What are the indications for Risk-Reducing Salpingo-Oophorectomy (RRSO) in women with a high risk of ovarian and fallopian tube cancer, particularly those with BRCA1 or BRCA2 gene mutations?

Indications for Risk-Reducing Salpingo-Oophorectomy (RRSO)

RRSO is indicated for women with confirmed BRCA1 or BRCA2 pathogenic or likely pathogenic variants who have completed childbearing, as it reduces ovarian/fallopian tube/peritoneal cancer risk by 80-85%, all-cause mortality by 77%, and provides substantial breast cancer risk reduction. 1

Primary Indications

BRCA1/2 Pathogenic Variant Carriers

• Women with confirmed BRCA1 pathogenic variants should undergo RRSO after completion of childbearing, with optimal timing between ages 35-40 years 1, 2

• Women with confirmed BRCA2 pathogenic variants should undergo RRSO after completion of childbearing, with optimal timing between ages 40-45 years, as their peak ovarian cancer risk occurs later (ages 60-69) compared to BRCA1 carriers 1

• The age-specific timing reflects that BRCA1 carriers have higher ovarian cancer prevalence (4.2%) compared to BRCA2 carriers (0.6%), with BRCA1 carriers showing 1.5% prevalence under age 40 and 3.8% between ages 40-49 1

Mortality and Morbidity Benefits

Cancer Risk Reduction

• Ovarian/fallopian tube/peritoneal cancer risk reduction of 80-85% (HR 0.15-0.20) is achieved with RRSO in BRCA1/2 carriers 1

• All-cause mortality reduction of 77% (HR 0.23; 95% CI 0.13-0.39) is demonstrated in BRCA1/2 carriers undergoing RRSO 1

• RRSO reduces mortality at all ages in BRCA1 carriers, but only between ages 41-60 years in BRCA2 carriers, making age-appropriate timing critical 1

Breast Cancer Risk Reduction

• Breast cancer risk reduction of approximately 50-56% occurs in BRCA1 carriers when RRSO is performed, particularly when done before age 40 (64% reduction) 1, 2

• BRCA2 carriers experience 43-46% breast cancer risk reduction following RRSO 1, 2

• Breast cancer-specific mortality decreases by 60% (HR 0.44) in BRCA carriers after RRSO 2

• The breast cancer protective effect diminishes significantly when RRSO is performed after age 50-51 (natural menopause age), making earlier intervention more beneficial 2

Detection of Occult Malignancy

• Occult invasive or intraepithelial neoplasms are detected in 2.5-4.6% of BRCA1 carriers and 3.5% of BRCA2 carriers at the time of RRSO 1, 3, 4

• Among detected occult cancers, 38-75% are stage I disease, representing a more favorable stage than cancers detected outside of RRSO 3, 4

• Postmenopausal status and abnormal preoperative CA-125 or transvaginal ultrasound are associated with higher likelihood of occult cancer detection 4

Important Caveats and Technical Considerations

Surgical Technique Requirements

• Complete removal of both fallopian tubes is essential, as incomplete removal leaves residual risk for serous tubal intraepithelial carcinoma (STIC), which is a precursor lesion 1

• Surgery performed at specialist oncological centers may achieve greater risk reduction (HR 0.03) compared to non-specialist centers (HR 0.11), likely due to more complete tissue removal and pathologic examination 5

• A residual 1-4.3% risk for primary peritoneal carcinoma persists even after RRSO, with 86% occurring in BRCA1 carriers specifically 1

Pathologic Examination Standards

• Complete (en toto) examination of ovarian and fallopian tube tissue is mandatory to detect occult malignancies 3

• Only 75% of specimens at major genetics centers and 30% at non-referral centers undergo adequate complete examination, representing an unacceptable gap in care 3

• Women who later develop peritoneal carcinomatosis after RRSO were older at surgery and had higher rates of STIC in their specimens, emphasizing the importance of thorough pathologic review 1

Endometrial Cancer Considerations

• BRCA1 carriers who undergo RRSO without concurrent hysterectomy have increased risk for serous/serous-like endometrial cancer, which should factor into surgical planning 1

Contraindications to Consider

• Women with BRCA1/2 mutations who have not completed childbearing should delay RRSO, as the procedure causes surgical menopause 1

• Women under age 35 (BRCA1) or 40 (BRCA2) have lower absolute ovarian cancer risk, and RRSO before these ages may not provide optimal risk-benefit balance unless family history suggests earlier onset disease 1

Post-RRSO Management

• Hormone replacement therapy (HRT) until age 50-51 years is recommended after RRSO to mitigate cardiovascular and bone health risks from premature menopause 2, 6

• Short-term HRT does not appear to negate the breast cancer risk reduction benefits of RRSO, particularly in BRCA2 carriers 6

• Continued breast cancer surveillance remains mandatory after RRSO, including annual MRI starting age 25, annual mammography starting age 30, and clinical breast examination every 6-12 months 2, 7