Genetic Counseling is the Most Appropriate Initial Step
The most appropriate initial step for an asymptomatic patient with a family history of ovarian cancer is referral for genetic counseling and risk assessment, not screening tests like pelvic ultrasound or CA-125. 1, 2
Why Screening Tests Are Not Appropriate
Routine screening with CA-125 or pelvic ultrasound is explicitly recommended against by the USPSTF (Grade D recommendation) for all asymptomatic women, including those with a family history of ovarian cancer. 3, 1 The evidence is clear:
The PLCO trial of 78,216 women (17% with family history) demonstrated no reduction in ovarian cancer mortality with annual CA-125 and transvaginal ultrasound screening (118 vs 100 deaths; relative risk 1.18). 3, 4
Screening causes substantial harm: approximately 10% of screened women receive false-positive results, with only 1-2% positive predictive value. 1, 4
For every 10,000 women screened annually, 20-65 women without cancer undergo unnecessary surgery, with nearly 21 major complications per 100 surgical procedures performed for false-positive results. 1, 4
The one-third of women with false-positives who undergo oophorectomy results in a 20:1 ratio of surgeries to screen-detected cancers. 4
The Correct Algorithmic Approach
Step 1: Detailed Family History Assessment
Determine if the patient meets criteria for high-risk family history 1, 2:
- Two or more first- or second-degree relatives with ovarian cancer, OR
- Combination of breast and ovarian cancer in the family, OR
- Ashkenazi Jewish descent with one first-degree relative (or two second-degree relatives on the same side) with breast or ovarian cancer 1
Step 2: Genetic Counseling Referral
If any high-risk criteria are met, refer for genetic counseling to evaluate for BRCA1/BRCA2 mutations or Lynch syndrome. 1, 2 This is particularly important if:
- The patient's mother was diagnosed at a young age 1
- There is additional family history of breast cancer 1
- There are other cancers suggesting Lynch syndrome 1
Step 3: Genetic Testing Strategy
Ideally, genetic testing should first be performed on an affected family member who has the highest likelihood of carrying a mutation. 2 If the affected relative tests positive, then the patient undergoes targeted testing for that specific familial mutation. 2
Step 4: Management Based on Results
If a deleterious BRCA1/BRCA2 mutation is identified:
- Enhanced surveillance with breast MRI and mammography starting at age 25-30 2
- Risk-reducing salpingo-oophorectomy typically recommended between ages 35-40 after childbearing is complete for BRCA1 carriers, and ages 40-45 for BRCA2 carriers 3, 2
- For patients who decline risk-reducing surgery, concurrent transvaginal ultrasound plus CA-125 every 6 months starting at age 35 years (or 5-10 years earlier than earliest age of ovarian cancer diagnosis in family) 3
If no mutation is identified but family history remains concerning:
- Clinical vigilance for symptoms (abdominal/pelvic pain, bloating, early satiety, unexplained weight loss) 1
- Discussion of proven risk-reduction methods: oral contraceptive use (reduces risk by ~50%), pregnancy, breastfeeding, bilateral tubal ligation 1, 4
Critical Pitfall to Avoid
Do not order CA-125 or pelvic ultrasound as initial screening tests in asymptomatic women with family history alone. 3, 1 This approach leads to unnecessary anxiety, false-positive results, and harmful surgeries without mortality benefit. The only exception is for women with confirmed BRCA mutations who decline risk-reducing surgery, where surveillance may be offered as part of specialized high-risk management. 3
Special Consideration for Very High-Risk Women
The UK Familial Ovarian Cancer Screening Study showed different results for women with ≥10% lifetime risk based on confirmed genetic mutation, with sensitivity of 81.3-87.5% and positive predictive value of 25.5%. 4 However, this applies only after genetic testing confirms high-risk status, not as an initial step. 4
Answer: None of the above - the correct initial step is referral for genetic counseling and risk assessment.