Diagnosis and management of isolated serous tubal intraepithelial carcinoma: A qualitative focus group study.

OBJECTIVE: A Serous Tubal Intraepithelial Carcinoma (STIC) without concomitant invasive carcinoma is occasionally identified and associated with a high risk of subsequent peritoneal carcinomatosis. Management needs optimisation. This study explores professionals' opinions and clinical practices regarding the diagnosis, counselling, treatment and follow-up of isolated STIC to facilitate clinical decision making and optimise the direction of future research. A secondary aim is to assess international clinical guidelines. DESIGN: Focus group study. SETTING: Four online sessions. POPULATION: International panel (n = 12 countries) of gynaecologists, gynaecologic oncologists, pathologists and medical oncologists (n = 49). METHODS: A semi-structured interview guide was used. Two independent researchers analysed transcripts by open and axial coding. Results were organised in domains. Relevant (inter)national guidelines were screened for recommendations regarding isolated STIC. MAIN OUTCOME MEASURES: Professionals' opinions and clinical practices regarding isolated STIC management. RESULTS: Regarding pathology, most professionals identified the SEE-FIM protocol as standard of care for high-risk patients, whereas variation exists in the histopathological examination of fallopian tubes in the general population. Confirmation of STIC diagnosis by a specialised pathologist was recommended. Regarding work-up and follow-up after STIC diagnosis, there was variety and discordance. Data on outcomes is limited. As for treatment, chemotherapy and PARP inhibitors were not recommended by most. Eleven guidelines provided limited recommendations. CONCLUSIONS: We identified recommendations and highlighted knowledge gaps in the diagnosis and management of isolated STIC. Moreover, recommendations in clinical guidelines are limited. There is an agreed need for international collaboration for the prospective registration of isolated STIC.

Consensus based recommendations for the diagnosis of serous tubal intraepithelial carcinoma: an international Delphi study.

AIM: Reliably diagnosing or safely excluding serous tubal intraepithelial carcinoma (STIC), a precursor lesion of tubo-ovarian high-grade serous carcinoma (HGSC), is crucial for individual patient care, for better understanding the oncogenesis of HGSC, and for safely investigating novel strategies to prevent tubo-ovarian carcinoma. To optimize STIC diagnosis and increase its reproducibility, we set up a three-round Delphi study. METHODS AND RESULTS: In round 1, an international expert panel of 34 gynecologic pathologists, from 11 countries, was assembled to provide input regarding STIC diagnosis, which was used to develop a set of statements. In round 2, the panel rated their level of agreement with those statements on a 9-point Likert scale. In round 3, statements without previous consensus were rated again by the panel while anonymously disclosing the responses of the other panel members. Finally, each expert was asked to approve or disapprove the complete set of consensus statements. The panel indicated their level of agreement with 64 statements. A total of 27 statements (42%) reached consensus after three rounds. These statements reflect the entire diagnostic work-up for pathologists, regarding processing and macroscopy (three statements); microscopy (eight statements); immunohistochemistry (nine statements); interpretation and reporting (four statements); and miscellaneous (three statements). The final set of consensus statements was approved by 85%. CONCLUSION: This study provides an overview of current clinical practice regarding STIC diagnosis amongst expert gynecopathologists. The experts' consensus statements form the basis for a set of recommendations, which may help towards more consistent STIC diagnosis.

TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: the TUBA-WISP II study protocol.

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.

Cancer worry among BRCA1/2 pathogenic variant carriers choosing surgery to prevent tubal/ovarian cancer: course over time and associated factors.

