Endometrial Docu Cleaned

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Endometrial &

Ovarian CancerEndometrial &Ovarian Cancer

Karen A. Zempolich, M.D.Karen A. Zempolich, M.D.Division of GynecologicOncology, Division of

Gynecologic Oncology,Dept. of Obstetrics &Gynecology Dept. ofObstetrics & GynecologyUniversity of Utah Universityof UtahHuntsman Cancer InstituteHuntsman Cancer Institute


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Endometrial &

Ovarian CancerEndometrial &Ovarian Cancer

Overview Overview EpidemiologyEpidemiology Signs & symptoms Signs

& symptoms Management / outcomeManagement / outcome When to refer to a sub

When to refer to a sub-specialist specialist


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Follow Follow-upsurveillance upsurveillance

EndometrialCancer

EndometrialCancerEpidemiology

Epidemiology 36,000 cases/yr; 6,500deaths 36,000 cases/yr;6,500 deaths

4th most commoncancer in women 4th mostcommon cancer in women


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(breast, lung, colon) (breast,lung, colon)

75% postmenopausal(avg. age 58 y.o.) 75%postmenopausal (avg. age58 y.o.)

5% cases: < 40 yearsold 5% cases: < 40 yearsold

EndometrialCancerEndometrialCancer


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Risk Factors Risk

Factors - DeleteriousDeleteriousRelative Risk Relative RiskObesity Obesity 2-11 11

Family history Familyhistory 1.5 1.5-2.8 2.8Nulliparity Nulliparity 3Infertility ( Infertility

(>3yrs) 3yrs) 3Endogenous estrogensEndogenous estrogens 1.51.5 - 4

Estrogen Estrogen-secretingtumors secreting tumors


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Unopposed exogenousestrogens Unopposedexogenous estrogens 2 -12 12Diabetes Diabetes 2 - 1010

TamoxifenTamoxifen 2 - 7

EndometrialCancer

EndometrialCancerRisk Factors Risk

Factors - ProtectiveProtective


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Oral contraceptives (1Oral contraceptives (1-5years) 5 years) 0.3 0.3-0.50.5 Cigarette smokingCigarette smoking 0.4

0.4-.08 .08 Parity Parity 0.3 0.3-0.50.5

EndometrialCancerEndometrialCancer-- --RiskFactors Risk Factors


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Hereditary HereditaryNonpolyposisNonpolyposis ColorectalCancer Colorectal Cancer 5% of colorectal cancers5% of colorectal cancers Mutations in DNAmismatch repair genesMutations in DNAmismatch repair genes

Lifetime Lifetime risk ofdeveloping: risk ofdeveloping: Colorectal cancer 80%

Colorectal cancer 80% Endometrial cancer 40%Endometrial cancer 40%


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Ovarian cancer 10%Ovarian cancer 10%

Other GI cancer 20%Other GI cancer 20%

Endometrial

CancerEndometrialCancerCarcinogenesisCarcinogenesis Precancerous LesionsPrecancerous Lesions

Hyperplasia HyperplasiaProgression to CancerProgression to Cancer


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Simple Simple 1% 1%Complex Complex 3% 3%Simple, atypical Simple,atypical 8% 8%Complex, atypicalComplex, atypical 29%

29%Kurman, 1985

EndometrialCancerEndometrialCancerSymptomsSymptoms


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Postmenopausalbleeding Postmenopausalbleeding Present in > 90%menopausal cases ofPresentin > 90% menopausal cases

ofendometrial cancerendometrial cancer 20% patients with PMB 20%patients with PMB

malignancy malignancy 5% patients with PMB 5%patients with PMB endoendo hyperplasia hyperplasia

PremenopausalPremenopausal patients


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patients abnormaluterine abnormal uterinebleeding bleeding

EndometrialCancer

EndometrialCancerSigns Signs

Most exams are normalMost exams are normal May have: May have: enlarged uterus enlarged

uterus Peripheral Peripheraladenopathy adenopathy Ascites Ascites


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vaginal vaginal mets mets adnexal adnexal mass mass

cul cul-de de-sac sacnodularity nodularity

EndometrialCancerEndometrialCancerDiagnosis Diagnosis Pap Smear PapSmearIn patients with

endometrial cancer: Inpatients with endometrialcancer:


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40 40-50% suspicious50% suspicious endo endocells on Pap cells on Pap 2-5% normalendometrial cells 5%normal endometrial cellsMontz 2001, Win 2001, Ashfag 2001, Sarode2001

EndometrialCancer

EndometrialCancerDiagnosis Diagnosis

Pap Smear PapSmear


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Postmenopausal women withnormal Postmenopausal

women with normal endoendo cells on cells onpap: pap: 20 20-40% pathology 40%pathology Polyps Polyps Hyperplasia 10 Hyperplasia 10-15% 15% Cancer 1 Cancer 1-5% 5%

2-5% asymptomatic 5%

asymptomatic pts with normalendometrial pts with normalendometrialcells: cells: cancer cancerMontz 2001, Win 2001, Ashfag 2001, Sarode 2001

EndometrialCancer


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Endometrial

CancerDiagnosis DiagnosisBiopsy Biopsy Inpatient (operative)dilation and curettageInpatient (operative)dilation and curettage(fractional) (fractional) Outpatient endometrialbiopsy Outpatientendometrial biopsy Pipelle Pipelle

Vabra Vabra, Novak , Novak


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Endometrial

CancerEndometrialCancer

Diagnosis Diagnosis Endometrial BiopsyEndometrial Biopsy MetaanalysisMetaanalysis 39studies (5 prospect) 39studies (5 prospect)

Office Office bx bxcompared to D&C, comparedto D&C, hyst hyst, or both , orboth


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Cancer: Cancer:Sensitivity Sensitivity 68to 81% 68 to 81%Specificity Specificity 99.6to 99.9% 99.6 to 99.9% Hyperplasia HyperplasiaSensitivity Sensitivity 75%75%Specificity Specificity 99%99%Dijkhuizen et al. Cancer 2000

Garnti JAAGL 2001

Endometrial

Cancer


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Endometrial

CancerHysteroscopyHysteroscopy -

CAVEAT CAVEATTranstubalTranstubalspread ofspread ofendoendo cells cells

Obermaier Obermaier etal et al (Cancer 2000) (Cancer 2000) 113 pts 113 ptsHSC/D&C HSC/D&C vs vs D&Calone D&C alone

12% 12% vs vs 2.5% pos.peritoneal cytology (p


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2.5% pos. peritoneal cytology(p


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Endometrial


Diagnosis DiagnosisTransvaginal

Transvaginal

UltrasoundUltrasound MetaanalysisMetaanalysis TVUS &

office biopsyTVUS &office biopsy


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Endometrial thicknessEndometrial thickness


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High High negativepredictive value (99%)negative predictive value(99%)Smith-Bindman JAMA 1998Langer, NEJM 1997

EndometrialCancerEndometrial

CancerDiagnosis Diagnosis -Summary Summary Office endometrial

biopsy Office endometrialbiopsy preferredpreferred


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method method Accurate, convenient

Accurate, convenientTV U/STV U/S caneffectively r/o disease ifcan effectively r/o disease

if


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Endometrial


Surgical SurgicalStaging StagingStage I Stage I UterusUterus (75 to 80%) (75 to

80%)A. A. endometriumendometriumB. B. myometriummyometrium


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Stage II Stage II CervixCervix (6 to 10%) (6 to10%)A. A. glands glandsB. B. stroma stroma


CancerSurgical SurgicalStaging StagingStage III Stage III

Extrauterine Extrauterine(8%) (8%)


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A. A. serosa serosa, ,adnexa adnexa, peritonealcytology , peritonealcytologyB. B. vagina, pelvicperitoneum vagina, pelvic

peritoneumC. C. lymph nodes(pelvic/abdominal) lymphnodes (pelvic/abdominal)

Stage IV Stage IV DistantDistant (5%) (5%)A. A. bowel/bladdermucosa bowel/bladder

mucosaB. B. intraabdominalintraabdominal, inguinal


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nodes, extra , inguinalnodes, extraabdominal abdominal

EndometrialCancer

EndometrialCancer

Treatment

Treatment----Surgery Surgery Hysterectomy /Hysterectomy /

salpingoophorectomysalpingoophorectomy (BSO)(BSO)


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If clinical cervicalinvolvement: If clinical

cervical involvement: Radical Radical hyst hystvs vs preop preop radiationradiation

Staging Staging selectedpatients selected patients Peritoneal cytologyPeritoneal cytology Lymph node dissection

