Transcript Ovarian Cancer

Ovarian Cancer
Ovarian Cancer
• Epithelial Tumor, postmenopausal women
• Germ cell, younger women
• Sex cord-stromal origin, any age
• Approximately 90% of ovarian cancer is epithelial
• significant therapeutic challenges (Epithelial
Tumor)
• other types of ovarian cancer are often localized
,more amenable to surgical resection, more
favorable px
• peritoneal serous carcinoma and fallopian tube
carcinoma (their clinical and management
considerations are similar to those of epithelial
ovarian cancer)
Epidemiology
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leading cause of gynecologic cancer mortality
The lifetime risk :1.7%,
familial predisposition :of 10% to 40%
The median age at diagnosis for sporadic disease
is 60 years,
• improvement in 5-year survival
• A higher risk for nulliparous women
• lower risk for those who have had children, who
have breastfed, who have undergone tubal
ligation, or who have taken oral contraceptives
Pathogenesis and Patterns of
Metastases
• arise from the surface epithelium covering the
ovary, which is contiguous with peritoneal
mesothelium. It is thought that malignant
transformation preferentially occurs within
epithelium that becomes trapped within ovarian
inclusion cysts during ovulation, where it can
develop into a variety of mullerian-type
histologies. Thus, ovarian serous carcinomas can
resemble the fallopian tube, ovarian mucinous
tumors may resemble the endocervix, and
ovarian endometrioid carcinomas may resemble
the endometrium.
Pathogenesis and Patterns of Metastases
• Germ cell tumors most likely originate in cells
derived from the primitive streak that
ultimately migrated to the gonads.
• The ovarian stroma consists of granulosa cells,
theca cells, and fibroblasts, which give rise to
the sex cord- stromal tumors.
• Several molecular abnormalities in patients with
epithelial ovarian cancer,
• Cytogenetic analysis may reveal complex
abnormalities
• Mutation in the p53 proto-oncogene occurs in
over 50% of cases,
• Mutations in the K-ras proto-oncogene are more
common in ovarian borderline tumors (which
typically do not undergo p53 mutation).
• Amplification of the Her-2/neu gene , 8%
• Overexpression of proapoptotic genes such as
BAX(Px good)
• Expression of (VEGF) (high serum :Px poor)
• exfoliate from the ovarian surface
• The tumor typically spreads to the omentum and
to peritoneal surfaces
• The lymphatic drainage
para-aortic region,
pelvic sidewall lymphatics, (external iliac,
obturator, and hypogastric chains)
inguinal lymph nodes.
• 10% to 15% appears to be localized to the ovaries
have metastases to para-aortic lymph nodes
• retroperitoneal lymph node involvement is found
in over 50% of patients with advanced disease.
• The most common site of extra-abdominal
spread is the pleural space (thought to occur
via transdiaphragmatic lymphatics), where it
causes a malignant pleural effusion in some
patients.
• Hematogenous metastases to the liver, spleen,
or lung
• Bone or central nervous system metastases
Histologic Classification of Epithelial
Tumors
• The nomenclature for these tumors reflects
the cell type, location of the tumor, and
degree of malignancy, ranging from benign
lesions to tumors of low malignant potential
(LMP) to invasive carcinomas
Tumors of LMP (borderline tumors)
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epithelial papillae with atypical cell clusters
excellent prognosis
increased mitotic activity
lack stromal invasion
Epithelial carcinomas
• characterized by histologic cell type and
degree of differentiation (tumor grade)
• The histologic cell type has limited prognostic
significance independent of clinical stage
• High tumor grade ,especially in patients with
early stage epithelial tumors.
• papillary serous variety of epithelial ovarian
cancer: psammoma bodies
• clear cell histology may also be associated
with endometriosis, hypercalcemia , relatively
resistant to chemotherapy
• mucinous ovarian cancers are chemoresistant,
sometimes associated with pseudomyxoma
peritonei, and may not be associated with
dramatic elevations of (CA 125)
COMMON EPITHELIAL TUMORS
• Malignant serous tumor
• Malignant mucinous tumor
• Malignant endometrioid tumor
SEX CORD - STROMAL TUMORS
• Granulosa - stromal cell tumor
• Androblastoma: Sertoli-Leydig cell tumor
• Germ cell tumor
DDx
• Gastric, breast (especially ILC), mesothelioma,
and colorectal cancers may occasionally present
with diffuse peritoneal implants, ascites, and
ovarian metastases that mimic primary ovarian
cancer.
• routine light microscopic histologic evaluation,
IHC
• cytokeratin CK7 +and CK20 - in most cases of
primary serous ovarian cancer,
• Staining for gross cystic disease fluid protein
(GCDFP) may be positive in up to 50% of patients
with breast cancer, whereas this marker should
be negative in patients with gastric, colorectal, or
ovarian cancer.
Common Histologic Types of Epithelial Ovarian
Cancer
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Papillary serous
Endometrioid
Mucinous
Clear cell
Papillary serous
• The most common type of epithelial ovarian
cancer.
• May contain psammoma bodies
• often associated with CA 125 elevation.
• Identical histology is observed for primary
peritoneal serous cancer (PPSC).
Endometrioid
• Sometimes associated with endometriosis or
an independent uterine cancer of similar
histology. May occur with early stage disease
in younger patients, although advanced
disease is also possible.
Mucinous
• May rarely be associated with pseudomyxoma
peritoneii. CA 125 levels may not be markedly
elevated. Relatively chemoresistant.
Differential diagnosis of a mucinous ovarian
tumor includes metastatic disease from an
appendiceal primary.
Clear cell
• The most chemoresistant type of ovarian
cancer. Often contains hobnail cells with
cleared out cytoplasm due to glycogen.
Sometimes associated with endometriosis or
humorally mediated hypercalcemia.
Diagnosis
• asymptomatic
• Symptomatic of spreads to the upper abdomen
• Approximately 70% with stage III or IV whereas
the majority of patients with borderline, germ
cell, and sex cord -stromal tumors present with
early stage disease limited to the pelvis
• mass on routine pelvic examination or because of
pelvic pain caused by ovarian torsion.
• ovarian germ cell malignancies tend to stretch
and twist the infundibulopelvic ligament, causing
severe pain
• Abdominal discomfort, bloating, and early
satiety (ascites and a pelvic mass on physical
examination)
• (Sister Mary Joseph's node) or a pleural
effusion
• The mass on pelvic examination is frequently
firm and fixed, with multiple nodularities
palpable in the cul-de-sac.
• The CA 125 serum level is elevated in more than
80% of serous epithelial ovarian cancers.
