Download Ovarian Cancer Prevention and Screening

Ovarian Cancer Prevention
and Screening
Nicole D. Fleming, MD
Assistant Professor
Department of Gynecologic Oncology
MD Anderson Cancer Center
MD Anderson Regional Care Centers
Sugar Land, Texas
Objectives
• Review symptoms and risk factors for ovarian
cancer
• Define high risk populations
– HBOC
– Lynch (HNPCC)
• Screening in the general population
• Cancer risk reduction strategies in high risk
patients
Gynecologic Cancers in 2013
• Uterine Cancer
– 49,560 new cases
8,190 deaths
• Ovarian Cancer
– 22,240 new cases
14,030 deaths
• Cervical Cancer
– 12,340 new cases
4,030 deaths
Cancer Facts & Figures 2013, ACS
Ovarian Cancer
Marcheline Bertrand
Gilda Radner
• Most common cause of death
among women with
gynecologic malignancies
• Mean age at diagnosis: 60 yrs
• 70% of cases have advanced
disease at time of diagnosis
• Symptoms can be vague
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–
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Bloating
Early satiety
Abdominal discomfort
Unintentional weight loss
Ovarian Cancer Risk Factors
• Increase Risk
– Family history
• BRCA 1/2
• HBOC
• Lynch
– Nulliparity
– Infertility
• Decrease Risk
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–
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Multiparity
Oral contraceptive pills
Breast feeding
Tubal ligation
**Infertility medications have not been
shown to increase risk of cancer
Strategies for Ovarian Cancer Risk Reduction
• Quantify lifetime risk
– General population (1.7%)
– High risk population
• BRCA (15-50%)
• Lynch (12%)
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•
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Screening
Chemoprevention
Risk reducing surgery
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Recommended for BRCA 1/2 mutation carriers or those
with Lynch syndrome
Bilateral salpingoophorectomy +/- hysterectomy by age
40 or when childbearing completed
Ovarian Cancer Screening
• Minimal requirements for a screening test
– High sensitivity ≥ 75%
– High specificity ≥ 99%
– Positive predictive value at least 10%
• PPV depends on disease incidence
Challenges to Screening for OC
• Age specific incidence
• Anatomy
• Biology
Age Specific Incidence is Low
•
Premenopausal women
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•
1 in 10,000
Postmenopausal women
–
1 in 2,500
Anatomic Barriers to Screening
• Need a diagnostic test to follow a positive
screening test
– Pap or Mammogram abnormal
• Diagnostic test=BIOPSY
– Ovarian cancer screen positive
•
Diagnostic test=SURGERY
Biologic Barriers to Screening
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•
•
•
Natural history is not completely understood
No premalignant lesion
No real animal models to study natural history
Very heterogenous disease
“Ovarian Cancer Screening Tests”
• Ovacheck (2004 Correlogic)
– Mass spec to identify ovarian cancer protein
signature
– Sensitivity 100%, Specificity 95%, PPV 94%
– Not reproducible
• Ovasure (2008 Labcorp)
– 6 marker panel
– Sensitivity 95%, Specificity 99%, PPV 99.3%
– Used incorrect incidence to calculate PPV (6.5%)
Is CA125 an Effective Screening Test?
