OBJECTIVES 10637 Describe and recognize the following regarding ovarian cancer:

1. OBJECTIVES 10637 Describe and recognize the following regarding ovarian cancer: etiology, risk factors, signs and symptoms, laboratory and diagnostic tests, treatment. 4244 Compare and contrast the common pathways of metastasis for ovarian cancers. 4397 List the risk factors associated with ovarian cancer.

2. Ovarian Cancer: THE FACTS • Lifetime risk: 1.4% • BUT is the 4th leading cause of cancer death in women • In ♀ > 50yo, ovarian tumour is malignant in >50% of cases

3. Etiology • Germ cells • Cystic Teratoma • Epithelial • Serous • Mucinous • Endometrioid • Metastatic • Breast • GI tract • Endometrium • Sex cord-stromal • Granulosa-theca • Sertoli-Leydig

5. GERM CELLS OVARIAN TUMOURS • 15-20% of ovarian tumours • Mainly young women 20-30s • Most common is benign cystic Teratoma (Dermoid) • Presentation: • Pelvic mass pain due to rapidly growing size • Usually caught at stage 1

6. EPITHELIAL OVARIAN TUMOURS • 65-70% of ovarian tumours • Accounts for 90% of malignant ovarian tumours • 5-10% of cases are familial • (mostly associated with BRCA1 and BRCA2 mutations) • Widespread metastases in peritoneum and on bowel surfaces • at time of dx • GI symptoms: • Abdominal pain • Bloating • Early satiety • Increased abdominal girth • On P/E: • ascites • abdominal/pelvic mass • omental nodules • Elevated CA125 (N <35 U/ml) ++ specificity post-menopausal

7. SEX-CORD STROMAL OVARIAN TUMOURS • 5-10% ovarian tumours • Hormonally active • Granulosa cell tumours – produce estrogen • 70% • Sertoli-Leydig tumours – produce androgen • Non-hormonally active • Fibroma = benign, Meig’s syndrome

8. METASTATIC • 5% of ovarian tumours • Genital tract, GI tract, breast

9. ♀ 63 yo, G0 CC/HPI: LLQ pain Intermittent nausea Abdominal pressure Bloating PMH: Mild obesity Right breast cancer HTN Infertile couple FH: Pre-menopausal breast cancer (mother, maternal aunt) P/E: Moderate ascites Prior investigations: CA125 = 719 (N <35 U/ml) Pelvic US – N uterus, Left adnexal mass (9cm, internal septations, papillary excrescences)

10. DDX:

11. Post-menopausal woman  Germ cell tumour unlikely GI symptoms  common in Epithelial cell tumour or Metastasis Personal Breast cancer Hx  Metastasis Familial Breast cancer Hx  Epithelial cell tumour related to BRCA1/BRCA2 mutation ↑ CA125 in post-menopausal woman  Epithelial cell tumour Imaging description of mass  features of malignancy (Vegetations/Papillary projections/Septations (>3mm), Ascites, Bilaterality, Complex cystic and solid components, Peritoneal nodularity)

12. (Epithelial Cell ovarian tumour) Risk/Protective Factors Nulliparity OCP, breast-feeding, tubal ligation, hysterectomy, prophylactic bilateral salpingo-oophorectomy in h. risk women ex: BRCA mutation carrier(protective) Caucasian History -family Increasing age (>40yo) Late menopause Delayed child-bearing

13. (Epithelial Cell ovarian tumour) • Clinical Presentation • Often asymptomatic (vague/non-specific sx) until disseminated disease • Typically: • GI sx (nausea, bloating, dyspepsia, anorexia, early satiety) • Mass effect sx (increased abdominal girth from tumour or ascites, urinary frequency, constipation) • Post-menopausal bleeding • SOB (due to malignant pleural effusion)

14. Investigations Is there a mass? Do we suspect malignancy? Bimanual exam  solid/irregular/fixed mass Abdominal & Breast exam Bloodwork: CA125, CBC, liver function tests, electrolytes, creatinine Pelvic US/Transvaginal US Pre-op evaluation /Characterization of mass and mets: Pelvic/Abdominal CT CXR Screening for Hereditary cancer syndromes - BRCA1 or BRCA2 mutations, Lynch syndrome (HNPCC)

15. Surgical Evaluation Removal of ovarian tumour and any other masses in peritoneal cavity  allows for histological dx and staging Staging procedure: Total extrafascialhysterectomy with bilateral salpingo-oophorectomy and pelvic and paraaortic lymph node dissection. Peritoneal cytology is collected after the incision is made. Staging also includes omentectomy and cytology of the diaphragm. Stage I - only the ovaries Stage II - extension to the uterus, fallopian tubes, and pelvic structures Stage III - peritoneal spread outside the pelvis, or retroperitoneal and inguinal lymph node involvement Stage IV - Disease outside the abdomen and in the liver parenchyma is malignant pleural effusions

16. Cytoreduction - associated with increased survival. The volume of residual disease remaining after cytoreductive surgery correlates inversely with survival Factors limiting achievement of optimal cytoreduction: ●Presence of extraabdominal or retroperitoneal disease, or large tumor bulk ●Bowel involvement ●Parenchymal liver involvement ●Presence of ascites ●Ability of patient to tolerate cytoreduction – This assessment is based on age, performance status, medical comorbidities, and preoperative nutritional status

17. Treatment: Primary surgical cytoreduction followed by systemic chemotherapy is the preferred initial management for women with stage III or IV EOC (75%). The standard IV regimen: platinumand taxaneagents - carboplatin plus paclitaxel. Patients who are not good candidates for surgery due to the location and volume of disease involvement or medical comorbidities at the time of diagnosis may be considered for neoadjuvant chemotherapy. Follow-up CA125 levels – to monitor response to tx

18. Malignant Ovarian Tumour prognosis Stage 1: 75-95% Stage 2: 60-75% Stage 3: 23-41% Stage 4: 11% Metastatic Progression: Ovarian cancer cells primarily disseminate within the peritoneal cavity and are only superficially invasive.

19. Resources: UpToDate Robbins Basic Pathology Cecil Essentials of Medicine Case Files: Obstetrics & Gynecology Toronto Notes Lange: Obstetrics & Gynecology