• not a reliable diagnostic test, since it can also be
elevated in a variety of benign gynecologic
conditions (such as endometriosis, pelvic
inflammatory disease, or pregnancy) and
nongynecologic malignancies (such as breast,
lung, and GI).
• the CA 125 level is elevated in 50% of patients
with early stage epithelial ovarian cancer,
• CA 19-9, which is elevated in some mucinous
ovarian carcinomas, and carcinoembryonic
antigen (CEA) are less frequently useful.
• It is typical for a patient with epithelial ovarian
cancer to have a normal CEA level in the setting
of a significantly elevated CA 125 level.
• Postoperatively, the CA 125 level provides a
sensitive way to monitor treatment response and
development of disease recurrence. Because
relapsed epithelial ovarian cancer is usually
incurable, however, there is currently no evidence
that early detection of recurrence through CA
125 levels confers a survival advantage in this
disease.
International Federation of
Gynecology and Obstetrics Staging
System for Epithelial Ovarian
Cancer
STAGE I
Tumor limited to ovary or ovariesa
IA
One ovary, without ascites, positive peritoneal
washings, surface involvement, or rupture.
IB
Both ovaries, without ascites, positive peritoneal
washings, surface involvement, or rupture.
IC
Ascites, positive peritoneal washings, surface
involvement, or rupture present.
STAGE II
Ovarian tumor with pelvic extensiona
IIA
Involvement of the uterus or fallopian tubes.
IIB
Involvement of other pelvic organs (e.g.,
bladder, rectum, or pelvic sidewall).
IIC
Pelvic extension, plus findings indicated for IC.
STAGE III
Tumor involving the upper abdomen or lymph nodes
IIIA
Microscopic disease outside of the pelvis, typically
involving the omentum.
IIIB
Gross deposits less than or equal to 2 cm in
diameter.b
IIIC
Gross deposits greater than 2 cm in diameter, or
nodal involvement.b
STAGE IV
Distant organ involvement, including pleural
spacec or hepatic/splenic parenchyma.
• aPatients with disease that appears to be
confined to the ovaries or pelvis require nodal
biopsy for complete staging, in order to exclude
the possibility of occult stage IIIC.
• bDisease measurements for staging purposes are
made before debulking has been attempted.
• cPleural effusion must be cytologically proven to
be malignant if used to define stage IV disease.
TVU
• diagnostic tool
• TVU is more sensitive (CTS)
• The classic sonographic finding of malignancy is a
complex cyst, defined as containing both solid and
cystic components, sometimes with septations and
internal echogenicity .
• Finding a complex cyst on sonography, especially in
the presence of signs and symptoms consistent with
ovarian cancer, often requires surgery for further
evaluation. It is best to avoid percutaneous biopsy
during the initial evaluation, which can result in cyst
rupture and spillage of malignant cells into the
peritoneal cavity. Bilateral ovarian involvement and
ascites are sometimes detected by sonography as well.
• Color Doppler imaging
Simple cysts
• Simple cysts in asymptomatic postmenopausal
do not always require surgical evaluation if
they are associated with normal CA 125 levels,
• Postmenopausal women with simple cysts in
association with elevated serum CA 125 levels,
simple cysts that exceed 5 to 10 cm in
diameter, or simple cysts in association with
abnormal color Doppler flow studies are often
referred for surgery.
Simple cysts In premenopausal
• may be functional (i.e., a corpus luteum cyst)
• a benign process such as a serous cystadenoma.
• simple cysts that are persistent or enlarging,
especially in the setting of a rising CA 125 level,
are reasonable candidates for surgical evaluation
to exclude malignancy.
• several benign conditions in premenopausal
women may also be associated with elevated CA
125 levels, such as pregnancy or endometriosis,
and there is no absolute CA 125 cutoff to
distinguish benign from malignant pathologies
• CT or (MRI) in defining the extent of
peritoneal disease
• However, for the patient with a complex
ovarian cyst and clinical signs and symptoms
to suggest ovarian cancer, these studies
generally do not obviate the need for surgical
exploration.
• CT may sometimes be helpful in
distinguishing a gynecologic malignancy from
a metastatic pancreatic neoplasm, for
instance, for which an exploratory laparotomy
may not be warranted. In selected patients, CT
may also assist in surgical planning by locating
the site of suspected bowel obstruction.
• MRI has not been shown to have a clear
advantage over CT in patients with an ovarian
mass, except for pregnant patients when
ultrasonography is inconclusive and there is a
desire to avoid radiation exposure.
• PET:there is currently no proven role for PET in
the diagnosis or subsequent follow-up of
patients with ovarian cancer.
• CXR may sometimes be performed to evaluate
the presence of pleural effusions, which occur
in 10% of patients with epithelial ovarian
cancer at diagnosis.
Screening and Early Detection
1. identifying the majority of patients with
precancerous lesions or early disease
2. major surgery
3. Costs
4. mortality
5. the false-positive rate
6. positive predictive value (PPV)
screening procedure
• serum tumor marker levels
• ultrasonography
• both
CA 125 serum level
• alone, is not a useful
• not specific for ovarian cancer
cirrhosis, peritonitis, pleuritis, pancreatitis,
endometriosis, uterine leiomyomata, benign ovarian
cysts, and pelvic inflammatory disease
• elevated in other malignancies
such as breast, lung, colorectal, pancreatic, and gastric
cancers.
• CA 125 level is elevated in the majority of patients with
advanced epithelial ovarian cancer, it is abnormal in
only 50 % of patients with early stage disease.
candidate markers
show promise for enhancing the accuracy of
CA 125 levels,
1. HE4 (human epididymis 4)
2. osteopontin
3. mesothelin
4. osteoblast-stimulating factor-2.
5. OVX-1
6. Lysophosphatidic acid
these markers may be complementary to CA 125
None of these tests has been proven to have
sufficient sensitivity and specificity for routine
screening at the current time.
CA 125+ TVU
• an attempt to improve screening.
• TVU suggested a sensitivity of close to 100%
but a specificity of 98%, which is insufficient to
achieve a PPV of 10%.
• color Doppler imaging improves the specificity
of TVU ,PPV?
• using a morphologic index?
• Two randomized controlled trials
measurement of CA 125 level (single threshold
elevation of more than 35 U/mL) and TVU
together, performed annually, as a first-line
screen
will require an average of 10 years of follow-up
• The second randomized screening trial is
currently being conducted in the United
Kingdom and uses CA 125 levels (or rate of
rise of CA 125) as a trigger for performing
TVU.