• Elevated in only 50% of stage I ovarian cancers
• Many other common conditions cause false
elevations
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Fibroids
Endometriosis
Heavy menses
Post-abdominal surgery
Liver disease
False elevations common in premenopausal women
PLCO Screening Trial
• Randomized trial of screening versus
observation
• 78,216 women age 55-74 years
• Screening arm - annual CA125 and pelvic US
• Results were sent to primary doctor for
management
• Main outcome was ovarian cancer mortality
• Secondary outcomes were incidence of OC and
complications from screening
• Follow up time 13 years
Buys SS et al. JAMA 2011
PLCO Results
• No difference in OC incidence in both groups
– Screening 212 and controls 176
(RR 1.21, CI 0.99-1.48)
• No difference in OC deaths
– Screening 118 and controls 100
(RR 1.18, CI 0.82-1.71)
• False positives, n=3285
– 1080 underwent surgery
– 163 (15%) > 1 major complication
• No difference in non-cancer associated death rates
Buys SS et al. JAMA 2011
PLCO Conclusions
• Screening with simultaneous CA125 and US did
NOT decrease ovarian cancer mortality
• False positives lead to an increase in
complications compared to usual follow up
Buys SS et al. JAMA 2011
U.S. ROCA study
• Single arm, prospective screening study
• Women age 50-74, no family history of cancer
• Computer algorithm to evaluate change in
CA125 over time and age
• ROCA risk score
– Normal risk—Repeat CA125 in one year
– Intermediate risk (5.8%)—Repeat CA125 in
3 months
– High risk (0.9%)– TVUS and refer to Gyn Onc
Lu KH et al. Cancer 2013
U.S. ROCA study
• Total 4051 participants over 11 years study
period (2001-2011)
• 117 (2.9%) underwent US and referral
• 10 underwent surgery
– 3 benign ovarian tumors
– 2 borderline tumors
– 4 invasive OC (stage IA, 2 stage IC, stage IIB)
– 1 endometrial cancer (stage IB)
• PPV 40% (95% CI=12.2%, 73.8%)
• Specificity 99.9% (95% CI=99.7%, 100%)
Lu KH et al. Cancer 2013
UKCTOCS Trial
• 3-arm, randomized controlled trial (2:1:1)
• Postmenopausal women, age 50-74
202,628 enrolled
No treatment
N=101,359
Annual CA125 using ROMA
w/TVUS if high risk (MMS)
N=50,640
Annual screening
with TVUS (USS)
N=50,639
Menon U et al. Lancet Oncol 2009
UKCTOCS Trial
UKCTOCS
MMS
USS
U.S. ROCA
Sensitivity
89.5%
75.0%
Specificity
99.8%
98.2%
Specificity
99.9%
PPV
35.1%
2.8%
PPV
40%
1. Menon U et al. Lancet Oncol 2009
2. Lu KH et al. Cancer 2013
ROCA and UKCTOCS Trials
• Majority of women returned for annual CA125
• Average “normal risk” ROCA was 91-93%
• Less than 1% referred for TVUS and
gynecologic oncology consultation
• Appears to be a cost effective screening method
in postmenopausal population
Screening in the General Population
• CA125 alone or annually with TVUS does not
decrease OC mortality
• ROCA with referral for TVUS and Gyn Onc was
feasible
• Awaiting results from large UKCTOCS study
designed to address sensitivity and mortality from
OC (likely in 2015)
• Screening in general population currently NOT
recommended unless done as part of a clinical trial
Screening in High Risk Population
LAB 06-0596
• Prospective database of women at increased risk for ovarian
or primary peritoneal cancer
• Eligibility criteria:
– 1. Personal history of breast cancer.
– 2. Family history of breast and/or ovarian cancer (one or more
relatives).
– 3. Carrier of a mutation in the BRCA1 or BRCA 2 gene, or the
presence of one of these mutations in a family member.
– 4. Personal history of colon or endometrial cancer.
– 5. Family history of colon or endometrial cancer (one or more
relatives).
– 6. Carrier of a mutation in the MLH1, MSH2, or MSH6 gene, or
the presence of one of these mutations in a family member.
•
Screening every 6-12 months
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Transvaginal US
Serum CA125 level
PI: Dr. Karen Lu
Ovarian Cancer Risk Stratification in
Patients with an Adnexal Mass
• OVA1 (Vermillion)
– Multivariate biomarker assay
– CA125, transferrin, transthyretin, apolipoprotein A1,
beta-2 microglobulin
– Use in patients WITH an adnexal mass to determine
need for referral to a gynecologic oncologist
– Sensitivity 96%, Specificity 51%
Good test to rule OUT cancer
– PPV 31%, NPV 98%
**OVA1 has NOT been approved for use as an ovarian
cancer screening tool, nor has it been proven to result in
early detection or reduce the risk of death from ovarian
cancer.
Bristow et al. Gynecol Oncol 2013
Conclusions
• Identifying women at increased risk for ovarian
cancer is necessary for successful screening
• Effective screening tests for the general
population are still needed
• Several options for cancer risk reduction in high
risk women (screening, chemoprevention,
surgery)