9/23/2015 Adnexal Masses in Disclosure Menopausal Women • I am a member of Vermillion’s Speakers’ Bureau Surgery or Surveillance? • I am NOT a paid consultant for Vermillion Inc. nor do I have a have financial interest in any related FRED TALK company IDEAS WORTH SPREADING Frederick R. Ueland, MD Professor and Director Division of Gynecologic Oncology University of Kentucky 2 Ovarian Tumors Ovarian Tumors Past Premenopausal Postmenopausal – 1980’s “palpable ovary syndrome” Many tumors, few cancers Few tumors, many cancers • • – 2000’s observation of unilocular cysts Low prevalence High prevalence – – 15% are malignant 50% are malignant • • – 2010’s observation of septate cysts Germ cell tumors Epithelial ovarian cancer – – Present Borderline tumors Metastatic cancer – – Epithelial cancers Granulosa cell tumors – – – 10% of women undergo surgery for adnexal mass in their Benign tumors Benign tumors • • lifetime 1 70% functional cysts – Cystadenoma – – 13% ‐ 21% of these masses are malignant 2 20% neoplastic – Fibroma – 10% endometrioma s – Thecoma – Other • Inflammatory – 1. Moore, McMeekin, Brown et al. Gynecol Oncol, 2009. 2. Jordan. Current Biomarker Findings, 2013. 1
9/23/2015 Frequency of Cysts 1 N=39,337 % Premenopausal 15 Ultrasound Incidence 15 Prevalence 35 Lessons Learned Postmenopausal 85 30 million 2 IOTA’s ADNEX Model Incidence 8 2.4 million Kentucky Morphology Index (MI) Prevalence 17 5 million Comparison Low Risk (70%) 21 Unilocular cysts 54 Cysts with septations 46 High Risk (30%) 9 Cysts with solid areas 80 Solid mass 20 23 ‐ Sep ‐ 15 1. Pavlik E, Ueland F, Miller R, et al. Obstet Gynecol, 2013. 2. United States Census Bureau, 2010. Available from: www.census.gov. 5 ADNEX Risk Model Lessons Learned International Ovarian Tumor Analysis Belgium, Italy, Czech Republic, Poland, UK, Sweden Using morphology ‐ based ultrasound helps stratify cancer risk. IOTA - ADNEX model ___ 1. Age of the patient at examination (years) Screening Strategy Surgeries/Cancer – UKCTOCS 35.2 2. Oncology center (referral center for gyn-oncol)? __________ 3. Maximal diameter of the lesion (mm) _____________ – PLCO 19.5 4. Maximal diameter of the largest solid part (mm) ____________________ – Kentucky 12.5 5. More than 10 locules? ______ • first decade (1990’S) 5.2 • second decade (2000’S) 6. Number of papillations (papillary projections) _______ 4.0 • third decade (2010’S) 7. Acoustic shadows present? ______ 8. Ascites (fluid outside pelvis) present? _____ _____ 9. Serum CA-125 (U/ml) 23 ‐ Sep ‐ 15 C lear 7 8 2
9/23/2015 Kentucky Morphology Index Kentucky MI MI Total Malignant ROM (%) 1 2,349 1 0.04 2 2,365 0 0.00 3 2,635 3 0.11 4 1,579 7 0.44 ? 5 1,061 29 2.73 6 241 9 3.73 7 87 11 12.64 85% 8 30 8 26.67 9 18 5 27.78 10 3 1 33.33 Total 10,368 74 0.71 Ueland F, DePriest P, Pavlik E, et al. Gynecol Oncol, 2003. Elder J, Pavlik E, Long A, et al. Gynecol Oncol, 2014. Comparing Models ADNEX Model Kentucky MI Biomarkers • ROM correlates with • ROM correlates with increased cancer risk increased cancer risk CA125 • 52% of cancers in • 15% of cancers in lowest OVA1 lowest ROM groups ROM groups ROMA • Limited as decision aid • High risk cutoff effectively to surgery identifies CA • Misses stage 1 cancers • Identifies stage 1 cancers Lefringhouse J, Ueland F, Ore R, et al. SGO Annual Meeting abstract, 2016. 23 ‐ Sep ‐ 15 11 3
9/23/2015 CA125 Performance Management of Adnexal Mass Sensitivity Specificity Cost ($ US) Bimanual exam 0.45 0.90 $ CA ‐ 125 0.78 0.78 $ US morphology 0.90 0.76 $$ US + Doppler 0.86 0.91 $$ CT scan 0.90 0.78 $$$$$$$$$$$ MRI 0.91 0.88 $$$$$$$$$$$$$$$ $=$200 Myers et al. Management of adnexal mass. Rockville (MD): U.S. Department of Health and Human Services, 2006 Myers et al. Management of adnexal mass. Rockville (MD): U.S. Department of Health and Human Services, 2006 13 14 Ovarian Tumor Biomarker Tests Comparing Biomarkers OVA1 OVA1 1,2 ROMA 3 CA125 ‐ II 1,4 Sensitivity • FDA ‐ cleared