Hereditary Ovarian Carcinoma
• 5% to 10% epithelial ovarian carcinoma carry a
germline mutation
• The breast -ovarian cancer syndrome 90% of
hereditary ovarian cancer and is often suspected
whenever the pedigree reveals multiple affected
family members with ovarian cancer, bilateral or
early onset breast cancer, both breast and
ovarian cancer in the same individual, or a male
relative with breast cancer.Fallopian tube cancer
and primary peritoneal serous cancer (PPSC)
Breast and ovarian cancers
• inherited germline mutations in the BRCA1 or
BRCA2 genes,
• transferred by either parent,
• these genes act as tumor suppressors and play
a critical role in the repair of double-stranded
DNA breaks.32
• The lifetime risk of ovarian cancer is 20% to 60%
for patients with BRCA1 mutations, and 10% to
35% for BRCA2 mutation carriers.
• Ovarian cancer with germline mutations of
BRCA1 appears to present with distinct clinical
and pathologic features compared with sporadic
ovarian cancer.
• The majority of BRCA1-associated cancers are
serous adenocarcinomas, with an average age at
diagnosis of 48 years, whereas the mean age for
BRCA2-associated ovarian cancers is 60 years.
Furthermore, BRCA-associated cancers may
have a more favorable course than sporadic
ovarian cancer.
• chemosensitivity may be partly due to the
inability of tumor cells to repair platinuminduced DNA damage in the setting of a
BRCA1 or BRCA2 mutation.
• The more favorable survival of patients with
BRCA1 or BRCA2 mutations when compared
to their sporadic counterparts is not
necessarily related to a higher rate of cure,
but may also be related to a longer duration of
responsiveness to chemotherapy agents used
in the relapsed setting.
Hereditary nonpolyposis colorectal cancer
• 5% to 10% of all hereditary ovarian cancer
• autosomal dominant
• right colon, as well as an increased risk of
developing endometrial, ovarian,
hepatobiliary, upper gastrointestinal, and
Gyn cancers.
• Colorectal and uterine cancers comprise the
majority of tumors developing in affected
families.
• A germline mutation in one of five genes
involved in DNA mismatch repair is
responsible for the HNPCC phenotype: hMSH2
(chromosome arm 2p), hMLH1 (chromosome
arm 3p), hPMS1 (chromosome arm 2q),
hPMS2 (chromosome arm 7p),
• The majority of affected patients are found to
have defects in either hMSH2 or hMLH1
• Patients with HNPCC due to germline
mutation of hMSH6 may be particularly
predisposed to uterine cancer. In addition,
HNPCC may account for approximately 7% of
cases with synchronous uterine and ovarian
cancers, which are often low grade and of
endometrioid histology
Patients at high risk of having a
hereditary cancer
• genetic counseling
• Multidisciplinary services available in such a
setting often include pretest and posttest
counseling, screening, treatment, and
psychosocial counseling.
Test results
• an identifiable mutation,
• no identifiable mutation
• a polymorphism of indeterminate clinical
significance.
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Management of patients with an inherited genetic
predisposition to ovarian cancer
complex
variable penetrance of genetic alterations
lack of effective early detection methods for ovarian
cancer
Although annual pelvic examinations, serum CA 125
determinations, and TVU are sometimes considered in
affected individuals, there is currently no conclusive
evidence that ovarian cancer mortality is reduced as a
result of these interventions
efficacy of prophylactic, risk reduction bilateral
salpingo-oophorectomy (RRSO) for patients with the
hereditary breast-ovarian cancer syndrome has been
more convincingly demonstrated.
Management of patients with an inherited genetic
predisposition to ovarian cancer
• RRSO
• Chemoprophylaxis
• Other risk-reducing strategies
• Even after RRSO, BRCA mutation carriers are
still at small risk for developing primary
peritoneal serous cancer, which is
histologically and clinically similar to epithelial
ovarian cancer. Such cancers represent
malignant transformation of the peritoneal
mesothelium, which is contiguous with
ovarian surface epithelium.
RRSO
• most effective preventative strategy
• at high risk for developing ovarian cancer and
who have completed childbearing, especially if
they are at least 35 years of age
• A laparoscopic approach
• The surgical pathologist must perform a careful
examination of the surgical specimens, as occult ovarian
and tubal carcinoma have been found in 2% to 10% of RRSO
specimens.
• Some patients with occult disease discovered after careful
pathological evaluation may require a second operation to
complete surgical staging in order to determine the need
for postoperative treatment .
• Significant issues regarding RRSO remain unresolved, such
as the physiologic adjustments to premature surgical
menopause and the safety of hormone replacement
therapy in this group, especially in those at high risk for
breast cancer.
• chemoprophylaxis with oral contraceptives for
5 years might decrease ovarian cancer risk by
50% in both the general population and in
high-risk women.
• Other risk-reducing strategies such as tubal
ligation and hysterectomy have also been
associated with a reduced incidence of
ovarian cancer among high-risk women.
Staging
1. laparotomy permits histologic confirmation
of disease,
2. Surgery is also necessary to determine the
extent of disease (staging), post opTX ,Px
3. debulking
optimally cytoreduced (defined as having less
than or equal to 1-cm diameter residual
tumor)
• midline incision
• ascitic fluid
• If intraperitoneal carcinomatosis is absent,
first resect the ovarian tumor
• The grossly normal, opposite ovary may
undergo biopsy, or any visible benignappearing cysts may be excised.
• Pelvic and para-aortic retroperitoneal lymph
nodes
• Any enlarged pelvic retroperitoneal lymph
nodes should be removed
The staging system for ovarian cancer is defined by
FIGO based on the findings at exploratory laparotomy
Staging
• fertility
• endometrioid ovarian cancer
incomplete surgy
• completing the surgical staging if the findings
would alter postoperative management(stage
IA, grade 1 or 2 )
• ( at least stage IC or stage II )or (tumor is
grade 3),less importent
• Laparoscopic techniques
• CT scan?
Prognostic Factors for Epithelial Ovarian Cancer
• FIGO stage,
• volume of residual disease after cytoreductive
surgery
• histologic subtype,
• histologic grade,
• age,
• malignant ascites.
• 5ys stage IA disease and grade 1 or 2 >90%
after surgery alone( or +stage IB, grade 1 or 2 )
• relapse rate without postop adj treatment is
30% to 40% for patients with stage IC , stage I,
grade 3 , or stage II
a 5-ys 80% after postop adj therapy
• Controversial: some investigators report that
rupture alone does not appear to confer a
worse prognosis if it occurred intraoperatively,
as opposed to preoperatively.
advanced-stage disease
• 5ys 20% to 30% After postoperative
treatment stage III optimally debulked, and
this decreases to less than 10% for patients
with suboptimally debulked stage III disease
or those with stage IV tumors.
• stage IIIA disease survivals in the range of
50% after postoperative adjuvant therapy.
