Adnexal Masses in Disclosure Menopausal Women Surgery or - PDF document

9/16/2017 Adnexal Masses in Disclosure Menopausal Women Surgery or Surveillance? I have no financial disclosures Frederick R Fr R. Ueland, MD Prof ofesso essor and r and Dire Direct ctor Divisi Division of of Gynec Gynecolo logi gic Onco Oncolo logy Univ Un iver ersity of sity of Kentucky ucky Ovarian Tumor Overview Wind River Range, WY July, 2017 Past  1980’s “palpable ovary syndrome”  2000’s observation of unilocular cysts  2010’s observation of septate cysts Present  10% require surgery for adnexal mass in their lifetime 1  13%-21% are malignant 2 1) Moore, McMeekin, Brown et al. Gynecol Oncol, 2009 2) Jordan. Current Biomarker Findings, 2013 1

9/16/2017 Ovarian Tumor Overview The Specifics 39,337 ultrasounds performed Premenopausal Menopausal  30% high risk (9%)  Many tumors, few cancers  Few tumors, many cancers  50% are malignant  15% are malignant solid - Epithelial ovarian cancer - Germ cell tumors cyst+solid unilocular - Metastatic cancer - LMP tumors - Granulosa cell tumors 70% 70% - Epithelial cancers  Benign tumors septate 30% 30%  Benign tumors - Cystadenoma - 70% functional cysts - Fibroma Normal Abnormal - 20% neoplastic - Thecoma - 10% endometriomas  70% low risk (21%)  Other - Inflammatory Pavlik E, Ueland F, Miller R, et al. Obstet Gynecol, 2013 Menopausal Women Incidence Prevalence Ultrasound Ultrasound Number of new ovarian Proportion who have cysts identified cysts at any given time Lessons Learned  8.2% 1  17% 1 Reducing Subjectivity IOTA: Simple Rules, ADNEX Model  3.3 million women 2  6.8 million women 2 Kentucky Morphology Index Most are low risk for malignancy 1) Pavlik E, Ueland F, Miller, R. et al. Obstet Gynecol, 2013 2) United States Census Bureau, 2010 2

9/16/2017 Lessons Learned Limiting Subjectivity ■ First International Consensus Report 1 Tumor morphology helps stratify cancer risk Screening trial Surgeries per cancer ■ International Ovarian Tumor Analysis (IOTA) - UKCTOCS 35.2 o Simple Rules 2 - PLCO 19.5 - Kentucky o ADNEX 3  first decade (1990’S) 12.5 ■ Kentucky Morphology index 4  second decade (2000’S) 5.2 ■ Serial sonography 5  third decade (2010’S) 4.0 1) J Ultrasound Med, 2017; 2) Ultrasound Obstet Gynecol, 2008; 3) Br Med J, 2014; 4) Gynecol Oncol, 16-Sep-17 2003; 5) Gynecol Oncol, 2014 9 IOTA Simple Rules M1 Irregular solid ■ M2 Presence of ascites ■ M3 At least 4 papillary projections ■ M4 Irregular multilocular solid, largest diameter ≥ 10 cm ■ M5 Very strong blood flow ■ B1 Unilocular ■ B2 Solid component < 7 mm ■ B3 Presence of acoustic shadows ■ B4 Smooth multilocular tumor, largest diameter < 10 cm ■ B5 No blood flow ■ Timmerman et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound Obstet Gynecol 31; 681-690, 2008 3

9/16/2017 ADNEX Risk Model Simple Rules Belgium, Italy, Czech Republic, Poland, UK, Sweden Malignan Malign ant If one or more M-rules apply in the absence of a B-rule, the IOTA - ADNEX model ___ mass is classified as malignant 1. Age of the patient at examination (years) __________ 2. Oncology center (referral center for gyn-oncol)? Benig Benign _____________ 3. Maximal diameter of the lesion (mm) If one or more B-rules apply in the absence of an M-rule, the 4. Maximal diameter of the largest solid part (mm) ____________________ mass is classified as benign. ______ 5. More than 10 locules? Indeterminat Inde ate _______ 6. Number of papillations (papillary projections) If both M-rules and B-rules apply, the mass cannot be ______ 7. Acoustic shadows present? classified. If no rule applies, the mass cannot be classified _____ 8. Ascites (fluid outside pelvis) present? _____ 9. Serum CA-125 (U/ml) Timmerman et al. Simple ultrasound-based rules for the diagnosis of ovarian cancer. Ultrasound C lear Obstet Gynecol 31; 681-690, 2008 Van Calster et al. Evaluating risk of ovarian cancer before surgery using the ADNEX model. BMJ, 2014 14 Kentucky Morphology Index Kentucky MI MI MI Total Maligna nant nt 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 Sensitivity 86% 5 1,061 29 2.73 Specificity 98% 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 Ueland F, DePriest P, Pavlik E, et al. Gynecol Oncol, 2003 4

