Ovarian
Content
Ovarian Cancer: Diagnosis and Screening in Primary Care Elise M. HughesHughes-Watkins, -Watkins, M.D. November 30, 2001
Ovarian Cancer: Burden of suffering 44th leading cause of cancer death in women in the U.S. (after lung, breast and colon) OOverall verall 55--year -year survival rate is 35% The The³si ³silen ³silent ³silent lentt kil killer killer´: ler´: ´: asy asymp asymptomatic asymptom mptom tomati atic atic c ininear early early ly sta stages stages ges 75 75% 75% % dia ddiagnosed iagn gnos osed ed wi with with th ad adva advanced vanc nced ed st stag stage agee dis ddisease; isea ease se;; 55-year survival only 1010 -28% -28% Wom Woman¶ Woman¶s an¶ss lif lifeti lifetime etime me ris risk risk k of oof f dying dy dying ing fr from from om ovar oovarian varian ian cancer is 1.1%
Cancer Incidence and Deaths in U.S.Women U.S.Wom en in 2000 Cancer C ancer type type
# new cases
#o off deaths deaths
Lung Lung
74,600
6 67,600 7,600
Breast Breast
182,800
4 40,800 0,800
Colon Colon
50,400
2 24,600 4,600
Ovarian Ovarian
23,100
1 14,000 4,000
Endometrial Endometrial
36,100
6 6,500 ,500
Cervical Cervical
12,800
4 4,600 ,600
Ada Adapte Adapted pted d from fro from m Paley PPaley,P, aley,P, ,P, Scre Screeni Screening ening ng for fo for r the th the e major m major ajor mal malign malignancies ignancie anciess affect aff affecting ecting ing wome w women: omen: n: Current guidelines. Am J Obstet Gynecol 2001;184:
Types of Ovarian Tumors Functional Follicle cyst Corpus luteum cyst Theca lutein cyst
Inflammatory Tubo--ovarian Tubo -ovarian abscess
Benign tumors/c tumors/cysts ysts* Endometriotic cyst Brenner tumor Benign teratoma (dermoid cyst) Fibroma *Rare or very rare potential for malignancy
Malignant (or malignant potential) Malignant teratoma Endometrioid carcinoma Dygerminoma Secondary ovarian tumor Cystadenoma, cystadenocarcinoma (>50% for serous, ~5% for mucinous) Granulosa cell tumor (15(1520%) Arrhenoblastoma (<20%) Theca cell tumor (<1%)
Epithelial Ovarian Cancer Overall Overall55--year survival rate is 75 75--95% if cancer confined to ovaries; decreases to 10--17% if distant metastases 10 Survival Survivalimproved improvedwhen whencancer cancerdetected detected in early stage Only Only25% 25%diagnosed diagnosedininStage StageII
Early Detection and Mortality No No direct evidence that women with early stage cancer found on screening have lower mortality than women with more advanced disease Indirect Indirectevidence evidencesupports supportsbenefits benefitsof ofearly early detection: ± Most important prognostic factor in patients with ± advanced ovarian cancer is tumor burden after initial debulking ± Surgical debulking and chemo more effective when ± cancer detected early
The challenge Natural Naturalhistory historyof ofovarian ovariancancer cancernot notwell well understood ± ± No No well well--defined precursor lesion ± Length of time from localized tumor to ± dissemination is unknown
Multiple Multipleefforts effortsunderway underwaytotodevelop develop effective screening method for early detection
R isk
factors
The Themajority majorityof ofwomen womenwith withovarian ovarian cancer have no known risk factors Most Mostsignificant significantrisk riskfactor factorisisgenetic genetic predisposition
R isk
factors: Heredity
Up Uptoto10% 10%of ofepithelial epithelialovarian ovariancancer cancercases casesare are familial 33familial familialsyndromes: syndromes:familial familialbreast breast--ovarian cancer syndrome, sitesite -specific ovarian cancer, and cancer family syndrome (Lynch type II) Familial Familialbreast breast--ovarian cancer and sitesite-specific ovarian cancer syndromes both associated with mutations of the BR CA1 suppressor gene; account for 90% of familial ovarian cancers R ollins,G.
