Ovarian CancerOvarian Cancer

Deri EdiantoDeri Edianto

Greatest clinical challenge.Greatest clinical challenge.Epithelial are most commonEpithelial are most common

⅔ cases with advanced ⅔ cases with advanced diseasedisease

No screening methodNo screening methodMajor surgical challengeMajor surgical challenge

90% from celomic 90% from celomic epitheliumepithelium

Histologic typing of epithelial Histologic typing of epithelial ovarian carsinoma ovarian carsinoma

Serous type Serous type : 40 – 50%: 40 – 50% Mucinous type Mucinous type : 12 – 15%: 12 – 15% Endometrioid type Endometrioid type : 25%: 25% Clear cellClear cell Malignant BrennerMalignant Brenner Undifferentiated carsinomasUndifferentiated carsinomas

Borderline tumorBorderline tumor

Low malignant potentialLow malignant potential Remain confined to the ovaryRemain confined to the ovary Good prognosisGood prognosis Metastatic implants may occurMetastatic implants may occur

Etiology : ? Etiology : ?

Variety of epidemiologic variablesVariety of epidemiologic variables Low parity and infertilityLow parity and infertility Talc useTalc use : : ↑↑ Tubal ligation :Tubal ligation :↓↓ Oral contraceptive ≥ 5 years :Oral contraceptive ≥ 5 years :↓↓ Genetic ( 5 – 10% )Genetic ( 5 – 10% ) Early menarche and late Early menarche and late

menopausemenopause

Prevention : oral Prevention : oral contraceptivecontraceptive

Screening :Screening : Tumor marker : ?Tumor marker : ? Ultrasonography (transvaginal)Ultrasonography (transvaginal) Gynecologic examinationGynecologic examination

Not cost effectiveNot cost effective

Hereditary ovarian cancerHereditary ovarian cancer

Accounting 5 – 10%Accounting 5 – 10% Most are sporadicMost are sporadic BR CA1 mutation : chromosome 17BR CA1 mutation : chromosome 17 BR CA2 mutation : chromosome 13BR CA2 mutation : chromosome 13 Ovarian and breast cancerOvarian and breast cancer HNPCC (Lynch II)HNPCC (Lynch II) Autosomal dominantAutosomal dominant 10 year younger than sporadic10 year younger than sporadic

Symptom and signSymptom and sign

No symptom for long periodNo symptom for long period Often vague and nonspecificOften vague and nonspecific Mass compressing symptomMass compressing symptom Pelvic mass on physical examinationPelvic mass on physical examination Solid, fixed, irregularSolid, fixed, irregular Ascites Ascites

Diagnosis Diagnosis

Requires an exploratory laparotomyRequires an exploratory laparotomy Frozen sectionFrozen section Paraffin blockParaffin block

Differential diagnosisDifferential diagnosis

Benign neoplasmBenign neoplasm Functional cystFunctional cyst Non gynecologicNon gynecologic

Patterns of spreadPatterns of spread

Cell exfoliationCell exfoliation Peritoneal cavity: tanscelomicPeritoneal cavity: tanscelomic Lymphatic disseminationLymphatic dissemination Hematogenous spreadHematogenous spread

Prognostic factorsPrognostic factors

1. Pathologic1. Pathologichystologic type : clear cellhystologic type : clear cellgradegrade

2. Biologic2. Biologicploidity : aneuploidploidity : aneuploidHER – 2 neu expressionHER – 2 neu expression

3. Clinical3. Clinicalstagestageresidual massresidual massageage

Staging Staging

II Tumor confined to the ovariesTumor confined to the ovaries IAIA tumor limited to one ovary, capsule intact . No tumor limited to one ovary, capsule intact . No

tumor tumor on ovarian surface. No malignant cells in on ovarian surface. No malignant cells in the ascites or the ascites or peritoneal washing.peritoneal washing.

IBIB tumor limited to the both ovaries, capsule intact. tumor limited to the both ovaries, capsule intact. No No tumor on ovarian surface. No malignant tumor on ovarian surface. No malignant cells in the cells in the ascites or peritoneal washing.ascites or peritoneal washing.

ICIC tumor limited to one or both ovaries, with any of tumor limited to one or both ovaries, with any of following: capsule rupture, tumor on following: capsule rupture, tumor on

ovarian surface, ovarian surface, positive malignant cells in positive malignant cells in the ascites or peritoneal the ascites or peritoneal washing.washing.

IIII Tumor involve one or both ovaries with pelvic Tumor involve one or both ovaries with pelvic extension.extension. IIAIIA extension and/or implants in uterus and/or tube. extension and/or implants in uterus and/or tube.

No No malignant cells in the ascites or peritoneal malignant cells in the ascites or peritoneal washing.washing.

IIBIIB extension to other pelvic organ. No malignant extension to other pelvic organ. No malignant cells in cells in the ascites or peritoneal washing.the ascites or peritoneal washing.