• mucinous or clear cell histologic have worse
Px
CA 125
• Preoperative serum CA 125 levels frequently reflect the
volume of disease and do not appear to have an
independent effect on survival, after correcting for
stage and debulking status.
• postoperative CA 125 levels, both during and after
completion of first-line chemotherapy, have prognostic
value.
• normalization of the serum CA 125 levels after three
cycles of cht is associated with more favorable
outcome, as well as achievement of a CA 125 nadir of
less than or equal to 10 U/mL upon completion of
treatment. Although this information has prognostic
significance, it has limited therapeutic value in the
absence of effective salvage regimens with curative
potential.
The prognostic significance
• DNA ploidy and S-phase fraction
aneuploidy?
relationship between histologic grade and the
degree of aneuploidy?
molecular prognostic factors
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markers of proliferation
drug resistance
levels of serum cytokines
growth factor receptors
expression of genes associated with
metastases.
Management of Early Stage Disease
• Postoperative Chemotherapy
• Postoperative Radiation Therapy
Postoperative Chemotherapy
• can improve both progression-free and overall
survival in patients with high-risk, early stage
ovarian cancer. Such patients include those
with stage I, grade 3, stage IC, or any stage II
disease.
• six cycles of adjuvant carboplatin plus
paclitaxel chemotherapy for high-risk, early
stage patients,
Postoperative Radiation Therapy
• different chemotherapy regimens
• whole abdominal radiotherapy (WAR)
• intraperitoneal (IP) administration of
radioactive phosphorus (32P).
In summary
• these randomized trials generally found WAR
or IP 32P was less effective or more toxic than
platinum-containing regimens. Hence,
adjuvant radiation therapy has fallen out of
use as the primary treatment for patients with
high-risk, early stage ovarian cancer
Management of Advanced-Stage
Disease
• Primary Cytoreductive Surgery
• Postoperative Chemotherapy for Epithelial
Ovarian Cancer
• Intraperitoneal Chemotherapy
• Interval Cytoreductive Surgery
• Radiotherapy After First-Line Chemotherapy
• Maintenance Therapy
Primary Cytoreductive Surgery
• The theoretical benefits of cytoreductive surgery
include removal of large, necrotic tumors with
poor blood supply that might lead to impaired
chemotherapy delivery.
• tumor debulking may permit residual tumor to
proliferate more rapidly and thereby enhance
sensitivity to postoperative chemotherapy.
• Although neither of these mechanisms has been
proven, the association between successful
cytoreduction and more favorable outcome has
been demonstrated in many surgical series.
optimal cytoreduction
• residual disease of 1 cm or smaller in
maximum individual diameter
• Primery cytoreduction refers to performance
of debulking surgery prior to administration of
first-line chemotherapy and is the standard
approach for managing most patients with
suspected epithelial ovarian cancer.
neoadjuvant chemotherapy and an
interval cytoreduction
• patients with a poor performance status
initiating neoadjuvant CHT →surgical
cytoreduction in responding patients after
three cycles of chemotherapy
• stage IV disease
neoadjuvant chemotherapy
• Potential advantages of neoadjuvant
chemotherapy are
1. a more rapid improvement in quality of life
2. a technically more feasible operation
3. shorter hospitalization
4. less morbidity.
Postoperative Chemotherapy for Advancedstage epithelial ovarian cancer
• It is a chemoresponsive disease in the majority of
cases, although relapse often occurs and
resistance eventually develops to most forms of
treatment.
• The platinum compounds remain the single most
active drugs in the treatment of this disease.
• the use of carboplatin instead of cisplatin
conferred an equivalent survival advantage, but
with less myelosuppression, neuropathy,
nephropathy, and emesis
P base + a taxane such as paclitaxel
• is now accepted as an appropriate first-line,
• The response rate as high as 70% for patients
with suboptimally debulked disease,
• over 80% for patients who are optimally
cytoreduced.
• nonoverlapping mechanisms of action,
Combination or sequential single
agents
• For individuals who may have difficulty tolerating
a combination regimen (e.g., those with marginal
performance status or significant comorbid
medical conditions), it is reasonable to initiate
treatment with intravenous single-agent
carboplatin and later add intravenous paclitaxel
to the regimen or deliver the drugs as sequential
single agents.
• For appropriate patients with stage III disease
who are optimally cytoreduced, intraperitoneal
chemotherapy is an important new option
• carboplatin (AUC = 5) plus paclitaxel (175 mg/m2)
• icarboplatin (AUC = 5) and docetaxel (75 mg/m2)
has shown equivalent response rates, progression-free, and
overall survival, although their toxicity profiles differed.
More grade 4 neutropenia occurred with the docetaxelcontaining regimen, and a greater incidence of grade 2 or 3
neuropathy was observed with the paclitaxel-containing
program.
• These data indicate that a carboplatin and docetaxel
combination is an acceptable first-line regimen for patients
with advanced ovarian cancer, especially in the setting of
pre-existing neuropathy (where paclitaxel may be difficult
to tolerate).
How many cycles
• There appears to be no value in extending
platinum-based first-line therapy beyond five
or six cycles to ten or 12 cycles.
• there is no convincing evidence to suggest a
benefit to the addition of cytotoxic drugs such
as liposomal doxorubicin, epirubicin,
topotecan, or gemcitabine to the platinum
and taxane doublet
• Bevacizumab ?
Intraperitoneal Chemotherapy
• The rationale for this approach is based on the
observation that many active drugs such as
cisplatin and paclitaxel have favorable
peritoneal to plasma concentrations, on the
order of 20 to 1 and 1,000 to 1, respectively.
• generally acceptable systemic side effects,
• limited penetration
1. receive either a control arm of IV paclitaxel (135
mg/m2 administered over 24 hours) and IV cisplatin
(75 mg/m2) for six cycles,
2. IV paclitaxel on day 1 (135 mg/m2 administered over
24 hours), IP cisplatin on day 2 (100 mg/m2), and IP
paclitaxel on day 8 (60 mg/m2), for six cycles.
The median overall-survival was 65.6 months for the IP
arm and 49.7 months for the IV arm (HR 0.75; 95% CI
0.58 to 0.97; P = .03).
This significant prolongation of median overall survival
was associated with several toxicities, including a
higher incidence of neutropenia, infection, catheter
blockage, neuropathy, abdominal pain, renal
dysfunction, and electrolyte abnormalities
• Although some investigators still feel that IP
chemotherapy should remain experimental,
others feel that these data offer strong
support for the IP approach.
IP therapy
no superior to IV treatment in
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stage IV disease,
suboptimally debulked residual disease
relapsed disease.
It should also be avoided in patients with
comorbid conditions such as renal
insufficiency, significant baseline neuropathy,
or extensive intra-abdominal adhesions.