Lymph node dissection Omentectomy Omentectomy(papillary serous/clear cellhistology) (papillary

serous/clear cell histology)EndometrialCancer


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Endometrial

CancerTreatmentTreatmentSurgery

2005 Surgery 2005 Increased role forIncreased role forlaparoscopic laparoscopic

staging staging LAVH/ BSO, staging ifindicated LAVH/ BSO, stagingif indicated Regardless of age, body

mass index Regardless of age,body mass index


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75 to 95% have full stagingby LSC 75 to 95% have full

staging by LSC Conversion to open lap forobesity, Conversion to openlap for obesity,intraperitoneal intraperitonealcancer, bleeding cancer,bleeding

Endometrial


TreatmentTreatmentSurgery2005 Surgery 2005


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LaparoscopicLaparoscopic hyst hyst/BSO/ staging / BSO/staging Equal node count Equalnode count

Equal survival Equal survival Decreased length of stayDecreased length of stay Longer OR time (230 minLonger OR time (230 min vs

vs 150 min) 150 min) Shorter delay for radiation (ifindicated) Shorter delay forradiation (if indicated)

EndometrialCancer


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Endometrial

CancerStaging Staging Patient Selection

Patient SelectionRisk of pelvic lymph nodeRisk of pelvic lymph node grade, depth ofgrade,

depth ofinvasion invasionDepth Depth G1 G1 G2 G2G3 G3EndometriumEndometrium 03


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0Inner 1/3 Inner 1/3 3 5 9Middle 1/3 Middle 1/3 0 94Outer 1/3 Outer 1/3 11 1119 19 34% 34%Creasman 1987

EndometrialCancer

EndometrialCancerStaging Staging

Patient SelectionPatient Selection


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Risk of lymph node Risk oflymph node tumorlocationPelvic LN Aortic LNFundus 8% 4%Isthmus

cervix 16% 14%Creasman 1987

EndometrialCancerEndometrialCancer - StagingStagingPatient SelectionPatient Selection


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Pre Pre-op Prediction

? op Prediction ? Grade 1 lesion Grade 1lesion 1 in 3 1 in 3 willrequire staging will

require staging 10 to 15% : outer 10 to15% : outer invasioninvasion 10% : isthmus / cervix

involvement 10% : isthmus /cervix involvement 20% upgraded 20%upgraded intraop intraop

EndocervicalEndocervical curettagecurettage


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10% false negative rate 10%false negative rate

High false positive (80 Highfalse positive (80-90%), unless90%), unless stromal stromalinvasion seen invasion seen


Cancer - StagingStagingPatient Selection

Patient Selection Pre Pre-op


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Prediction? op

Prediction?TransvaginalTransvaginalultrasound/MRI

ultrasound/MRI 80% accurate: 80%accurate: myometrialmyometrial invasion invasion 33% accurate: cervix /

isthmus involvement 33%accurate: cervix / isthmusinvolvement

Therefore: no good

Therefore: no good preoppreop predictor of needpredictor of need


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for staging for staging

PostoperativeTreatmentPostoperative

Treatment

Stage I ControversyStage I Controversy Intermediate risk (5

Intermediate risk (5-10%recur) 10% recur) Grade 1 or 2 with: Grade 1or 2 with: Middle 1/3 Middle 1/3

myoinvasion myoinvasion orcervix / isthmus or cervix /isthmus


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High risk (>10% recur)High risk (>10% recur) Grade 3 or outer 1/3invasion Grade 3 or outer 1/3invasion

?? ?? whole pelvis

radiation vs. whole pelvisradiation vs.vaginal vaginalbrachytherapy

brachytherapy vs. vs.surgery alone surgeryalone ?? ??

Endometrial

Cancer


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Endometrial

CancerStage I ControversyStage I Controversy--

--RadiationRadiation GOG 99 GOG 99 Stage IB Stage IB-II, 390 pts

II, 390 ptsTAH/BSO/LNDTAH/BSO/LND pelvic pelvic rad rad or noor no rad rad Decreased Decreased pelvic

recurrence (12% pelvicrecurrence (12% vs vs 1.7 %1.7 % )


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Improved Improved diseasefree survival (94% disease

free survival (94% vs vs 85% )85% ) No difference No differencein overall survival in overallsurvival