Ann Int Med 2000;133:10212000;133:1021-1024
Additional R isk Factors Age ± Women over age 50 account for ~80% of all cases (ave. age at dx is 61)
Reproductive history ± early menarche, nulliparity or age >30 at first childchild-bearing, and late menopause
Fertility drugs ± prolonged use of Clomid, especially without achieving pregnancy
Personal history of breast cancer Hormone replacement therapy > 10 years ± May be associated with 30% increased risk
Talcum powder ± Some studies have shown slightly increased risk in women who use talc powder on genital area American Cancer Society, 2001
Protective factors Multiparity: Multiparity: First Firstpregnancy pregnancybefore beforeage age30 30 Oral Oralcontraceptives: contraceptives: 55years yearsof ofuse usecuts cutsrisk risk nearly in half Tubal Tuballigation ligation Hysterectomy Hysterectomy Lactation Lactation Bilateral Bilateraloopherectomy oopherectomy
Delays in Diagnosis Lack Lackof ofseverity severityand andspecificity specificityof ofearly early symptoms ± Early signs/symptoms may include bloating, ± gas, indigestion, abdominal fullness or discomfort, constipation, pelvic pressure, urinary frequency, abnormal vaginal bleeding, fatigue, back pain, leg pain
Early Earlystage stagetumors tumorsdifficult difficultto todetect detecton on pelvic exam
Diagnostic tools History History Pelvic PelvicExam Exam(including (includingrectal) rectal) Transvaginal TransvaginalUltrasound Ultrasound ± ± detection of masses and mass characteristics Tumor Tumormarkers markers ± ± CA CA--125, LPA (plasma lysophosphatidic acid) CT CT ±± assess spread to LN, pelvic and abdominal structures M MR I ±± best best for distinguishing malignant from benign tumors
Work--up of Adnexal Mass Work Must Mustfirst firstcategorize categorizeas asfunctional, functional,benign benign neoplastic or potentially malignant Diagnostic Diagnosticapproach approachdepends dependson: on: Age Age
Ultrasound Ultrasoundconfiguration configuration
Size Sizeof ofmass mass
Color Color -flow Doppler flow
Unilateral Unilateralvs. vs.bilateral bilateral
Presence Presenceof ofsymptoms symptoms
CA CA--125 levels
Diagnostic approach IfIfpremenopausal premenopausaland andasymptomatic, asymptomatic,with with unilateral, mobile, simple cystic mass <8<810cm and no family history, can observe for 4-6 weeks and then repeat TVUS and pelvic exam. ± If resolved, no further work ± work -up necessary ± If larger or unchanged, or if character of mass ± has changed on TVUS, surgical evaluation required
Diagnostic Approach IfIfpostmenopausal postmenopausaland andasymptomatic, asymptomatic,with with unilateral simple cyst <5cm AND normal CA--125, can follow closely with repeat CA TVUS All Allother otherpostmenopausal postmenopausalwomen womenwith with ovarian mass require surgical evaluation
Surgical Evaluation R efer
to GynGyn-Onc specialist
Exploratory Exploratorylaparotomy laparotomyhas hasbeen beenthe thegold gold standard and includes: ± Peritoneal washings for cytology ± ± Evaluation of frozen section ± ± Complete staging procedure if borderline or ± malignant tumor on frozen section
Surgical Evaluation Laparoscopy Laparoscopycan canbe beconsidered consideredin in premenopausal woman with ovarian mass small enough to remove via laparoscopic approach; not recommended if high suspicion for malignancy
Stages Ia, Ib, Ic
Stages IIa, IIb, IIc
Stages IIIa, IIIb, IIIc
Stage IV
Treatment Depends Dependson onstaging, staging,tumor tumortype, type,age, age,desire desire for future fertility Can Caninclude includesurgery, surgery,chemotherapy chemotherapyand/or and/or radiation therapy Clinical Clinicaltrials trialsare areongoing ongoing
Surgical treatment Primary Primarydebulking debulkingand andcytoreduction; cytoreduction;may may include: ± Bilateral ± Bilateral salpingo salpingo--oopherectomy ± Hysterectomy ± ± Lymphadenectomy (para ± (para--aortic, inguinal) ± Omentectomy ± ± ³brushing´ of diaphragm, examination of liver ±
Chemotherapy and R adiation Usually Usually66cycles cyclesof ofchemotherapy chemotherapy Cisplatin Cisplatin(or (orCarboplatin) Carboplatin)plus plusPaclitaxel Paclitaxel most commonly used combination therapy XXR T
