What is the most appropriate initial step in managing a postmenopausal woman with a family history of ovarian cancer who is asymptomatic and has no known genetic testing?

Genetic Counseling and Risk Assessment is the Most Appropriate Initial Step

For a postmenopausal woman with a family history of ovarian cancer who is asymptomatic, the most appropriate initial step is genetic counseling referral and risk assessment—NOT routine screening with pelvic ultrasound or CA-125, as screening has been proven harmful without mortality benefit in this population. 1

Why Screening is NOT Recommended

The evidence against routine ovarian cancer screening is definitive and comes from the highest-quality randomized controlled trials:

• The USPSTF gives a Grade D recommendation (harms outweigh benefits) against screening for ovarian cancer in asymptomatic women, even those with a family history. 1 This is based on no mortality benefit and significant harms from false-positive results and unnecessary surgeries.

• The PLCO trial of 78,216 women (17% with family history) demonstrated no reduction in ovarian cancer deaths with annual CA-125 and transvaginal ultrasound screening, with 118 vs 100 deaths (relative risk 1.18). 1

• Approximately 10% of screened women receive false-positive results, with a positive predictive value of only 1-2%. 1 This means 98-99% of positive screening tests are false positives. 2

• One-third of women with false-positives undergo oophorectomy, resulting in a 20:1 ratio of surgeries to screen-detected cancers. 1 Nearly 21 major complications occur per 100 surgical procedures performed for false-positive results. 1

• The 2017 ACR Appropriateness Criteria confirmed that the PLCO trial found no significant shift in stage distribution and no statistically significant reduction in cancer-specific mortality, with 1,080 women undergoing surgery with oophorectomy and 163 (15%) experiencing major complications. 3

The Correct Initial Approach: Genetic Counseling Referral

Women with a family history of ovarian cancer should be evaluated for genetic counseling referral based on specific family history details: 1

• Referral criteria include: Two or more first- or second-degree relatives with ovarian cancer, or a combination of breast and ovarian cancer. 1

• For Ashkenazi Jewish women: One first-degree relative or two second-degree relatives on the same side of the family with breast or ovarian cancer is sufficient for referral. 1

• If genetic counseling reveals a BRCA mutation, management changes entirely. 1 Women with known BRCA mutations should be managed differently, potentially including risk-reducing bilateral salpingo-oophorectomy. 1

• Only 5-10% of ovarian cancer patients have a significant family history, but three familial syndromes exist: site-specific ovarian cancer, familial breast-ovarian cancer syndrome, and cancer familial syndrome (Lynch type II). 3

• Women with BRCA1 mutations have a cumulative ovarian cancer risk of 56% by age 70. 3

What Should Be Done Instead of Screening

The American College of Family Physicians recommends focusing on symptom awareness rather than screening tests: 1

• Educate patients about ovarian cancer symptoms (abdominal pain, bloating, urinary urgency and frequency). 4

• Emphasize that early-stage disease is usually asymptomatic. 1, 5

• Discuss risk-reducing factors: Oral contraceptive use reduces ovarian cancer risk by approximately 50%. 1, 5 Other protective factors include pregnancy, breastfeeding, and bilateral tubal ligation. 1

Important Caveats

• The UK Familial Ovarian Cancer Screening Study showed different results for high-risk women (those with ≥10% lifetime risk based on family history or known genetic mutation), with sensitivity of 81.3-87.5% and PPV of 25.5%. 3 However, this study was for women with documented high genetic risk, not simply family history without genetic testing.

• Screening may be considered for women with confirmed BRCA mutations or very strong family history (multiple affected relatives), using transvaginal ultrasound and CA-125 with the ROCA algorithm. 3 But this determination should be made AFTER genetic counseling, not before.

• The lifetime risk for any woman developing ovarian cancer is approximately 1 in 54 (about 1.1%). 6 More than 80% of cases are diagnosed in women over 50 years of age. 6

Answer to the Multiple Choice Question

C. No need for screening test until the patient becomes symptomatic is the correct answer based on USPSTF Grade D recommendation against screening. 1 However, this answer is incomplete—the patient DOES need genetic counseling referral and risk assessment as the initial step, followed by symptom education and discussion of risk-reducing factors. 1