Improve the tolerability of IP therapy
• reduction of the day-2 IP cisplatin dose,
• administration of day-1 IV paclitaxel over 3 hours instead
of 24 hours,
• and/or omitting day-8 IP paclitaxel until patient tolerance
to the first cycle of IP cisplatin can be assessed.
• reduce toxicity while still preserve the benefits of the IP
approach?
• use of IP carboplatin instead of IP cisplatin
it is not yet known whether carboplatin is as effective as
cisplatin when administered via the IP route.
Technical Aspects of Intraperitoneal
Chemotherapy Administration
• either cisplatin or paclitaxel
• a catheter with a subcutaneous access port in
the anterior chest wall region, just below the
breast, which then tunnels subcutaneously
downward to the midabdomen, where it
enters the peritoneal cavity. IP catheter
insertion can be performed at the time of
primary cytoreductive surgery, or afterward by
laparoscopy.
• Based on the available data, colon resection
with fecal contamination or left colon
resection would appear to represent relative
contraindications to placement of an IP
catheter at the time of primary cytoreduction
1. Tenckhoff catheter
adhesion formation within the peritoneal catheter
related to the development of a fibrous sheath
surrounding the catheter fenestrations, and
intestinal obstruction due to the Dacron sheath
migrating into the peritoneal cavity
2. a single-lumen silicone catheter with an
implantable port designed for IV injection may
be preferable,
Catheter insertion typically involves the following steps
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A separate 5 to 6 cm transverse incision is made two to three
fingerbreadths above the left inferior costal margin in the
midclavicular line and is carried down to the fascia.
A subcutaneous pocket is created to house the implantable port
The port is sutured to the fascia at the four corners
A tonsil clamp or similar instrument is tunneled subcutaneously
above the fascia for approximately 10 cm from the port. At a point
about 6 cm lateral to the umbilicus, a small aperture is made in
the peritoneum.
The proximal end of the catheter is grasped with the clamp and
brought through from the peritoneal cavity, through the
subcutaneous tunnel, to the port.
The catheter is connected to the port, and it is trimmed to allow
approximately 10 cm of catheter within the peritoneal cavity
The catheter is flushed with heparinized saline to check patency.
The transverse skin incision is closed
• Intraperitoneal instillation
• If the infusion rate is slow, repositioning the
patient may be beneficial in an attempt to
move the catheter tip away from bowel loops
or a pocket caused by adhesions.
• a second prewarmed liter of fluid
• Standard premedications
Interval Cytoreductive Surgery
• Interval cytoreduction is defined as a debulking
procedure performed after several cycles of
chemotherapy have been administered, typically
in those patients who had a suboptimal cytoreduction at the time of initial surgery.
• a randomized trial : improvement in median
overall survival (P = .01), suggesting a role for this
strategy in suboptimally debulked patients who
are responding to first-line chemotherapy.
• the negative results of the GOG study than in the
EORTC trial, are partly due to
1. definition of suboptimally debulked disease
2. performance of initial surgery by a gynecologic
oncologist,
3. more effective paclitaxel and cisplatin regimen
in the GOG trial (compared to
cyclophosphamide and cisplatin in the EORTC
trial) may have negated any added value of
interval cytoreduction.
• Thus, patients who are deemed to be
suboptimally debulked after a cytoreductive
effort performed by a surgeon skilled in this
procedure, who then receive first-line paclitaxeland platinum-based chemotherapy, are not likely
to benefit from interval cytoreduction.
• For those patients who did not adequate attempt
at initial cytoreduction (due to being a poor
operative candidate or due to lack of surgical
expertise), the EORTC study suggests that an
attempt at interval cytoreduction is reasonable if
disease control can be achieved during the first
three cycles of chemotherapy.
Radiotherapy After First-Line
Chemotherapy
Cht+ :
1. WAR
2. Pelvis +para aort
3. IP 32P
4. observe
In conclusion ?
• the value of radiation therapy as consolidation
therapy following chemotherapy for patients
with ovarian cancer is uncertain.
• Routine use of consolidation radiotherapy
after chemotherapy is not generally
recommended.
Maintenance Therapy
• There is no evidence that continuing first-line
platinum-based chemotherapy beyond five to
six cycles confers added benefit for patients
with advanced ovarian cancer
• There is currently great interest in studying
the value of antiangiogenic agents such as
bevacizumab, which is a humanized
monoclonal antibody that neutralizes vascular
endothelial growth factor in the maintenance
setting.
Surveillance After First-Line
Chemotherapy
• Over 50% of newly diagnosed patients with
advanced-stage epithelial ovarian cancer will
achieve a clinical complete remission after
platinum and taxane induction chemotherapy.
• Clinical complete remission is defined as no
evidence of disease on physical examination, a
normal CA 125 level, and normal radiographic
studies such as CT.
• Patients with advanced-stage disease who
achieve a clinical complete remission have a
high chance of relapse
• follow
1. pelvic examinations
2. CA 125 determinations
CTS
• Routine performance of CT in the absence of
symptoms, findings on physical examination,
or an elevated CA 125 level has no proven
value in the management of patients with this
disease. This is partly due to the lack of
sensitivity of CT compared to serologic testing
with CA 125, which is currently the most
sensitive method for detection of early relapse
• There is currently no proven benefit for
routine surveillance with other radiographic
tests such as PET scans in the posttreatment
setting
second-look laparotomy
• Although performance of a second-look laparotomy after
completion of first-line therapy will reveal residual disease
in over half of all patients with advanced ovarian cancer
who have achieved a complete clinical remission, this
procedure does not appear to confer a survival advantage.
This is due to the current lack of curative treatment options
for patients with disease that persists after platinum-based,
first-line therapy.
• In addition, a negative second-look laparotomy does not
guarantee against the development of disease relapse,
which occurs in 50% of patients with advanced stage
disease who have a negative second-look procedure.
• For these reasons, second-look laparotomy is
no longer considered a standard procedure in
the assessment of patients after completion of
first-line therapy, although it is sometimes
used as an investigation tool in the context of
clinical trials.
Management of Recurrent Disease
•
•
•
•
Hormonal Therapy
Chemotherapy
Surgery
Radiation Therapy
Hormonal Therapy
• (marker-only relapse)
• Unfortunately, the majority of patients with
recurrent ovarian cancer are destined to die of
their tumors, regardless of the second-line
treatment modality used. Patients who
demonstrate marker-only evidence of relapse,
are often initially managed with a drug like
tamoxifen or an aromatase inhibitor. These
drugs are potentially active in ovarian cancer
and are generally well tolerated.
