PURPOSE: After risk-reducing salpingo-oophorectomy (RRSO), BRCA1/ 2 pathogenic variant (PV) carriers have a residual risk to develop peritoneal carcinomatosis (PC). The etiology of PC is not yet clarified, but may be related to serous tubal intraepithelial carcinoma (STIC), the postulated origin for high-grade serous cancer. In this systematic review and individual patient data meta-analysis, we investigate the risk of PC in women with and without STIC at RRSO. METHODS: Unpublished data from three centers were supplemented by studies identified in a systematic review of EMBASE, MEDLINE, and the Cochrane library describing women with a BRCA-PV with and without STIC at RRSO until September 2020. Primary outcome was the hazard ratio for the risk of PC between BRCA-PV carriers with and without STIC at RRSO, and the corresponding 5- and 10-year risks. Primary analysis was based on a one-stage Cox proportional-hazards regression with a frailty term for study. RESULTS: From 17 studies, individual patient data were available for 3,121 women, of whom 115 had a STIC at RRSO. The estimated hazard ratio to develop PC during follow-up in women with STIC was 33.9 (95% CI, 15.6 to 73.9), P < .001) compared with women without STIC. For women with STIC, the five- and ten-year risks to develop PC were 10.5% (95% CI, 6.2 to 17.2) and 27.5% (95% CI, 15.6 to 43.9), respectively, whereas the corresponding risks were 0.3% (95% CI, 0.2 to 0.6) and 0.9% (95% CI, 0.6 to 1.4) for women without STIC at RRSO. CONCLUSION: BRCA-PV carriers with STIC at RRSO have a strongly increased risk to develop PC which increases over time, although current data are limited by small numbers of events.

Introduction: In the work‐up of patients with suspected pelvic congestion syndrome, venography is currently the gold standard. Yet if non‐invasive diagnostic tools are found to be accurate, invasive venography might no longer be indicated as necessary.Material and methods: A literature search in Pubmed and EMBASE was performed from inception until 6 May 2017. Studies comparing non‐invasive diagnostic tools to a reference standard in the work‐up of patients with (suspected) pelvic congestion syndrome were included. Relevant data were extracted and methodological quality of individual included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) tool.Results: Nine studies matched our inclusion criteria. Six studies compared ultrasonography to venography and three studies described a magnetic resonance imaging technique. In using transvaginal ultrasonography, the occurrence of a vein greater than five mm crossing the uterine body had a specificity of 91% (95% CI; 77–98%) and occurrence of pelvic varicoceles a sensitivity and specificity of 100% (95% CI; 89–100%) and 83–100% (95% CI; 66–93%), respectively. In transabdominal ultrasonography, reversed caudal flow in the ovarian vein accounted for a sensitivity of 100% (95% CI; 84–100%). Detection of pelvic congestion syndrome with magnetic resonance imaging techniques resulted in a sensitivity varying from 88 to 100%.Conclusions: The sensitivity of ultrasonography and magnetic resonance imaging seem to be adequate, which indicates a role for both tests in an early stage of the diagnostic workup. However, due to methodological flaws and diversity in outcome parameters, more high standard research is necessary to establish a clear advice for clinical practice.

Background Risk-reducing salpingectomy with delayed oophorectomy has gained interest for individuals at high risk for tubo-ovarian cancer as there is compelling evidence that especially high-grade serous carcinoma originates in the fallopian tubes. Two studies have demonstrated a positive effect of salpingectomy on menopause-related quality of life and sexual health compared with standard risk-reducing salpingo-oophorectomy. Primary Objective To investigate whether salpingectomy with delayed oophorectomy is non-inferior to the current standard salpingo-oophorectomy for the prevention of tubo-ovarian cancer among individuals at high inherited risk. Study Hypothesis We hypothesize that postponement of oophorectomy after salpingectomy, to the age of 40–45 (BRCA1) or 45–50 (BRCA2) years, compared with the current standard salpingo-oophorectomy at age 35–40 (BRCA1) or 40–45 (BRCA2) years, is non-inferior in regard to tubo-ovarian cancer risk. Trial Design In this international prospective preference trial, participants will choose between the novel salpingectomy with delayed oophorectomy and the current standard salpingo-oophorectomy. Salpingectomy can be performed after the completion of childbearing and between the age of 25 and 40 (BRCA1), 25 and 45 (BRCA2), or 25 and 50 (BRIP1, RAD51C, and RAD51D pathogenic variant carriers) years. Subsequent oophorectomy is recommended at a maximum delay of 5 years beyond the upper limit of the current guideline age for salpingo-oophorectomy. The current National Comprehensive Cancer Network (NCCN) guideline age, which is also the recommended age for salpingo-oophorectomy within the study, is 35–40 years for BRCA1, 40–45 years for BRCA2, and 45–50 years for BRIP1, RAD51C, and RAD51D pathogenic variant carriers. Major Inclusion/Exclusion Criteria Premenopausal individuals with a documented class IV or V germline pathogenic variant in the BRCA1, BRCA2, BRIP1, RAD51C, or RAD51D gene who have completed childbearing are eligible for participation. Participants may have a personal history of a non-ovarian malignancy. Primary Endpoint The primary outcome is the cumulative tubo-ovarian cancer incidence at the target age: 46 years for BRCA1 and 51 years for BRCA2 pathogenic variant carriers. Sample size The sample size to ensure sufficient power to test non-inferiority of salpingectomy with delayed oophorectomy compared with salpingo-oophorectomy requires 1500 BRCA1 and 1500 BRCA2 pathogenic variant carriers. Estimated Dates for Completing Accrual and Presenting Results Participant recruitment is expected to be completed at the end of 2026 (total recruitment period of 5 years). The primary outcome is expected to be available in 2036 (minimal follow-up period of 10 years). Trial Registration Number NCT04294927.