Screening Strategies Ultrasound Ultrasound(transvaginal (transvaginalvs vstransabdominal) transabdominal) Color Color -flow doppler CA CA--125 Other Othertumor tumormarkers markers
Ultrasound Both Bothtranabdominal tranabdominaland andtransvaginal transvaginal techniques techniques identify enlarged ovaries or abnormal morphology; TVUS has better resolution One Onelarge largestudy studyof ofTVUS TVUSunderway underwayhas hasreported reported sensivity of 81% and specificity of 98.9% Major Majorlimitations limitationsare arepoor poorPPV PPVin inasymptomatic asymptomatic women and inability to detect malignances when ovaries are normal size Allows Allowsearlier earlierstage stagedetection detection
Color--flow Doppler Color Used Usedininconjunction conjunctionwith withTVUS TVUS Measures Measuresresistance resistancein inblood bloodvessels vessels supplying the ovaries May Mayprovide provideadditional additionalinformation informationto tohelp help distinguish malignant from benign masses
CA--125 CA Sustained Sustainedelevation elevationinin82% 82%of ofwomen womenwith with advanced ovarian cancer, but fewer than 1% of healthy women Poor Poorsensitivity sensitivity(elevated (elevatedin inonly only50% 50%of of women with Stage I disease) Poor Poorspecificity specificity(elevated (elevatedin inmany many gynecologic and nonnon-gynecologic malignancies as well as benign conditions)
CA--125 CA Malignant conditions Cervical CervicalCA CA Fallopian Fallopiantube tubeCA CA Endometrial EndometrialCA CA Pancreatic PancreaticCA CA Colon ColonCA CA Breast BreastCA CA Lymphoma Lymphoma Mesothelioma Mesothelioma
Benign conditions Endometriosis/Menses Endometriosis/Menses Uterine Uterinefibroids fibroids PID PID Pregnancy Pregnancy Diverticulitis Diverticulitis Pancreatitis Pancreatitis Liver Liverdisease disease R enal failure Appendicitis Appendicitis IBD IBD
Lysophosphatidic acid (LPA) Tumor Tumormarker markerbeing beinginvestigated investigatedfor forscreening screening Phospholipid Phospholipidwith withmitogenic mitogenicand andgrowth growthfactor factor-like actions In In11small smallstudy studyLPA LPAwas wasdetected detectedin in99of of10 10 patients with Stage I ovarian CA, 24/24 with advanced cancer, and 14/14 with recurrent cancer. Only 28 of 47 pts had elevated CA CA--125, including 2 of 9 with Stage I disease
Current Screening Guidelines ³³R outine screening for ovarian cancer by ultrasound, the measurement of serum tumor markers, or pelvic examination is not recommended. There is insufficient evidence to recommend for or against the screening of asymptomatic women at increased risk of developing ovarian cancer.´ U.S.Preventive Services Taskforce, Guidelines from Guide to Clinical Preventive Services, 2nd edition, 1996
Screening Guidelines± Guidelines± cont¶d NIH NIHConsensus ConsensusConference Conference (1994) (1994) ± women with presumed hereditary cancer syndrome ± should undergo annual pelvic exams, CACA -125 measurements, and TVUS until childbearing is complete or at age 35, at which time prophylactic bilateral oopherectomy is recommended.
ACP ACP ± counsel high risk women about potential harms and ± benefits of screening
Screening, cont¶d American AmericanCancer CancerSociety, Society,AAFP AAFPand and ACOG do not recommend screening for ovarian cancer in the general population Canadian CanadianTask TaskForce Forceon onPeriodic PeriodicHealth Health Examination ± ³insufficient evidence to recommend for or ± against screening in highhigh -risk women´
Where do we go from here? Several Severalstrategies strategiesfor forscreening screeningcurrently currently under investigation ± TVUS as primary screening method ± ± Multimodal strategy using CA ± CA-125 as initial indicator and if elevated, TVUS used for secondary testing ± LPA (phospholipid with mitogenic and GF ± GF -like actions) may be more sensitive than CACA -125 in detecting early stage cancers
Ovarian Cancer Screening Trials 1.
The United Kingdom Collaborative Trial of Ovarian Cancer Screening: will compare TVUS and multimodal screening to control
2.
The European Study: R CT to screen women with TVUS at 1818-month or 33-year intervals
3.
