Ovarian Cancer Risk, Screening and Surgery - PowerPoint Presentation

1. Ovarian Cancer Risk, Screening and SurgeryStuart SalfingerGynaecologic OncologistMBBS, FRANZCOG, CGO, Dip Surg Ed

2. Ovarian CarcinomaLeading cause fatality gynaecologic cancerIncidence 1.5% lifetime risk75% present stage 3+Stage 3 disease 30% 5 year survival

3. ScreeningNO NO NO

4. Screening principlesRequires strong evidence baseBenefit > harmDisease criteria important problem latent or early asymptomaticTest criteria sensitivity, specificity validation safety high PPV NPV

5. Limitations of screeningNo premalignant or precursor lesionCurrent screening tests can not detect ovarian carcinoma early enough to alter the natural history of diseaseLow prevalence affects sensitivity and specificityExample 100,000 tested, prevalence 0.05%Even with sensitivity 99.9% Specificity 97.5%Results in 50 True positives and 2500 False positives (PPV 1.96%)Because of the high mortality need high sens. and spec. to intervene

6. Ca125CA125 levels alone cannot be used to rule in or rule out ovarian cancerCommonly elevated in premenopausal womenElevation may be related to benign disease both gynaecological and non-gynaecological

7. Ca125Poor sensitivity and SpecificityNormal 50% with early stage diseaseIncreased many benign conditions

8. UltrasoundImproved technologyOperator dependantUsed in combination with markers improves sens. and spec.Risk of Ovarian Cancer (ROC) algorithm serial measurements of CA125 (UK Collaborative Trial of Ovarian Cancer Screening trial.)

9. Combined USSReduces false positivesRepeat Ca 125 over time even betterROC algorithmUK Collaborative Trial Ovarian Cancer Screening

10. Biomarkersgene microarray profiling proteomic technology Biomarker panels no results are available on the use of these new biomarkers from prospective randomised trials in a healthy, asymptomatic population and there is no evidence for survival advantage using these markers in the screening context.

11. Screening for high riskOnly improvement in outcomes – prophylactic surgeryNo demonstrated role for screeningNo improvement mortality

12. Trials – high risk women1261 Women FHx, 6082 screens (Karlan et al, Am J O&G, 1999) 3 early stage cancers detected 7 cases advanced disease missed383 Women HBOC gene (Meeuwissen et al, Gyn Onc, 2005) 20 exploratory surgeries (abnormal screen) 1 malignancy found – (metastatic breast!) 2 interval cancers missed despite screening312 BRCA Women (Olivier et al, Gyn Onc, 2006) Sens 40%, Spec 99% 4 early stage cancers (3 at prophylactic surgery with normal screen)888 BRCA women (Hermsen et al, Br J Cancer, 2007) 10 incident cancers, 5 had normal screen, 80% stage 328460 Women high risk history PLCO (Lacey et al, Obst Gyn, 2006) PPV 2.8% in highest risk group

13. TrialsPLCO (Prostate, Lung, Colorectal, Ovarian)Prospective RCT 70,000 women, Ca125 & USSPPV combined 23.5%Finished after 2010UKCTOCS (UK Collaborative Trial Ovarian Cancer Screening)Prospective RCT 200,000 women, 3 arms, control, TVUSS, Ca1256 and USS in algorithmScreening till 2011, results…

14. HBOC syndrome womenThe evidence indicates limited effectiveness of screening in this population, and clinicians and patients should not be falsely reassured by negative screening test results.Consideration of OCP useThe ONLY proven intervention to decrease the risk of ovarian carcinoma in this population is prophylactic surgery

15. Asymptomatic women THERE IS NO ROLE FOR SCREENINGUS Preventive Services Task Force National Comprehensive Cancer NetworkAmerican College of Obstetricians and GynecologistsCanadian Task Force on the Periodic Health ExaminationThe National Cancer InstituteRoyal Australian New Zealand College Obstetrics & GynaecologyNational Breast and Ovarian Cancer CentreAustralian Society Gynaecologic Oncologists

16. What is the risk1/77 – 1.3% lifetime riskHBOC – 15-25% ovarian ca geneticBRCA 1 40-65%BRCA 2 20-40%HNPCC 15% (50% Endometrial)

17. NBOCC, RANZCOG, ASGO StatementPopulation screening and early detection of ovarian cancer in asymptomatic womenThere is currently no evidence that any test, including pelvic examination, CA125 or other biomarkers, ultrasound (including transvaginal ultrasound), or combination of tests, results in reduced mortality from ovarian cancer.There is no evidence to support the use of any test, including pelvic examination, CA125, or other biomarkers, ultrasound (including transvaginal ultrasound), or combination of tests, for routine population based screening for ovarian cancer.Further validation in large clinical trials is required before current or new biomarkers could be recommended for routine use in a population screening setting.

