Background: Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard method of ovarian cancer risk reduction, but the data are conflicting regarding the impact on breast cancer (BC) outcomes. This study aimed to quantify BC risk/mortality in BRCA1/BRCA2 carriers after RRSO. Methods: We conducted a systematic review (CRD42018077613) of BRCA1/BRCA2 carriers undergoing RRSO, with the outcomes including primary BC (PBC), contralateral BC (CBC) and BC-specific mortality (BCSM) using a fixed-effects meta-analysis, with subgroup analyses stratified by mutation and menopause status. Results: RRSO was not associated with a significant reduction in the PBC risk (RR = 0.84, 95%CI: 0.59–1.21) or CBC risk (RR = 0.95, 95%CI: 0.65–1.39) in BRCA1 and BRCA2 carriers combined but was associated with reduced BC-specific mortality in BC-affected BRCA1 and BRCA2 carriers combined (RR = 0.26, 95%CI: 0.18–0.39). Subgroup analyses showed that RRSO was not associated with a reduction in the PBC risk (RR = 0.89, 95%CI: 0.68–1.17) or CBC risk (RR = 0.85, 95%CI: 0.59–1.24) in BRCA1 carriers nor a reduction in the CBC risk in BRCA2 carriers (RR = 0.35, 95%CI: 0.07–1.74) but was associated with a reduction in the PBC risk in BRCA2 carriers (RR = 0.63, 95%CI: 0.41–0.97) and BCSM in BC-affected BRCA1 carriers (RR = 0.46, 95%CI: 0.30–0.70). The mean NNT = 20.6 RRSOs to prevent one PBC death in BRCA2 carriers, while 5.6 and 14.2 RRSOs may prevent one BC death in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers, respectively. Conclusions: RRSO was not associated with PBC or CBC risk reduction in BRCA1 and BRCA2 carriers combined but was associated with improved BC survival in BC-affected BRCA1 and BRCA2 carriers combined and BRCA1 carriers and a reduced PBC risk in BRCA2 carriers.

The number of patients desiring fertility-preserving treatment for endometrial cancer rather than standard surgical management continues to increase. We aimed to evaluate the efficacies of fertility-preserving treatments on the live birth rate, remission and relapse rates for women with stage 1a grade 1 endometrial carcinoma to support patient counselling. We performed a meta-analysis for our primary outcomes of overall remission and relapse rate, and for secondary analysis, we divided papers into treatment type: systemic progestins, intrauterine progestins or hysteroscopic resection and adjuvant hormonal treatment. Thirty-five observational studies met inclusion criteria, with a total of 624 patients. Overall, conservative treatment of endometrial cancer showed a remission rate of 77% (95% CI: 70-84%), a relapse rate of 20% (95% CI: 13-27%) and a live birth rate of 20% (95% CI: 15-25%) with more favourable outcomes for the hysteroscopic resection group. Hysteroscopic resection and adjuvant hormonal treatment had the most favourable fertility and oncological outcomes. Further high-quality prospective multi-centre trials are warranted to determine the optimal treatment regimen and dosage and risk stratification for these patients.

Policymakers require robust cost-effectiveness evidence of risk-reducing-surgery (RRS) for decision making on resource allocation for breast cancer (BC)/ovarian cancer (OC)/endometrial cancer (EC) prevention. We aimed to summarise published data on the cost-effectiveness of risk-reducing mastectomy (RRM)/risk-reducing salpingo-oophorectomy (RRSO)/risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) for BC/OC prevention in intermediate/high-risk populations; hysterectomy and bilateral salpingo-oophorectomy (BSO) in Lynch syndrome women; and opportunistic bilateral salpingectomy (OBS) for OC prevention in baseline-risk populations. Major databases were searched until December 2021 following a prospective protocol (PROSPERO-CRD42022338008). Data were qualitatively synthesised following a PICO framework. Twenty two studies were included, with a reporting quality varying from 53.6% to 82.1% of the items scored in the CHEERS checklist. The incremental cost-effectiveness ratio/incremental cost-utility ratio and cost thresholds were inflated and converted to US$2020, using the original currency consumer price index (CPI) and purchasing power parities (PPP), for comparison. Eight studies concluded that RRM and/or RRSO were cost-effective compared to surveillance/no surgery for BRCA1/2, while RRESDO was cost-effective compared to RRSO in one study. Three studies found that hysterectomy with BSO was cost-effective compared to surveillance in Lynch syndrome women. Two studies showed that RRSO was also cost-effective at ≥4%/≥5% lifetime OC risk for pre-/post-menopausal women, respectively. Seven studies demonstrated the cost-effectiveness of OBS at hysterectomy (n = 4), laparoscopic sterilisation (n = 4) or caesarean section (n = 2). This systematic review confirms that RRS is cost-effective, while the results are context-specific, given the diversity in the target populations, health systems and model assumptions, and sensitive to the disutility, age and uptake rates associated with RRS. Additionally, RRESDO/OBS were sensitive to the uncertainty concerning the effect sizes in terms of the OC-risk reduction and long-term health impact. Our findings are relevant for policymakers/service providers and the design of future research studies.