The NIH Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: 1010 -year study using multimodal strategy
Take home points Screening Screeningnot notindicated indicatedatatthis thistime time ASK ASKabout aboutfamily familyhistory historyof ofcancers cancers LISTEN LISTENwhen whenwomen womenpresent presentwith withnon non-specific GI complaints; include OC in DDx DO DOperform performcareful carefulbimanual bimanualexam examand and rectal exam as part of pelvic exam R efer
women with + Family Hx to GynOnc
R eferences 1. 2. 3.
4.
5. 6.
American Cancer Society. Guidelines Guidelines for the cancercancer -related checkup: and update. Atlanta: American Cancer Society, 1993. Daly M, Obrams GI. Epidemiology and risk assessment for ovarian cancer. Semin Oncol 1998;25(3):2551998;25(3):255-264 DePriest PD, Gallion HH, van Nagell JJR Jr et al. Transvaginal sonography as a screening method for the detection of early ovarian cancer. Gynecol Oncol 1997;65(3):4081997;65(3):408-414 Hensley ML, Castiel M, R obson ME. Screening for ovarian cancer: what we know, what we need to know. Oncology (Huntingt) 2000;14(11):1601--1607 2000;14(11):1601 Holschneider Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol 2000;19(1):32000;19(1):3-10 Jacobs IJ, Skates SJ, et al. Screening for ovarian cancer: a pilot randomised controlled trial. Lancet 1999;353(9160):12071999;353(9160):1207-1210
R eferences, 7.
cont¶d
Kurtz AB, Tsimikas JV, et al. Diagnosis and Staging Staging of Ovarian Ovarian Cancer: Comparative Values of Doppler and Conventional US, CT and MR Imaging Correlated with Surgery and Histopathologic Analysis--R eport of the R adiology Diagnostic Oncology Group. Analysis 1999;212(1):19-27 R adiology 1999;212(1):198. NIH NIH Consensus Development Conference Statement. Ovarian cancer: screening, treatment, and followfollow -up. Gynecol Oncol 1994;55(3 Pt2):S4Pt2):S4-14. 9. Paley P. Screening for the major malignancies affecting affecting women: women: Current guidelines. Am J Obstet Gynecol 2001;184:10212001;184:1021-1030. 10. R ollins G. Developments in Cervical and Ovarian Cancer Screening: Implications for Current Practice. Ann Int Med 2000;133: 10211021-1024
Ovarian Cancer: Burden of suffering 44th leading cause of cancer death in women in the U.S. (after lung, breast and colon) OOverall verall 55--year -year survival rate is 35% The The³si ³silen ³silent ³silent lentt kil killer killer´: ler´: ´: asy asymp asymptomatic asymptom mptom tomati atic atic c ininear early early ly sta stages stages ges 75 75% 75% % dia ddiagnosed iagn gnos osed ed wi with with th ad adva advanced vanc nced ed st stag stage agee dis ddisease; isea ease se;; 55-year survival only 1010 -28% -28% Wom Woman¶ Woman¶s an¶ss lif lifeti lifetime etime me ris risk risk k of oof f dying dy dying ing fr from from om ovar oovarian varian ian cancer is 1.1%
Cancer Incidence and Deaths in U.S.Women U.S.Wom en in 2000 Cancer C ancer type type
# new cases
#o off deaths deaths
Lung Lung
74,600
6 67,600 7,600
Breast Breast
182,800
4 40,800 0,800
Colon Colon
50,400
2 24,600 4,600
Ovarian Ovarian
23,100
1 14,000 4,000
Endometrial Endometrial
36,100
6 6,500 ,500
Cervical Cervical
12,800
4 4,600 ,600
Ada Adapte Adapted pted d from fro from m Paley PPaley,P, aley,P, ,P, Scre Screeni Screening ening ng for fo for r the th the e major m major ajor mal malign malignancies ignancie anciess affect aff affecting ecting ing wome w women: omen: n: Current guidelines. Am J Obstet Gynecol 2001;184:
Types of Ovarian Tumors Functional Follicle cyst Corpus luteum cyst Theca lutein cyst
Inflammatory Tubo--ovarian Tubo -ovarian abscess
Benign tumors/c tumors/cysts ysts* Endometriotic cyst Brenner tumor Benign teratoma (dermoid cyst) Fibroma *Rare or very rare potential for malignancy
Malignant (or malignant potential) Malignant teratoma Endometrioid carcinoma Dygerminoma Secondary ovarian tumor Cystadenoma, cystadenocarcinoma (>50% for serous, ~5% for mucinous) Granulosa cell tumor (15(1520%) Arrhenoblastoma (<20%) Theca cell tumor (<1%)
Epithelial Ovarian Cancer Overall Overall55--year survival rate is 75 75--95% if cancer confined to ovaries; decreases to 10--17% if distant metastases 10 Survival Survivalimproved improvedwhen whencancer cancerdetected detected in early stage Only Only25% 25%diagnosed diagnosedininStage StageII