• The response to hormonal agents is typically
slow and may require approximately 2 to 3
months before a reduction in the CA 125 level
is evident
Chemotherapy
• Chemotherapy for recurrent disease is usually
indicated for the development of tumorrelated symptoms, objective evidence of
significant disease on examination or CT, or
failure of hormonal therapy.
• Platinum is the most active agent in the
management of patients with epithelial
ovarian cancer, and retreatment with this drug
may produce valuable responses that
translate into improvement in quality of life.
• However, the likelihood of benefit depends on
the interval between the last dose of platinum
and the time of relapse (i.e., the platinum-free
interval, PFI).
In patients with PFI:
• less than 6 months are less likely to respond to
second-line platinum and are often managed
with an alternative agent, (platinum resistant)
• between 6 and 24 months have an approximately
30% chance of benefit from second-line platinum
used at the time of relapse.
• very prolonged PFI (e.g., greater than 2 years),
the response rate with second-line platinum may
be as high as 60% to 70%.
• Patients with a PFI of greater than 6 months
are referred to as potentially platinum
sensitive and are often treated with either
single-agent platinum or a combination of
platinum with another agent such as paclitaxel
or gemcitabine.
• combination chemotherapy compared to
single-agent platinum in the setting of
potentially platinum-sensitive relapse (PFI
greater than 6 months)?
• combination second-line chemotherapy with
regimens like paclitaxel and carboplatin or
gemcitabine and carboplatin are a reasonable
consideration in selected patients who are
potentially platinum sensitive, based on their
PFI.
• since the primary goal of relapse management
is palliation of symptoms, the decision to use
combinations in this setting should be based
on patient age, amount of disease, kinetics of
relapse, and patient preference after a
discussion of the issues
• For older patients who require chemotherapy
for asymptomatic, minimal volume,
potentially platinum-sensitive relapse, it is
reasonable to use single-agent carboplatin as
a first step.
• liposomal doxorubicin is a generally welltolerated alternative if there is a contraindication
to the use of carboplatin, if carboplatin fails to
induce a response, or if an allergic reaction
develops to carboplatin that precludes further
administration.
• With either single-agent carboplatin or liposomal
doxorubicin, patients have minimal problems
with alopecia or myelosuppression, and their
quality of life is generally well preserved.
• For younger patients who wish to adopt an
aggressive approach to the management of
potentially platinum-sensitive relapse,
combination chemotherapy with either
paclitaxel and carboplatin or gemcitabine and
carboplatin is reasonable.
aggressive approach
• This is especially the case for the symptomatic patient
with kinetically brisk relapse, or the patient who has
undergone a successful secondary cytoreduction after
a very long PFI.
• Some physicians prefer the use of gemcitabine and
carboplatin in this setting if there is persistent
peripheral neuropathy related to first-line therapy.
• Given concerns over toxicity, the decision to use
combination chemotherapy for patients with
potentially platinum-sensitive relapse should be
individualized.
• There are currently no data supporting a role
for combination chemotherapy regimens in
the management of patients with platinumresistant relapse.
• Patients who are platinum resistant, as defined
by a short PFI of less than 6 months or
progression during platinum-based
chemotherapy, or those who tolerate second-line
platinum poorly are typically treated with a
variety of single agents. Potentially non “crossresistant drugs with activity in the platinumresistant setting include liposomal doxorubicin,
paclitaxel, docetaxel, topotecan, gemcitabine, or
oral etoposide.
• Liposomal doxorubicin is often well tolerated in
doses of 40 mg/m2 given every 4 weeks, although
the development of palmer-planar
erythrodysesthesia (hand-foot syndrome) or
mucositis may require dose reductions and
treatment delays.
• Topotecan may cause significant
myelosuppression and fatigue, although this
agent is generally well tolerated through the use
of weekly dosing schedules
• Unfortunately, the likelihood of obtaining a
response to any of these agents in the
platinum-resistant setting is less than 20%,
responses are generally short lived (median
PFS in the range of 4 to 6 months), and they
tend to become progressively shorter with
each subsequent regimen.
• Bevacizumab
• Randomized data in metastatic colorectal, breast, and
lung cancers have shown a survival advantage for the
use of this drug in combination with chemotherapy.
• As a single agent, bevacizumab has been shown by the
GOG to induce responses in 18% of patients with
relapsed ovarian cancer (either platinum sensitive or
platinum resistant, treated with less than or equal to
two prior regimens), with 39% of patients progressionfree at 6 months.
• the risk of bowel perforation with
bevacizumab in the recurrent ovarian cancer
setting might be related to a higher number of
prior treatment regimens, radiographic
evidence of bowel wall involvement , or bowel
obstruction These and other possible risk
factors for this complication will require
further evaluation.
No approved
•
•
•
•
ET743 (trabectedin)
halichondrin B
pertuzumab
Epothilones
Secondary cytoreductive surgery
• an attempt at surgical debulking of disease at the
time of relapse and is performed in selected patients
prior to the administration of second-line
chemotherapy.
• a successful secondary cytoreduction: no gross
residual disease greater than 1 cm in diameter,
• However, it is possible that the ability to perform a
successful secondary cytoreduction may simply
identify those patients with biologically less
aggressive disease or those with a lower tumor
burden at the time of relapse.
Secondary cytoreductive surgery
•
relapse within 12 months after completion of
first-line therapy, especially if they have ascites,
are generally not candidates for this procedure.
1. late relapses (i.e., greater than 2 to 3 years after
finishing chemotherapy)
2. apparently isolated relapses
may experience a prolonged disease-free interval
after successful secondary cytoreduction
followed by additional chemotherapy.
Combination Chemotherapy1519
cervix 4b
• Most reports of combination chemotherapy for carcinoma of the
cervix have described small, uncontrolled phase II trials of drug
combinations. However, the results of two phase III randomized
trials, published in 2004 and 2005, have provided the first solid
evidence that combination chemotherapy can improve both
progression-free survival (cisplatin plus paclitaxel vs. single-agent
cisplatin,272 cisplatin plus topotecan vs. single-agent cisplatin273)
and overall survival (cisplatin plus topotecan273) when it is
administered as treatment for recurrent or metastatic carcinoma
of the cervix. In the cisplatin-topotecan trial, the combination
regimen (cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days
1 to 3 every 3 weeks) was associated with a median overall survival
of 9.4 months, compared with 6.5 months (P = .17) for single-agent
cisplatin.273 An ongoing GOG phase 3 trial is directly comparing
several platinum-based combination chemotherapy regimens in this
clinical setting.
