This document provides an overview of epithelial ovarian cancer including epidemiology, risk factors, pathology, clinical presentation, diagnosis, staging, treatment options, and outcomes. It discusses that ovarian cancer is the second most common gynecologic malignancy in Western countries. Seventy percent of patients present with advanced stage disease. Treatment depends on stage but typically involves surgery and platinum-based chemotherapy. Outcomes have improved over time but remain poor for advanced and recurrent disease.

1. Epithelial Ovarian Cancer Clinical Presentation, Diagnosis, Staging (1) Treatment (2) Jan B. Vermorken, MD, PhD Department of Medical Oncology Antwerp University Hospital Edegem, Belgium ESO student course, Ioannina, 2011

2. Antwerp University Hospital

9. Ovarian Cancer Clinical Presentation Early disease: no specific signs / symptoms nausea, indigestion, lower abominal disconfort, abnormal vaginal bleeding Advanced disease: GI symptoms – constipation Urinary symptoms – frequency Abdominal symptoms – pain, distension

10. Distended abdomen: ovarian mass

14. FIGO Staging (2008) Ovarian Cancer IA Confirmed to one ovary, no ascites, intact capsule IB Confirmed to both ovaries (same criteria as IA) IC IA or IB + tumor surface/capsule rupture/pos. cells IIA Extension to the uterus or tubes IIB Extension to other pelvic tissues IIC IIA or IIB + tumor surface/capsule rupture/pos. cells III One or both ovaries + extension outside pelvis or limited to true pelvis + extension to small bowel or omentum IIIA LN Θ , extension only microscopically IIIB LN Θ , extension not exceeding 2 cm in diameter IIIC LN + (RP/inguinal) and/or extension >2 cm in diameter IV One or both ovaries + DM (or parenchymal liver mets)

17. Five-year Survival in Ovarian Cancer 30 years of experience Vol. Year Cases Ia IV Overall (n) % 16 1963-68 4588 66.7 5.0 27.3 19 1976-78 6724 72.3 4.5 29.8 21 1982-86 10912 82.3 8.0 35.0 23 1990-92 7059 83.5 11.1 41.6 25 1996-98 4116 89.3 13.4 46.4 26* 1999-01 4911 89.3 18.6 49.7 Int. J Gynecol Obstet 2006 (Suppl 1)

21. ICON1 + ACTION Two Parallel Randomised Phase III Trials of Adjuvant Chemotherapy in Patients with Early Stage Epithelial Ovarian Cancer ICON1 (International Collaborative Ovarian Neoplasm studies) launched in 1991 ACTION (EORTC: Adjuvant Clinical Trial In Ovarian Neoplasm) launched in 1990

22. Results in High-Risk Early Ovarian Cancer Adjuvant platinum-based Chemotherapy 105 460 75 465 Events Total Adjuvant chemotherapy No adjuvant chemotherapy S u r v i v a l 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Months from randomisation 0 12 24 36 48 60 72 84 96 108 120 HR=0.64; P=0.001 HR=0.68; P=0.01 Recurrence-free survival Overall survival ICON1 + ACTION 140 460 98 465 Events Total Adjuvant chemotherapy No adjuvant chemotherapy P e r c e n t a g e 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Months from randomisation 0 12 24 36 48 60 72 84 96 108 120

27. When to Treat? Harries and Gore, 2002

28. Trial Design Ovarian cancer in complete remission after first-line platinum based chemotherapy and a normal CA125 CA125>2 x upper limit of normal RANDOMIZED Early treatment Clinician and patient informed Delayed treatment Clinician not informed , treatment delayed until clinically indicated REGISTER Blinded CA125 measured every 3 months Rustin GJ et al, Lancet 2010; vol 376: 1155-1163

29. Overall Survival HR=1.00 (95%CI 0.82-1.22) p=0.98 Early Delayed Abs diff at 2 years= 0.1% (95% CI diff= -6.8, 6.3%) Rustin GJ et al, Lancet 2010; vol 376: 1155-1163

31. Single Agent Chemotherapy in ROC Relationship with platinum sensitivity Agent Response rates (%; range) Refractory Resistant Sensitive Platinum < 10 27-34 59-77 Paclitaxel 3-22 11-37 22-55 Topotecan 6-11 15-18 19-33 Gemcitabine 15-20 19-27 34 Epirubicin 11 a 14 36 Liposomal dox 11 9-15 18-37 Vinorelbine 15-30 21-33 29 Etoposide 27 27 34 Altretamine 10-14 40 Conte PF, 2000; Vermorken JB 2000 ( a PFI < 3 mo) Johnston & Gore 2001, Stebbing & Gaya 2002