Early Detection and Mortality No No direct evidence that women with early stage cancer found on screening have lower mortality than women with more advanced disease Indirect Indirectevidence evidencesupports supportsbenefits benefitsof ofearly early detection: ± Most important prognostic factor in patients with ± advanced ovarian cancer is tumor burden after initial debulking ± Surgical debulking and chemo more effective when ± cancer detected early
The challenge Natural Naturalhistory historyof ofovarian ovariancancer cancernot notwell well understood ± ± No No well well--defined precursor lesion ± Length of time from localized tumor to ± dissemination is unknown
Multiple Multipleefforts effortsunderway underwaytotodevelop develop effective screening method for early detection
R isk
factors
The Themajority majorityof ofwomen womenwith withovarian ovarian cancer have no known risk factors Most Mostsignificant significantrisk riskfactor factorisisgenetic genetic predisposition
R isk
factors: Heredity
Up Uptoto10% 10%of ofepithelial epithelialovarian ovariancancer cancercases casesare are familial 33familial familialsyndromes: syndromes:familial familialbreast breast--ovarian cancer syndrome, sitesite -specific ovarian cancer, and cancer family syndrome (Lynch type II) Familial Familialbreast breast--ovarian cancer and sitesite-specific ovarian cancer syndromes both associated with mutations of the BR CA1 suppressor gene; account for 90% of familial ovarian cancers R ollins,G.
Ann Int Med 2000;133:10212000;133:1021-1024
Additional R isk Factors Age ± Women over age 50 account for ~80% of all cases (ave. age at dx is 61)
Reproductive history ± early menarche, nulliparity or age >30 at first childchild-bearing, and late menopause
Fertility drugs ± prolonged use of Clomid, especially without achieving pregnancy
Personal history of breast cancer Hormone replacement therapy > 10 years ± May be associated with 30% increased risk
Talcum powder ± Some studies have shown slightly increased risk in women who use talc powder on genital area American Cancer Society, 2001
Protective factors Multiparity: Multiparity: First Firstpregnancy pregnancybefore beforeage age30 30 Oral Oralcontraceptives: contraceptives: 55years yearsof ofuse usecuts cutsrisk risk nearly in half Tubal Tuballigation ligation Hysterectomy Hysterectomy Lactation Lactation Bilateral Bilateraloopherectomy oopherectomy
Delays in Diagnosis Lack Lackof ofseverity severityand andspecificity specificityof ofearly early symptoms ± Early signs/symptoms may include bloating, ± gas, indigestion, abdominal fullness or discomfort, constipation, pelvic pressure, urinary frequency, abnormal vaginal bleeding, fatigue, back pain, leg pain
Early Earlystage stagetumors tumorsdifficult difficultto todetect detecton on pelvic exam
Diagnostic tools History History Pelvic PelvicExam Exam(including (includingrectal) rectal) Transvaginal TransvaginalUltrasound Ultrasound ± ± detection of masses and mass characteristics Tumor Tumormarkers markers ± ± CA CA--125, LPA (plasma lysophosphatidic acid) CT CT ±± assess spread to LN, pelvic and abdominal structures M MR I ±± best best for distinguishing malignant from benign tumors
Work--up of Adnexal Mass Work Must Mustfirst firstcategorize categorizeas asfunctional, functional,benign benign neoplastic or potentially malignant Diagnostic Diagnosticapproach approachdepends dependson: on: Age Age
Ultrasound Ultrasoundconfiguration configuration
Size Sizeof ofmass mass
Color Color -flow Doppler flow
Unilateral Unilateralvs. vs.bilateral bilateral
Presence Presenceof ofsymptoms symptoms
CA CA--125 levels
Diagnostic approach IfIfpremenopausal premenopausaland andasymptomatic, asymptomatic,with with unilateral, mobile, simple cystic mass <8<810cm and no family history, can observe for 4-6 weeks and then repeat TVUS and pelvic exam. ± If resolved, no further work ± work -up necessary ± If larger or unchanged, or if character of mass ± has changed on TVUS, surgical evaluation required
Diagnostic Approach IfIfpostmenopausal postmenopausaland andasymptomatic, asymptomatic,with with unilateral simple cyst <5cm AND normal CA--125, can follow closely with repeat CA TVUS All Allother otherpostmenopausal postmenopausalwomen womenwith with ovarian mass require surgical evaluation
Surgical Evaluation R efer
to GynGyn-Onc specialist
