TheThe AdnAdneexxaall MassMass andand EarlyEarly OOvarianvarian CanCanccerer FredFred UelanUelandd,, MMDD UniversiUniversityty ofof KentucKentuckkyy GynGynecolecoloogicgic OncolOncolooggyy ““NeveNeverr givegive in.in. NNeverever givegive in.in. NeveNeverr,, neveneverr,, nnever,ever, nevernever-- inin nothinothinngg greatgreat oror smsmallall,, larglargee oror petpetttyy-- nevernever givegive in,in, exexceceptpt toto convictionsconvictions ooff hohonnoror andand goodgood sense.sense.”” Sir Winston Churchill OvarianOvarian TTuumorsmors WhoWho Cares?Cares? Surgical costs exceed $5,000,000,000 annually 144 million women in USA – 5-10% will undergo a surgical procedure for a suspected ovarian neoplasm during their lifetime 30 million women over age 50 – 17% develop cystic ovarian tumors – 2 million have persistent tumors RiskRisk ofof MalMaliignancygnancy ManagManageemmentent chalchalllengeenge isis anan accuaccurratatee riskrisk ofof malignanmalignanccyy aasssseesssmsment.ent. RiskRisk ofof malignanmalignanccyy withinwithin anan ovarovariaiann neoplaneoplasmsm varivarieess wwithith age:age: – 10% in children – 15% in reproductive age women – 50% in postmenopausal women OvarianOvarian TTuumorsmors PremenPremenoopaupausasall WomenWomen NonNon--inflinflaammmmatoratoryy ovarianovarian ttumumorsors – 70% functional cysts – 20% neoplastic – 10% endometriomas 15%15% ofof oovarianvarian neoplaneoplasmsmss inin reproductivereproductive ageage wwomomeenn aarree mamalignantlignant OtherOther – Inflammatory process, bowel OvarianOvarian TTuumorsmors PremenPremenoopaupausasall WomenWomen FunctionalFunctional cystscysts – < 8 cm – Unilateral – Simple, unilocular on TVS – No ascites InitialInitial reprepeeatat TTVSVS 66--88 weeksweeks OCPsOCPs dodo notnot incrincreeasease likelihoodlikelihood ofof resolution,resolution, butbut mamayy dedeccrereaasese riskrisk ofof recurrecurrrenceence OvarianOvarian TTuumorsmors Spanos W. Am J Obstet Gynecol 1973 Type of Cyst # of Patients % Regressed under observation 205 72 Required exploratory laparotomy 81 28 Ovarian neoplasms 46 16 Benign epithelial 32 11 Benign teratoma 9 3 Malignant epithelial 4 1.4 Dysgerminoma 1 0.3 Endometriosis 28 10 Para-ovarian cyst 4 1.4 Hydrosalpinx 3 1 Functional cysts 0 0 OvarianOvarian TTuumorsmors Modesitt et al, Gyn Oncol 2003 SpontaneousSpontaneous ResoResollutioutionn 22612261 (69%)(69%) CystCyst ++ SSepteptuumm 537537 (17%)(17%) PersistentPersistent CCysystt 220220 (7%)(7%) CystCyst +Solid+Solid aarreeaa 168168 (5%)(5%) SolidSolid MasMasss 2121 (0.6%)(0.6%) RRememovedoved byby unreunrellatedated surgesurgeryry 4040 (1.2%)(1.2%) 3,2593,259 EndometriEndometrioomama MucinousMucinous CystadenomCystadenomaa MatureMature CCysystticic TeratomaTeratoma OvarianOvarian DyDyssgerminomagerminoma OvarianOvarian TTuumorsmors PostmenoPostmenoppauaussalal WomenWomen BenignBenign epithelialepithelial ttuumomorr StrStromomalal ttuumormor – Granulosa cell – Fibroma – Thecoma EpithelialEpithelial cancanccerer MetMetaastatistaticc cancanccerer OvarianOvarian TTuumorsmors PostmenoPostmenoppauaussalal WomenWomen 50%50% mmalignantalignant AsAsyymptmptoommatiaticc ssiimmpleple cyscystt << 1010 