EndometrialCancerEndometrialCancerStage I ControversyStage I Controversy--

--RadiationRadiation


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GOG 99 GOG 99morecontroversy! morecontroversy! Final analysis only reported2 yr survival data Finalanalysis only reported 2 yr

survival data Only 20% pts high risk(outer 1/3, Only 20% pts highrisk (outer 1/3, Gr Gr 3) 3)


CancerStage I ControversyStage I Controversy--


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--Radiation

Radiation PORTEC: PORTEC: 715pts 715 pts Stage IB Stage IB Gr Gr 2,3 ,

IC 2,3 , IC Gr Gr 2TAH / BSOTAH / BSO pelvic pelvic rad rad or no orno rad rad Decreased Decreased pelvicrecurrence (14% pelvicrecurrence (14% 4%) 4%) No difference No differencein survival in survival

BUT BUT: Excluded IC, :Excluded IC, Gr Gr 3


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Endometrial


Stage I ControversyStage I ControversyRadiation Radiation Vaginal Vaginal

Brachytherapy Brachytherapy(post op) (post op) 18 to 22 18 to 22 Gy Gy Decreases vaginalrecurrence 12% to 2%

Decreases vaginal recurrence12% to 2%


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RT for local recurrence RTfor local recurrence

Vaginal recur: Vaginal recur:68% 5 yr survival 68% 5 yrsurvival Pelvic recur: Pelvic recur: 20to 50% 5 yr survival 20 to50% 5 yr survival Pelvic control of tumor: 50 to65% Pelvic control of tumor:50 to 65%Ackerman 1996, Sears 1994, Morgan 1993, Wylie

2000 Ackerman 1996, Sears 1994, Morgan 1993,Wylie 2000

EndometrialCancer

EndometrialCancer


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Stage I Treatment

Stage I Treatment U of U / LDSH U of U /LDSHPatients: TAH/BSO andextended pelvic/aortic LNDPatients: TAH/BSO andextended pelvic/aortic LNDMyometrial MyometrialInvasion Invasion

None None 50%G1 G1 0 0 VG2 G2 0 V VG3 G3 V V V+P

(V = vaginal RT; P = pelvic RT)


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Endometrial


Stage I TreatmentStage I Treatment U of U / LDSH

U of U / LDSHPatients: Patients: no nolymph node dissection lymphnode dissectionMyometrial MyometrialInvasion InvasionNone None 50%


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G1 G1 0 0 V+PG2 G2 0 V P+V

G3 G3 V V+P P+V(V = vaginal RT; P = pelvic RT)

EndometrialCancerEndometrialCancerSubspecialty Impact

Subspecialty Impact Primary management:Primary management:Gyn Gyn onc onc vs vs

OB/GYN OB/GYN


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207 cases, 49% 207cases, 49% Gyn Gyn onconc / 51% GYN / 51% GYN Gyn Gyn onc onc pts:pts: Complete staging 2x more

often (94 Complete staging 2xmore often (94 vs vs 45%)45%) In hi risk Stage I, even moreoften (96 In hi risk Stage I,even more often (96 vs vs19%) 19%) Higher Higher avg avg #nodes (20 # nodes (20 vs vs

8) 8)Roland 2004 Roland 2004


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Endometrial


Subspecialty ImpactSubspecialty Impact Fewer Fewer Gyn Gynonc onc pts received

adjuvant radiation ptsreceived adjuvantradiation 8.6 8.6 vs vs 21.7% 21.7%

No No Gyn Gyn onc oncpts with T1, N0 disease


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rec pts with T1, N0disease recdradiation radiation 18 GYN pts with T1, N0or NX rec 18 GYN pts withT1, N0 or NX recd

radiation d radiationRoland 2004 Roland 2004

EndometrialCancerEndometrialCancer

TreatmentTreatment Stage IIIStage III


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Survival, 5 yr Survival, 5yr 10 to 30% gross extrauterine disease 10 to 30%gross extra uterine disease 40 to 80% microscopic 40 to

80% microscopicTreatment:Treatment: Nodes/ Nodes/ serosaserosa/ / adnexa adnexa/

vagina / vagina RT RT Positive Cytology PositiveCytology High dose High dose progestinsprogestins if PR positive if PR

positive Chemo vs. whole abdominal RTChemo vs. whole abdominal RT


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Endometrial


TreatmentTreatment Stage IVStage IV Survival, 5 year Survival,5 year 5 - 10% 10%

Treatment:Treatment: Hormonal therapy Hormonal

therapy ChemotherapyChemotherapy


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Local radiation Localradiation