9/16/2017 Comparing Models ADNEX Model Kentucky MI Biomark Biomarkers  ROM correlates with  ROM correlates with increased cancer risk increased cancer risk Diagnostic  52% of cancers in  15% of cancers in lowest Triage lowest ROM groups ROM groups Comparison  Efficacy in surveillance  MI change over time is is unknown useful for surveillance  Misses stage 1 cancers  Identifies stage 1 cancers 16-Sep-17 17 Lefringhouse J, Ueland F, Ore R, et al. SGO, 2016 CA125 Performance ‘Diagnostic’ Biomarkers Triage Biomarkers • CEA • OVA1 * • CA19 ‐ 9 • LDH • ROMA • β‐ hCG • Overa + • AFP • HE ‐ 4 • CA125 * Multivariate Index Assay + MIA2G Myers et al. Management of adnexal mass. Rockville (MD): U.S. Department of 19 Health and Human Services, 2006 20 5

9/16/2017 Triage Biomarker Tests Triage Biomarker Tests OVA1 Overa • FDA-cleared September, 2009 • FDA-cleared September, 2016 • Multivariate Index Assay • Multivariate Index Assay-2G Range 0 nge 0-10 Prem emeno enopaus ausal Post Po st • CA125, HE-4, FSH, Apolipoprotein A1, Transferrin Low Risk < 5.0 < 4.4 High Risk ≥ 5.0 ≥ 4.4 Range 0- Rang e 0-10 Result sult ROMA Low Risk < 5.0 • FDA-cleared September, 2011 High Risk ≥ 5.0 • Dual marker test CA125 + HE4 Range 0 nge 0-10 Prem emeno enopaus ausal Po Post st Low Risk < 1.31 < 2.77 High Risk ≥ 1.31 ≥ 2.77 21 22 Comparing Biomarkers Recommended Ev commended Evalu aluation tion Sensitivity Overa 1 OVA1 2,3 ROMA 4 CA125 ‐ II 2,5 All malignancies 91% 93% 89% 69% Epithelial ovarian cancers 95% 99% 94% 82% Early stage EOC 89% 98% 75% 66% Determine Malignant Risk with Ultrasound Premenopausal women 90% 94% 76% 36% 1. Low risk ‐ surveillance Postmenopausal women 92% 100% 92% 80% 2. Indeterminate ‐ secondary testing Specificity All malignancies 69% 54% 75% 87% 3. High ris k ‐ refer to Gynecologic Oncologist OVA1 detected 76% of malignancies missed by CA125 1 1) Coleman R, Herzog T, Chan D, et al. Am J Obstet Gynecol, 2016 2) Ueland F, DeSimone C, Seamon L, et al. Obstet Gynecol, 2011 3) Bristow R, Smith A, Zhang Z, et al. Gynecol Oncol, 2013 4) Moore R, McMeekin S, Brown A, et al. Gynecol Oncol, 2009 5) Myers et al. Management of adnexal mass. Rockville (MD): U.S. Department of HHS, 2006 6

9/16/2017 Low Risk Recommended Evaluation Malignant • Smooth-walled Low Indeterminate High Risk • Unilocular or septate Distribution 65% 25% 10% Partly solid, Mostly solid, US Unilocular small wall papillary morphology or septate abnormalities projections Secondary No YES No testing Septate cyst 3 Surgery No Maybe YES Unilocular cyst 1,2 1) Modesitt et al. Gynecol Oncol, 2003; 2) Bailey et al. Gynecol Oncol, 1998; 3) Saunders B. 25 et al. Gynecol Oncol, 2010 Resolution for Low Risk Malignant Potential for Low Risk Resolution T Re Time Cyst & Cys & Type o Ty of Abnormality Cyst Cys Cyst & & Soli Solid Soli olid Septae Sep Scans 6,239 1790 581 154 Abnormalities 1,288 366 122 24 Average Scans 4.8 4.9 4.8 6.4 Mean (mo) 31.0 26.5 23 26.4 Summary of Valentin et al, 2013 33% unilocular Median (mo) 17 14.1 8.3 12.7 1% malignant • 0.54% Premenopausal 75th percentile 38.4 36.0 33.8 38.7 • 2.76% Postmenopausal (mo) 7/11 had solid or papillary component on visual surgical inspection 90th percentile 70.9 64.5 64.3 93.8 (mo) 16-Sep-17 Valentin, Ameye, Franchi et al. Ultrasound Obstet Gynecol, 2013 27 28 Ore R, Ueland F, Lefringhouse J, et al. SGO Annual Meeting abstract, 2016 7

9/16/2017 Indeterminate Risk Recommended Evaluation • Small, irregular wall abnormalities Malignant Low Indeterminate High • Partly solid Risk • Atypical, non-papillary projections Distribution 65% 25% 10% Partly solid, Mostly solid, US Unilocular small wall papillary morphology or septate abnormalities projections Secondary No YES No testing Surgery No Maybe YES 16-Sep-17 29 30 Serial Morphology Index ∆ MI MI N ∆ MI MI P-value P-value per month Surgery for epithelial 50 * 1.9 1. 0.9 0.9 P<0.001 P<0.001 ovarian malignancy Tumor type MI score Surgery for non-malignancy 272 0.7 0.7 P<0.001 0.2 0.2 P<0.001 • Malignant Increase Resolved ovarian cysts 5811 -2.7 -2.7 P<0.001 -1.1 -1 P<0.001 • Non ‐ malignant Stable or gradual rise • Resolving Decrease * 24 subjects had 1 scan only 31 Elder J, Pavlik E, Long A et al. Gynecol Oncol 135; 8-12, 2014 8