Exploratory Exploratorylaparotomy laparotomyhas hasbeen beenthe thegold gold standard and includes: ± Peritoneal washings for cytology ± ± Evaluation of frozen section ± ± Complete staging procedure if borderline or ± malignant tumor on frozen section
Surgical Evaluation Laparoscopy Laparoscopycan canbe beconsidered consideredin in premenopausal woman with ovarian mass small enough to remove via laparoscopic approach; not recommended if high suspicion for malignancy
Stages Ia, Ib, Ic
Stages IIa, IIb, IIc
Stages IIIa, IIIb, IIIc
Stage IV
Treatment Depends Dependson onstaging, staging,tumor tumortype, type,age, age,desire desire for future fertility Can Caninclude includesurgery, surgery,chemotherapy chemotherapyand/or and/or radiation therapy Clinical Clinicaltrials trialsare areongoing ongoing
Surgical treatment Primary Primarydebulking debulkingand andcytoreduction; cytoreduction;may may include: ± Bilateral ± Bilateral salpingo salpingo--oopherectomy ± Hysterectomy ± ± Lymphadenectomy (para ± (para--aortic, inguinal) ± Omentectomy ± ± ³brushing´ of diaphragm, examination of liver ±
Chemotherapy and R adiation Usually Usually66cycles cyclesof ofchemotherapy chemotherapy Cisplatin Cisplatin(or (orCarboplatin) Carboplatin)plus plusPaclitaxel Paclitaxel most commonly used combination therapy XXR T
Screening Strategies Ultrasound Ultrasound(transvaginal (transvaginalvs vstransabdominal) transabdominal) Color Color -flow doppler CA CA--125 Other Othertumor tumormarkers markers
Ultrasound Both Bothtranabdominal tranabdominaland andtransvaginal transvaginal techniques techniques identify enlarged ovaries or abnormal morphology; TVUS has better resolution One Onelarge largestudy studyof ofTVUS TVUSunderway underwayhas hasreported reported sensivity of 81% and specificity of 98.9% Major Majorlimitations limitationsare arepoor poorPPV PPVin inasymptomatic asymptomatic women and inability to detect malignances when ovaries are normal size Allows Allowsearlier earlierstage stagedetection detection
Color--flow Doppler Color Used Usedininconjunction conjunctionwith withTVUS TVUS Measures Measuresresistance resistancein inblood bloodvessels vessels supplying the ovaries May Mayprovide provideadditional additionalinformation informationto tohelp help distinguish malignant from benign masses
CA--125 CA Sustained Sustainedelevation elevationinin82% 82%of ofwomen womenwith with advanced ovarian cancer, but fewer than 1% of healthy women Poor Poorsensitivity sensitivity(elevated (elevatedin inonly only50% 50%of of women with Stage I disease) Poor Poorspecificity specificity(elevated (elevatedin inmany many gynecologic and nonnon-gynecologic malignancies as well as benign conditions)
CA--125 CA Malignant conditions Cervical CervicalCA CA Fallopian Fallopiantube tubeCA CA Endometrial EndometrialCA CA Pancreatic PancreaticCA CA Colon ColonCA CA Breast BreastCA CA Lymphoma Lymphoma Mesothelioma Mesothelioma
Benign conditions Endometriosis/Menses Endometriosis/Menses Uterine Uterinefibroids fibroids PID PID Pregnancy Pregnancy Diverticulitis Diverticulitis Pancreatitis Pancreatitis Liver Liverdisease disease R enal failure Appendicitis Appendicitis IBD IBD
Lysophosphatidic acid (LPA) Tumor Tumormarker markerbeing beinginvestigated investigatedfor forscreening screening Phospholipid Phospholipidwith withmitogenic mitogenicand andgrowth growthfactor factor-like actions In In11small smallstudy studyLPA LPAwas wasdetected detectedin in99of of10 10 patients with Stage I ovarian CA, 24/24 with advanced cancer, and 14/14 with recurrent cancer. Only 28 of 47 pts had elevated CA CA--125, including 2 of 9 with Stage I disease
Current Screening Guidelines ³³R outine screening for ovarian cancer by ultrasound, the measurement of serum tumor markers, or pelvic examination is not recommended. There is insufficient evidence to recommend for or against the screening of asymptomatic women at increased risk of developing ovarian cancer.´ U.S.Preventive Services Taskforce, Guidelines from Guide to Clinical Preventive Services, 2nd edition, 1996
Screening Guidelines± Guidelines± cont¶d NIH NIHConsensus ConsensusConference Conference (1994) (1994) ± women with presumed hereditary cancer syndrome ± should undergo annual pelvic exams, CACA -125 measurements, and TVUS until childbearing is complete or at age 35, at which time prophylactic bilateral oopherectomy is recommended.
