Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal (PROTECTOR): protocol for a prospective non-randomised multi-center trial

Int J Gynecol Cancer. 2021 Feb;31(2):286-291. doi: 10.1136/ijgc-2020-001541. Epub 2020 Sep 8.

Abstract

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).

Keywords: gynecologic surgical procedures; ovarian cancer; surgery.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein
  • BRCA2 Protein
  • Female
  • Humans
  • Multicenter Studies as Topic
  • Neoplasms, Cystic, Mucinous, and Serous / genetics
  • Neoplasms, Cystic, Mucinous, and Serous / prevention & control*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / prevention & control*
  • Ovariectomy / adverse effects
  • Ovariectomy / methods*
  • Premenopause
  • Prospective Studies

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human

Associated data

  • ISRCTN/ISRCTN25173360