IICIIC IIA/B with positive malignant cells in the ascites IIA/B with positive malignant cells in the ascites oror peritoneal washing peritoneal washing

Staging Staging

III III Tumor involve one or both ovaries with Tumor involve one or both ovaries with microscopically confirmed peritoneal microscopically confirmed peritoneal

metastasis metastasis outside the pelvic and /or regional outside the pelvic and /or regional lymph node lymph node metastasismetastasis IIIAIIIA microscopic peritoneal metastasis beyond the microscopic peritoneal metastasis beyond the

pelvispelvis IIIBIIIB macroscopic peritoneal metastasis beyond the macroscopic peritoneal metastasis beyond the

pelvis pelvis 2cm or less in greatest dimension2cm or less in greatest dimension IIICIIIC peritoneal metastasis beyond pelvis more than 2 peritoneal metastasis beyond pelvis more than 2

cm in cm in greatest dimension and/or regional lymph greatest dimension and/or regional lymph node node metastasismetastasis

IVIV Distant metastasis beyond the peritoneal Distant metastasis beyond the peritoneal cavitycavity

Surgery Surgery

StagingStaging Fluid : cytologic examinationFluid : cytologic examination Peritoneal washingPeritoneal washing Systematic abdominal explorationSystematic abdominal exploration Biopsy at any suspicious areasBiopsy at any suspicious areas Omentum resectionOmentum resection Lymph node evaluationLymph node evaluation TAH + BSOTAH + BSO Conservative : I A + preserve fertilityConservative : I A + preserve fertility Debulking or cytoreductive surgeryDebulking or cytoreductive surgery

Rationale for cytoreductiveRationale for cytoreductive

Physiologic benefitPhysiologic benefit Improve tumor perfusionImprove tumor perfusion Increase growth fractionIncrease growth fraction Enhance immunologicEnhance immunologic

Physiologic benefitPhysiologic benefit

Reduce ascites volumeReduce ascites volume Alleviate nausea and satietyAlleviate nausea and satiety Restore intestinal functionRestore intestinal function Improve nutritional statusImprove nutritional status

Tumor perfusionTumor perfusion

Bulky tumor : poor Bulky tumor : poor vascularisationvascularisation

Chemotherapy concentration Chemotherapy concentration ↓↓ Poorly oxygenatedPoorly oxygenated

Growth fractionGrowth fraction

Non dividing / resting phase (G0)Non dividing / resting phase (G0) Resistant to the therapyResistant to the therapy Fractional cell kill hypothesisFractional cell kill hypothesis

Immunologic Immunologic

Large mass Large mass → immunosuppressive→ immunosuppressive Host defense mechanism ↓Host defense mechanism ↓ Cytotoxic lymphocyte ↓Cytotoxic lymphocyte ↓

Adjuvant therapyAdjuvant therapy

No adjuvantNo adjuvant ChemotherapyChemotherapy RadiationRadiation HormonalHormonal Immunotherapy Immunotherapy

No adjuvantNo adjuvant

Stage I A grade 1Stage I A grade 1 Stage I A – I B grade 1 & 2Stage I A – I B grade 1 & 2 Non high riskNon high risk

Chemotherapy Chemotherapy

High riskHigh risk CombinationCombination Cisplatin baseCisplatin base Cisplatin + paclitaxelCisplatin + paclitaxel IntravenousIntravenous Intraperitoneal : ?Intraperitoneal : ? NeoadjuvantNeoadjuvant Interval debulkingInterval debulking

Radiation Radiation

Whole abdomenWhole abdomen Some institution in CanadaSome institution in Canada Not been tested against Not been tested against

chemotherapychemotherapy

Hormonal Hormonal

Not appropriate as primary therapyNot appropriate as primary therapy Progestional agentProgestional agent Recurrent caseRecurrent case For : well differentiated endometrioidFor : well differentiated endometrioid (+) ve estrogen receptor (+) ve estrogen receptor

Immunotherapy Immunotherapy

Various trialVarious trial Corynebacterium parvumCorynebacterium parvum Bacillus Calmette – Guerin (BCG)Bacillus Calmette – Guerin (BCG) Conjunction with cytotoxic chemotherapyConjunction with cytotoxic chemotherapy Benefit : ?Benefit : ? Cytokine, interferon, interleukinCytokine, interferon, interleukin Monoclonal directed antibodyMonoclonal directed antibody Herceptin : HER – 2 / neuHerceptin : HER – 2 / neu

Nonephitelial ovarian andNonephitelial ovarian and Fallopian tube cancer Fallopian tube cancer

Uncommon (Uncommon (± 10%)± 10%) Germ cell originGerm cell origin Sex cord – stromal originSex cord – stromal origin Metastasis carcinomaMetastasis carcinoma SarcomaSarcoma Fallopian tube carcinomaFallopian tube carcinoma

Histologic typing of ovarian germ cell tumorsHistologic typing of ovarian germ cell tumors DysgerminomaDysgerminoma TeratomaTeratoma

A. matureA. mature B. immatureB. immature

solidsolid CysticCystic

Dermoid cyst (mature cystic teratoma)Dermoid cyst (mature cystic teratoma) Dermoid cyst with malignant transformationDermoid cyst with malignant transformation