ACP ACP ± counsel high risk women about potential harms and ± benefits of screening
Screening, cont¶d American AmericanCancer CancerSociety, Society,AAFP AAFPand and ACOG do not recommend screening for ovarian cancer in the general population Canadian CanadianTask TaskForce Forceon onPeriodic PeriodicHealth Health Examination ± ³insufficient evidence to recommend for or ± against screening in highhigh -risk women´
Where do we go from here? Several Severalstrategies strategiesfor forscreening screeningcurrently currently under investigation ± TVUS as primary screening method ± ± Multimodal strategy using CA ± CA-125 as initial indicator and if elevated, TVUS used for secondary testing ± LPA (phospholipid with mitogenic and GF ± GF -like actions) may be more sensitive than CACA -125 in detecting early stage cancers
Ovarian Cancer Screening Trials 1.
The United Kingdom Collaborative Trial of Ovarian Cancer Screening: will compare TVUS and multimodal screening to control
2.
The European Study: R CT to screen women with TVUS at 1818-month or 33-year intervals
3.
The NIH Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: 1010 -year study using multimodal strategy
Take home points Screening Screeningnot notindicated indicatedatatthis thistime time ASK ASKabout aboutfamily familyhistory historyof ofcancers cancers LISTEN LISTENwhen whenwomen womenpresent presentwith withnon non-specific GI complaints; include OC in DDx DO DOperform performcareful carefulbimanual bimanualexam examand and rectal exam as part of pelvic exam R efer
women with + Family Hx to GynOnc
R eferences 1. 2. 3.
4.
5. 6.
American Cancer Society. Guidelines Guidelines for the cancercancer -related checkup: and update. Atlanta: American Cancer Society, 1993. Daly M, Obrams GI. Epidemiology and risk assessment for ovarian cancer. Semin Oncol 1998;25(3):2551998;25(3):255-264 DePriest PD, Gallion HH, van Nagell JJR Jr et al. Transvaginal sonography as a screening method for the detection of early ovarian cancer. Gynecol Oncol 1997;65(3):4081997;65(3):408-414 Hensley ML, Castiel M, R obson ME. Screening for ovarian cancer: what we know, what we need to know. Oncology (Huntingt) 2000;14(11):1601--1607 2000;14(11):1601 Holschneider Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol 2000;19(1):32000;19(1):3-10 Jacobs IJ, Skates SJ, et al. Screening for ovarian cancer: a pilot randomised controlled trial. Lancet 1999;353(9160):12071999;353(9160):1207-1210
R eferences, 7.
cont¶d
Kurtz AB, Tsimikas JV, et al. Diagnosis and Staging Staging of Ovarian Ovarian Cancer: Comparative Values of Doppler and Conventional US, CT and MR Imaging Correlated with Surgery and Histopathologic Analysis--R eport of the R adiology Diagnostic Oncology Group. Analysis 1999;212(1):19-27 R adiology 1999;212(1):198. NIH NIH Consensus Development Conference Statement. Ovarian cancer: screening, treatment, and followfollow -up. Gynecol Oncol 1994;55(3 Pt2):S4Pt2):S4-14. 9. Paley P. Screening for the major malignancies affecting affecting women: women: Current guidelines. Am J Obstet Gynecol 2001;184:10212001;184:1021-1030. 10. R ollins G. Developments in Cervical and Ovarian Cancer Screening: Implications for Current Practice. Ann Int Med 2000;133: 10211021-1024