Background: BRCA1/2 mutation carriers’ choice between risk‐reducing salpingo‐oophorectomy (RRSO) and salpingectomy with delayed oophorectomy is very complex. Aim was to develop a patient decision aid that combines evidence with patient preferences to facilitate decision making.Design: Systematic development of a patient decision aid in an iterative process of prototype development, alpha testing by patients and clinicians and revisions using International Patient Decision Aid Standards (IPDAS) quality criteria. Information was based on the available literature and current guidelines. A multidisciplinary steering group supervised the process.Setting and participants: Pre‐menopausal BRCA1/2 mutation carriers choosing between RRSO and salpingectomy with delayed oophorectomy in Family Cancer Clinics in the Netherlands.Main outcome measures: IPDAS quality criteria, relevance, usability, clarity.Results: The patient decision aid underwent four rounds of alpha testing and revisions. Finally, two paper decision aids were developed: one for BRCA1 and one for BRCA2. They both contained a general introduction, three chapters and a step‐by‐step plan containing a personal value clarification worksheet. During alpha testing, risk communication and information about premature menopause and hormone therapy were the most revised items. The patient decision aids fulfil 37 of 43 (86%) IPDAS criteria for content and development process.Discussion and conclusions: Both BRCA1/2 mutation carriers and professionals are willing to use or offer the developed patient decision aids for risk‐reducing surgery. The patient decision aids have been found clear, balanced and comprehensible. Future testing among patients facing the decision should point out its effectiveness in improving decision making.

Steenbeek MP, et al. J Gynecol Oncol. 2018 Aug;30(1):e2. https://doi.org/10.3802/jgo.2019.30.e2

Objective: To compare menopause‐related quality of life (QoL) after risk‐reducing salpingectomy (RRS) versus risk‐reducing salpingo‐oophorectomy (RRSO) until 3 years of post‐surgery.Design: A prospective study (TUBA study) with treatment allocation based on patients' preference. Data were collected pre‐surgery and at 3 months, 1 and 3 years of post‐surgery.Setting: Multicentre prospective preference trial in thirteen hospitals in the Netherlands.Population: BRCA1/2 pathogenic variant (PV) carriers aged 25–40 (BRCA1) or 25–45 (BRCA2), who were premenopausal, without a future child wish and without current (treatment for) malignancy.Methods: Treatment allocation was based on patients' preference: either RRS from the age of 25 years with delayed oophorectomy at the maximum age of 45 (BRCA1) or 50 (BRCA2), or RRSO between the ages of 35–40 (BRCA1) or 40–45 (BRCA2). After RRSO, hormone replacement therapy (HRT) was recommended, if not contraindicated. Primarily, menopause‐related QoL as measured with the Greene Climacteric Scale (GCS) was compared between the RRS and RRSO without HRT group. Secondarily, GSC‐scores of the RRS group were compared with the scores of the RRSO with HRT after surgery group. A higher GSC‐score reflects more climacteric symptoms.Results: Until April 2023, 410 participants had undergone RRS and 160 RRSO. The BRCA1/BRCA2 proportions were 51.4%/48.6%. The mean age at surgery (SD) was 37.9 (3.5) years. Participants 3 years after RRSO without HRT had a 4.3 (95% CI 2.1–6.5; p < 0.001) point higher increase in GCS‐score from baseline compared to those after RRS, while the difference was 7.9 (95% CI 5.9–9.8) and 8.5 (95% CI 6.5–10.5) points at 3 and 12 months, respectively. Among participants with HRT after surgery, the RRSO group had a 2.4 (95% CI 0.8–3.9; p = 0.002) point higher increase in GCS‐score from baseline compared to the RRS group.Conclusions: In this multicentre preference trial, menopause‐related QoL was better after RRS than after RRSO, even with HRT after RRSO. Differences between arms were most pronounced until one‐year post‐surgery.