Ovarian Cancer. Stacey N. Akers, MD July 14, 2015

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1 Ovarian Cancer Stacey N. Akers, MD July 14, 2015

2 Ovarian cancer Statistics Risk factors Inherited Syndromes Prevention Diagnosis Staging Treatment Overview

3 Ovarian Cancer

4 Epidemiology 9 th most common cancer among women 22,000 5 th most common cause of cancer death 15,000 Leading three malignancies among women: Breast, Lung, Colon Jemal. Cancer Statistics 2012

5 Epithelial Ovarian Cancer (EOC) Most common type of ovarian cancer Epithelial (75%) Germ cell (15 20%) Sex cord Stromal (5%) Median age of presentation 65 Overall lifetime risk is 1 in % of patients are diagnosed with Stage III or IV disease

6 Ovarian Cancer Risk Factors Poorly understood 85 90% sporadic Screening General Population?? Low prevalence in women <50 (40/10,000)

7 Risk Factors Family history (primarily 2 or more first degree relatives) Age (besides family history, this is the most important risk factor) Nulliparity Early menarche, late menopause Late childbirth (age >35) Environmental factors not yet defined

8 Lifetime Risk for Ovarian Cancer Family History of Ovarian Cancer Lifetime Risk None 1.4% 1 first degree relative (parent, child, sibling) 2 first degree relatives 5% 7%

9 Symptoms of Ovarian Cancer Largely non specific Increase in abdominal girth (ascites) Bloating Fatigue Abdominal pain Early satiety Indigestion Constipation Weight loss, unexplained New onset of urinary frequency or incontinence

10 Risk Reduction Oral Contraceptive Pills Breast Feeding Tubal ligation Risk reducing oophorectomy

11 THE DEVELOPMENT OF A HEREDITARY CANCER 2 normal genes 1 damaged gene 2 damaged genes 1 normal gene Tumor develops In hereditary cancer, one damaged gene is inherited. 1 damaged gene 1 normal gene 2 damaged genes Tumor develops Myriad Genetics, Inc Myriad Genetic Laboratories, Inc.

12 Cancer Syndromes Hereditary Breast Cancer Syndromes BRCA1/2 Hereditary Colorectal Cancer Syndromes HNPCC SYNDROME

13 BRCA 1+ Women Angelina s mom was diagnosed with ovarian cancer at 56 She died in 2007 Recently underwent risk reducing mastectomy And removal of both ovaries and fallopian tubes Christina was diagnosed with breast cancer at age 36 Her mom is a breast cancer survivor

14 Hereditary Breast and Ovarian Cancer Syndromes

15 Hereditary Ovarian Cancer Account for 10 15% of EOC BRCA1, BRCA2 (Hereditary Breast and Ovarian Cancer HBOC) Estimated 1/300 to 1/800 individuals carry a BRCA 1 or 2 mutation Estimated 1/40 Ashkenazi Jews carry a BRCA 1 or 2 mutation Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Colorectal Cancer before age 50 Endometrial cancer before age 50

16 Hereditary Ovarian Cancer BRCA 1 Germline Mutations Tumor suppressor gene Autosomal dominant 65 to 74% Breast Cancer risk 39 46% Ovarian Cancer risk ACOG Practice Bulletin #103, 2009.

17 Hereditary Ovarian Cancer BRCA2 Germline Mutations Tumor suppressor gene 65 74% Breast Cancer risk 12 20% Ovarian Cancer risk

18 Lifetime Risks in Patients with Hereditary Gynecologic Cancers Gene BRCA 1 BRCA 2 Hereditary Ovarian Cancer Syndrome Lynch Hereditary Cancer Lifetime Risk 30 40% risk of ovarian cancer 15 25% risk of ovarian cancer 40% 40 60% risk of uterine cancer 6 20% risk of ovarian cancer

19 Hereditary Ovarian Cancer HNPCC Autosomal dominant 80% risk of developing colon cancer 60% risk of developing endometrial cancer 10 15% risk of developing ovarian cancer Mismatch repair gene defects

20 RRSO for BRCA BRCA1 Risk of cancer rises in late 30 s and early 40 s (2 3%) Risk of ovarian cancer is 10 21% by age 50 Average age of ovarian cancer diagnosis 53 years BRCA2 Risk of ovarian cancer is 2 3% by age 50 Risk of breast cancer is 26 34% by age 50 Women with BRCA1 and 2 mutations should be offered RRSO by age 40 or when child bearing is complete RRSO reduces a woman s risk of developing breast cancer by 40 70% (the protective effect is strongest among premenopausal women) Finch et al. JAMA. 2006

21 RRSO for HNPCC Average age of ovarian cancer 42 years Average age of endometrial cancer is 50 years RRSO associated near 100% reduction in endometrial, ovarian, fallopian and primary peritoneal adenocarcinoma Women with HNPCC mutations should be offered hysterectomy/rrso by age or when child bearing is complete

22 Who To Test? Offer testing to every patient with epithelial ovarian cancer

23 Why Should I Test Everyone with Ovarian Cancer? 19 44% of patients with BRCA 1&2 mutations do not have a family history Standard of care is to refer all women with breast cancer under the age of 45 Mutation risk is 4.7% Mutation risk is 7.7% for a single case of ovarian cancer At any age, regardless of family history Berchuck A. Obstet Gynecol 2012;120(2): [Editorial to Schrader paper] Schrader et al. Obstet Gynecol 2012;120(2): Alsop et al. JCO 2012;30(21):