September, 2009. First preoperative test for ovary All malignancies 93% 89% 69% • Multivariate Index Assay Epithelial ovarian cancers 99% 94% 82% Range 0 ‐ 10 Premenopausal Postmenopausal Early stage EOC 98% 75% 66% Low Risk < 5.0 < 4.4 High Risk ≥ 5.0 ≥ 4.4 Premenopausal women 94% 76% 36% Postmenopausal women 100% 92% 80% ROMA Specificity • FDA ‐ cleared September, 2011 All malignancies 54% 75% 87% • Dual marker test CA125 + HE4 Range 0 ‐ 10 Premenopausal Postmenopausal OVA1 detected 76% of malignancies missed by CA125 1 Low Risk < 1.31 < 2.77 High Risk ≥ 1.31 ≥ 2.77 1. Ueland F, DeSimone C, Seamon L et al. Obstet Gynecol, 2011. 2. Bristow R, Smith A, Zhang Z, et al. Gynecol Oncol, 2013. 3. Moore R, McMeekin S, Brown A et al. Gynecol Oncol, 2009. 4. Myers et al. Management of adnexal mass. Rockville (MD): U.S. Department of Health and Human Services, 2006 15 4
9/23/2015 Evaluation Strategy Evaluation Strategy Malignant Risk Low Indeterminate High Determine Malignant Risk with Ultrasound 1. Low risk tumors ‐ monitor without surgery Distribution 65% 25% 10% 2. Indeterminate tumors ‐ secondary testing Partly solid, Mostly solid, Unilocular or US morphology small wall papillary • Serial ultrasound septate abnormalities projections • Biomarkers Biomarker testing No YES No 3. High risk tumors ‐ refer to Gynecologic Oncologist for surgery Surgery No Maybe YES 18 Low Risk Resolution for Low Risk • Unilocular or septate • Smooth ‐ walled Resolution Time Cyst & Type of Structure Cyst Cyst & Solid Solid Septation Scans, n 6239 1790 581 154 Structures, n 1288 366 122 24 Average Scans, n 4.8 4.9 4.8 6.4 Mean (mo) 31.0 26.5 23 26.4 Septate cyst 3 Median (mo) 17 14.1 8.3 12.7 75th percentile (mo) 38.4 36.0 33.8 38.7 Unilocular cyst 1,2 1 Modesitt et al. Gynecol Oncol, 2003. 2 Bailey et al. Gynecol Oncol, 1998. 90th percentile (mo) 70.9 64.5 64.3 93.8 3 Saunders B. et al. Gynecol Oncol, 2010. 20 Ore R, Ueland F, Lefringhouse J, et al. SGO Annual Meeting abstract, 2016. 5
9/23/2015 Malignant Potential for Low Risk Evaluation Strategy Malignant Risk Low Indeterminate High Distribution 65% 25% 10% Small solid wall, Mostly solid, Unilocular or US morphology atypical papillary septate projections projections Summary 33% unilocular Biomarker testing No YES No 1% malignant • 0.54% Premenopausal • 2.76% Postmenopausal 7/11 had solid or papillary component on visual surgical inspection Surgery No Maybe YES Valentin, Ameye, Franchi et al. Ultrasound Obstet Gynecol, 2013. 23 ‐ Sep ‐ 15 21 22 Indeterminate Risk Small, irregular wall abnormalities • • Partly solid tumors • Atypical, non ‐ papillary projections ∆ MI N ∆ MI P ‐ value P ‐ value per month Surgery for epithelial 50 * 1.9 P<0.001 0.9 P<0.001 ovarian malignancy Surgery for non ‐ malignancy 272 0.7 0.2 P<0.001 P<0.001 Resolved ovarian cysts 5811 ‐ 2.7 ‐ 1.1 P<0.001 P<0.001 23 ‐ Sep ‐ 15 * 24 subjects had 1 scan only 23 6
9/23/2015 Serial Morphology Index ‘Diagnostic’ Biomarkers Triage Biomarkers • CEA • CA19 ‐ 9 • OVA1* • LDH • ROMA • β‐ hCG • AFP • HE ‐ 4 • CA125 Tumor type MI score • Malignant Increase *Multivariate Index Assay • Non ‐ malignant Stable or gradual rise • Resolving Decrease 25 26 Elder J, Pavlik E, Long A et al. Gynecol Oncol, 2014. Evaluation Strategy High Risk • Irregular, solid Malignant Risk Low Indeterminate High • Papillations • Ascites Distribution 65% 25% 10% Partly solid, Mostly solid, Unilocular or US morphology small wall papillary septate abnormalities projections • ROM >25% Biomarker testing No YES No • Refer to Gynecologic Oncologist Surgery No Maybe YES 23 ‐ Sep ‐ 15 27 28 7
9/23/2015 Summary 1. Ultrasound is best for menopausal ovarian tumors 2. Determine risk: • Low ‐ monitor without surgery ‒ 6 months, then annually • Indeterminate ‐ additional testing ‒ Serial ultrasound ‒ Biomarker testing (consider OVA1 or ROMA) • High ‐ surgery ‒ Refer to a Gynecologic Oncologist 29 8
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