CancerControversy: EstrogenReplacement Controversy:Estrogen ReplacementTherapyTherapyArguments against:Arguments against:Increase recurrence

Increase recurrence ? Epidemiologic studies:Epidemiologic studies:


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Unopposed estrogenUnopposed estrogen risk

developing risk developingendo endo ca ca In vitro studies: In vitrostudies: growth of cultured cellswith estrogen therapy growthof cultured cells with estrogentherapy

EndometrialCancerEndometrialCancerControversy: EstrogenReplacement Controversy:Estrogen Replacement


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TherapyTherapyArguments in support:Arguments in support: Benefits: Benefits: bone /bone / neuro neuro /symptoms / symptoms

Likelihood of ( Likelihood of(oncologic oncologic) harm: )harm: Early stage, low grade: ERpositive Early stage, low grade: ER

positiveLeast Least recurrent recurrent High stage, high grade: higherrecurrence High stage, high grade:higher recurrencemost most ER negative ER negative

EndometrialCancer


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Endometrial

CancerEstrogen ReplacementTherapy EstrogenReplacement Therapy249 pts, stages I, II, III(cohort study) 249 pts,stages I, II, III (cohortstudy) 130 pt 130 pt ERT (50%with progesterone) ERT (50%with progesterone) Age/stage matched controls

(75 pairs) Age/stage matchedcontrols (75 pairs) Similar in Similar insurgicopathology


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surgicopathology, treatment ,treatment

ERT users ERT users 1%recurrence 1% recurrence Non ERT Non ERT 14%recurrences 14% recurrencesSuriano Suriano et al 2001 etal 2001

EndometrialCancer

EndometrialCancer

Treatment

TreatmentERTprotocol ERT protocol GOG 137 GOG 137


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Stage I / occult stage IIendometrial cancer Stage I /

occult stage II endometrialcancer Premarin 0.625/ day vs.placebo Premarin 0.625/ dayvs. placebo Plan: 3 years treatment, 2yrfl/u Plan: 3 years treatment,2yr fl/u Closed prematurely due to

accrual Closed prematurelydue to accrual

EndometrialCancer

EndometrialCancer


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ERT protocol ERT

protocolGOG 137GOG 137 Median f/u 30 mo, 1234pts Median f/u 30 mo,

1234 pts ERT: ERT: Recurrence 12 pts (1.9%)Recurrence 12 pts (1.9%) Death due to Death due toendom endom Ca 3 pts (0.5%)Ca 3 pts (0.5%)

Placebo: Placebo: Recurrence 10 pts (1.6%)

Recurrence 10 pts (1.6%)


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Death due to Death due toendom endom Ca 4 pts (0.6%)

Ca 4 pts (0.6%) (NOT statistically valid)NOT statistically valid)

Endometrial

CancerEndometrialCancerSummary Summary 4th th most commoncancer in women mostcommon cancer in women Caught early, excellentsurvival Caught early,excellent survival


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Abnormal bleedingmerits evaluationAbnormal bleeding meritsevaluation Office biopsy, pursuediagnosis if persists! Office

biopsy, pursue diagnosis ifpersists!

Family predispositionFamily predisposition

endometrial, HNPCCendometrial, HNPCC Family Cancer AssessmentClinic Family CancerAssessment Clinic

EndometrialCancer


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Endometrial

CancerSummary Summary Full staging may foregoradiation Full staging may

forego radiation Grade 1 Grade 1 preoppreop biopsies biopsies33% need staging 33%

need staging Laparoscopy is the newparadigm in Laparoscopyis the new paradigm in

endometrial cancerendometrial cancer


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Ovarian Cancer

Ovarian Cancer Second most commongynecologic cancerSecond most common

gynecologic cancerin the US in the US Responsible for 25,000cases annuallyResponsible for 25,000cases annually 14,500 deaths annually14,500 deaths annually Most lethal gynecologic

cancer Most lethalgynecologic cancer


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70% of women arediagnosed present with

70% of women arediagnosed present withadvanced diseaseadvanced diseaseAmerican Cancer Society

2000

Ovarian Cancer:Ovarian Cancer:Stage Distribution and

Survival StageDistribution andSurvival

Stage Stage Percent

Percent SurvivalSurvival


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I-- --ovary ovary 2424 95% 95%II II-- --pelvis pelvis 665% 65%III III-- --

abdomen abdomen55 55 15 15-30% 30%IV IV-- --distantdistant 15 15 0-20%

20%Overall Overall 50%50%American Cancer Society 2000 AmericanCancer Society 2000

