
Combination Chemotherapy for Advanced Epithelial
Ovarian Cancer : Recommended Regimens
Drugs
Dose
Infusion
time(hr)
Interval
No. of cycles
Standard Regimen
Taxol
Carboplatin
175mg/m2
AUC 5-6
24
Q3W
Q3W
6 cycles
6 cycles
135 mg/m2
75 mg/m2
3
Q3W
Q3W
6 cycles
6 cycles
Taxol
Cisplatin
Alternative Drugs( can be given with platinum )
Cyclophosphamide
600-750 mg/m2
Topotecan
1.0-1.25 mg/m2
Gemcitabin
800-1000 mg/m2
Q3W
Daily x 5 D
Q3W
Q3W
Administration of Chemotherapy and
Amelioration of Toxicity
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Taxol :
 The principal concern of Taxol + Carboplatin is the
patential for enhanced bone marrow toxicity.
 In general, 3 hrs infusion tend to reduce the likehood
of bone marrow depression than 24 hrs infusion.
 The principal concern of Taxol + cisplatin is the
potential for neurotoxicity.
Administration of Chemotherapy and
Amelioration of Toxicity
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Carboplatin :
 The renal and GI toxicities of carboplatin are modest
compared with cisplatin, and therefore do not require
prehydration and outpatient administration is more
feasible.
 Carboplatin does tend to have appreciable bone
marrow toxicity.
 G-CSF 250 ug/m2 given sc. From D2-14 may be
protective .
Administration of Chemotherapy and
Amelioration of Toxicity
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Cisplatin :
 Is given Q3W by IV infusion not over 1mg/min .
 Required prehydration, 1/2 saline given iv at a rate of
300-500 ml/hr for 2-4 hours until the urine output is
greater than 100 ml/hr .
 The principal toxicities of Taxol + cisplatin are renal,
GI, hematologic, and neurologic. The renal and
neurologic toxicities usually limit the duration of
treatment to six cycles.
Radiation Therapy
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An alternative to combination chemotherapy for selected
patients with metastatic ovarian cancer is the use of
whole-abdomimal radiation therapy.
The treatment involves a radiation field that extends from
1 to 2 cm above the level of the diaphragm to include the
entire pelvis.
Whole-abdominal radiation appears useful in patients
whose metastatic disease is microscopic or completely
resected.
No definite role in the treatment of ovarian cancer.
Hormonal Therapy
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There is no evidence that hormonal therapy alone is
appropriate primary therapy for advanced ovarian cancer.
The us of progestational agents in the treatment of
recurrent, well-differentiated endometrioid cancer is
supported by the current data.
The reported response rates by Rendina et al, is 57%
(17/30) in recurrent epithelial cancer, with 10% (3/30)
complete response, all responding patients had well
differentiated , estrogen recepor-positive tumors.
Immunotherapy
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Various trials using nonspecific immunostimulants to treat
patients with ovarian cancers.
Most frequently, agents such as corynebacterium parvum
and bacillus Calmette-Guerin (BCG) have been used
systemically in conjunction with cytotoxic chemotherapy.
None as yet has demonstrated efficacy as primary treatment.
The use of cytokines has been tested in a second-line
setting, and the activity of interferon-a, interferon-r, and
interleukin- 2 has been demonstrated
Immunotherapy
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Trials of monoclonal antibodies directed toward ovarian
cancer- associated antigens are being conducted.
Antibodies directed toward CA125 and the human milk
fat globulin (HMFG) tumor- associated antigens are
underway.
Herceptin, an antibody directed toward the extracellular
protein produced when the HER-2/neu oncogene is
overexpressed, has been used extensivelly in breast
cancer.
Trials of Herceptin in HER-2/neu overexpressing ovarian
cancer are ongoing.
Antibodies against the protein produced by the mutated
P53 tumor suppressor gene are also undergoing clinical
studies.
Treatment Assessment
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Tumor Markers :
 CA-125 : a surface glycoprotein associated with
mullerian epithelial tissue, is elevated in
approximately 80% of patients with epithelial ovarian
cancer, particularly those with nonmucinous tumors.
 The level of CA-125 have been correlated with the
findings at second-look operations. Positive levels are
useful in predicting the presence of disease, but
negative levels are an insensitive determinant of the
absence of disease.
Treatment Assessment
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Tumor markers :
 Positive predictive value : 100%
 Negative predictive value : 56%
 The change in level usually correlates with response.
Those patients with persistently elevated titers after
three cycles of treatment most likely have resistant
clones.
Radiologic Assessment :
 The false-negative rate of a CT scan is approximately
45%.
Treatment Assessment
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Second-look Operations :
 Is performed to determined the response to therapy on a
patient who has clinical complete response after a
prescribed course of chemotherapy.
 5 sites (cul-de-sac, bil paracolic gutter & bil subdiaphragm )
cytology and biopsies of the peritoneal surface, particularly
in any areas of previously documented tumor.
 Any adhesions or surface irregularities should be sampled.
 Biopsy specimens should be taken from the pelvic sidewalls,
the pelvic cul-de-sac, the bladder, the paracolic gutters, the
residual omentum, and the diaphragm.
Treatment Assessment
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Second-look operation :
 A pelvic and paraaortic lymph node dissection should
be performed in those patients whose nodal tissue
have not been previously removed.
 Approximately, 30% of patients with no evidence of
macroscopic disease have microscopic metastases.
 Also, in many patients with microscopic disease, it is
detected only in the occasional biopsy or cytologic
specimen.
 If gross tumor is disclosed at second-look operation,
resected all the tumor tissue may be performed to
faciliate response to salvage therapies.
Second-Look Operation



Has not been shown to influence patient survival,
although the information obtained at second look is
highly prognostic.
The reported relapse rates after negative second-look
operation is around 30-50 % at 5 years.
Initial Stage : Patients whose tumors are initially stage I
& II have negative second-look rates of 85-95% and 7080%. Whereas the rates for patients with stage III or IV
disease is 30-45%.
Second-Look Operation



Tumor grade : The likelihood of a negative second look
in patients at all stages is about 60%-70% for those with
grade I tumors, 40-50% for those with grade II, and only
20% for those with grade III.
Type of chemotherapy : In patients with optimally
resected stage III disease treated with the taxol +
platinum, the negative second look rate is about 45-50%.
Second-look laparoscopy ? role
Second-Line Chemotherapy


The response rates for second-line chemotherapies have
been 15 to 35% for most drugs tested by the oral or IV
route.
Single-agent drugs are sometimes used for second-line
chemotherapy because of their relative ease of
administration and low toxicity.
Second-Line Chemotherapy in Recurrent/Persistant
Epithelial Ovarian Cancer
Drug
Cisplatin
Carboplatin
Taxol
Topotecan
Etoposide
Liposomal Doxorubicin
Gemcitabine
Holoxan
Hexamethylmelamine
Platinum Response
Sensitive
Resistant
Sensitive
Resistant
Sensitive
Resistant
Sensitive
Resistant
Sensitive
Resistant
Sensitive
Resistant
Sensitive
Resistant
Both
Both
% Response
77%
28%
33%
19%
22%
13%
26%
13%
36%
27%
26%
15%
20%
13%
17%
27%
Response/Patients
17/22
14/50
24/72
38/202
28/127
33/255
35/134
34/263
16/44
25/94
9/35
15/103
7/35
8/60
5/29
13/49