OBJECTIVE: High cancer risks, as applicable to BRCA1 and BRCA2 pathogenic variant (PV) carriers, can induce significant cancer concerns. We examined the degree of cancer worry and the course of this worry among BRCA1/2-PV carriers undergoing surgery to prevent ovarian cancer, and identified factors associated with high cancer worry. METHODS: Cancer worry was evaluated as part of the multicentre, prospective TUBA-study (NCT02321228) in which BRCA1/2-PV carriers choose either novel risk-reducing salpingectomy with delayed oophorectomy or standard risk-reducing salpingo-oophorectomy. The Cancer Worry Scale was obtained before and 3 and 12 months after surgery. Cancer worry patterns were analysed using latent class growth analysis and associated factors were identified with regression analysis. RESULTS: Of all 577 BRCA1/2-PV carriers, 320 (57%) had high (≥ 14) cancer worry pre-surgery, and 54% had lower worry 12 months post-surgery than pre-surgery. Based on patterns over time, BRCA1/2-PV carriers could be classified into three groups: persistently low cancer worry (56%), persistently high cancer worry (6%), and fluctuating, mostly declining, cancer worry (37%). Factors associated with persistently high cancer concerns were age below 35 (BRCA1) or 40 (BRCA2), unemployment, previous breast cancer, lower education and a more recent BRCA1/2-PV diagnosis. CONCLUSIONS: Some degree of cancer worry is considered normal, and most BRCA1/2-PV carriers have declining cancer worry after gynaecological risk-reducing surgery. However, a subset of these BRCA1/2-PV carriers has persisting major cancer concerns up to 1 year after surgery. They should be identified and potentially offered additional support. CLINICAL TRIAL REGISTRATION: The TUBA-study is registered at ClinicalTrials.gov since December 11th, 2014. Registration number: NCT02321228.

Evaluation of a patient decision aid for BRCA1/2 pathogenic variant carriers choosing an ovarian cancer prevention strategy.

OBJECTIVE: Risk-reducing surgery is advised to BRCA1/2 pathogenic variant (PV) carriers around the age of 40 years to reduce ovarian cancer risk. In the TUBA-study, a multicenter preference study (NCT02321228), BRCA1/2-PV carriers are offered a choice: the standard strategy of risk-reducing salpingo-oophorectomy or the novel strategy of risk-reducing salpingectomy with delayed oophorectomy. We evaluated feasibility and effectiveness of a patient decision aid for this choice. METHODS: Premenopausal BRCA1/2-PV carriers were counselled for risk-reducing surgical options in the TUBA-study; the first cohort was counselled without and the second cohort with decision aid. Evaluation was performed using digital questionnaires for participating women and their healthcare professionals. Outcome measures included actual choice, feasibility (usage and experiences) and effectiveness (knowledge, cancer worry, decisional conflict, decisional regret and self-estimated influence on decision). RESULTS: 283 women were counselled without and 282 women with decision aid. The novel strategy was chosen less frequently in women without compared with women with decision aid (67% vs 78%, p = 0.004). The decision aid was graded with an 8 out of 10 by both women and professionals, and 78% of the women would recommend this decision aid to others. Users of the decision aid reported increased knowledge about the options and increased insight in personal values. Knowledge on cancer risk, decisional conflict, decisional regret and cancer worry were similar in both cohorts. CONCLUSIONS: The use of the patient decision aid for risk-reducing surgery is feasible, effective and highly appreciated among BRCA1/2-PV carriers facing the decision between salpingo-oophorectomy or salpingectomy with delayed oophorectomy.

Fallopian tube abnormalities in uterine serous carcinoma.

OBJECTIVE: Uterine serous carcinoma (USC) is presumed to arise from endometrial intra-epithelial carcinoma (EIC), whereas tubo-ovarian high-grade serous carcinomas have similar precursor lesions in the Fallopian tube, i.e. serous tubal intra-epithelial carcinoma (STIC). The presence of Fallopian tube abnormalities and their clonal relationship to the concurrent USC was investigated. METHODS: In this multicenter study, all patients treated for USC between 1992 and 2017 were retrospectively identified. Histopathological diagnosis of USC, EIC and STIC was revised by an expert pathologist. Additionally, all Fallopian tube sections were immunohistochemically stained (p53 and Ki-67). Fallopian tube abnormalities were classified as either p53 signature, serous tubal intra-epithelial lesion (STIL) or STIC. The USCs and Fallopian tube abnormalities were analyzed by targeted next-generation sequencing. RESULTS: In 168 included patients, Fallopian tube abnormalities were found in 27.4% (46/168): p53-signatures in 17.9% (30/168), STILs in 3.0% (5/168) and STICs in 6.5% (11/168). In subgroup analysis, STICs were found in 9.5% (11/115) of patients with at least one section of the fimbriated end embedded. Next-generation sequencing showed identical TP53-mutations in the STIC and corresponding USC. CONCLUSIONS: In conclusion, the presence of Fallopian tube abnormalities was shown in a high percentage of patients with USC, representing either true precursor lesions or metastasized disease.

Hysterectomy with opportunistic salpingectomy versus hysterectomy alone.