Ovarian Cancer:Risk Factors


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Ovarian Cancer:

Risk FactorsIncrease IncreaseDecrease DecreaseAge Age Oral

Contraceptives OralContraceptives(50% decrease) (50%decrease)

Family history Familyhistory PregnancyPregnancy and andBreastfeeding

BreastfeedingInfertility/low parityInfertility/low parity


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Personal cancerPersonal cancerhistory historyHysterectomy/RemovalHysterectomy/Removalof Both Ovaries of Both

OvariesOvarian Cancer:Hereditary RisksOvarian Cancer:Hereditary RisksFamily History ofOvarian Family History

of OvarianCancer Cancer LifetimeRiskLifetime Risk


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None None 1.8% 1.8%1 first 1 first-degreerelative degree relative5% 5%2 first 2 first-degreerelatives degree

relatives 7% 7%Hereditary ovariancancer Hereditaryovarian cancer

syndrome syndrome40% 40%Known BRCA1 orBRCA2 Known BRCA1

or BRCA2


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inherited mutationinherited mutation 3535-65% 65%

Ovarian Cancer:Ovarian Cancer:

HereditarySyndromesHereditarySyndromes

Account for only 10%of ovarian cancerAccount for only 10% ofovarian cancer

Inherited from eitherparent Inherited fromeither parent


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IncompleteIncomplete penetrancepenetrance Associated withbreast, colon, prostateAssociated with breast,

colon, prostateand endometrialcancers andendometrial cancers

Ovarian Cancer:Ovarian Cancer:How is Ovarian

Cancer Diagnosed?How is OvarianCancer Diagnosed?


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Vaginal Vaginal -rectal exam rectalexam TransvaginalTransvaginalultrasound ultrasound

CA 125 blood test CA125 blood test Surgical biopsy /resection Surgical

biopsy / resectionOvarian CarcinomaOvarian Carcinoma--

--SymptomsSymptoms


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95% of women DO reportsymptoms 95% of women DO

report symptoms80 to 90% of pts with Stage

I/ II disease 80 to 90% of ptswith Stage I/ II disease

More often, more acuteonset ofMore often, moreacute onset ofsx sx, more ,moresevere severe

Vague and often non Vagueand often non-gynecologicgynecologic

abdominal bloating, abdominalbloating, incr incr girth, pressure

girth, pressureFatigue Fatigue


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GI (nausea, gas, constipation,diarrhea) GI (nausea, gas,

constipation, diarrhea)Urinary frequency/ incontinenceUrinary frequency/ incontinence

Abdominal/ pelvic painAbdominal/ pelvic pain

Weight loss/ gain Weight loss/

gainShortness of breath Shortness of

breath

Ovarian Carcinoma

Ovarian CarcinomaPrimary ManagementPrimary Management

Initial surgery Initial

surgery


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Thorough surgicalstagingThorough surgicalstaging

Aggressive tumorresection ( Aggressivetumor resection

(debulking debulking, ,cytoreductioncytoreduction)

Combination

chemotherapyCombinationchemotherapy

6 cycles: 6 cycles:

carboplatin carboplatin &paclitaxel paclitaxel


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Ovarian Carcinoma

Ovarian CarcinomaPrimary ManagementPrimary ManagementInitial SurgeryInitial Surgery

Surgical Staging SurgicalStaging

Hyst Hyst / BSO / / BSO /

Omentectomy OmentectomyWashings, peritoneal biopsies

Washings, peritoneal biopsiesPelvic/ Pelvic/ Paraaortic Paraaortic

LymphadenectomyLymphadenectomy

80% of ovarian cancer ptsreceive inadequate 80% of


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ovarian cancer pts receiveinadequate

staging from non staging fromnon gyn gyn-onc onc surgeonsurgeon

May translate into choicebetween 2 May translate intochoice between 2nd nd surgeryor surgery orchemotherapy chemotherapy

Ovarian Carcinoma

Ovarian CarcinomaPrimary ManagementPrimary Management

Initial SurgeryInitial Surgery


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Reoperation Reoperationwithin 3 months for within 3

months for debulkingdebulking/ staging / staging

Population based study, 3355pts Population based study, 3355pts

Pts Pts less likely to have lesslikely to have reoperationreoperation ififdone: done:

In high In high- or or intermedintermed- volume hospital (RR0.24) volume hospital (RR 0.24)

By By Gyn Gyn Onc Onc (RR0.04) (RR 0.04)

By general Ob/ By general Ob/Gyn Gyn (RR 0.37) (RR 0.37)

By high volume surgeon (RR

0.09) By high volume surgeon (RR0.09)(> 10 ovarian cancer cases/ yr) (>10 ovarian cancer cases/ yr)


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Elit et al, Gyn Oncol 200

Ovarian CarcinomaOvarian CarcinomaPrimary ManagementPrimary Management

DebulkingDebulkingResidual Disease ResidualDisease 5 yr survival 5 yr

survival< 1 cm < 1 cm 50% 50%1 to 2 cm 1 to 2 cm 20% 20%> 2 cm > 2 cm 13% 13%Baker et al, Cancer 1994

Ovarian CarcinomaOvarian Carcinoma


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Primary Management

Primary ManagementDebulkingDebulkingResidual Disease Residual

Disease Median survivalMedian survival< 0.5cm < 0.5cm 40 months40 months0.5 to 1.5 cm 0.5 to 1.5 cm 18months 18 months> 1.5 cm > 1.5 cm 6 months6 monthsHacker N, Ob & Gyn 1983

Ovarian CarcinomaOvarian Carcinoma


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Primary Management

Primary ManagementInitial SurgeryInitial Surgery

Survival advantage for

advanced stage pts treatedSurvival advantage foradvanced stage pts treatedby by gyn gyn onc onc

25% reduction in death at 3yrs, (

25% reduction in death at 3yrs, (vsvs general Ob/ general Ob/GynGyn)

JunorJunor et al, Br J et al, Br J Ob&GynOb&Gyn 1999 1999

Survival advantage for ptstreated in high Survivaladvantage for pts treated inhigh-volume volume


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hospital hospital55% 55% vs vs 34% 5 yr survival

for high 34% 5 yr survival for highvs vs low volume low volumeIoka Ioka et al, Cancer et al, Cancer Sci Sci2004 2004

Pelvic Mass:

Preoperative PelvicMass: PreoperativePrediction of

MalignancyPrediction ofMalignancy

5 to 25% 5 to 25%

premenopausalpremenopausal aremalignant are malignant


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1/3 1/3rd rd in pts < 21 y.o.(solid/ cystic) in pts < 21 y.o.

(solid/ cystic)> 50% in > 50% in

premenarchal premenarchalpts (solid/ cystic) pts (solid/cystic)

35 to 63%postmenopausal aremalignant 35 to 63%postmenopausal are

malignantPreop Preop

assessment of likelihoodofassessment of

likelihood of


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malignancy can allowappropriate malignancycan allow appropriatesurgical planning surgicalplanning

PreoperativePrediction ofMalignancyPreoperative

Prediction ofMalignancy

Indicators (suspicious)Indicators (suspicious)

Pelvic examination Pelvicexaminationfixed, nodular,fixed, nodular, ascites ascites


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Tumor markersTumormarkers

CA125 > 35U/ CA125 > 35U/ mLmL

AFP >10 AFP >10 ng ng/ / mLmL or or hCG hCG >15 >15 mIUmIU/ / mL mL (non (nonpregnant) pregnant)

LDH > 350 U/ L LDH > 350 U/ L

UltrasonographicUltrasonographic findingsfindings solid, cystic with

solid, cystic withmural nodules mural nodulesRoman et al, Ob &Gyn 1997

Preoperative

Prediction ofMalignancy


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Preoperative

Prediction ofMalignancyIf all 3 indicators If all 3

indicators nonsuspicious

nonsuspicious::99% of pre 99% of pre- &

postmenopausal masses &postmenopausal massesbenign benign

If all 3 indicators If all 3indicators suspicioussuspicious, ,

77% of77% of

premenopausalpremenopausal massesmasses malignant malignant


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1/3 1/3rd rd borderline, 2/3borderline, 2/3rd rd invasive invasive

Nodules >2cm, size>10cm mostpredictive Nodules >2cm,size>10cm most predictive

83% of postmenopausalmasses 83% of

postmenopausal massesmalignant malignantborderline, borderline, invasive invasive