Introduction: Ovarian cancer is associated with a venous thromboembolism risk of at least 7.2% by 2 years from diagnosis, and although patients undergoing surgery benefit from routine thromboprophylaxis, those undergoing neoadjuvant chemotherapy do not. This study aims to determine the venous thromboembolism incidence in patients with ovarian cancer undergoing neoadjuvant chemotherapy, and explore whether any subset is at higher risk, in order to evaluate whether thromboprophylaxis is justified in some or all of these patients.Material and methods: This was a retrospective review of all women undergoing neoadjuvant chemotherapy for FIGO radiological stages III and IV primary ovarian, fallopian tube, and primary peritoneal cancer, between 2000 and 2015, in a London tertiary cancer center. The primary outcome was venous thromboembolism rate among women undergoing neoadjuvant chemotherapy. The secondary outcomes were patient or treatment factors associated with venous thromboembolism risk, including age, body mass index, smoking status, performance status, and tumor stage.Results: We identified 278 eligible women from the ovarian cancer database. Fifty‐eight women (20.9%) developed venous thromboembolism between initial presentation and the immediate postoperative period, of which 45 (77.6%) developed a pulmonary embolism. In all, 15.1% of women developed venous thromboembolism from the start of neoadjuvant chemotherapy. Age, body mass index, smoking, or other comorbidities were not significantly associated with venous thromboembolism risk. One woman died from massive pulmonary embolism, 27 women underwent inferior vena cava filter insertion, and 10 had surgery delayed.Conclusions: This study demonstrates an unacceptably high rate of avoidable venous thromboembolism including pulmonary embolism in these women, which complicates and delays treatment. Thromboprophylaxis during neoadjuvant chemotherapy should now be assessed prospectively.

Background/Objective: Platinum-resistant ovarian cancer (PROC) has limited therapeutic options, and the role of cytoreductive surgery (CRS) in improving survival outcomes remains uncertain. We performed a systematic review to evaluate the oncological benefit of CRS on PROC patients and the associated surgical morbidity and mortality. Methods: We followed a prospective protocol according to PRISMA guidelines. We searched PubMed, Medline, and Embase till October 2024. We used a “Population Intervention Comparator Outcomes (PICO)” framework. Our population included women with epithelial PROC who underwent CRS with/without chemotherapy. Our outcomes included overall survival (OS), progression-free-survival (PFS), post-operative morbidity and mortality and Quality of Life. Results: Our search yielded 6590 citations; six studies (N = 155 patients) were included. There is limited evidence available on the role of CRS in PROC, with notable variation in reported outcomes and outcomes’ measures; therefore, we were unable to perform quantitative synthesis. CRS demonstrated survival benefits in well-selected PROC patients, particularly those with limited, isolated recurrences, low tumour burden, and good performance status. Complete resection (R0) was associated with significantly longer OS/PFS compared to those who had suboptimal surgeries (R1/R2). Conclusions: CRS seems to extend survival in carefully selected PROC patients, especially those with limited disease spread and favourable surgical profiles. Nevertheless, CRS carries substantial surgical risks, and its benefits appear contingent upon achieving R0. Further prospective trials with standardised patient selection criteria are needed to define CRS’s role in PROC. At present, CRS in PROC should be considered within a multidisciplinary approach in specialised gynaecological oncology centres, with the careful assessment of patient-specific risk factors and potential for R0 resection.

Background: Risk-reducing hysterectomy (RRH) is the gold-standard prevention for endometrial cancer (EC). Knowledge of the impact on quality-of-life (QoL) is crucial for decision-making. This systematic review aims to summarise the evidence. Methods: We searched major databases until July 2022 (CRD42022347631). Given the paucity of data on RRH, we also included hysterectomy as treatment for benign disease. We used validated quality-assessment tools, and performed qualitative synthesis of QoL outcomes. Results: Four studies (64 patients) reported on RRH, 25 studies (1268 patients) on hysterectomy as treatment for uterine bleeding. There was moderate risk-of-bias in many studies. Following RRH, three qualitative studies found substantially lowered cancer-worry, with no decision-regret. Oophorectomy (for ovarian cancer prevention) severely impaired menopause-specific QoL and sexual-function, particularly without hormone-replacement. Quantitative studies supported these results, finding low distress and generally high satisfaction. Hysterectomy as treatment of bleeding improved QoL, resulted in high satisfaction, and no change or improvements in sexual and urinary function, although small numbers reported worsening. Conclusions: There is very limited evidence on QoL after RRH. Whilst there are benefits, most adverse consequences arise from oophorectomy. Benign hysterectomy allows for some limited comparison; however, more research is needed for outcomes in the population of women at increased EC-risk.