Management of Recurrent
Disease1582ovary relapse
• Two randomized trials have investigated the value of combination
chemotherapy compared to single-agent platinum in the setting of
potentially platinum-sensitive relapse (PFI greater than 6 months). The
ICON-4 trial compared combination chemotherapy with paclitaxel and
platinum to single-agent platinum in patients with potentially platinumsensitive disease, with most patients having a PFI of 12 months or
greater.111 This study demonstrated a statistically significant improvement
in overall survival for the combination regimen, with an absolute
difference at 2 years of 7% (P = .023). However, 58% of patients in the
single-agent platinum arm never received a taxane as part of first-line
therapy, and 69% of patients in the single-agent platinum arm never
received a taxane as part of relapse management (i.e., after progression
on single-agent platinum). Thus, 40% of patients in the single-agent
platinum arm never received a taxane at any point during the course of
their disease. Given the proven survival benefit of taxanes in this disease,
the imbalance in the use of taxanes between these two treatment arms
makes the results of ICON-4 difficult to interpret.
Palliative surgery
• colostomy
• lysis of adhesions
• management of small bowel obstruction
surgery
gastrostomy tube
• Surgery generally plays no role in
management of patients with a pseudoobstructive pattern due to intra-abdominal
carcinomatosis, with infiltration of the
myoenteric plexus of the small bowel.
TX :Metoclopramide
Radiation Therapy
• A minority of patients with localized
recurrences may experience prolonged
survival after WAR or limited-field irradiation.
RT?
• The small number of highly selected patients
in these series and the use of multiple
concurrent treatment modalities make it
difficult to adequately assess whether
radiation therapy truly improves long-term
outcome in this setting.
palliation
• Symptoms from a growing pelvic mass can cause pain,
bleeding, and rectal narrowing.
• Palliative pelvic radiotherapy can provide rapid relief
and, in some cases, may prevent or delay the need for
diverting colostomy. Doses of 8 to 10 Gy in a single
fraction, 20 Gy in five fractions, 30 Gy in ten fractions,
or higher total doses given in smaller fractions have
produced acceptable short-term results, with serious
complications in 5% or fewer patients.
• Finally, patients with epithelial ovarian cancer may
rarely develop isolated cerebral or bone metastases
that can sometimes be successfully palliated with
radiotherapy.
Borderline Tumors
Definition and Clinical Features
•
•
•
•
absence of stromal invasion
low malignant potential (LMP
serosal implants
majority of patients present with early stage
disease
• The median age : 40 years, 20 years younger
than the median age for women with
epithelial ovarian cancer.
• asymptomatic mass
• pelvic pain
• Nonspecific GI symptoms
• serous feature:
more common
bilateral in 10% to 20%
• mucinous feature
larger than their serous counterparts
infrequently bilateral,
pseudomyxoma peritonei
• pseudomyxoma peritonei
1. mucinous borderline ovarian tumor
2. mucinous ovarian carcinoma
3. gastrointestinal tumors such as appendiceal
mucinous cystadenocarcinoma.
The mainstay of treatment for pseudomyxoma
peritonei is intermittent surgery
• careful examination of the tissue blocks
• The presence of microinvasion
• Mucinous borderline tumors are characterized
by multiloculated cystic masses, with smooth
outer surfaces and areas of papulations and
solid thickening on the inner surface
• Greater than 90% of patients with early stage
borderline tumors are alive at 10 years
• more than 50% of patients with advanced
disease experience long-term survival.
• survival does not appear to be improved by
postoperative adjuvant treatment with either
chemotherapy or radiation
• borderline serous tumors may behave more
aggressively if they are associated with
micropapillary features, and/or invasive
implants elsewhere in the peritoneal cavity.
• Patients with serous borderline tumors
without invasive implants have expected 10year survival rates of greater than 95%,
whereas those with serous borderline tumors
and invasive implants have survival rates of
approximately 60% to 70% at 10 years.
• Thus, it is possible that micropapillary features
portend a poorer prognosis because of their
association with invasive implants, although
this is still an area of controversy.
Surgical Management
• TAH, BSO, tumor debulking, and full staging
• Conservative surgery
An appendectomy is considered in patients
with suspected mucinous borderline tumors
because of its occasional association with a
primary appendiceal carcinoma.
Conservative surgery
• with preservation of the uterus, the contralateral
ovary and fallopian tube, and in some cases the
ipsilateral ovary (i.e., cystectomy)
One of the largest studies found a 12% recurrence
rate for patients treated conservatively compared
to 2.5% for TAH, BSO.
Recurrences or progression to carcinoma (1.5%)
were more common among patients with
invasive implants or advanced-stage disease.
• Borderline ovarian tumors during pregnancy.
Postoperative Management
• Without adjuvant therapy, long-term survival is
generally excellent
• simple observation with serial examinations, with
radiographic studies as needed to investigate new
symptoms or findings on examination.
• long-term follow-up
• Surgery is the mainstay of treating recurrent disease
• Tx multiple recurrences : HT(as tamoxifen )
• CHT
Germ Cell Tumors of the Ovary
Definition and Clinical Features
• 2% to 3% of all ovarian cancers
• in younger women( early 20s)
• It is often possible to cure these malignancies
while preserving fertility,
WHO classification for germ cell tumors of the ovary
• Dysgerminoma(male seminoma )
• Nondysgerminoma
Endodermal sinus tumor (AFP)
Embryonal carcinoma(both AFP and HCG elevation)
Polyembryoma
Choriocarcinoma(HCG)
Immature teratoma
Mature dermoid cyst with malignant transformation
Monodermal and highly specialized
Struma ovarii
Carcinoid
Struma ovarii and carcinoid
Others
Mixed forms
• Abdominal pain,
abdominal pain can be severe(hemorrhage,
rupture, or ovarian torsion)
• distension,
• pelvic fullness,
• urinary symptoms
rapid growth
palpable adnexal mass
TVU, which may show a complex cyst
comprised of solid and cystic region
(AFP)
(HCG)
• Pure immature teratoma : normal levels of
AFP and HCG, although the AFP may be
elevated in 30% of cases.
• Mature cystic teratoma (dermoid cyst), a
benign germ cell tumor, usually have normal
levels of AFP and HCG.
• choriocarcinoma
hyperthyroidism
• mature cystic teratoma
hyperthyroidism
a Coomb's positive hemolytic anemia
Germ cell tumors
• 60% to 70% are stage I at diagnosis
• Stages II and IV tumors are relatively
uncommon
• stage III disease accounts for about 25% to
30% of tumors.
• Bilateral ovarian involvement
dysgerminoma and mature cystic teratoma may
be bilateral in 10% to 15% of cases
• More advanced disease may involve
retroperitoneal lymph nodes and multiple
peritoneal surfaces, although ascites is
infrequent.