BACKGROUND: Ovarian cancer has the highest mortality rate of all gynaecological malignancies with an overall five-year survival rate of 30% to 40%. In the past two decades it has become apparent and more commonly accepted that a majority of ovarian cancers originate in the fallopian tube epithelium and not from the ovary itself. This paradigm shift introduced new possibilities for ovarian cancer prevention. Salpingectomy during a hysterectomy for benign gynaecological indications (also known as opportunistic salpingectomy) might reduce the overall incidence of ovarian cancer. Aside from efficacy, safety is of utmost importance, especially due to the preventive nature of opportunistic salpingectomy. Most important are safety in the form of surgical adverse events and postoperative hormonal status. Therefore, we compared the benefits and risks of hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy. OBJECTIVES: To assess the effect and safety of hysterectomy with opportunistic salpingectomy versus hysterectomy without salpingectomy for ovarian cancer prevention in women undergoing hysterectomy for benign gynaecological indications; outcomes of interest include the incidence of epithelial ovarian cancer, surgery-related adverse events and postoperative ovarian reserve. SEARCH METHODS: The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two clinical trial registers were searched in January 2019 together with reference checking and contact with study authors. SELECTION CRITERIA: We intended to include both randomised controlled trials (RCTs) and non-RCTs that compared ovarian cancer incidence after hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For assessment of surgical and hormonal safety, we included RCTs that compared hysterectomy with opportunistic salpingectomy to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were ovarian cancer incidence, intraoperative and short-term postoperative complication rate and postoperative hormonal status. Secondary outcomes were total surgical time, estimated blood loss, conversion rate to open surgery (applicable only to laparoscopic and vaginal approaches), duration of hospital admission, menopause-related symptoms and quality of life. MAIN RESULTS: We included seven RCTs (350 women analysed). The evidence was of very low to low quality: the main limitations being a low number of included women and surgery-related adverse events, substantial loss to follow-up and a large variety in outcome measures and timing of measurements.No studies reported ovarian cancer incidence after hysterectomy with opportunistic salpingectomy compared to hysterectomy without opportunistic salpingectomy in women undergoing hysterectomy for benign gynaecological indications. For surgery-related adverse events, there were insufficient data to assess whether there was any difference in both intraoperative (odds ratio (OR) 0.66, 95% confidence interval (CI) 0.11 to 3.94; 5 studies, 286 participants; very low-quality evidence) and short-term postoperative (OR 0.13, 95% CI 0.01 to 2.14; 3 studies, 152 participants; very low-quality evidence) complication rates between hysterectomy with opportunistic salpingectomy and hysterectomy without opportunistic salpingectomy because the number of surgery-related adverse events was very low. For postoperative hormonal status, the results were compatible with no difference, or with a reduction in anti-Müllerian hormone (AMH) that would not be clinically relevant (mean difference (MD) -0.94, 95% CI -1.89 to 0.01; I2 = 0%; 5 studies, 283 participants; low-quality evidence). A reduction in AMH would be unfavourable, but due to wide CIs, the postoperative change in AMH can still vary from a substantial decrease to even a slight increase. AUTHORS' CONCLUSIONS: There were no eligible studies reporting on one of our primary outcomes - the incidence of ovarian cancer specifically after hysterectomy with or without opportunistic salpingectomy. However, outside the scope of this review there is a growing body of evidence for the effectiveness of opportunistic salpingectomy itself during other interventions or as a sterilisation technique, strongly suggesting a protective effect. In our meta-analyses, we found insufficient data to assess whether there was any difference in surgical adverse events, with a very low number of events in women undergoing hysterectomy with and without opportunistic salpingectomy. For postoperative hormonal status we found no evidence of a difference between the groups. The maximum difference in time to menopause, calculated from the lower limit of the 95% CI and the natural average AMH decline, would be approximately 20 months, which we consider to be not clinically relevant. However, the results should be interpreted with caution and even more so in very young women for whom a difference in postoperative hormonal status is potentially more clinically relevant. Therefore, there is a need for research on the long-term effects of opportunistic salpingectomy during hysterectomy, particularly in younger women, as results are currently limited to six months postoperatively. This limit is especially important as AMH, the most frequently used marker for ovarian reserve, recovers over the course of several months following an initial sharp decline after surgery. In light of the available evidence, addition of opportunistic salpingectomy should be discussed with each woman undergoing a hysterectomy for benign indication, with provision of a clear overview of benefits and risks.

