Background Risk-reducing salpingo-oophorectomy is the 'gold standard' for preventing tubo-ovarian cancer in women at increased risk. However, when performed in pre-menopausal women, it results in premature menopause and associated detrimental health consequences. This, together with acceptance of the central role of the fallopian tube in etiopathogenesis of high-grade serous carcinoma, by far the most common type of tubo-ovarian cancer, has led to risk-reducing early salpingectomy with delayed oophorectomy being proposed as a two-step surgical alternative for pre-menopausal women declining/delaying oophorectomy.
Primary Objective To evaluate the impact on sexual function of risk-reducing early salpingectomy, within a two-step, risk-reducing, early salpingectomy with delayed oophorectomy tubo-ovarian cancer prevention strategy in pre-menopausal women at increased risk of tubo-ovarian cancer.
Study Hypothesis Risk-reducing early salpingectomy is non-inferior for sexual and endocrine function compared with controls; risk-reducing early salpingectomy is superior for sexual/endocrine function, non-inferior for quality-of-life, and equivalent in satisfaction to the standard risk-reducing salpingo-oophorectomy.
Trial Design Multi-center, observational cohort trial with three arms: risk-reducing early salpingectomy with delayed oophorectomy; risk-reducing salpingo-oophorectomy; controls (no surgery). Consenting individuals undergo an ultrasound, serum CA125, and follicle-stimulating hormone measurements and provide information on medical history, family history, quality-of-life, sexual function, cancer worry, psychological well-being, and satisfaction/regret. Follow-up by questionnaire takes place annually for 3 years. Women receiving risk-reducing early salpingectomy can undergo delayed oophorectomy at a later date of their choosing, or definitely by the menopause.
Major Inclusion/Exclusion Criteria Inclusion criteria: pre-menopausal; aged >30 years; at increased risk of tubo-ovarian cancer (mutation carriers or on the basis of a strong family history); completed their family (for surgical arms). Exclusion criteria: post-menopausal; previous bilateral salpingectomy or bilateral oophorectomy; pregnancy; previous tubal/ovarian/peritoneal malignancy; <12 months after cancer treatment; clinical suspicion of tubal/ovarian cancer at baseline.
Primary Endpoint Sexual function measured by validated questionnaires.
Sample Size 1000 (333 per arm).
Estimated Dates for Completing Accrual and Presenting Results It is estimated recruitment will be completed by 2023 and results published by 2027.
Trial Registration Number ISRCTN registry: 25 173 360 (https://doi.org/10.1186/ISRCTN25173360).
- gynecologic surgical procedures
- ovarian cancer
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Collaborators PROTECTOR team: Katie Snape, Sadaf Ghaem-Maghami, Gautam Mehra, Angela Brady, Adam Rosenthal, Michelle MacKintosh, Ian Harley, Sudha Sundar, Claire Newton, Omer Devaja, Tim Duncan, Supratik Chattopadhyay, Natalia Povolotskaya, Rema Iyer, Lucy Side, Anil Tailor, Manon van Seters, Suma Kodiathodi, Partha Sengupta, Iain Cameron, Sonali Kaushik, Karin Williamson, Katherine Edey, Sian Taylor, Andrew Phillips, Mark Willett, Tony Chalhoub, Sanjay Rao,Nicholas Matthews, Aarti Sharma, Scott Fegan, Mahalakshmi Gurumurthy, Kalpana Ragupathy, Beena Abdul, Ibraheem Hamoodi, Claire Park, Jane Borley, Richard Hutson, Kerryn Lutchman-Singh, Richard Peevor.
Contributors Trial conception and design: RM. Protocol development: RM, UM, GE, NS, FG, MB, RL, WGM, RG, NW, GB, GR. Pathology committee: NS, WGM, NW, RG, GB, GR, RA, RM, FG. Trial management: RM, FG, SR, CT, NS, UM, GE, ES, HH. Preparation of tables and figures: FG, RM. Initial draft of manuscript: FG, RM. Statistical aspects: MB, RM, RL. Manuscript writing and approval: all authors.
Funding This trial is funded by Barts and The London Charity and Roseetrees Trust.
Competing interests RM declares research funding from Barts and The London Charity and Roseetrees Trust for the PROTECTOR Study and is chief investigator. RM declares research funding from The Eve Appeal and Cancer Research UK outside this work, as well as an honorarium for grant review from Israel National Institute for Health Policy Research and from MSD and Astrazneca for advisory board meetings. RM is supported by an NHS Innovation Accelerator (NIA) Fellowship for population testing. UM has a financial interest in Abcodia, Ltd, a company formed to develop academic and commercial development of biomarkers for screening and risk prediction. The authors declare no conflict of interest. GE is supported through the NIHR Manchester Biomedical Research Centre (IS-BRC1215-20007).
Patient consent for publication Not required.
Provenance and peer review Commissioned; internally peer reviewed.
Data availability statement All relevant data are included in the article or uploaded as supplementary information. A copy of the protocol can be requested from the corresponding author or the study team.