24 ACOG Guidelines: Genetic Referral and Testing Non Ashkenazi Jewish women 2 first degree relatives with breast cancer, one diagnosed before 50 3 or more first or second degree relatives with breast cancer at any age Combination of breast and ovarian cancer among first and second degree relatives First degree relative with bilateral breast cancer Two or more first or second degree relatives with ovarian cancer at any age A first or second degree relative with both breast and ovarian cancer at any age A male relative with breast cancer ACOG Practice Bulletin #89 January 2008, reaffirmed 2012

25 Screening Guidelines for BRCA and HNPCC Patients BRCA Begin at age or 5 10 years before earliest diagnosed cancer in family annual CA125 annual TVS HNPCC Start at age 25 or 10 years before earliest diagnosed cancer in family annual EMB annual TVS annual Colonoscopy

26 Screening High risk patients Genetic counseling CA 125 and pelvic ultrasound every six months No evidence for improved survival DO NOT RECOMMEND ROUTINE SCREENING US Preventive Service Task Force American Cancer Society American College of Obstetricians and Gynecologist National Comprehensive Cancer Network

27 Screening for Ovarian Cancer There is no evidence that screening for Ovarian Cancer leads to earlier detection or improved survival Nonetheless, the following have been or are being used TVS CA125

28 Screening (Multimodal) Simultaneous screening with CA125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality

29 Misconceptions about genetic testing 1. Testing is not covered by insurance. In most instances insurance covers the cost of testing like any other medical expense. 2. Testing is complicated. True and false choosing the appropriate test is not always simple, there are significant opportunities for misinterpretation. Seek consultation with a health care provider (nurse practitioner, genetic counselor, MD) specializing in hereditary cancer. 3. Testing will cause you to lose your insurance. Concerns exist about genetic discrimination, but after nearly 15 years of clinical testing, no significant problems have been seen. Members of group health insurance plans have protection under Federal Law (HIPPA, 1996). GINA signed into law May 2008, extends protections from discrimination based on genetic information to those with private health insurance

30 DISCRIMINATION FEDERAL AND STATE LAWS PROHIBIT THE USE OF GENETIC INFORMATION AS A PRE EXISTING CONDITION NO DOCUMENTED CASES OF GENETIC DISCRIMINATION NEJM 2008

31 Management of Adnexal Masses Adnexal masses often present both diagnostic and management dilemmas Need to determine: Malignant vs. benign Surgery vs. conservation ACOG Practice Bulletin #83, 2007.

32 Differential Diagnosis Gynecologic Benign Functional cyst Leiomyomata Endometrioma TOA Ectopic Teratoma Cystadenoma Malignant EOC Germ Cell Sex cord stromal Non gynecologic Benign Diverticular abscess Appendiceal abscess Nerve sheath tumors Pelvic Kidney Malignant Colon cancer Breast cancer Gastric cancer

33 Current GYN/Oncology referral guidelines for a pelvic mass ACOG committee Postmenopausal women with suspicious pelvic mass as suggested by at least one of the following: elevated CA125 ascites nodular or fixed pelvic mass evidence of distant metastasis

34 Current GYN/Oncology referral guidelines for a pelvic mass Premenopausal patient with pelvic mass suspicious for ovarian cancer as evidenced by the presence of one of the following: Very elevated CA125 ascites evidence of metastasis

35 How is ovarian cancer diagnosed? Labs Imaging CT, Ultrasound Surgery

36 FIGO Staging Stage I IA Tumor confined to a single ovary, negative washings, capsule intact, surface of ovary uninvolved IB Tumor found in both ovaries, negative washings, capsule intact, surface of ovary uninvolved IC Tumor on one or both ovaries, ruptured capsule, positive cytology or ovarian surface involvement Stage II IIA Extension or metastasis to uterus and/or tubes IIB Extension to other pelvic structures IIC Tumor on one or both ovaries, ruptured capsule, positive cytology or ovarian surface involvement Stage III IIIA Tumor on one or both ovaries with microscopic spread to abdominal peritoneal surface (ex. Liver serosa) IIIB Tumor implant <2cm to abdominal peritoneal surface IIIC Tumor implant >2cm to abdominal peritoneal surface and/or positive retroperitoneal or inguinal lymph nodes Stage IV Distant metastasis Pleural effusion with positive cytology Parenchymal liver metastasis

37 Survival Rates for Ovarian Cancer Need to be Improved Ovarian Cancer 5-yr Survival Rate by Stage Stage Distribution at Diagnosis Survival Rate Stage I 20-27% 73-93% Stage II 5-10% 45-70% Stage III 52-58% 21-37% Stage IV 11-17% 11-25% Heintz APM, et al. FIGO Annual Report on the Results of Treatment in Gynecologic Cancers. 2000; 24 : Holschneider CH, Berek JS. Semin Surg Oncol. 2000;19:3-10.

38 Histology Histology Incidence Serous 40-50% Most common Endometrioid 15-25% 2 nd most common Mucinous 6-16% Clear Cell 5-11% Other

39 Principles of Ovarian Cancer Surgery Purpose of Surgery Staging of disease Prognosis and treatment depend upon surgical findings and subsequent stage Debulking (cytoreduction) Overall reduction of tumor burden to less than 1 cm (preferably no gross residual disease) improves survival

40 Principles of Ovarian Cancer Surgery In most cases, hysterectomy with bilateral salpingo oophorectomy is indicated

41 Treatment Surgery Chemotherapy

42 Advanced ovarian cancer (Stage III, Stage IV) Despite the best efforts at early detection, 70 80% of women will be diagnosed with advanced epithelial ovarian cancer Prognosis is poor 25 35% 5 year survival, 10% 10 year survival Maximal effort/time/expense has been dedicated to better screening and more effective therapy Over the past 20 years, we have not been successful in changing the survival rate