Noninvasive diagnostic tools for pelvic congestion syndrome: a systematic review.

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.

A patient decision aid for risk-reducing surgery in premenopausal BRCA1/2 mutation carriers: Development process and pilot testing.

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.

Cervicovaginal specimen biomarkers for early detection of ovarian and endometrial cancer: A review.

BACKGROUND: In the last decade, technical innovations have resulted in the development of several minimally invasive diagnostic cancer tools. Within women at high risk of developing ovarian or endometrial cancer (EC) due to hereditary cancer syndrome, there is an urgent need for minimally invasive and patient-friendly methods to detect ovarian cancer and EC at an early stage. MATERIALS AND METHODS: We performed a systematic search of studies using DNA methylation or mutation analysis, microbiome, or proteomics performed on cervicovaginal specimens (smear, swab, or tampon) intended to detect ovarian and EC published until January 2024. RESULTS: Included studies (n = 36) showed high heterogeneity in terms of biomarkers used and outcomes, and only a few studies reported on the detection of biomarkers in high-risk subgroups. CONCLUSION: Based on the findings in this review, DNA methylation techniques seem to be the most promising for detecting ovarian and EC at early stages in the general population. Future validation of cervicovaginal DNA methylation techniques is needed to determine whether this technique might be beneficial in hereditary high-risk subgroups.

Recommendations for diagnosing STIC: a systematic review and meta-analysis.

Our understanding of the oncogenesis of high-grade serous cancer of the ovary and its precursor lesions, such as serous tubal intraepithelial carcinoma (STIC), has significantly increased over the last decades. Adequate and reproducible diagnosis of these precursor lesions is important. Diagnosing STIC can have prognostic consequences and is an absolute requirement for safely offering alternative risk reducing strategies, such as risk reducing salpingectomy with delayed oophorectomy. However, diagnosing STIC is a challenging task, possessing only moderate reproducibility. In this review and meta-analysis, we look at how pathologists come to a diagnosis of STIC. We performed a literature search identifying 39 studies on risk reducing salpingo-oophorectomy in women with a known BRCA1/2 PV, collectively reporting on 6833 patients. We found a pooled estimated proportion of STIC of 2.8% (95% CI, 2.0-3.7). We focused on reported grossing protocols, morphological criteria, level of pathologist training, and the use of immunohistochemistry. The most commonly mentioned morphological characteristics of STIC are (1) loss of cell polarity, (2) nuclear pleomorphism, (3) high nuclear to cytoplasmic ratio, (4) mitotic activity, (5) pseudostratification, and (6) prominent nucleoli. The difference in reported incidence of STIC between studies who totally embedded all specimens and those who did not was 3.2% (95% CI, 2.3-4.2) versus 1.7% (95% CI, 0.0-6.2) (p 0.24). We provide an overview of diagnostic features and present a framework for arriving at an adequate diagnosis, consisting of the use of the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, rational use of immunohistochemical staining, and obtaining a second opinion from a colleague.

Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis.

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.

No signs of subclinical atherosclerosis after risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers.

BACKGROUND: BRCA1/2 mutation carriers are generally exposed to early menopause due to risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 years. This risk-reducing intervention is based on a 10-40% life-time risk of ovarian cancer in this population. Although effective, premature and acute menopause induces non-cancer related morbidity in both the short and long term. Little is known about the impact of RRSO on the cardiovascular system. METHODS: This cross-sectional study explored the relationship between time since RRSO and signs of subclinical atherosclerosis, as measured by carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), in 165 BRCA1/2 mutation carriers. All participants, aged 40 to 63 years, underwent RRSO before the age of 45 years, and at least 5 years ago. Cardiovascular risk factors were assessed by questionnaires and a single screening visit. Data were analyzed using linear regression models. RESULTS: Mean CIMT was 692.7 µm (SD 87.0), and mean central PWV 6.40 m/s (SD 1.42). After adjustment for age and several relevant cardiovascular risk factors, time since RRSO was not associated with CIMT (ß=0.68 µm; 95% CI -4.02, 5.38) and PWV (ß=44 mm/s; 95% CI -32, 120). Compared to women of a reference group from the general population, lower systolic blood pressure [mean difference 12 mmHg; 95% confidence interval (CI) 10, 14] was found in BRCA1/2 mutation carriers. CONCLUSIONS: We found that, in BRCA1/2 mutation carriers, at 5 to 24 years follow-up, time since RRSO is not related to development of subclinical atherosclerosis. However, the follow-up period in these relatively young women might have been too short.