C. monodermal and highly specializedC. monodermal and highly specialized Struma ovariiStruma ovarii CarcinoidCarcinoid Struma ovarii and carsinoidStruma ovarii and carsinoid OthersOthers

Endodermal sinus tumorEndodermal sinus tumor Embryonal carcinomaEmbryonal carcinoma Polyembrioma Polyembrioma Choriocarsinoma Choriocarsinoma Mixed formMixed form

Epidemiology Epidemiology

Only 10% are malignantOnly 10% are malignant More frequent in Asian and black More frequent in Asian and black

womenwomen First two decade of lifeFirst two decade of life

Symptom and signSymptom and sign

Grow rapidly (than epithelial)Grow rapidly (than epithelial) Hemorrhage and necrosisHemorrhage and necrosis Pressure symptom to Pressure symptom to

bladder/rectumbladder/rectum May torsion or ruptureMay torsion or rupture Palpable adnexal massPalpable adnexal mass Ascites at advanced casesAscites at advanced cases

Diagnosis Diagnosis

Premenarchal girl : Premenarchal girl : ≥ 2 cm≥ 2 cm Premenopausal : ≥ 8 cmPremenopausal : ≥ 8 cm Tumor marker : hCG & AFPTumor marker : hCG & AFP Karyotype evaluation (dysgenetic Karyotype evaluation (dysgenetic

gonad = Y chromosome) gonad = Y chromosome)

Dysgerminoma Dysgerminoma

Most common germ malignantMost common germ malignant Younger age (10 – 30 years)Younger age (10 – 30 years) Rarely after 50 yearsRarely after 50 years Always in stage IAlways in stage I Young women : complete surgery ?Young women : complete surgery ? Conservative surgeryConservative surgery Chemo and radiosensitiveChemo and radiosensitive With Y chromosome : BSOWith Y chromosome : BSO

Radiation Radiation

Very sensitiveVery sensitive 2.500 – 3.500 cGy2.500 – 3.500 cGy Loss of fertilityLoss of fertility Rarely use as first line therapyRarely use as first line therapy

Chemotherapy Chemotherapy

The treatment of choiceThe treatment of choice Preservation of fertilityPreservation of fertility Cisplatin based combinationCisplatin based combination

Recurrent diseaseRecurrent disease

Most in the first yearMost in the first year Depend on first treatmentDepend on first treatment Chemo or radiationChemo or radiation Relaparotomy : later Relaparotomy : later

Immature teratomasImmature teratomas

Resemble tissue derived from Resemble tissue derived from embryoembryo

Combination with other germ cellCombination with other germ cell Malignant transformation from Malignant transformation from

mature teratoma is raremature teratoma is rare Usually unilateralUsually unilateral

Diagnosis Diagnosis

Same as other germ cellSame as other germ cell

Treatment Treatment

SurgerySurgery Fertility preserve : conservative Fertility preserve : conservative

surgerysurgery No fertility need : complete surgicalNo fertility need : complete surgical Chemotherapy : initiated a s a pChemotherapy : initiated a s a p Except : stage IA grade 1Except : stage IA grade 1 Radiation : not as primary treatmentRadiation : not as primary treatment

Endodermal sinus tumor Endodermal sinus tumor (EST)(EST)

Referred as yolk sac Referred as yolk sac carsinomascarsinomas

Derived from primitive yolk sacDerived from primitive yolk sac Abdominal / pelvic painAbdominal / pelvic pain Most secrete AFPMost secrete AFP

Treament Treament

SurgerySurgery Fertility can be preservedFertility can be preserved Chemotherapy : all patientsChemotherapy : all patients

Embryonal carsinomaEmbryonal carsinoma

Extremely rare tumorExtremely rare tumor Very young ( 4 – 20 years)Very young ( 4 – 20 years) May secrete estrogen : May secrete estrogen :

pseudopubertypseudopuberty Frequently secrete AFP and hCGFrequently secrete AFP and hCG Treatment : same as for ESTTreatment : same as for EST

Choriocarsinoma of the Choriocarsinoma of the ovaryovary

Pure non gestationalPure non gestational Extremely rareExtremely rare Secrete hCGSecrete hCG Chemotherapy same as Chemotherapy same as

gestationalgestational

Sex cord – stromal tumorsSex cord – stromal tumors

Derived from sex cord and ovarian Derived from sex cord and ovarian stromastroma

Composed various combinationComposed various combination Female cells : granulosa and theca Female cells : granulosa and theca

cellcell Male cells : Sertoli and LeydigMale cells : Sertoli and Leydig

Treatment Treatment

SurgerySurgery Chemo and radiation : ?Chemo and radiation : ?

Fallopian tube cancerFallopian tube cancer

Only 0,3% of female genital tumorOnly 0,3% of female genital tumor Feature and behavior = ovarian Feature and behavior = ovarian

cancercancer Exclusively or predominantly involve Exclusively or predominantly involve

the fallopian tubethe fallopian tube Treatment = epithelial ovarian Treatment = epithelial ovarian

cancercancer