CA125 > 100, suspicious U/Smost predictive CA125 > 100,suspicious U/S most predictiveRoman 1997

ACOG / SGOReferral Guidelines


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ACOG / SGO

Referral GuidelinesNewly DiagnosedPelvic Mass Newly

Diagnosed PelvicMass

PremenopausalPremenopausal (200 U/ mlascites ascites abd abd/ distant / distant

mets metsFamily Family Hx Hx Breast/Breast/


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Ovarian cancer (1st Ovariancancer (1st

degree) degree)Postmenopausal (>50)Postmenopausal (>50) CA125 > 35 U/ ml CA125 > 35U/ mlascites ascites abd abd/ distant / distantmets metsFamily Family Hx Hx Breast/

Breast/Ovarian cancer (1st Ovariancancer (1stdegree) degree) nodular/ fixed mass nodular/

fixed massACOG Committee Opinion 2002Im et al, Ob &Gyn 2005


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ACOG / SGO

Referral GuidelinesACOG / SGOReferral Guidelines

Predictive ValuePredictive Value

1,035 pts, 7 hospitals1,035 pts, 7 hospitals

30% ovarian cancer30% ovarian cancer

25% of cancer cases25% of cancer cases-- --

premenopausalpremenopausal


92/100

chart / path reviewchart / path reviewCA125 CA125

preop preop pelvic exampelvic exam

imaging studies imagingstudiespath report path report

Im et al, Ob &Gyn 2005

Referral Guidelines

Referral GuidelinesPredictive ValuePredictive Value--

--Pre PremenopausalmenopausalCriteria PPV (%) NPV (%)


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CA125 70 85Ascites 58 89Mets 64 89Family Hx 19 82Overall 34 92Im et al, Ob &Gyn 2005

Referral GuidelinesReferral GuidelinesPredictive Value

Predictive Value----PostPostmenopausalmenopausalCriteria PPV (%) NPV (%)CA125 74 85


94/100

Ascites 79 72Pelvic exam 66 61Mets 84 77Family Hx 42 56Overall 60 91Im et al, Ob &Gyn 2005

Referral GuidelinesReferral GuidelinesPatient Distribution

Patient DistributionSpecialty Ovarian CancerBenign MassPremenopausalGyn Onc 70% 31%

OB/ Gyn 30% 69%PostmenopausalGyn Onc 94% 42%


95/100

OB/ Gyn 6% 58%

Modified ReferralGuidelinesModified Referral

GuidelinesPremenopausalPremenopausal ( 50 U/ mlascites ascites abd abd/ distant /

distant mets metsPostmenopausal (>50)Postmenopausal (>50)


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CA125 > 35 U/ ml CA125> 35 U/ ml

ascites ascites abd abd/ distant /distant mets metsIm et al, Ob &

Gyn 2005Im et al, Ob &Gyn 2005

Referral GuidelinesReferral Guidelines

Patient DistributionPatient DistributionSpecialty Ovarian Cancer BenignMass

PremenopausalGyn Onc 85% 27%OB/ Gyn 15% 73%Postmenopausal


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Gyn Onc 90% 24%OB/ Gyn 10% 76%

Ovarian &EndometrialCancer Ovarian &

EndometrialCancerSurveillance

SurveillanceFrequency: Frequency:Q 3 months x 2 yrs Q 3months x 2 yrs

Q 4 months x 1 yr Q 4 monthsx 1 yrQ 6 months until year 5, Q 6months until year 5,


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then, annually then, annually(roughly 75 to 90% recur

(roughly 75 to 90% recurin 1st 3 years) in 1st 3 years)Each visit: Each visit:Physical / Physical / Pelvicexam Pelvic examPap smear Pap smear

Tumor markers (CA125,Tumor markers (CA125,CEA) CEA)

Annual: Annual:Chest Xray Chest XrayCBC, metabolic panel CBC,metabolic panel

Endometrial &Ovarian Cancer


99/100

Endometrial &

Ovarian Cancer Early detection Earlydetection-- --improveimproves survival s

survival Heighten awareness ofsympto Heighten awarenessof symptoms! ms!

Staging & completeStaging & completedebulking debulkingdecreases decreasesmorbidity and increasessurvival morbidity andincreases survival


100/100

Consider consultationwith gynecologic Considerconsultation withgynecologiconcologist (801 oncologist(801-585 585-2477) 2477)

Endometrial Docu Cleaned

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