ccmm wwithith nonormrmalal CCAA--125125 – serial TVS “Any“Any ovarianovarian ttuummoror inin aa pospostmtmenopenopaausalusal wwomomanan thatthat doedoess notnot mmeeeett thethe aboveabove critercriteriiaa shouldshould bebe assassumumeded toto bebe mamalignant”lignant” – Antiquated? SerousSerous OOvvaarianrian CancerCancer WhoWho GGetsets RReeferredferred toto aa CCaancnceerr SpecSpeciialist?alist? BenefitsBenefits ofof SurgicalSurgical Staging?Staging? PatientsPatients inin whwhomom cocompmprrehensiveehensive surgicalsurgical stagingstaging conficonfirrmsms eearlarlyy--stagestage disdiseeasasee havehave aa betterbetter prognosisprognosis tthhanan thosethose whowho wweerree thouthougghtht toto havehave eeaarlyrly ssttageage disdiseeasease bbutut werweree unstagedunstaged AccuraAccurattee identificidentificaationtion ofof wwoomenmen wwhhoo requirerequire adjuvantadjuvant cchheemothmotheerapyrapy AppropriateAppropriate StagingStaging WWomomeenn withwith earearlyly stagestage ovarianovarian ccancerancer – N=291 CCoomplemplettee surgisurgiccalal staging:staging: – 97% gynecologic oncologists – 52% general obstetrician/gynecologists – 35% general surgeons McGowan L, et al. Obstet Gynecol 1985;65:568-72. ReferralReferral PaPattternsterns Utah Cancer Registry: 848 new ovarian cancers diagnosed 1992-1998 Only 39% were ever seen by a Gyn Onc Patients with advanced disease had significant survival advantage when managed by Gyn Onc (median survival 26 mo vs. 15 mo, p < 0.01) Age < 40, age > 70, and residence in a rural area were not seen by a gynecologic oncologist Carney ME, et al. Gynecol Oncol 2002;84:36-42. ValueValue ofof SpSpeecialcialiistssts Meta-analysis (18 studies) concluded marked benefit with Gynecologic Oncologist (Giede 2005) – Complete surgical staging with early stage disease – Optimal cytoreductive surgery with advanced disease – Improved median and overall survival Others supporting GO involvement: – NCCN guidelines – SGO, ACOG – SOGC clinical practice guidelines – NIH consensus statement – London Medical Advisory statement SuggestiveSuggestive ofof MalignancyMalignancy ACACOOG,G, SSGGOO ExExamaminationination – Fixed or nodular ImImagingaging studystudy – Mostly solid tumor or distant mets – Ascites CACA--125125 – premenopausal > 200 – postmenopausal > 35 Im et. al. Obstet Gynecol , 2005 SoSo HHooww DoDo II KnowKnow WhoWho GGetsets ReferReferrreded aanndd WhoWho DoDoeesn’sn’tt?? ExExamaminationination ImImagingaging SerSerumum PelvicPelvic ExExamaminationination PelvicPelvic ExExamaminationination InaccuraInaccuracycy Patient age ≥ 55 – 30% Patient weight ≥ 200 lb – 9% Uterine weight ≥ 200 g – 16% Ueland et al, Gyn Oncol 2005 SoSo HHooww DoDo II KnowKnow WhoWho GGetsets ReferReferrreded aanndd WhoWho DoDoeesn’sn’tt?? ExExamaminationination ImImagingaging SerSerumum PelvicPelvic ExExamam vs.vs. UltrasoundUltrasound Pelvic Exam Ultrasound P value Patient age 0.30 0.74 < 0.001 ≥ 55 Patient wt 0.09 0.73 < 0.001 ≥ 200 lb Uterine wt 0.16 0.80 < 0.001 ≥ 200 g Ueland et al, Gyn Oncol 2005 UltrasoundUltrasound DifferentiatDifferentiatiingng OvarianOvarian TumorsTumors Author Number Prevalence Sens(%) Spec (%) PPV(%) PPV (at 20%) Kobayashi, 1976 406 15 70 73 31 39 Hermann, 1987 241 21 82 93 75 73 Finkler, 1988 102 36 62 95 88 75 Benacerraf, 1990 100 30 80 87 72 62 Granberg, 1990 180 22 82 92 74 73 Sassone, 1991 143 10 100 83 37 59 Ueland, 2003 442 12 98 81 41 56 *Definition of (+) US varied with each author SonogSonogrraphaphiicc ChChaaractracteeristristicicss OvarianOvarian TumorsTumors Benign Malignant Unilateral Bilateral Simple (MI < 5) Complex (MI ≥ 5) Doppler – Partly solid – PI > 1.0, RI > 0.4 – Internal papillations – Peripheral flow Doppler No ascites – PI < 1.0, RI < 0.4 – Central flow Resolution Ascites Persistence or growth KentuckyKentucky MMorphologyorphology IInndexdex Ueland et al Gyn Oncol 2003 UK gynecologic ultrasound database 442 women with confirmed ovarian tumor – Morphology Indexing – Color Flow Doppler – Surgery TumorTumor StruStrucctureture ScoreScore == 00 TumorTumor StruStrucctureture ScoreScore == 33 TumorTumor StruStrucctureture ScoreScore == 55 MorphologyMorphology IndexIndex TotalTotal ScoreScore (0(0--4)4) 100 90 80 70 60 50 % Benign 40 % Cancer 30 20 10 0 0 1 2 3 4 MorphologyMorphology IndexIndex TotalTotal ScoreScore (5(5--10)10) 100 90 92 80 83 70 77 60 50 % Benign 40 % Cancer 38 30 32 20 20 10 0 5 6 7 8 9 10 KentuckyKentucky MMorphologyorphology IInndexdex MIMI << 55 benignbenign MIMI ≥≥ 55 mamalignantlignant KentuckyKentucky MMorphologyorphology IInndexdex SensitivitySensitivity 0.9810.981 SpecificitSpecificityy 0.8070.807 PositivePositive predictivepredictive valuevalue 0.4090.409 NegativeNegative predictipredictivvee valuvaluee 0.9970.997 AccurAccuraaccyy 0.8280.828 Disease Prevalence = 12% WhatWhat aboutabout Doppler?Doppler? DopplerDoppler Sens Spec PPV NPV MI 0.981 0.807 0.409 0.997 PI < 1.00 0.528 0.776 0.288 0.905 RI < 0.4 0.222 0.867 0.222 0.867 No flow 0.163 0.640 0.056 0.854 f0 = transmitted US frequency v cos θ = target velocity c = velocity of surrounding medium TVSTVS probeprobe θθ vesselvessel ∆∆ff == 2f2f0 vv (cos(cos θθ)) // cc DopplerDoppler RReeproducibilitproducibilityy ∆∆ff == 2f2f0vv (cos(cos θθ)) // cc IsIs thethe angleangle ofof insonationinsonation constantconstant ((θθ))?? – 2 to 3 fold change for ∆ θ (from 30°-80°)* – Optimal angle and frequency depends on depth of vessel IsIs eeaachch DopplerDoppler mmeasureasureemmentent ofof thethe ssameame vessel?vessel? AreAre thesthesee vesselsvessels ststrraighaightt?? *J Vasc Surg 1990; 11:688-94 UltrasoundUltrasound ConclusionConclusionss 1. MIMI ≥≥ 55 40% malignant 2. MIMI << 55 0.3% malignant 3. DopplerDoppler addsadds littllittlee OtherOther IImagingmaging CTCT scanscan abdabdomomenen andand pelvispelvis – IV and PO contrast – CT-guided biopsy Accuracy exceeds 90% for solid tumors What about high risk cystic tumors? MRIMRI PETPET CTCT ScanScan Omental cake Ovarian tumor SoSo HHooww DoDo II KnowKnow WhoWho GGetsets ReferReferrreded aanndd WhoWho DoDoeesn’sn’tt?? ExExamaminationination ImImagingaging SerSerumum CACA--125125 Antigen derived from: – coelomic epithelium (pericardium, pleura, peritoneum) – mullerian epithelium (tubal, endometrial, endocervical) Two different assays – Assay I < 35 U/ml – Assay II < 20 U/ml Expressed by 80%