Progress and Prospects in Ovarian Cancer Screening and Prevention

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1 Progress and Prospects in Ovarian Cancer Screening and Prevention Rebecca Stone, MD MS Assistant Professor Kelly Gynecologic Oncology Service The Johns Hopkins Hospital 1

2 No Disclosures 4/12/2016 2

3 Ovarian Cancer Facts & Figures Lifetime risk of 1.3%; median age 63 yo Majority (90%) are derived from ovarian epithelium Serous (75%) Clear cell & Endometrioid Mucinous 75% of patients present with stage III/IV disease Cure rate estimated to be ~20% 4/12/2016 3

4 Ovarian Cancer Staging & Survival Stage 1 Stage 2 bladder bladder tube tube uterus ovary tumor malignant cells in washing uterus ovary tumor malignant cells in washing colon colon Stage 3 tumor cancer in lymph nodes Stage 4 tumor Metastases brain ovary lymph nodes ovary lung liver bone omentum 4/12/2016 4

5 Treatment of Ovarian Cancer Carboplatin Taxol Courtesy of R. Coleman 4/12/2016 5

6 FDA Has Only Approved 2 New Drugs for the Treatment of Ovarian Cancer Over the Past 10 Years 4/12/2016 6

7 Ovarian Cancer Incidence, Mortality & 5 year Survival in the US Year New Cases - SEER 9 Deaths - US /12/

8 How can we have the biggest impact on ovarian cancer incidence & mortality? Screening Prevention Treatment 4/12/2016 8

9 Ovarian Cancer Screening: History Symptoms CA-125 & other blood tests Imaging... 4/12/2016 9

10 Ovarian Cancer Screening: Symptom Recognition Diagnosing Ovarian Cancer Early (DOvE) Study Objective: Does expedited assessment of symptomatic women with CA-125 and US increase the chance of diagnosing ovarian cancer early? Bloating Frequency Persistence Incr. Severity Short Duration Gilbert L et al. Lancet Oncology, /12/

11 Ovarian Cancer Screening: Symptom Recognition Positive Symptom Index: increased abdominal girth/bloating pelvic/abdominal pain difficulty eating/feeling full >12d per month and for < 1 year Goff, B et al. Cancer, /12/

12 Ovarian Cancer Screening: CA 125 Only elevated in 50% of women with stage 1 ovarian cancer. Can be elevated in many non-malignant conditions. In premenopausal women, varies with menses: CA-125: Postmenopausal women < 35 U/mL is normal 4/12/

13 Ovarian Cancer Screening: Serum Biomarkers OvaSure (6 proteins) and OvaCheck (11 proteins) OVA-1: CA-125, transthyretin, apolipoprotein A1, beta2 microglobulin, transferrin ROMA: CA-125 & HE4 sensitivity specificity NPV CA-125 OVA-1 ROMA H ROMA L 77% 68% 87% 94% 35% 93% 76/92% 75% 93% 100/92% 75% 99% $50 $600 $100 Sensitivity: the chance that if you have the disease, the test will detect it high sensitivity = low false negative rate Specificity: the chance that if you don t have the disease, the test will be negative high specificity = low false positive rate Negative predictive value: the chance that if the test is negative, you don t have the disease high NPV = low false positive rate 4/12/ Li, A. Contemporary OB/GYN, 2012

14 Ovarian Cancer Screening: UKTOCS Study ROCA = Risk of Ovarian Cancer Algorithm 4/12/

15 UK Collaborative Trial of Ovarian Cancer Screening ROCA 48% of invasive cancers were early stage I/II Primary Endpoint: 30% in ovarian cancer mortality NOT MET Lancet Oncology /12/

16 Where is the Wave of the Future Headed? CA-125 & Ultrasound >>>>>> Single Cancer Cells in Body Fluids 4/12/

17 Repurposing the Pap Smear: One Step Closer to Gynecologic Cancer Screening 4/12/ Science Translational Medicine 2013

18 Circulating Tumor DNA (ctdna) 4/12/2016 Bettegowda et al Sci Transl Med

19 Ovarian Cancer Susceptibility Genes 20 24% of ovarian cancers attributable to germline mutations Lynch Others: BRIP1, TP53, PTEN, BARD1, CHEK2, ATM ATR, NBN, PALB2 Gynecol Oncol /12/

20 Commercially Available BRCA 1 and 2 Genetic Tests & Hereditary Cancer Risk Panels Gynecol Oncol /12/

21 Testing Criteria for Hereditary Breast and Ovarian Cancer Syndrome 4/12/

22 In the US, the number of carriers of actionable mutations in BRCA1/2 is between 1 in 300 to 500 women = 250,000 to 400,000 adult women Identification of gene mutations in women after a cancer diagnosis is a failure of cancer prevention Identification of mutation carriers should be independent of family history & physician referral 4/12/

23 Risk Reducing Interventions for High Risk Women tamoxifen mastectomy removal of tubes and ovaries OCPs cancer risk reduction breast cancer ovarian cancer 4/12/

24 Ovarian Cancer Risk After Salpingectomy in the General Population Denmark Sweden Acta Obstet. Gynecol. Scand and J. Natl. Cancer Inst /12/

25 SMALL COST, HUGE IMPACT Symptom recognition Referral to gynoncologists Family history Genetic counseling Risk reducing interventions for high risk women Opportunistic salpingectomy 4/12/