Association of Salpingectomy With Delayed Oophorectomy Versus Salpingo-oophorectomy With Quality of Life in BRCA1/2 Pathogenic Variant Carriers: A Nonrandomized Controlled Trial.

IMPORTANCE: Most women with a BRCA1/2 pathogenic variant undergo premature menopause with potential short- and long-term morbidity due to the current method of ovarian carcinoma prevention: risk-reducing salpingo-oophorectomy (RRSO). Because the fallopian tubes play a key role in ovarian cancer pathogenesis, salpingectomy with delayed oophorectomy may be a novel risk-reducing strategy with benefits of delaying menopause. OBJECTIVE: To compare menopause-related quality of life after risk-reducing salpingectomy (RRS) with delayed oophorectomy with RRSO in carriers of the BRCA1/2 pathogenic variant. DESIGN, SETTING, AND PARTICIPANTS: A multicenter nonrandomized controlled preference trial (TUBA study), with patient recruitment between January 16, 2015, and November 7, 2019, and follow-up at 3 and 12 months after surgery was conducted in all Dutch university hospitals and a few large general hospitals. In the Netherlands, RRSO is predominantly performed in these hospitals. Patients at the clinical genetics or gynecology department between the ages of 25 and 40 years (BRCA1) or 25 to 45 years (BRCA2) who were premenopausal, had completed childbearing, and were undergoing no current treatment for cancer were eligible. INTERVENTIONS: Risk-reducing salpingo-oophorectomy at currently recommended age or RRS after completed childbearing with delayed oophorectomy. After RRSO was performed, hormone replacement therapy was recommended for women without contraindications. MAIN OUTCOMES AND MEASURES: Menopause-related quality of life as assessed by the Greene Climacteric Scale, with a higher scale sum (range, 0-63) representing more climacteric symptoms. Secondary outcomes were health-related quality of life, sexual functioning and distress, cancer worry, decisional regret, and surgical outcomes. RESULTS: A total of 577 women (mean [SD] age, 37.2 [3.5] years) were enrolled: 297 (51.5%) were pathogenic BRCA1 variant carriers and 280 (48.5%) were BRCA2 pathogenic variant carriers. At the time of analysis, 394 patients had undergone RRS and 154 had undergone RRSO. Without hormone replacement therapy, the adjusted mean increase from the baseline score on the Greene Climacteric Scale was 6.7 (95% CI, 5.0-8.4; P < .001) points higher during 1 year after RRSO than after RRS. After RRSO with hormone replacement therapy, the difference was 3.6 points (95% CI, 2.3-4.8; P < .001) compared with RRS. CONCLUSIONS AND RELEVANCE: Results of this nonrandomized controlled trial suggest that patients have better menopause-related quality of life after RRS than after RRSO, regardless of hormone replacement therapy. An international follow-up study is currently evaluating the oncologic safety of this therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02321228.

Factors influencing decision-making around opportunistic salpingectomy: a nationwide survey.

OBJECTIVE: To explore current practice and influencing factors on adoption of the opportunistic salpingectomy (OS), particularly regarding the decision making, to eventually enhance the development and implementation of clear guidelines. METHODS: This nationwide cross-sectional survey study was conducted in all hospitals in the Netherlands. An anonymous online survey was sent to gynecologists with special interest in gynecological oncology, gynecological endoscopy or urogynecology and all Dutch gynecology trainees. The survey mainly focused on current practice regarding OS and identification of influencing factors on the level of innovation, organization, healthcare professional and individual patient. RESULTS: The response rate was 348 out of 597 gynecologists (58.3%) and 142 out of 340 trainees (41.8%). Current practice of discussing and performing the OS varied widely, with ovarian cancer (OC) risk reduction as most important supportive factor on innovation level. Supportive factors on the level of organization and healthcare provider were; working in a non-training hospital, knowledge of current literature and extensive work experience (in years and annual number of hysterectomies). On individual patient level, a vaginal approach of hysterectomy, negative family history for OC and the presence of firm adhesions were suppressive factors for the OS. CONCLUSION: In this study we evaluated the current practice regarding the opportunistic salpingectomy in the Netherlands and identified influencing factors on different levels to raise awareness and attribute to development of a targeted implementation strategy, on both national and international level.