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PROTECTOR

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  1. PROTECTOR Study (BCI)
  2. Information for health professionals
  3. Background

Background

  • In the UK, ovarian cancer is diagnosed in around 7,500 women each year.
  • Ovarian cancer has the highest mortality rate of all the gynaecological cancers.
  • Despite significant efforts to develop new drugs and treatment strategies, ovarian cancer survival rates have remained much poorer than other cancers. 

Familial cancers are responsible for 15-20% of ovarian cancers and mutations in the BRCA1/BRCA2 genes account for most of the known hereditary risk. BRCA1/BRCA2 carriers have ~69-72% and ~17-44% risk of developing breast and ovarian cancer, respectively. Screening is not currently available or recommended outside the context of a clinical trial.

Primary surgical prevention remains the most proven effective method for reducing population incidence of ovarian cancer. Risk Reducing Salpingo-Oophorectomy (RRSO) is the gold standard for ovarian cancer risk reduction in those at increased (high and intermediate) risk. Traditionally, women at ≥10% life time risk were considered to be high risk and offered options of risk management and surgical prevention. We recently defined the threshold for surgical prevention to be ≥5% life time risk of ovarian cancer, thus showing clinical utility and enabling intermediate risk women to access surgical prevention.  This includes those with recently identified moderate penetrance genetic mutations (ovarian cancer risks 5-11%) such as RAD51C, RAD51D, BRIP1, and PALB2, and mutation negative women with a strong family history of ovarian cancer.  

Rationale for study

RRSO has been reported to reduce the risk of epithelial ovarian cancer (EOC) by >80%. RRSO leads to a reduction in cancer specific and all-cause mortality. However RRSO is not without detrimental consequences. In pre-menopausal women it leads to surgical menopause and the cessation of fertility. Women must be adequately counselled regarding the effects of premature surgical menopause and its detrimental health sequelae including increased risk of cardiovascular disease, osteoporosis, vasomotor symptoms, dementia/cognitive dysfunction and sexual dysfunction, particularly in women who do not or are unable to take hormone replacement therapy (HRT). As a result, a number of women choose to delay surgery until after menopause.  

With growing evidence that the fallopian tube is the site of origin of a large proportion of EOC, Risk-reducing Early Salpingectomy with Delayed Oophorectomy (RRESDO) has been suggested as an attractive two-stage alternative prevention strategy to RRSO. This has the advantage of providing some level of risk reduction to women who wish to decline or delay RRSO whilst conserving ovarian function and avoiding the detrimental sequelae of early surgical menopause. However, prospective outcome data for this approach is lacking. The exact extent of ovarian cancer risk reduction plus long-term consequences on ovarian function are not known.

 

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