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Ovarian Cancer Screening Dr Karen Mizia SAN Ultrasound for Women 0562/SAH/1112/SAH Learning Objectives • Review the current evidence with regard to ovarian cancer screening • How to assess the importance of an ovarian mass • When to refer Ovarian Cancer • High mortality rate • Stage I 90% 5 year survival • Stage III or IV 30% survival • Leading cause of death from gynaecological malignancy • Relatively uncommon with an incidence of 10 in 100 000 • Aim to improve mortality rate with screening Ovarian Cancer Screening Trials PLCO (USA) UKC-TOCS (UK) Multi-centre (Japan) University of Kentucky (USA) Ovarian Cancer Screening Trials PLCO (USA) UKC-TOCS (UK) Multi-centre (Japan) University of Kentucky (USA) • Randomised controlled trial of 78,216 women aged 5574 • Annual screening with TVUS and serum Ca-125 for 4 years or their usual gynae care • US screen positive: ovarian volume > 10 cc, any cyst > 10 cc, any cyst with any solid area • Physician informed of abnormal results within 3 weeks • Treatment left to the discretion of the treating doctor • 71% of OvCa detected by TVUS alone were stage I-II • Ratio of surgeries to screen detected OvCa 19.5:1 • No evidence of a shift to earlier stage disease with screening • Survival rates similar Ovarian Cancer Screening Trials PLCO (USA) UKC-TOCS (UK) Multi-centre (Japan) University of Kentucky (USA) • 202 638 post menopausal women aged 50-74 years randomly assigned to: • No treatment • Annual Ca125 with TVUS as a second line • TVUS annually • US Screen positive: complex ovarian mass, simple cyst >60 cc, ascites • Abnormal primary screen repeat TVUS 6-8 weeks abnormal scan referred for clinical assessment • Clinical assessment then involved further Ca125, TVUS with Colour Doppler studies, CT/MRI • In TVUS arm: • Surgeries to screen detected OvCa 18.8:1 • 50% had stage I or II (26% in control arm) • Multimodal arm: • Surgeries to screen detected OVCa 2.8:1 • 47% has stage I or II • Mortality result pending Ovarian Cancer Screening Trials PLCO (USA) UKC-TOCS (UK) Multi-centre (Japan) University of Kentucky (USA) • Prospective randomised trial • 41 688 asymptomatic post menopausal women • Screen arm (annual pelvic exam, TVUS and Ca125) or control • US screen positive: malignant impression, > 4 cm • Management at discretion of oncologist • TVUS associated with increase in early stage (63% vs 38%) • Mortality result pending Ovarian Cancer Screening Trials PLCO (USA) UKC-TOCS (UK) Multi-centre (Japan) University of Kentucky (USA) • 41 413 women aged over 50 or above 25years with family history • Case control: screening group compared to matched controls in the same hospital • Screen positive repeat screen 4 weeks Ca125 repeat TVUS with colour Doppler and tumour indexing laparoscopic tumour removal within 8 weeks • 68% stage I or II (27% controls), higher sub-stage shift • 12 interval cancers • 5 year survival 75% vs 53% No current benefit to screening the asymptomatic women • • • • • • • • • • RANZCOG RCOG ACOG American Task Force US Preventative Services Task Force National Comprehensive Cancer Network Canadian Task Force on the Periodic Health Exam National Cancer Institute National Breast and Ovarian Cancer centre Australian Society of Gynaecology Oncologists So a patient walks in… • • • • History Family history Serum biomarkers Ultrasound • Age: mean is 63 years • In early age group benign more likely than malignant • Reproductive age more likely functional cyst, epithelial ca rare but borderline and sex cord stromal ca can occur • Symptoms • Most cysts asymptomatic • Pain, pressure, bloating, frequency, early satiety (PPV 1%) • Bimanual • Inaccurate for detecting and characterising cysts • Firmness and nodularity on POD So a patient walks in… • History • Family history • Serum biomarkers • Ultrasound Past History Relative risk Infertility 2.8 Nulliparous 1.6 Breast feeding 0.81 Oral contraceptive pill 0.65 Tubal ligation 0.59 Nagell and Hoff (2014) Transvaginal ultrasounograhpy in ovarian cancer: current perspectives, International Journal of Women’s Health, 6,25-33 So a patient walks in… • History • Family history • Serum biomarkers • Ultrasound • Genetic predisposition: • family cancer syndromes have 3050% lifetime risk • x1 relative 3.7% • x2-3 relatives 5.5% • Only 10% OvCa occur in patients with a family history • ACOG recommend period screening So a patient walks in… • • • • History Family history Serum biomarkers Ultrasound • Ca125 • Elevated in 50% of stage I, 90% stage III • Not specific: elevated with other cancer, benign disease • Change over time • HE4 • Improved sensitivity with Ca125 • Promising for triage not screening • OvPlex • Developed by HelathLinx Lmt • Marketed as early detection test • Measures ca125 and 4 other protein biomarkers • Company reports sensitivity 94.1% and specificity 91.3% Nossov et al (2008) the early detection of ovarian cancer from traditional methods to proteomics, 199, 215-23 OvPlex So a patient walks in… • History • Family history • Serum biomarkers • Ultrasound • Some features seen on ultrasound are diagnostic Dermoid cyst Endometrioma Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian cancer, UOG, 6, 681-690 So a patient walks in… • History • Family history • Serum biomarkers • Ultrasound • International Ovarian Tumour Association (IOTA) • Compared simple ultrasound rules, logistic regression models, risk of malignancy index and clinical skill • 75% of masses defined as benign or malignant with simple rules • 93% sensitivity and 90% specificity IOTA simple rules Benign Malignant Unilocular cyst Irregular solid tumour Solid component where the largest is < 7 mm in largest dimension Ascites Acoustic shadowing At least 4 papillary projections Smooth multilocular cyst < 100 mm in largest dimension Irregular multilocular solid tumour at least 100 mm in largest dimension No detectable blood flow on Colour Doppler Imaging Very high colour component on Colour Doppler Imaging ONE OR MORE BENIGN, NO MALIGNANT FEATURES = BENIGN ONE OR MORE MALIGNANT, NO BENIGN FEATURES = MALIGNANT Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian cancer, UOG, 6, 681-690 Ultrasonic features Predictive value For predicting a malignant tumour (M features) M1—Irregular solid tumour M2—Presence of ascites M3—At least four papillary structures 96 (88 to 98); 64/67 97 (93 to 99); 157/162 88 (80 to 93); 75/85 M4—Irregular multilocular solid tumour with largest diameter ≥100 mm 84 (77 to 90); 103/122 M5—Very strong blood flow (colour score 4) 88 (82 to 92); 131/149 At least one M feature 87 (84 to 90); 340/389 For predicting a benign tumour (B features) B1—Unilocular 99 (98 to 99); 673/681 B2—Presence of solid components, of which largest solid component has largest diameter <7 mm 100 (90 to 100); 33/33 B3—Presence of acoustic shadows 95 (92 to 97); 223/234 B4—Smooth multilocular tumour with largest diameter <100 mm 99 (97 to 100); 190/191 B5—No blood flow (colour score 1) 98 (96 to 99); 615/629 At least one B feature 97 (96 to 98); 1083/1112 Rule 1: If one or more M features are present in absence of B feature, mass is classified as malignant. Rule 2: If one or more B features are present in absence of M feature, mass is classified as benign. Rule 3: If both M features and B features are present, or if no B or M features are present, result is inconclusive and second stage test is recommended. 10% of multilocular cysts proved to be malignant functional mucinous cystadenoma Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian cancer, UOG, 6, 681-690 Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian cancer, UOG, 6, 681-690 • Unilocular solid • Borderline malignant serous papillary cystadenoma • Malignancy found in 37% of solid masses Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian cancer, UOG, 6, 681-690 Malignancy found in 43% of multilocular solid masses Borderline serous papillary adenocarcinoma Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian cancer, UOG, 6, 681-690 • Colour doppler flow image of solid mass in 28 yo • Dysgerminoma • 65% of solid tumours proved to be malignant Timmerman et al (2008) Simple ultrasound rules for the diagnosis of ovarian cancer, UOG, 6, 681-690 Learning Objectives • Review the current evidence with regard to ovarian cancer screening No evidence to suggest routine population screening is helpful • How to assess the importance of an ovarian mass Consider the complexity Combining markers with clinical suspicion improves detection when an adnexal mass is detected improves sensitivity and specificity • When to refer Benign features conservative management or to gynaecologist Malignant features, raised tumour markers or uncertain to gynae-oncologist