18. ScreeningThe holy grail!Jacobs Sorry pages of statistics don’t justify the media release Post hoc subgroup analysis2 in 10,000 women screened for 10 years – Not statistically significant

19. SurgeryThe only option for risk reduction in at risk women.Removal entire tube and ovary? Uterus…Decreases breast cancer risk 50%Risk incidental cancer 5-15%

20. ScenariosHysterectomy for benign diseasePatient for surgical sterilisationPatient with no other risk factors ovarian caPatient with Breast cancerPatient with Triple negative breast cancerPatient with strong family history ovarian caPatient with BRCA gene mutation

21. NBOCC GuidelinesKey points:• Decisions about timing of risk reducing surgery also need to take into account the family history of ovarian , particularly the earliest age at diagnosis in an affectedfamily member, and other possible health sequelae of this surgery.• The decision to have risk-reducing gynaecological surgery is complex and best made in a multi-disciplinary environment.

22. Risk Reduction Surgery4 to 8 percent chance of detecting occult malignancy20% Risk of malignancy in older women (45yrs +)Consent for full staging procedure recommendedSurgeon must be competent to do this

23. Risk Reduction SurgeryMinimum required BSOPeritoneal washingsMethodologic survey of: Abdomen (diaphragm, liver, omentum, bowel, paracolic gutters, appendix), Pelvis (ovaries, tubes, uterus, posterior cul de sac) Entire peritoneum Some surgeons also perform an omental biopsy and cytologic smear of the diaphragm, and liberal biopsies of any peritoneal irregularityRemove as much of the fallopian tube as possible, but complete cornual resection does not appear to be necessary

24. Risk Reduction SurgeryAll ovarian tissue should be removed, and as much of the fallopian tube as possible.If adhesions between the ovary and other peritoneal structures are present, the entire adhesion should be resected with the ovary to ensure that no residual ovarian cells remain attached to the peritoneal surface.The ovarian artery and vein should be clamped and cut at least 2 cm proximal to the ovary, and preferably at the pelvic brim, to avoid leaving any ovarian tissue behind. The pelvic peritoneum should be opened to visualize the ureter and isolate the infundibulopelvic ligament before transection.

25. Timing of SurgeryAs soon as childbearing complete, benefit lost with ageBRCA 1 – significant increase risk at 35 yearsBRCA 2 – significant increase risk at 40-45 yearsIf delay surgery will lose some of breast cancer risk reduction

26. Concurrent HysterectomyUnopposed estrogen therapy —unopposed estrogen can be given after hysterectomy, oestrogen alone appears to be associated with a lower breast cancer risk than combined.Tamoxifen — Women with BRCA mutations may want to take the selective estrogen receptor modulator tamoxifen for chemoprophylaxis of breast cancer. Tamoxifen use is associated with an increased risk of endometrial cancer. Women with HNPCC — Endometrial cancer is the most common malignancy.BRCA carriers — BRCA carriers may be at increased risk for some forms of endometrial cancer. (papillary serous carcinoma)

27. Pathology, Follow up & HRTSerial sectioning of entire ovary and tubeFollow up probably unnecesaryHRT – Balance risks and QOL benefits

28. SurgeryRequires adequate surgeryOR 20 (2-167) CGO vs GynRequires adequate pathologyOR 3.1 (1.4-6.7) CGO vs GynKiely, Friedlander et al Familial Cancer 2011

29. Why the tubesFrequent presence SIC in BRCA women6-39% (Salvador, IJGC 2009)26% (Hirst IJGC 2009)Molecular origins (Dietl Hum Reprod 2011)Ov & Tubal co-exist 50% cases (Marquez, Clin Can Research 2005)

30. STIC

31. Scenario - HysterectomyMinimal addition surgeryOvarian reserve unaffected (Dietl, Human Reprod 2011, Morelli, Gyn Onc 2013)A logical step, counsel removal

32. Scenario - Tubal ligationFilshie, coagulation – reversibleBS – irreversibleRisk of Regret 20% (Peterson, Telinde’s 2008)Counsel pros and cons

33. Indication in BRCA/High Risk WomenRRSO is standard treatmentNo evidence to support RRS aloneMaybe, just maybe in BRCA mutation carriers who wish to delay oophorectomy but want to take some form of action

34. Tube ScenariosIncidental at time of Hyst or sterilisation ✔Low risk women ✗Selected carefully counseled high risk women?

35. SummaryMultidisciplinary team approachRisk assessmentPre test counselingPost test counseling Screening chemoprevention Surgery