• Hematogenous spread to the liver, lung, and
brain can be observed, especially with
choriocarcinoma
Surgical Management
‫برداشت یک تخمدان‬.1
‫برداشت یک تخمدان و سیستکتومی یا بیوپسی تخمدان دیگر‬.2
‫درمان روتین‬.3
second-look operations
In some patients whose tumor contains
teratomatous elements, however, a secondlook procedure may be beneficial
Postoperative Management of Dysgerminoma
• stage IA disease can be observed without further
postoperative treatment.
Approximately 15% to 25% of such patients will
experience recurrence, although salvage
chemotherapy is almost always successful
• Dysgerminoma in patients with higher than stage IA
disease is typically treated with platinum-based
chemotherapy
PVB ,BEP
Postoperative Management of
Nondysgerminoma
Tx:
Surgery followed by combination chemotherapy,
as even patients with early stage
nondysgerminomas have a significant risk of
relapse that can be reduced by postoperative
adjuvant therapy
Current regimen of choice is BEP
 Toxicities
bleomycin-induced pulmonary damage
etoposide-induced leukemia,
platinum-induced neuropathy and nephropathy.
 Many patients will regain fertility after
completion of treatment
 However, patients are known to be at increased
risk for development of premature menopause
following chemotherapy.
• In pure immature teratoma with stage IA,
grade 1 (5-ys :90%), there is no evidence to
suggest that CHT improves outcome
• Patients with stage IA, grade 2 and 3
immature teratoma have a higher relapse rate
that generally warrants consideration of
postoperative chemotherapy
• The Children's Oncology Group (COG) is
currently studying the approach of surgery
followed by surveillance in patients with stage
I germ cell tumors of the ovary. Although this
strategy appears to be potentially promising,
further study, particularly in adult patients, is
warranted to ensure its safety and efficacy
Sex Cord-Stromal Tumors
Definition and Clinical Features
• Patients often present with stage I disease
• long-term follow-up
• Granulosa cell tumors are the most common
type
Sex cord-stromal tumors such as granulosa cell
tumors may secrete:
• Estradiol
• inhibin
• mullerian inhibitory substance
• The hormonal manifestations :
1. precocious puberty
2. amenorrhea or abnormal menses, intraabdominal hemorrhage that mimics an
ectopic pregnancy
3. postmenopausal bleeding due to
endometrial hyperplasia (or a separate
uterine carcinoma)
• Surgical staging of sex cord-stromal tumors is
the same as that for epithelial ovarian cancer.
• Surgical management of sex cord-stromal
tumors is based on the stage of the tumor as
well as the age of the patient.
1. premenarchal women or patients presenting
in the reproductive years with stage I disease
2. In women who have completed childbearing,
Postoperative Management
Stage is the most important prognostic factor,
• 10-year survivals of over 85% for stage I
• 50% to 65% for stage II disease
• 17% to 33% for stages III and IV.
Tx
• stages II to IV sex cord-stromal tumors are
reasonable candidates for additional therapy after
initial surgery,
• although the survival benefit of such therapy has not
been proven
• Approximately 30% to 50% of patients will respond
to platinum-based chemotherapy,
• cyclophosphamide, doxorubicin, and cisplatin
(CAP)
• PVB,
• BEP
• paclitaxel and carboplatin
•
•
•
•
BEP
bleomycin-induced lung damage,
etoposide-induced leukemia
, renal dysfunction, hypertension
Raynaud's phenomenon
• in the older patient
EP (without bleomycin)
• in the young patient
paclitaxel and carboplatin
(S1)Who has higher risk?
• large tumor size (greater than 10 to 15 cm in
diameter)
• high mitotic count (greater than 4 to 10 mitoses
per 10 high-power fields).
• Rupture
• surface involvement
• Age
Relapse
• may recur several years after the original
diagnosis
• abdominal or pelvic discomfort, a mass on
pelvic examination, or an asymptomatic rise in
serum tumor markers such as estradiol or
inhibin
• hematogenous spread to the liver, lung, or
bone
S-CHT or RT
Tx Relapse :
1. surgical resection
2. postoperative therapy such as platinum-based
treatment ,resistant to platinum-based
chemotherapy, in which case single-agent
paclitaxel, or the use of progestational agents or
leuprolide, may be considered.
3. radiotherapy.
In cases in which the recurrence is isolated and can
be encompassed in a radiation field, older
literature suggests that radiation therapy may be
of value for granulosa cell histology.
Primary Peritoneal Serous Carcinoma
• PPSC is a distinct clinical entity that resembles
ovarian cancer histologically, clinically, and in
its response to treatment
• multifocal fashion
• PPSC occurs at a higher incidence in patients
with germline mutations in BRCA1 and BRCA2,
differential diagnosis
1. epithelial ovarian carcinoma
2. metastatic breast cancer(expression of
GCDFP)
3. peritoneal mesothelioma
4. gastric or pancreatic cancers, and
hepatobiliary tumors.
• Dx an exploratory laparotomy is usually
necessary to establish the histologic diagnosis
and to perform tumor cytoreduction.
• almost all patients with PPSC present with
stages III or IV disease.
• Tx are the same as those for epithelial ovarian
cancer.
• Px is likely to be the same, as for epithelial
ovarian cancer.
• There is currently no effective screening
procedure that enables early detection of
PPSC in this clinical setting.
Fallopian Tube Cancer
• papillary serous adenocarcinoma or other
mullerian histologies such as endometrioid
tumors
• A minority are bilateral
• the majority are confined to the tubes and
pelvic structures.
• a higher propensity for retroperitoneal lymph
node spread
• Advanced stage disease may occur with a
pattern of intraperitoneal dissemination
• Postmenopausal vaginal bleeding
• colicky lower abdominal pain
• intermittent abdominal pain and leucorrhea
are common presentations.
• Occasionally, a Papanicolaou smear revealing
abnormal glandular cells with negative
cervical or endometrial findings
DDX
• metastatic ovarian carcinoma
• the main criterion used to establish the
diagnosis of a primary fallopian tube
carcinoma is histologic evidence of a transition
between in situ carcinoma and invasive
malignancy within the fallopian tube
epithelium.
• tubo-ovarian carcinoma.
• Survival is partly dependent on the depth of
invasion of the primary lesion.
• For intramucosal lesions, the 5-year survival is
91%, compared with 53% for tumors that invade
the muscular wall, and less than 25% for tumors
that have penetrated the tubal serosa.
• Histologic differentiation and lymphatic capillary
space involvement may also have prognostic
significance.
surgical management
• identical to that of patients with epithelial
ovarian cancer.
• Postoperatively : paclitaxel and carboplatin in
patients with fallopian tube carcinoma that has
spread beyond the tube.
• reasonable candidates for postoperative adjuvant
treatment, based on features :
muscle wall invasion,
serosal extension,
high-grade histology